Peripheral Arterial Disease

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Peripheral Arterial Disease

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Peripheral Arterial Disease Editors Robert S. Dieter, MD, RVT Assistant Professor of Medicine Vascular and Endovascular Medicine Cardiology Loyola University Maywood, Illinois Raymond A. Dieter Jr., MD, MS Past World President, International College of Surgeons President, Center for Surgery Glen Ellyn, Illinois Raymond A. Dieter III, MD Associate Professor of Surgery Cardiothoracic Surgery University of Tennessee Medical Center Knoxville, Tennessee

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To my wonderful wife who has been patient and supportive through all of my training and pursuits, my children who bring a smile to my face every day, my parents and family who taught me to always strive to do my best. To God who makes it all possible.

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Contents Contributors ix Foreword xvii Preface xix

1

The Epidemiology of Peripheral Arterial Disease 1 Victor Aboyans and Michael H. Criqui

2

Gender Differences in the Epidemiology and Management of Vascular Disease 27 Parveen K. Garg, Suneel M. Udani, Arti Rupani, Karen Moncher, and Robert S. Dieter

3

Lipids in the Pathogenesis of Peripheral Arterial Disease 41 Jay Giri and Emile R. Mohler III

4

Vulnerable Plaque and the Role of Inflammation in Arterial Disease 49 Ghazanfar Khadim, Javed Butler, and Raymond Q. Migrino

5

The Endothelium in Health and Disease 65 Rainer H. B¨oger

6

7

Clinical Assessment of Endothelial Function 81

15 Connective Tissue Disorders in Peripheral Arterial Disease 233 David Liang and Gerald J. Berry

16 History and Physical Examination 249 Jessica A. Sutherland, Ferdinand S. Leya, and Robert S. Dieter

17 Noninvasive Arterial Imaging 269 Kevin P. Cohoon, John E. Gocke, Susan Bowes, and Robert S. Dieter

18 Magnetic Resonance Imaging in Peripheral Arterial Disease 307 Christopher Francois, James C. Carr, and Alex J. Auseon

19 CT Angiography 327

Flow Dynamics and Arterial Physiology 93

20 Peripheral Angiography 341

Blood Pressure Regulation 113 Kailash Prasad

9

Eamonn S. Molloy, Jos´e Hernandez-Rodr´ ´ ıguez, and Gary S. Hoffman

Julian P. J. Halcox, Ann E. Donald, and John E. Deanfield Patrick Segers, Luc M. Van Bortel, and Pascal R. Verdonck

8

14 Vasculitis 197

Hypertension 125 Kailash Prasad

10 Hypercoagulability and Peripheral Arterial Disease 141 Kathryn L. Hassell

11 Infections of the Peripheral Arterial System 157 Charulata Ramaprasad and David Pitrak

12 Overlap of Atherosclerotic Disease 177 Madhurmeet Singh, Ali Morshedi-Meibodi, Lowell H. Steen, and Robert S. Dieter

13 Coronary Artery Disease in Patients with Peripheral Arterial Disease 185 Pranab Das, Lowell H. Steen, and Debabrata Mukherjee

Michael Davis and Sanjay Rajagopalan Sohail Ikram, Massoud Leesar, and Ibrahim Fahsah

21 Intravascular Ultrasound in Peripheral Arterial Disease 375 Daniel H. Steinberg, Esteban Escolar, Robert A. Gallino, and Neil J. Weissman

22 Arterial Diseases of the Eye 393 Robert J. Barnes

23 Intracranial Arterial Disease 401 Ramachandra P. Tummala, Babak S. Jahromi, and L. Nelson Hopkins

24 Extracranial Carotid Disease 443 Timothy M. Sullivan and Gustavo Oderich

25 Vertebrobasilar Disease 467 Monica Simionescu and Michael Schneck

26 Ascending Thoracic Aorta 483 Jose D. Amortegui and Thomas E. Gaines vii

viii • Contents

27 Ascending Thoracic Aorta and Aortic Arch 513 Thomas E. Gaines

40 Gene Therapy for Peripheral Arterial Disease 803 Daniel R. Guerra and Brian H. Annex

28 Aortic Arch Vessels and Upper Extremity Arteries 539 David C. Cassada and Trent L. Prault

29 Descending Thoracic Aorta 551 Daniel Alterman and Raymond A. Dieter III

41 Peripheral Arterial Brachytherapy 819 Ron Waksman

42 Diabetic Peripheral Arterial Disease 827 James M. Scanlon, Robyn A. Macsata, Richard F. Neville, and Anton N. Sidawy

30 Abdominal Aorta 569 J. William Mix, Sridevi R. Pitta, Jeffrey P. Schwartz, J. Michael Tuchek, Robert S. Dieter, and Michael B. Freeman

31 Mesenteric Artery Disease 593 Pranab Das, Aravinda Nanjundappa, John P. Pacanowski Jr., M. Habeeb Ahmed, Michael L. Eng, and Raymond A. Dieter Jr.

32 Renal Artery Disease 619 Brian Guttormsen and Giorgio Gimelli

33 Lower Extremity Peripheral Arterial Disease 639 Ravi K. Ramana, Bruce E. Lewis, and Robert S. Dieter

34 Medical Therapy of Intermittent Claudication 703 Manu Rajachandran and Robert M. Schainfeld

43 Wound Care 843 David G. Stanley

44 Erectile Dysfunction 853 Ryan Payne and Peter Langenstroer

45 Embolic Disorders of the Pulmonary Artery 865 Tina M. Dudney, Michael T. McCormack, and Jeffrey H. Freihage

46 Nonembolic Disorders of the Pulmonary Artery 901 Jeffrey H. Freihage, Tina M. Dudney, and Michael T. McCormack

47 Steal Syndromes 935 Raymond A. Dieter Jr. and George B. Kuzycz

48 Hemodialysis Access 945 35 Approach to the Patient with Critical Limb Ischemia of the Lower Extremities: Chronic Peripheral Arterial Disease 713 Christy M. Lawson and Oscar Grandas

36 Acute Limb Ischemia 737 Brian Reed and Mitchell H. Goldman

37 Lower Extremity Revascularization for Atherosclerotic Occlusive Disease 747 John B. Chang, Robert W. Chang, and L. Michael Graver

John B. Chang, Robert W. Chang, and Lorena De Marco Garcia

49 Vascular Trauma 959 Brian J. Daley, J. Fernando Aycinena, Ali F. Mallat, and Dana A. Taylor

50 Primary Vascular Tumors 993 Samuel L. Johnston, Terrence C. Demos, Edward J. Keuer, Mamdouh Bakhos, and Robert S. Dieter

51 Contemporary Treatment of Congenital Vascular Malformations 1025 Dirk A. Loose

38 Endovascular Therapies in Peripheral Arterial Disease 787 Michael H. Lebow and Scott L. Stevens

39 The Vascular Biology and Clinical Efficacy of DrugEluting Stents for the Treatment of Peripheral Arterial Disease 795 Robert S. Dieter, Leonardo Clavijo, Scott L. Stevens, and John R. Laird

52 Arterial Complications in Transplantation 1041 Roberto Gedaly, Salik Jahania, and Dinesh Ranjan

53 Diagnosis and Management of Perioperative Ischemic Stroke 1053 Michael J. Schneck and Simona Velicu Index 1061

Contributors Victor Aboyans, MD, PhD Department of Family and Preventive Medicine University of California, San Diego La Jolla, California Department of Thoracic and Cardiovascular Surgery and Angiology Dupuytren University Hospital Limoges, France M. Habeeb Ahmed, MD, RVT Director, Center for Cardiovascular Care San Jose, California Daniel Alterman, MD Department of Surgery Graduate School of Medicine University of Tennessee Knoxville, Tennessee Jose D. Amortegui, MD Department of Surgery Graduate School of Medicine University of Tennessee Knoxville, Tennessee Brian H. Annex, MD Division of Cardiology Department of Medicine Durham Veterans Affairs and Duke University Medical Center Durham, North Carolina Alex J. Auseon, DO Division of Cardiovascular Medicine Department of Internal Medicine Ohio State University College of Medicine Columbus, Ohio J. Fernando Aycinena, MD Department of Surgery University of Tennessee Medical Center at Knoxville Knoxville, Tennessee Mamdouh Bakhos, MD Professor and Chairman, Department of Thoracic and Cardiovascular Surgery Loyola University Medical Center and Stritch School of Medicine Maywood, Illinois

Robert J. Barnes, MD Associate Clinical Professor of Ophthalmology Loyola University Medical Center Maywood, Illinois Gerald J. Berry, MD Professor of Pathology Director of Cardiac Pathology Stanford University Medical Center Stanford, California Rainer H. Boger, MD ¨ Clinical Pharmacology Unit Institute of Experimental and Clinical Pharmacology University Hospital Hamburg-Eppendorf Hamburg, Germany Susan Bowes, RVT Director Non-Invasive Cardiology and Vascular Services Washington Hospital Center Washington, DC Javed Butler, MD, MPH Cardiology Division Emory Crawford Long Hospital Atlanta, Georgia James C. Carr, MD Department of Radiology Feinberg School of Medicine Northwestern University Chicago, Illinois David C. Cassada, MD Division of Vascular/Transplant Surgery University of Tennessee Medical Center Knoxville, Tennessee John B. Chang, MD Professor of Clinical Surgery Albert Einstein College of Medicine Bronx, New York Director Long Island Vascular Center Roslyn, New York Robert W. Chang, MD Department of Surgery Division of Vascular Surgery Dartmouth-Hitchcock Medical Center Lebanon, New Hampshire ix

x • Contributors

Leonardo Clavijo, MD, PhD Assistant Professor of Clinical Medicine Director of Vascular Medicine and Peripheral Interventions University of Southern California Los Angeles, California Kevin P. Cohoon, DO Cardiology Loyola University Medical Center Maywood, Illinois Michael H. Criqui, MD, MPH Department of Medicine Department of Family and Preventive Medicine University of California, San Diego La Jolla, California Brian J. Daley, MD Department of Surgery Graduate School of Medicine University of Tennessee Knoxville, Tennessee Pranab Das, MD Cardiology Loyola University Stritch School of Medicine Maywood, Illinois Michael Davis, MD Division of Cardiovascular Medicine Ohio State University School of Medicine Davis Heart and Lung Research Institute Columbus, Ohio John E. Deanfield, MB BHF Vandervell Professor of Cardiology Great Ormond Street Hospital and Institute of Child Health University College London London, England, United Kingdom Terrence C. Demos, MD Professor, Department of Radiology Loyola University Medical Center and Stritch School of Medicine Maywood, Illinois Raymond A. Dieter Jr., MD, MS Past World President International College of Surgeons President, Center for Surgery Glen Ellyn, Illinois Raymond A. Dieter III, MD Associate Professor of Surgery Cardiothoracic Surgery University of Tennessee Medical Center Knoxville, Tennessee

Robert S. Dieter, MD, RVT Assistant Professor of Medicine Cardiology Loyola University Maywood, Illinois Ann E. Donald, AVS Clinical Vascular Scientist (Research) Department of Clinical Pharmacology St. Thomas’ Hospital London, England, United Kingdom Tina M. Dudney, MD Pulmonary Disease Fellowship Program Director Assistant Professor of Medicine Graduate School of Medicine University of Tennessee Division Chief of Pulmonary/Critical Care and Section Chief of Pulmonary Medicine University of Tennessee Medical Center Knoxville, Tennessee Michael L. Eng, MD Assistant Professor Department of Thoracic and Cardiovascular Surgery Loyola University Medical Center Maywood, Illinois Esteban Escolar, MD Washington Hospital Center and Georgetown University Washington, DC Ibrahim Fahsah, MD Interventional Cardiology University of Louisville Louisville, Kentucky Christopher Francois, MD Department of Radiology Feinberg School of Medicine Northwestern University Chicago, Illinois Michael B. Freeman, MD Professor of Surgery Department of Surgery Chief, Division of Vascular Surgery Graduate School of Medicine University of Tennessee Knoxville, Tennessee Jeffrey H. Freihage, MD Cardiology Loyola University Medical Center Maywood, Illinois Thomas E. Gaines, MD Cardiothoracic Surgery Graduate School of Medicine University of Tennessee Knoxville, Tennessee

Contributors • xi

Robert A. Gallino, MD Washington Hospital Center and Georgetown University Washington, DC Lorena De Marco Garcia, MD Department of Surgery North Shore University Hospital North Shore-Long Island Jewish Health System Manhasset, New York Parveen K. Garg, MD, MPH Department of Medicine New York University School of Medicine New York, New York Roberto Gedaly, MD Department of Surgery Transplant Division University of Kentucky Lexington, Kentucky Giorgio Gimelli, MD Director, Cardiac Catheterization Laboratory Cardiovascular Medicine Division University of Wisconsin School of Medicine and Public Health Madison, Wisconsin Jay Giri, MD, MPH Department of Medicine Massachusetts General Hospital Harvard University Boston, Massachusetts John E. Gocke, MD, MPH, RVT, RPVI Medical Director Vascular Laboratory Adventist La Grange Memorial Hospital La Grange, Illinois Mitchell H. Goldman, MD Professor and Chairman Department of Surgery Graduate School of Medicine University of Tennessee Knoxville, Tennessee Oscar Grandas, MD Assistant Professor of Surgery Department of Surgery University of Tennessee Knoxville, Tennessee L. Michael Graver, MD Clinical Professor of Surgery Chairman Department of Cardiothoracic Surgery Long Island Jewish Medical Center New Hyde Park, New York

Daniel R. Guerra, MD Division of Cardiology Department of Medicine Durham Veterans Affairs and Duke University Medical Center Durham, North Carolina Brian Guttormsen, MD Cardiovascular Medicine Division University of Wisconsin School of Medicine and Public Health Madison, Wisconsin Julian P.J. Halcox, MA, MD Professor of Cardiology Cardiff University Wales Heart Research Institute Cardiff, Wales, United Kingdom Kathryn L. Hassell, MD Associate Professor of Medicine Division of Hematology University of Colorado Denver and Health Sciences Center Denver, Colorado Jose´ Hernandez-Rodr´ ıguez, MD, PhD ´ Center for Vasculitis Care and Research Department of Rheumatic and Immunologic Diseases Cleveland Clinic Cleveland, Ohio Gary S. Hoffman, MD, MS Center for Vasculitis Care and Research Department of Rheumatic and Immunologic Diseases Cleveland Clinic Cleveland, Ohio L. Nelson Hopkins, MD Professor and Chairman of Neurosurgery, Professor of Radiology, and Director of Toshiba Stroke Research Center State University of New York at Buffalo, New York Chairman, Department of Neurosurgery Millard Fillmore Gates Hospital Kaleida Health Buffalo, New York Sohail Ikram, MD Associate Professor of Medicine Director of Peripheral Vascular Interventions Associate Director of Interventional Cardiology University of Louisville Louisville, Kentucky Salik Jahania, MD Department of Surgery Transplant Division University of Kentucky Lexington, Kentucky

xii • Contributors

Babak S. Jahromi, MD, PhD Assistant Instructor of Clinical Neurosurgery and Endovascular Neurosurgery Fellow Department of Neurosurgery and Toshiba Stroke Research Center State University of New York at Buffalo, New York Department of Neurosurgery Millard Fillmore Gates Hospital Kaleida Health Buffalo, New York Samuel L. Johnston, MD Cardiology Loyola University Medical Center and Stritch School of Medicine Maywood, Illinois Edward J. Keuer, MD Department of Medicine (Dermatology) and Pediatrics Loyola University Medical Center and Stritch School of Medicine Maywood, Illinois Ghazanfar Khadim, MD Division of Cardiovascular Medicine Medical College of Wisconsin Milwaukee, Wisconsin George B. Kuzycz, MD Cardiothoracic and Vascular Surgery Northern Illinois Center for Surgery Naperville, Illinois John R. Laird, MD Medical Director Vascular Center University of California Davis Medical Center Sacramento, California Peter Langenstroer, MD, MS Associate Professor of Urology Department of Urology Medical College of Wisconsin Milwaukee, Wisconsin Christy M. Lawson, MD Department of Surgery University of Tennessee Knoxville, Tennessee Michael H. Lebow, MD Department of Surgery Graduate School of Medicine University of Tennessee Knoxville, Tennessee

Massoud Leesar, MD Professor of Medicine Director of Cardiac Catheterization Laboratory Director of Interventional Cardiology University of Louisville Louisville, Kentucky Bruce E. Lewis, MD Professor Cardiology Loyola University Medical Center Maywood, Illinois Ferdinand S. Leya, MD Professor of Medicine and Cardiology Medical Director Cardiac Catheterization Laboratories Loyola University Medical Center Maywood, Illinois David Liang, MD, PhD Director Stanford Center for Marfan Syndrome and Related Aortic Disorders Associate Professor of Medicine Division of Cardiovascular Medicine Stanford University School of Medicine Stanford, California Dirk A. Loose, MD European Centre for the Diagnosis and Treatment of Vascular Malformations Hamburg, Germany Robyn A. Macsata, MD Department of Surgery Washington Hospital Center Washington, DC Ali F. Mallat, MD Department of Surgery University of Michigan Ann Arbor, Michigan Michael T. McCormack, MD Director of Basic Science and Research Pulmonary Disease Fellowship Program Clinical Assistant Professor of Medicine Graduate School of Medicine University of Tennessee Staff Physician University of Tennessee Medical Center Knoxville, Tennessee

Contributors • xiii

Raymond Q. Migrino, MD Division of Cardiovascular Medicine Medical College of Wisconsin Milwaukee, Wisconsin

Ryan Payne, MD Department of Urology Medical College of Wisconsin Milwaukee, Wisconsin

J. William Mix, MD Department of Surgery Division of Vascular Surgery Graduate School of Medicine University of Tennessee Knoxville, Tennessee

David Pitrak, MD Professor of Medicine Chief of Infectious Diseases University of Chicago Chicago, Illinois

Emile R. Mohler III, MD, MS Cardiovascular Division Vascular Medicine Section University of Pennsylvania School of Medicine Philadelphia, Pennsylvania

Sridevi R. Pitta, MD Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

Eamonn S. Molloy, MD, MS Center for Vasculitis Care and Research Department of Rheumatic and Immunologic Diseases Cleveland Clinic Cleveland, Ohio

Kailash Prasad, MD, PhD Professor Emeritus Department of Physiology College of Medicine University of Saskatchewan Saskatoon, Saskatchewan, Canada

Karen Moncher, MD Assistant Professor of Medicine Division of Cardiovascular Medicine University of Wisconsin School of Medicine Madison, Wisconsin Ali Morshedi-Meibodi, MD Coast Cardiology Medical Associates Los Angeles, California Debabrata Mukherjee, MD Gill Heart Institute and Division of Cardiovascular Medicine University of Kentucky Lexington, Kentucky Aravinda Nanjundappa, MD, RVT Associate Professor of Medicine and Surgery West Virginia University Charleston West Virginia Richard F. Neville, MD Associate Professor Department of Surgery Chief, Division of Vascular Surgery Georgetown University Hospital Washington, DC Gustavo Oderich, MD Division of Vascular Surgery Mayo Clinic Rochester, Minnesota John P. Pacanowski Jr., MD Vascular Surgery Agave Medical Associates Tucson, Arizona

Trent L. Prault, MD Department of Vascular Surgery and Endovascular Interventions Harbin Clinic Rome, Georgia Manu Rajachandran, MD Director Comprehensive Vascular Program Chair Department of Endovascular Medicine Deborah Heart and Lung Center Clinical Associate Professor of Medicine UMDNJ-Robert Wood Johnson Medical School New Brunswick, New Jersey Sanjay Rajagopalan, MD Division of Cardiovascular Medicine Ohio State University School of Medicine Davis Heart and Lung Research Institute Columbus, Ohio Ravi K. Ramana, DO Cardiology Division of Cardiology Loyola University Medical Center Maywood, Illinois Charulata Ramaprasad, MD, MPH Infectious Diseases University of Chicago Chicago, Illinois

xiv • Contributors

Dinesh Ranjan, MD Department of Surgery Transplant Division University of Kentucky Lexington, Kentucky Brian Reed, MD Department of Surgery Graduate School of Medicine University of Tennessee Knoxville, Tennessee Arti Rupani, MD Loyola University Maywood, Illinois James M. Scanlon, MD George Washington University Medical Center Washington, DC Robert M. Schainfeld, DO Associate Director Vascular Medicine Massachusetts General Hospital Associate Physician Harvard Medical School Boston, Massachusetts Michael J. Schneck, MD Associate Professor of Neurology and Neurosurgery Department of Neurology Loyola University Stritch School of Medicine Maywood, Illinois Jeffrey P. Schwartz, MD Cardiovascular and Thoracic Surgery Loyola University Medical Center Maywood, Illinois Patrick Segers, PhD Cardiovascular Mechanics and Biofluid Dynamics Institute Biomedical Technology Ghent University Ghent, Belgium Anton N. Sidawy, MD Department of Surgery Washington Hospital Center and Georgetown University Hospital Washington, DC Monica Simionescu, MD Department of Neurology Loyola University Chicago Stritch School of Medicine Maywood, Illinois

Madhurmeet Singh, DO Loyola University Medical Center Maywood, Illinois David G. Stanley, MD Medical Director Wound Treatment Center Methodist Medical Center Oak Ridge, Tennessee Lowell H. Steen, MD Cardiology Loyola University Stritch School of Medicine Maywood, Illinois Daniel H. Steinberg, MD Washington Hospital Center and Georgetown University Washington, DC Scott L. Stevens, MD Division of Vascular/Transplant Surgery University of Tennessee Medical Center Knoxville, Tennessee Timothy M. Sullivan, MD Vascular and Endovascular Surgery North Central Heart Institute Sioux Falls, South Dakota Jessica A. Sutherland, MD Division of Cardiology Caritas St. Elizabeth’s Medical Center Boston, Massachusetts Dana A. Taylor, MD Department of Surgery University of Tennessee Medical Center at Knoxville Knoxville, Tennessee J. Michael Tuchek, DO Cardiac Surgery Associates Loyola University Medical Center Maywood, Illinois Ramachandra P. Tummala, MD Assistant Professor of Neurosurgery, Neurology, and Radiology University of Minnesota Medical School Minneapolis, Minnesota Suneel M. Udani, MD, MPH John H. Stroger Hospital of Cook County Chicago, Illinois Luc M. Van Bortel, MD, PhD Heymans Institute of Pharmacology Ghent University Ghent, Belgium

Contributors • xv

Simona Velicu, MD Department of Neurology Loyola University Stritch School of Medicine Maywood, Illinois

Ron Waksman, MD Washington Hospital Center Washington, DC

Pascal R. Verdonck, PhD Cardiovascular Mechanics and Biofluid Dynamics Institute Biomedical Technology Ghent University Ghent, Belgium

Neil J. Weissman, MD Washington Hospital Center and Georgetown University Washington, DC

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Foreword Vascular disease has affected mankind since at least the beginning of recorded history. Ancient Egyptian mummies show evidence of calcification, atheromatous lesions, and other degenerative changes in the aorta, coronary, and peripheral arteries. Only since the mid-twentieth century, however, has vascular care evolved into a distinct specialty. To a great extent, this specialty owes its existence to surgical experience gained during wartime. Other important advances include the development of synthetic grafts and, later, of angioplasty procedures. Today, owing to the advent of minimally invasive technologies, the endovascular approach is widely used in the repair of vascular lesions. As the average age of the population continues to rise and as obesity, diabetes, and other chronic conditions take a growing toll, the need for vascular treatment can only be expected to increase. The present book, Peripheral Arterial Disease, edited by my colleague and friend Ray Dieter Jr. and his sons Ray

Dieter III and Robert Dieter, is a welcome addition to the literature about vascular disorders. This comprehensive, multiauthored volume covers all the major organ systems involved in peripheral arterial disease. In addition to discussing the pathogenesis, diagnosis, treatment, and prevention of such disease, the authors cover various supporting services that are integral to vascular care. The text is enhanced by a generous array of references, figures, and tables, all presented in an eye-pleasing format. I congratulate the editors for producing this excellent volume, which should be an outstanding reference book for clinicians, researchers, and other professionals concerned with the management of peripheral arterial disease. Denton A. Cooley, MD President Emeritus and Surgeon-in-Chief Texas Heart Institute Houston, Texas

xvii

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Preface Our goal with this textbook on peripheral arterial disease is to make it a reference which crosses disciplines. The comprehensive approach of this text and each outstanding chapter is truly a reflection of the efforts of all the contributing authors. We sincerely appreciate their hard work and contribution to this reference. To many, peripheral arterial disease represents only diseases (mainly atherosclerotic) of the lower extremities. We have, however, decided to use a broader definition of peripheral arterial disease, to reflect extracardiac arterial diseases. This is a more encompassing definition, designed to allow a discussion of arterial diseases in multiple arterial beds. We recognize that some readers, including us at times, wish to restrict this term to the lower extremities. We have intentionally not attempted to draw strict borders between chapters. Such distinctions are neither

practical nor how we approach diseases and patients. The textbook attempts to regionalize arterial diseases, but we recognize the significant overlap of diseases and thus some chapters will cover topics that are also found in other chapters. Furthermore, although this book is centered around diseases of the arterial circulations, there are obviously areas and diseases that overlap with lymphatic, venous, and other diseases, and these are discussed when appropriate. Finally, we hope that the reader, of any discipline, finds this textbook useful. We greatly appreciate the assistance of the staff at McGraw-Hill. Robert S. Dieter, MD, RVT Raymond A. Dieter Jr., MD, MS Raymond A. Dieter III, MD

xix

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chapter

1

The Epidemiology of Peripheral Arterial Disease Victor Aboyans, MD, PhD / Michael H. Criqui, MD, MPH

•

INTRODUCTION

Peripheral arterial disease (PAD) is one of the several terms referring to a partial or complete obstruction of one or more arteries below the aortic bifurcation. Although the term PAD is sometimes inclusive of all peripheral arteries and/or any etiology, in this chapter PAD refers to atherosclerotic occlusive disease of lower extremity arteries. Other terms used for this affliction in the literature are peripheral vascular disease (PVD), peripheral arterial occlusive disease (PAOD), and lower extremity arterial disease (LEAD). The epidemiologic data regarding this condition have evolved dramatically over the past three decades. Initially, only symptomatic PAD was studied. However, with the development of investigative methods applicable in epidemiology, several studies have suggested that during the natural course of this disease, symptomatic PAD is preceded by a long period of asymptomatic disease. These studies showed that asymptomatic PAD is not innocuous, since patients at this initial stage of the disease are already at a higher risk of cardiovascular events. Consequently, the more recent studies have used objective investigation methods and typically include both symptomatic and asymptomatic forms of the disease. This has led to better estimates of PAD prevalence and incidence. PAD that exhibits typical symptomatology, usually in the form of leg pain brought about by walking, has been conservatively estimated to reduce the quality of life in at least 2 million Americans and in some cases leads to revascularization or amputation.1 Recent estimates place the total number of persons with PAD in the United States at more than 8 million.2

•

SYMPTOMS AND MEASURES OF PAD IN EPIDEMIOLOGY

It was recognized as long ago as the 18th century that an insufficient blood supply to the legs could cause pain and dysfunction. This type of pain is known as intermittent claudication (IC) and is characterized as leg muscle pain occurring when walking and relieved at rest. IC is generally indicative of exercise-induced ischemic pain. Early studies focused primarily on claudication as the chief symptomatic manifestation of PAD. A number of patient questionnaires have been developed to uniformly identify claudication and to distinguish it from other types of leg pain. The first of these was the Rose questionnaire, also referred to as the World Health Organization questionnaire.3 However, despite initial good results of the questionnaire to accurately detect PAD, this questionnaire is known as to present a low sensitivity, from 68% down to 9% in different studies.4 Two attempts have been made to improve the diagnostic performances. The Edinburgh Claudication Questionnaire5 is a modification of the Rose questionnaire, presenting 47% to 91% sensitivity and 95% to 99% specificity in different studies.5−7 The San Diego Claudication Questionnaire is another modified version of the Rose questionnaire and additionally captures information on the laterality of symptoms.8 The interviewer administered form of the San Diego Claudication Questionnaire is presented in Table 1-1. Although considered as typical, it should be emphasized that the classical IC is not the sole clinical pattern related to PAD. Besides rest pain, occurring at a more evolved stage of the disease, several patterns of atypical pain can be related

2 • CHAPTER 1

TABLE 1-1. The San Diego Claudication Questionnaire (Interviewer Administered Version)8

1. Do you get pain or discomfort in either leg or either buttock on walking? (If no, stop) 2. Does this pain ever begin when you are standing still or sitting? 3. In what part of the leg or buttock do you feel it? a. Pain includes calf/calves b. Pain includes thigh/thighs c. Pain includes buttock/buttocks

4. Do you get it when you walk uphill or hurry?

5. Do you get it when you walk at an ordinary pace on the level? 6. Does the pain ever disappear while you are walking? 7. What do you do if you get it when you are walking? 8. What happens to it if you stand still? (If unchanged, stop) 9. How soon?

No. . . Yes. . . No. . . Yes. . . No. . . Yes. . . No. . . Yes. . . No. . . Yes. . . No. . . Yes. . . Never walks uphill/hurries. . . No Yes. . . No. . . Yes. . . Stop or slow down. . . Continue on. . . Lessened or relieved. . . Unchanged. . . 10 minutes or less. . . More than 10 minutes. . .

Right

Left

1 2 1 2 1 2

1 2 1 2 1 2

1 2 1 2 1 2 3 1 2 1 2 1 2 1 2

1 2 1 2 1 2 3 1 2 1 2 1 2 1 2

1 2

1 2

(1) No pain – Q1 = 1. (2) Pain at rest – Q1 = 2 and Q2 = 2. (3) Noncalf – Q1 = 2 and Q2 = 1 and Q3a = 1 and Q3b = 2 or Q3c = 2. (4) Non-Rose calf – Q1 = 2 and Q2 = 1 and Q3a = 2, and not Rose. (5) Rose – Q1 = 2 and Q2 = 1 and Q3a = 2 and Q4 = 2 or 3 (and if Q4 = 3, then Q5 = 2), and Q6 = 1 and Q7 = 1 and Q8 = 1 and Q9 = 1.

to PAD. For example, in the PAD Awareness, Risk, and Treatment: New Resources for Survival (PARTNERS) program, more than half of the PAD patients reported symptoms, but few reported classic Rose claudication.9 In another similar study in a large Dutch population, the typical “Rose” claudication was reported only in 1.6%, whereas overall 6.6% had different patterns of vascular claudication, including other localization than calves.10 The definitional distinctions used to separate IC from other types of leg pain make the former more specific to arterial disease, but less sensitive to other types of pain that may in some cases be related to arterial disease. Spinal stenosis can cause leg pain during exercise that is similar to arterial IC. Neurogenic IC accounts for almost 5% to 10% of patients with claudication referred to vascular clinics,11 but this ratio is unknown in general population. Two attempts, both using the San Diego Claudication Questionnaire (Table 1-2), have been made to qualify different patterns of nontypical pain. In one report, five categories of symptoms have been proposed8 : no pain, pain on exertion and rest, noncalf pain, atypical calf pain, and eventually classic claudication (Table 1-2). A respectively increasing prevalence of PAD was found in these five groups.

In another study, McDermott et al.12 proposed a sixth category by splitting the “no pain” group according to whether people walk enough to experience exertional pain (Table 1-2). They also divided atypical leg pain according to whether the subject stops or carries on with this pain. The authors not only found different mean ABI values in different categories, but also found several concomitant disorders (i.e., neurological and articular), which can make symptoms ischemic muscle cramp less typical.12 Patients with PAD may present more severe clinical forms of PAD, with pain in the legs at rest, trophic lesions, or both. In this situation the vitality of the limb is threatened because of severe arterial insufficiency and the risk of limb loss in the absence of medical care is high. Consequently, this clinical pattern is defined as critical limb ischemia (CLI), grouping typical chronic ischemic rest pain and ischemic skin lesions, either ulcers or gangrene.13

•

ANKLE–BRACHIAL INDEX

In addition to difficulties to define PAD according to different symptoms categories, it is now well established that

THE EPIDEMIOLOGY OF PERIPHERAL ARTERIAL DISEASE • 3

TABLE 1-2. Different Classifications of Typical/Atypical Pain in PAD Based on the San Diego Claudication Questionnaire Criqui et al.8 Asymptomatic

McDermott et al. [12]

Pain Category

Definition

Pain Category

Definition

No pain

No pain in either leg or buttock on walking

No exertional pain/active

No pain in either leg or buttock on walking. Subject walking >6 blocks. No pain in either leg or buttock on walking. Subject not walking >6 blocks.

No exertional pain/inactive Atypical pain

Pain on exertion/rest

Noncalf pain

Atypical calf pain

Typical “Rose” pain

Classic claudication

Pain in either leg or buttock on walking, can sometimes begin when standing still or sitting Pain not in calf region but in thighs or buttocks, only when walking. Pain in calf region, starting only when walking, but different from classic claudication pain

Pain on exertion/rest

Pain in either leg or buttock on walking, can sometimes begin when standing still or sitting.

Atypical exertional leg pain/stop Atypical exertional leg pain/ carry on

Noncalf pain, starting only when walking, the subject stops walking. Pain starting only when walking, the subject carries on walking.

Pain in calf region, starting only when walking, does not disappear during walk, causing subject to halt or slow down; pain is lessened or relieved within 10 min if walking halted

Intermittent claudication

Pain in calf region, starting only when walking, does not disappear during walk, causing subject to halt or slow down. Pain is lessened or relieved within 10 min if walking halted.

atherosclerosis may have been developing for many years before claudication begins, and the extent to which it occurs is influenced by factors other than disease per se, such as the patient’s level of activity.14 For all these reasons, another method of diagnosing PAD was needed. Low blood pressure at the ankle was proposed as a test for PAD as early as 195015 and led to the development of a simple measure called the ankle–brachial index (ABI). Also sometimes called the ankle–brachial pressure index (ABPI)16 or the ankle–arm index (AAI),17 the ABI is the ratio of the systolic blood pressure at the ankle to that in the arm. An abnormally low value of ABI is indicative of atherosclerosis of the lower extremities. The ABI has been shown to have good receiver operating curve characteristics as a test for PAD. Although there is no clear-cut threshold to confirm or exclude the presence of PAD, an ABI less than or equal to 0.90 is commonly used in both clinical practice and epidemiologic research to define PAD. More recently, it has been suggested that an ABI between 0.90 and 1.00 is correlated to atherosclerotic disease in other vascular territories,18 and is associated with higher rates of IC19 and CV events than in subjects with ABI >1.00.20−22 In a large German primary care cohort, compared to the reference group with an ABI ≥1.1, mortality rates were increased for ABI values within the 0.9 to 1.1 interval.23 At least for the 0.9 to 1.0 ABI interval, it is suggested to

consider this situation as “borderline PAD.” It is estimated that one out of four subjects with an ABI in the interval 0.90 to 1.00 actually have PAD.2 The major interest of ABI-defined PAD is in that it covers both symptomatic and asymptomatic PAD. In the Rotterdam study, 99.4% of subjects with ABI ≥0.9 did not have claudication, but only 6.3% of subjects with ABI 0) and velocity increases (dU > 0). This is a forward compression wave. (2) Blowing on the right side of the tube—pressure increases (dP > 0), but velocity decreases (dU < 0) with our convention. This is a backward compression wave. (3) Sucking on the left side of the tube—pressure decreases (dP < 0) as well as the velocity (dU < 0) decreases, but the wavefront propagates from left to right. This wave type is a forward expansion wave. (4) Finally, sucking on the right side of the tube— pressure (dP < 0) decreases, but velocity (dU > 0) increases. This is a backward expansion wave. The nature of a wave is most easily comprehended by analyzing the wave intensity, dI , which is defined as the

product of dU and dP , and is the energy flux carried by the wavelet: dI = dU dP. It can be deduced from the above that dI is always positive for forward running waves and always negative for backward waves, irrespective of the fact that it is a compression or expansion wave. When dI is positive, forward waves are dominant; otherwise, backward waves are dominant. Analysis of dP reveals whether the wave is a compression or an expansion wave. These wavelets are easily calculated from a measured pressure and flow velocity signal; dP (dU) is simply the difference between pressure (flow velocity) measured at instant n minus the value at instant n − 1: dP = P (n) − P (n− 1). Since the absolute value of the difference depends on the sampling rate of the signal, one can also calculate a socalled normalized value, which is dP /dt = [P (n) − P (n − 1)]/[t(n) − t(n − 1)] with t the time. Similar equations apply to the flow velocity. Figure 7-12 shows the wave intensity calculated from the data displayed in Figure 7-8, showing a typical aortic wave intensity pattern characterized by three major peaks. The first peak is a forward compression wave, associated with the ejection of blood from the ventricle. The second positive peak is associated with a forward running wave, but dP < 0, and is therefore a forward running expansion wave because of ventricular relaxation, slowing down the ejection from the heart. During systole, reflected waves are dominant, resulting in a negative wave intensity but with, in this case, positive dP . The negative peak is thus a backward compression wave, resulting from the peripheral wave reflections. It can further be mentioned that, similar to the Westerhof work,26 here also, the wavelets dP and dU can be decomposed into their forward and backward components.29 It can be derived that d P± =

1 (dP ± ␳ PWV dU) 2

and dU± = ±

1 2



 dP ± dU . ␳ PWV

The total forward and backward  pressure and flow wave can be obtained as P+ = Pd + tt=0 dP+ , with Pd the diastolic bloodpressure, which is added to the forward wave, and P− = tt=0 dP− .29 Similarly, for the forward t and back= ward velocity wave, it applies that U + t=0 dU+ and  U− = tt=0 dU− . Wave intensity in itself, dI , can also be separated in a net forward and backward wave intensity: dI+ = dP+ dU+ and dI− = dP− dU− , with dI = dI+ + dI− . Wave intensity is certainly an appealing method to gain insight into complex wave (reflection) patterns, as in the arterial system, and the method is increasingly being used.31−33 The drawback of the method is the fact that dI is calculated as the product of two derivatives dP and dU,

FLOW DYNAMICS AND ARTERIAL PHYSIOLOGY • 103

• FIGURE 7-12.

Wave intensity pattern obtained from the aorta pressure and flow from Figure 7-8. Pressures were converted to kPa; flow velocity was derived from the flow assuming the aortic diameter to be 2.5 cm. The typical pattern with the forward compression wave (ventricular ejection), backward compression wave (wave reflection in the periphery), and forward expansion wave (ventricular relaxation) are retrieved.

and thus highly sensitive to noise in the signal. Adequate filtering of basic signals and derivatives is mandatory. As for the more “classic” impedance analysis, it is also required that pressure and flow be—preferably simultaneously— measured at the exact same location.

whether they provide a measure of the entire (systemic) circulation.

•

These measurements are based on local measurements of arterial pressure and vessel diameter, and are applied to superficial arteries such as the radial, brachial, carotid, and femoral artery, with the carotid artery considered representative for the large, central elastic arteries, and the radial, brachial, and femoral artery for the more peripheral, muscular arteries. When measuring local arterial stiffness, it is important that pressures are being measured at the same anatomical location as where the diameter measurements are being exerted. We have developed a tonometry-based measurement platform for that purpose. Applanation tonometry yields the profile of the pressure wave, but it does not provide reliable values of pressure. The tonometry curves therefore require calibration. The method that we commonly use starts from tonometry measurements at the level of the brachial artery (see also Figure 7-13). This is the only location in the body where the peak and trough of the measured pressure waveform equal the sphygmomanomer systolic and diastolic blood pressure. As such, this curve can be perfectly scaled. With this calibrated curve, it is possible to accurately determine mean arterial blood pressure as the average of that curve. Others have shown that diastolic and mean blood pressure remain as good as constant over the larger arteries (but not systolic blood pressure that is amplified toward the periphery, at least up to the level of large- and mid-sized arteries). With the knowledge of diastolic and mean blood pressure from the brachial

(CLINICAL) APPROACH TO MEASURE ARTERIAL PROPERTIES

One of the main obstacles impeding the clinical implementation of “textbook” hemodynamics and impedance analysis is the practical applicability of the methodology. The above-mentioned analysis is based on simultaneous measurement of central pressure and flow waveforms, which is often not doable in a clinical setting that requires noninvasive measurements. Although it is feasible to noninvasively measure aortic flow (using Doppler ultrasound technology), and carotid or subclavian pressure tracings (by applanation tonometry) as surrogate for central aortic pressure, the processing of the data is complex and time consuming and provides only an estimate of arterial properties because of the assumptions underlying the data. In addition to the complex measurement, the interpretation of impedance patterns remains complex and, as mentioned before, it is a gross measure of arterial function, which is not likely to provide a measure that is sensitive to subtle changes in arterial properties. As such, in the past few years, several “clinically applicable” methods have emerged in the literature, all claiming to measure (aspects of) the function of the arterial system and/or wave reflection. In an attempt to provide some sort of classification, we have categorized the methods as to whether they measure arterial properties at one specific location (local measurements), over an arterial segment, or

Measuring Local Arterial Stiffness: DC and CC

104 • CHAPTER 7

• FIGURE 7-13.

Measuring local blood pressures: Sequence of measurement and calibration when applying tonometry at the carotid artery. The pressure wave is first measured and calibrated at the level of the brachial artery (two upper graphs). The left panel shows a sequence of 20 seconds with indication of the cycles that are used to calculate an average curve (in red) and the rejected cycles (in cyan). The right panel shows the averaged wave (dark blue line). Next, waveforms are measured at another location (here the carotid artery; lower graphs). After averaging, the averaged waveform is calibrated using the mean and diastolic blood pressure determined at the brachial artery. The pictures on the left show the measuring platform and the pen-type Millar tonometer (SPT301, Millar, Houston, TX) that was used.

artery, one can calibrate tonometry curves at other locations and obtain an estimate of local systolic and PP34−36 (Figure 7-13). For measurement of the arterial diameter (or, better, the cyclic change of diameter, also called the distension), there are several commercially available systems, all based on ultrasound. Some systems, such as the Wall Track or ART.LAB system (Easote Europe, Maastricht, The Netherlands), automatically detect the vessel wall from the measured radiofrequency ultrasound data, and track the displacement of the vessel wall as a function of time using algorithms based on cross- or autocorrelation methods. As we have demonstrated using a prototype wall tracking system (Vivid7, GE Vingmed Ultrasoud, Horten, Norway), knowledge of which point in the vessel wall is being tracked, is important.37 Irrespective of eventual inhomogeneities in the vessel wall, tracking the inside of the blood vessel (e.g., the transition between the lumen and vessel intimal layer) will yield substantially larger displacements than when tracking the outside of the vessel (e.g., the transition

between the media layer and the adventitia).37 This simply follows from the law of conservation of mass. Commercial systems most frequently detect and track the easy-to-find media-adventitia transition. The information that one minimally obtains from these measurements are the local distensibility (DC) and compliance coefficient (CC), defined as DC = (A/A)/P

(in mm Hg−1 or Pa−1 )

CC = A/P

(in mm2 · mm Hg−1 or mm2 · Pa−1 ),

where A is the cross-sectional area of the artery in diastole, A the systolic–diastolic difference in cross-sectional area, and P the locally assessed PP.38 DC describes the intrinsic stiffness of the vessel that is studied, while CC reflects the local buffer capacity. Ideally, it is also possible to construct pressure–diameter curves that allow us to calculate CC or DC at different blood pressure levels, or to assess other parameters obtained from fitting a prescribed pressure– diameter law, such as an exponential or the arc-tangent

FLOW DYNAMICS AND ARTERIAL PHYSIOLOGY • 105

relation of Langewouters et al., through the data.39,40 Note that these indices describe the function of the vessel; they do not provide any intrinsic insight into the properties of the wall material in itself.

Regional Measurements: Pulse Wave Velocity An often applied method to assess the stiffness of an arterial segment is to measure the velocity by which a “perturbation” propagates over that arterial segment.41 This perturbation can be a pressure wave, but also a diameter distension or flow velocity wave. What is required are measurements of pressure/diameter/flow velocity at two locations, a distance x of each other (Figure 7-14).42,43 Because of the elasticity of the vessel, it will take an instant (T) before the perturbation has propagated from location 1 to location 2. The ratio x/T is the propagation speed of the

• FIGURE 7-14.

wave (pulse wave velocity). For a uniform, straight cylindrical tube, PWV is directly related to the aforementioned DC9,38 :  PWV = 1/ ␳ DC, with ␳ the density of blood. Although the arterial system is not a uniform tube with continuous changes in vessel diameter and stiffness and numerous branches, PWV is still generally considered as one of the most pure (and certainly one of the easiest to measure) indices of arterial stiffness.44 Ideally, PWV is derived from simultaneous measurements at the two locations. If this is practically impossible, sequential measurements can be performed using, for instance, the time delay between the R-top of the ECG signal and the foot of the wave on these two locations. A bigger problem is the measurement of the distance x. One often calculates PWV from measurements on the carotid and femoral artery. In that case, one should compensate for the fact that

Principle of measuring pulse wave velocity (PWV). The propagation of a “perturbation” in the arterial tree is measured, illustrated here using measurements of the distension of the carotid and femoral artery, a distance x apart.

106 • CHAPTER 7

while traveling up the carotid (a proximal branch of the aorta) the pulse has also already traveled further down the aorta. In older people, and in patients with aortic pathologies, the aorta may be tortuous, complicating the reliable measurement of x. It appears that especially carotid-femoral PWV, which best approximates the stiffness of the aorta, carries important prognostic information. Increased PWV implies an increased risk of cardiovascular incidents in high-risk patients (diabetes, hypertension, etc.), but recent studies have shown that, also in the general population, PWV has added prognostic value, on top of all known classical risk factors, including systolic blood pressure and PP.45−47 Global Measures of the Complete (Systemic) Circulation: Total Arterial Compliance As mentioned above, it is not totally impossible to measure central pressure and flow in a clinical setting using noninvasive technology. Aortic flow can be measured with Doppler ultrasound, while carotid or subclavian applanation tonometry yields a surrogate for central blood pressure. From these data, the arterial input impedance as well as, probably more useful, the number of indices or parameters that describe the properties of the complete arterial tree, such as the total arterial compliance, can be assessed.8 A disadvantage of these global indices is that they are strongly determined by height and weight of the individual, introducing considerable variability in these measurements. The necessity of measurement of pressure and flow also impedes the clinical use of these measures. The assessment of total arterial compliance from pressure and flow is generally based on an approximation of the arterial tree by a simple, lumped parameter windkessel model. In the following section, the two-element windkessel model and some of the more complex models, as well as how they can be used to estimate total arterial compliance, are discussed. The procedures commonly include a curve fitting part. A generic methodology for all models described is to use the measured flow (or pressure) as input into the model and to calculate the pressure (or flow) response predicted by the model with an initial set of parameter values. By optimizing the parameter set, one can minimize the difference between the measured pressure (or flow) and the output predicted by the model. The parameter set that yields the closest agreement between the measured and predicted signal is then considered as the optimal representation of the arterial system. The Two-Element Windkessel Model. While there are

many different windkessel models in use,8,48 the two basic components contained within each model are a compliance element, C (mL mm Hg−1 ), and a resistor element, R (mm Hg mL−1 s). C represents the volume change associated with a unit change in pressure; R represents the pressure drop over the resistor associated with a unit flow.

In diastole, when there is no new inflow of blood into the windkessel, the arterial pressure decays exponentially following P (t) = P0 e −t/RC . RC is the product of R and C and is called the arterial decay time. The higher the RC time, the slower the pressure decay. It is the time required to reduce P0 to 37% of its initial value (note that the 37% is a theoretical value, usually not reached in vivo because the next beat impedes a full pressure decay). One can make use of this property to estimate the arterial compliance: Fitting an exponential curve to the diastolic decaying pressure, RC is obtained and thus, when R is known, so is C.8,49−51 This method is known as the decay time (or time decay) method. The question how well a windkessel model represents the actual arterial system can be answered by studying the input impedance of both. In the complex formulation, the input impedance of a two-element windkessel model is given as Zi−WK2 =

R , 1 + i␻RC

where i is the complex constant, ␻ = 2␲f, and f is the frequency. The DC value (0 Hz) of Zin is thus R; at high frequencies, it becomes zero. The phase angle is 0 at 0 Hz, and –90 degrees for all other frequencies. Compared to input impedance as measured in mammals, the behavior of a two-element windkessel model reasonably represents the behavior of the arterial system for the low frequencies (up to third harmonic), but not for higher frequencies8,19,52 (Figure 7-15). This means that it is justified to use the model for predicting the low-frequency behavior of the arterial system, that is, the low-frequency response to a flow input. This property is used in the so-called pulse pressure method—an iterative method to estimate arterial compliance: With R assumed known, the PP response of the twoelement windkessel model to a (measured) flow stimulus is calculated with varying values of C. The value of C yielding the PP response matching the one measured in vivo is considered to be the correct one.53 In Comparison to the decay time method the pulse pressure method is insensitive to deviations of the decaying pressure from the true exponential decay.51 The Three-Element and Higher-Order Windkessel Models. The major shortcoming of the two-element

windkessel model is the inadequate high-frequency behavior.8,12,19 Westerhof et al. resolved this problem by adding a third resistive element proximal to the windkessel, accounting for the resistive-like behavior of the arterial system in the high-frequency range.12 This model yields markedly improved fitting between measured and model predicted data (Figure 7-15). The third element represents the characteristic impedance of the proximal part of the ascending aorta and integrates the effects of inertia and compliance. Adding the element, the input impedance of the three-element windkessel model becomes Zi−WK3 = Z 0 +

R . 1 + i␻RC

FLOW DYNAMICS AND ARTERIAL PHYSIOLOGY • 107

• FIGURE 7-15.

Windkessel model fittings. Measured flow (from Figure 7-8) is used as input into the two- and three-element windkessel model, and the model parameters are adjusted until the difference between the measured and estimated pressure is minimal. Panels A and B show the electrical and mechanical analogs, panel C shows the comparison between measured pressure and optimized model response, and panels D and E illustrate the comparison in modulus and phase of the measured input impedance and the impedance obtained for the two- and three-element windkessel model after parameter optimization.

The effect is that the phase angle is negative for lower harmonics, but returns to zero for higher harmonics, where the impedance modulus asymptotically reaches the value of Z0 . For the systemic circulation, the ratio of Z0 and R is 0.05:0.1.54 The major disadvantage of the three-element windkessel model is that Z0 , which should represent the highfrequency behavior of the arterial system, plays a role at all frequencies, including at 0 Hz. This has as a negative consequence: When the three-element windkessel model is used to fit data measured in the arterial system, the compliance is systematically overestimated.51,55 The only way to “neutralize” the contribution of Z0 at the low frequencies is to artificially increase the compliance of the model. The “ideal” model would incorporate both the lowfrequency behavior of the two-element windkessel model and the high frequency Z0 , though without interference of the latter at the low frequencies. This can be achieved by adding an inertial element in parallel to the characteristic impedance, as demonstrated by Stergiopulos et al.,56 elab-

orating on a model first introduced by Burattini et al.57 For the DC component and low frequencies, Z0 is bypassed through the inertial element. For the high frequencies, Z0 takes over. It has been demonstrated, fitting the four-element windkessel model to data generated using an extended arterial network model, that L effectively represents the total inertia present in the model.56 Obviously, by adding more elements, it is possible to develop models that are able to further enhance the matching between model and arterial system behavior,8,48 but the uniqueness of the model may not be guaranteed, and the physiological interpretation of the model elements is not always clear. Although lumped parameter models cannot explain all aspects of hemodynamics, they are very useful as a concise representation of the arterial system. Mechanical versions are frequently used in hydraulic bench experiments, or as highly controllable afterload systems for in vivo experiments. An important field of application of the mathematical version is of parameter identification: Fitting arterial

108 • CHAPTER 7

pressure and flow data measured in vivo to these models, the arterial system can be characterized and quantified (e.g., the total arterial compliance) through the model parameter values.8,19 It is important to stress that these lumped models represent the behavior of the arterial system as a whole and that there is no relation between model components and anatomical parts of the arterial tree.19 For instance, although Z0 represents the properties of the proximal aorta, there is no drop in mean pressure along the aorta, which one would expect if the three-element windkessel model were to be interpreted in a strict anatomical way. The combination of elements simply yields a model that represents the behavior of the arterial system as it is seen by the heart.

flective” compliance. The theoretical basis of the method has also been questioned, and the methodology has a very high black box character with strong assumptions regarding the cardiac output (which is required in the parameter estimation process). Nevertheless, there are several studies that have reported a decrease especially in C2 in highrisk patient populations such as patients with hypertension or diabetes.61,62 In our opinion, the method is sensitive to changes in radial pressure wave morphology—and hence yields changes in the value of model parameters59 —but the physiological foundation of the model and the method are debatable,63 and the parameter C2 is not likely to relate to arterial stiffness at any level. Ratio of Stroke Volume and PP. Irrespective of the mod-

The Goldwyn and Watt Four-Element Windkessel Model. Finally, it is worth to mention a windkessel model

that is the backbone of an arterial system analysis method promoted by Dr. Cohn and coworkers. This four-element windkessel model was described in 1967 and contains, apart from the obligatory total arterial compliance (C1 ) and total vascular resistance (R), two extra components: a second, smaller compliance (C2 ) and an inductance (L) that reflects the inertia of the blood in the vasculature.58 This model is used to describe the diastolic part of the pressure curve measured at the level of the radial artery (Figure 7-16). The shape of this curve is an exponentially decaying pressure, on which a sinusoidally varying part can be superimposed.58 The model contains enough parameters to adequately describe this shape, and curve fitting techniques generally provide excellent fittings of the model to the data. The problem, however, is the obscure physical/physiological meaning of the model parameters C2 and L,59,60 which is reflected in the changing nomenclature for the parameter C2 and has earlier been termed “distal,” “oscillatory,” or “re-

• FIGURE 7-16.

Illustration of the system identification method based on the four-element windkessel model of Goldwyn and Watt. The diastolic part of a pressure waveform measured at the radial artery is selected, and the model is fitted to the data. Resulting parameters are RC1 , RC2 , and L/R. When cardiac output is known, resistance R can be calculated and model parameters can be derived.

els and methods that have been discussed in the preceding sections, a simple approximation of total arterial compliance (C) is the ratio of stroke volume (SV) and central PP: C ≈ SV/PP. For typical hemodynamic conditions in humans at rest (systolic/diastolic pressure of 120/80 mm Hg, respectively, stroke volume 80 mL), SV/PP is 2 mL mm Hg−1 . This value is considered as an overestimation of the actual arterial compliance8,52 as it is assumed that the total SV is buffered during systole, which is not the case.

•

CLINICAL APPROACH TO WAVE REFLECTION: THE AUGMENTATION INDEX

As mentioned before, the pressure wave is the superposition of a forward running, incident component, and a backward running, reflected component. The contour of the pressure wave depends on the magnitude and timing of these components (Figure 7-17). The gold standard quantification of wave reflection is through the reflection coefficient or the ratio of the amplitude of the backward to forward wave (|Pb |/|Pf |). Because of the requirement of simultaneous pressure and flow measurement, it is not always possible to assess this index in a clinical environment. To resolve this problem, the so-called augmentation index (AIx) has been proposed. AIx aims to quantify the contribution of the reflected pressure wave to the total PP (Figure 7-17).64 Measurement of AIx requires only the contour of the pressure wave, and the identification of a “characteristic point” on the curve (P ∗ , Figure 7-17) that identifies the instant in time when the reflected wave starts to contribute to the total pressure. Once this point is known, one can calculate the augmented pressure (AP, augmented pressure) as well as the AIx itself 9 : AIx = 100 × AP/PP. For an A-type wave with early return of the reflected pressure wave, AP equals SBP − P ∗ and yields a positive value (SBP is the systolic blood pressure). The AIx will therefore be positive in older and in short subjects. For Ctype waves (young, tall subjects) with a late inflection point,

FLOW DYNAMICS AND ARTERIAL PHYSIOLOGY • 109

• FIGURE 7-17.

Definition of the augmentation index in case of an A-type wave (old subject; left figure) or C-type wave (young subject; right figure). The characteristic point is first defined to identify the nature of the wave. Then, augmented pressure is calculated. AIx is the ratio of augmented pressure to pulse pressure, expressed as a percentage.

the augmented pressure is negative (P ∗ − SBP), as will be AIx. In these days, AIx is frequently assessed in clinical studies, in part thanks to the work of O’Rourke and colleagues who were also the driving force behind the development of a commercial system (Sphygmocor©, Atcor Medical, Sydney, Australia). In that system, central blood pressure is mathematically calculated from a pressure wave, measured noninvasively at the level of the radial artery by use of a socalled generalized pressure transfer function that expresses the mathematical relation between the radial and aortic blood pressure.65,66 The arteries in the arm are here considered as a type of catheter with its tip ending in the aorta. The pressure transfer function describes the characteristics of this “catheter.” This approach certainly raises some questions. The transfer function used is a generalized one, measured in a relatively low number of patients, despite the fact that one might expect some interindividual variability in the transfer function.67 Another concern relates to the observation that there is a very strong correlation between AIx values that are derived directly from the radial pressure waveform and those derived from the mathematically transformed central pressure waveform,34,68 with correlation coefficients exceeding 0.9. There is little doubt that this is because of the assumption of a generalized transfer function, which implies that the information contents carried by the radial pressure wave is essentially the same as the information contents carried by the transformed curve. The added value of transforming the radial pressure waveform is then indeed debatable. Finally, it has also been observed that the value of AIx (from the central pressure) reaches a plateau level from the age of 55 to 60 onward, with an upper limit of about 50%.69 As such, one cannot expect AIx to be a sensitive and specific index for assessing cardiovascular risk in older patient populations; from that perspective, the augmented pressure in itself might be a better marker. Although there are some studies suggesting an association between AIx and cardiovascular risk in

specific patient populations,70 the extra prognostic value of AIx remains to be demonstrated in the general population. Furthermore, the interpretation of AIx is also not always straightforward, as there are many factors that affect the relative timing of the interaction between the forward and backward running pressure waves, such as the height of a subject, the distance to the effective reflection site, but also the heart rate and the pattern of left ventricular ejection. It is therefore unclear whether AIx is an appropriate measure of pressure wave reflection, and it should certainly not be used as a measure of arterial stiffness.71

•

WHAT TO MEASURE IN CLINICAL PRACTICE AND WHY SHOULD ONE CARE FOR ARTERIAL STIFFNESS?

Of all above-mentioned methods to assess the (elastic) properties of the arterial tree, there is little doubt that PWV is, at present, the most widely investigated and applied method. It is probably also the most promising method, as PWV is the only measure that appears to have prognostic value that adds to the classical risk factors.46 For the other methods, data are less conclusive. Nevertheless, at present, one seems to live to the principle that, while awaiting conclusive data, it does not harm to measure several parameters of arterial function.72 A number of researchers, predominantly based in Europe, have assembled consensus documents with guidelines for measurement of central blood pressure and arterial stiffness.44 These documents provide some structure in this highly unstructured research domain, but the documents largely remain inconclusive with respect to which arterial property should be measured. Largescale longitudinal studies, with comparison of the different methodologies, are awaited to assess the prognostic value of each of these indices. What is certainly important to stress is the relevance of measuring central blood pressure. Blood pressure in the upper arm is not an exact replica of blood pressure in the

110 • CHAPTER 7

aorta, and thus of the blood pressure faced by the heart during ventricular ejection. It is well known that there is central-to-peripheral amplification of the pressure pulse, and it has been demonstrated that certain drugs have a different effect on central and peripheral blood pressure, especially those drugs affecting heart rate, e.g., ␤blockers.73 When addressing arterial physiology, it is advisable to measure central blood pressure (as well as aortic flow), whenever possible, with a preference for the earlier described method of applanation tonometry at the brachial and carotid artery.34,35 Nevertheless, from a clinical standpoint, it is acknowledged that, until now, there is no scientific evidence showing that central blood pressure would have a higher prognostic value than the blood pressure value measured at the brachial artery. Although there is a growing interest in measuring arterial properties, it remains a fairly small field of research with mainly the interest of angiologists, nephrologists, and intensivists treating patients with hypertension. There are, however, many reasons cardiologists in general should show interest in this matter. Studies focussing on ventriculoarterial coupling and interaction clearly demonstrate that arterial stiffening is paralleled by “ventricular stiffening,”74 with an increase in the end-systolic elastance. Arterial stiffness also leads to the so-called isolated systolic hypertension, where systolic blood pressure is elevated while diastolic blood pressure is normal or even low. This condition is unfavorable to the heart for many reasons: r Because of the high systolic blood pressure, the energy

expenditure of the heart increases, and the heart of-

r

r r

r

r

ten responds through the development of ventricular hypertrophy. The diastolic passive properties of hypertrophic hearts change, with an increase in diastolic ventricular stiffness and less optimal filling of the ventricles. The perfusion of the endocardium may be hampered by the increase in thickness of the myocardium. Hearts with elevated end-systolic elastance become sensitive to blood volume shifts, and small changes in filling pressures have large effects in the pressure generated by these ventricles. An increased afterload of the heart directly affects its diastolic function via a reduction in the active relaxation of the ventricle, which may further increase the diastolic dysfunction of the heart. The lower diastolic blood pressure in the circulation also reduces the coronary perfusion pressure with potential consequences for myocardial perfusion.

Given these arguments, it is no surprise that an increase in arterial stiffness is associated with a reduction of the exercise capacity of patients.74 As a general conclusion, it is therefore safe to state that (also for cardiologists), it is most relevant to look beyond the coronary arteries, and we plead for more attention for the (systemic) arterial circulation. It is, however, the task of researchers active in the domain of arterial function and stiffness to come to a general consensus on which parameters to measure, how they should be measured, and to provide standardization of measurement techniques.

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12. Westerhof N, Elzinga G, Sipkema P. An artificial arterial system for pumping hearts. J Appl Physiol. 1971;31(5):776781.

5. Womersley J. The Mathematical Analysis of the Arterial Circulation in a State of Oscillatory Motion. Wright Air Development Center; 1957. WADC-TR56-614.

13. Hales S. Statical Essays: Containing Haemostatics (reprint 1964). New York: Hafner Publishing; 1733.

6. Womersley JR. Mathematical theory of oscillating flow in an elastic tube. J Physiol. 1955;127(2):37P-38P. 7. Bernoulli D. Hydrodynamica. 1738. 8. Segers P, Verdonck P. Principles of vascular physiology. In: Lanzer P, Topol EJ, eds. Pan Vascular Medicine. Integrated Clinical Management. Heidelberg: Springer-Verlag; 2002. 9. Nichols W, O’Rourke M. McDonald’s Blood Flow in Arteries. Theoretical, Experimental and Clinical Principles. 5th ed. London: Hodder Arnold–Oxford University Press; 2005.

14. Frank O. Die Grundfurm des arteriellen Pulses. Erste Abhandlung. Mathematische analyse. Z Biol. 1899;37:483-526. 15. Frank O. Der Puls in den Arterien. Z Biol. 1905;46:441-553. 16. Asmar RG, London GM, O’Rourke ME, Safar ME. Improvement in blood pressure, arterial stiffness and wave reflections with a very-low-dose perindopril/indapamide combination in hypertensive patient: a comparison with atenolol. Hypertension. 2001;38(4):922-926. 17. O’Rourke MF. Mechanical principles. Arterial stiffness and wave reflection. Pathol Biol (Paris).1999;47(6):623-633.

FLOW DYNAMICS AND ARTERIAL PHYSIOLOGY • 111

18. Laurent S, Cockcroft J, Van Bortel L, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006;27(21):25882605. 19. Westerhof N, Stergiopulos N, Noble M. Snapshots of Hemodynamics. An Aid for Clinical Research and Graduate Education. New York: Springer Science + Business Media; 2004. 20. Nichols WW, O’Rourke MF. McDonald’s Blood Flow in Arteries. 3rd ed. London: Edward Arnold; 1990. 21. Milnor WR. Hemodynamics. 2nd ed. Baltimore, MD: Williams & Wilkins; 1989.

sure: importance of brachial-to-radial pressure amplification. Hypertension. 2005;46(1):244-248. 36. Van Bortel LM, Balkestein EJ, van der Heijden-Spek JJ, et al. Non-invasive assessment of local arterial pulse pressure: comparison of applanation tonometry and echo-tracking. J Hypertens. 2001;19(6):1037-1044. 37. Segers P, Rabben SI, De Backer J, et al. Functional analysis of the common carotid artery: relative distension differences over the vessel wall measured in vivo. J Hypertens. 2004;22(5):973-981.

22. Wang DM, Tarbell JM. Nonlinear analysis of oscillatory flow, with a nonzero mean, in an elastic tube (artery). J Biomech Eng. 1995;117(1):127-135.

38. Van Bortel L, Segers P. Direct measurement of local arterial stiffness and pulse pressure. In: Safar M, MF OR, eds. Handbook of Hypertension—Arterial Stiffness in Hypertension: Amsterdam: Elsevier; 2006:35-51.

23. Campbell K, Lee CL, Frasch HF, Noordergraaf A. Pulse reflection sites and effective length of the arterial system. Am J Physiol. 1989;256:H1684-H1689.

39. Meinders JM, Hoeks AP. Simultaneous assessment of diameter and pressure waveforms in the carotid artery. Ultrasound Med Biol. 2004;30(2):147-154.

24. Latham R, Westerhof N, Sipkema P, Rubal B, Reuderink P, Murgo J. Regional wave travel and reflections along the human aorta: a study with six simultaneous micromanometric pressures. Circulation. 1985;72:1257-1269.

40. Hayashi K. Experimental approaches on measuring the mechanical properties and constitutive laws of arterial walls. J Biomech Eng. 1993;115:481-488.

25. Berger D, Li J, Laskey W, Noordergraaf A. Repeated reflection of waves in the systemic arterial system. Am J Physiol. 1993;264:H269-H281. 26. Westerhof N, Sipkema P, van den Bos CG, Elzinga G. Forward and backward waves in the arterial system. Cardiovasc Res. 1972;6:648-656. 27. Westerhof BE, Guelen I, Westerhof N, Karemaker JM, Avolio A. Quantification of wave reflection in the human aorta from pressure alone: a proof of principle. Hypertension. 2006;48(4):595-601. 28. Dujardin J, Stone D. Characteristic impedance of the proximal aorta determined in the time and frequency domain: a comparison. Med Biol Eng Comput. 1981;19:565-568. 29. Khir AW, O’Brien A, Gibbs JS, Parker KH. Determination of wave speed and wave separation in the arteries. J Biomech. 2001;34(9):1145-1155. 30. Parker KH, Jones CJ. Forward and backward running waves in the arteries: analysis using the method of characteristics. J Biomech Eng. 1990;112(3):322-326. 31. Bleasdale RA, Mumford CE, Campbell RI, Fraser AG, Jones CJ, Frenneaux MP. Wave intensity analysis from the common carotid artery: a new noninvasive index of cerebral vasomotor tone. Heart Vessels. 2003;18(4):202-206. 32. Wang Z, Jalali F, Sun YH, Wang JJ, Parker KH, Tyberg JV. Assessment of left ventricular diastolic suction in dogs using wave-intensity analysis. Am J Physiol Heart Circ Physiol. 2004;24. 33. Sun YH, Anderson TJ, Parker KH, Tyberg JV. Effects of left ventricular contractility and coronary vascular resistance on coronary dynamics. Am J Physiol Heart Circ Physiol. 2004;286(4):H1590-H1595. 34. Segers P, Rietzschel E, Heireman S, et al. Carotid tonometry versus synthesized aorta pressure waves for the estimation of central systolic blood pressure and augmentation index. Am J Hypertens. 2005;18(9, pt 1):1168-1173. 35. Verbeke F, Segers P, Heireman S, Vanholder R, Verdonck P, Van Bortel LM. Noninvasive assessment of local pulse pres-

41. Bramwell CJ, Hill A. The velocity of the pulse wave in man. Proc R Soc Lond [Biol].1922;93:298-306. 42. Avolio A, Chen S, Wang R, Zhang C, Li M, O’Rourke M. Effects of aging on changing arterial compliance and left ventricular load in a northern Chinese urban community. Circulation. 1983;68:50-58. 43. Lehmann E, Gosling R, Fatemi-Langroudi B, Taylor M. Noninvasive Doppler ultrasound technique for the in vivo assessment of aortic compliance. J Biomed Eng. 1992;14:250-256. 44. Van Bortel LM, Duprez D, Starmans-Kool MJ, et al. Clinical applications of arterial stiffness, Task Force III: recommendations for user procedures. Am J Hypertens. 2002;15(5):445452. 45. Laurent S, Boutouyrie P, Asmar R, et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension. 2001;37(5):12361241. 46. Willum-Hansen T, Staessen JA, Torp-Pedersen C, et al. Prognostic value of aortic pulse wave velocity as index of arterial stiffness in the general population. Circulation. 2006;113(5):664-670. 47. Mattace-Raso FU, van der Cammen TJ, Hofman A, et al. Arterial stiffness and risk of coronary heart disease and stroke: the Rotterdam Study. Circulation. 2006;113(5):657-663. 48. Toy SM, Melbin J, Noordergraaf A. Reduced models of arterial systems. IEEE Trans Biomed Eng. 1985;32:174-176. 49. Liu Z, Brin K, Yin F. Estimation of total arterial compliance: an improved method and evaluation of current methods. Am J Physiol. 1986;251:H588-H600. 50. Simon A, Safar L, London G, Levy B, Chau N. An evaluation of large arteries compliance in man. Am J Physiol. 1979;237:H550-H554. 51. Stergiopulos N, Meister JJ, Westerhof N. Evaluation of methods for the estimation of total arterial compliance. Am J Physiol. 1995;268:H1540-H1548. 52. Chemla D, Hebert J-L, Coirault C, et al. Total arterial com´ pliance estimated by stroke volume-to-aortic pulse pressure ratio in humans. Am J Physiol. 1998;274:H500-H505.

112 • CHAPTER 7 53. Stergiopulos N, Segers P, Westerhof N. Use of pulse pressure method for estimating total arterial compliance in vivo. Am J Physiol. 1999;276:H424-H428.

64. Kelly R, Hayward C, Avolio A, O’Rourke M. Noninvasive determination of age-related changes in the human arterial pulse. Circulation. 1989;80(6):1652-1659.

54. Westerhof N, Elzinga G. Normalized input impedance and arterial decay time over heart period are independent of animal size. Am J Physiol. 1991;261(1, pt 2):R126-R133.

65. Chen CH, Nevo E, Fetics B, et al. Estimation of central aortic pressure waveform by mathematical transformation of radial tonometry pressure. Validation of generalized transfer function. Circulation. 1997;95(7):1827-1836.

55. Segers P, Brimioulle S, Stergiopulos N, et al. Pulmonary arterial compliance in dogs and pigs: the three-element windkessel model revisited. Am J Physiol. 1999;277:H725-H731. 56. Stergiopulos N, Westerhof B, Westerhof N. Total arterial inertance as the fourth element of the windkessel model. Am J Physiol. 1999;276:H81-H88. 57. Burattini R, Gnudi G. Computer identification of models for the arterial tree input impedance: comparison between two new simple models and first experimental results. Med Biol Eng Comput. 1982;20:134-144. 58. Goldwyn R, Watt T. Arterial pressure pulse contour analysis via a mathematical model for the clinical quantification of human vascular properties. IEEE Trans Biomed Eng. 1967;14:1117. 59. Segers P, Qasem A, De Backer T, Carlier S, Verdonck P, Avolio A. Peripheral “oscillatory” compliance is associated with aortic augmentation index. Hypertension. 2001;37(6):14341439. 60. Segers P, Verdonck P, Verhoeven R. Evaluation of the non-invasive determination of arterial compliance with the Goldwynn–Watt model. J Cardiov Diagn Proc. 1997;14(1): 3-8. 61. McVeigh G, Finkelstein S, Cohn J. Assessment of arterial compliance in hypertension. Curr Opin Nephrol Hypertens. 1993;2:82-86. 62. McVeigh GE, Bratteli CW, Morgan DJ, et al. Age-related abnormalities in arterial compliance identified by pressure pulse contour analysis: aging and arterial compliance. Hypertension. 1999;33(6):1392-1398. 63. Fogliardi R, Burattini R, Shroff SG, Campbell KB. Fit to diastolic arterial pressure by third-order lumped model yields unreliable estimates of arterial compliance.Med Eng Phys. 1996;18:225-233.

66. Karamanoglu M, O’Rourke M, Avolio A, Kelly R. An analysis of the relationship between central aortic and peripheral upper limb pressure waves in man. Eur Heart J. 1993;14:160167. 67. Segers P, Carlier S, Pasquet A, et al. Individualizing the aortoradial pressure transfer function: feasibility of a model-based approach. Am J Physiol. 2000;279:H542-H549. 68. Millasseau SC, Patel SJ, Redwood SR, Ritter JM, Chowienczyk PJ. Pressure wave reflection assessed from the peripheral pulse: is a transfer function necessary? Hypertension. 2003;41(5):1016-1020. 69. McEniery CM, Yasmin, Hall IR, Qasem A, Wilkinson IB, Cockcroft JR. Normal vascular aging: differential effects on wave reflection and aortic pulse wave velocity: the AngloCardiff Collaborative Trial (ACCT). J Am Coll Cardiol. 2005;46(9):1753-1760. 70. Weber T, Auer J, O’Rourke MF, et al. Arterial stiffness, wave reflections, and the risk of coronary artery disease. Circulation. 2004;109(2):184-189. 71. Segers P, De Backer JF, Devos D, et al. Aortic reflection coefficients and their association with global indices of wave reflection in healthy controls and patients with Marfan disease. Am J Physiol Heart Circ Physiol. 2006;290(6):H2385-H2392. 72. Woodman RJ, Kingwell BA, Beilin LJ, Hamilton SE, Dart AM, Watts GF. Assessment of central and peripheral arterial stiffness: studies indicating the need to use a combination of techniques. Am J Hypertens. 2005;18(2, pt 1):249-260. 73. Takazawa K, Tanaka N, Takeda K, Kurosu F, Ibukiyama C. Underestimation of vasodilator effects of nitroglycerin by upper limb blood pressure. Hypertension. 1995;26(3):520-523. 74. Kass DA. Ventricular arterial stiffening: integrating the pathophysiology. Hypertension. 2005;46(1):185-193.

chapter

8

Blood Pressure Regulation Kailash Prasad, MD, PhD

•

ARTERIAL PRESSURE

Definition Lateral pressure exerted by the column of blood against the arterial wall is called the arterial pressure (blood pressure), and this pressure is referred to as the height of the column of blood supported by the force within a blood vessel. In a cardiac cycle, the highest pressure attained is the systolic pressure and the lowest pressure is the diastolic pressure. The equation “MAP – RAP = CO × TPR” is used to derive mean arterial pressure (MAP), where RAP is right arterial pressure, CO is cardiac output, and TPR is total peripheral resistance. Since RAP is very small, MAP (mm Hg) is the product of CO (liters per minute) and total peripheral resistance (mm Hg/liter/minute). The MAP is the geometric mean, and the calculation of MAP requires integration of pressure pulse. An approximate estimate of MAP can be derived from the following equations: MAP = (systolic pressure + 2 diastolic pressure)/3 MAP = diastolic pressure + 1/3 of pulse pressure. Normal Arterial Pressure Normal arterial pressure varies with age. It is approximately 70/50 mm Hg on the first day after birth, and gradually increases during the next several months to approximately 90/60 mm Hg. During subsequent years the rise is very slow and reaches 115/70 mm Hg at adolescence. There is a progressive increase in the pressure with age in the average population. The systolic pressure rises approximately 1 mm Hg/yr from 110 mm Hg at the age of 15 years. This probably reflects progressive reduction in arterial compliance. Diastolic pressure increases approximately 0.4 mm Hg/yr from 70 mm Hg at the age of 15 years. This

rise probably reflects an increase in total peripheral resistance. The progressive increase in arterial pressure with age could also result from the effects of aging on the longterm blood pressure control mechanisms. Although average pressure in a population rises with age, the pressure never rises with age in certain people. MAP for a population is composed of individuals whose blood pressure does not change with advancing age and of individuals whose pressure increases with advancing age. There is no dividing line between normal and high blood pressure. An arbitrary level of normal blood pressure has been established to define those who have an increased risk of developing morbid cardiovascular events and/or clearly benefit from medical therapy. Arterial pressure is somewhat damaging. Life expectancy is inversely proportional to arterial pressures. The logic is to define hypertension at levels where treatment can provide benefits that outweigh risks. Males with normal diastolic pressure but elevated systolic pressure (> 158 mm Hg) have a 2.5-fold increase in cardiovascular mortality rates when compared to individuals with similar diastolic pressure but normal systolic pressure. Arterial pressure is slightly higher in the right arm than in the left arm. Simultaneous measurement of blood pressure in both arms shows a difference of 10 mm Hg (both systolic and diastolic) in approximately 3% of normotensive and 6% of hypertensive subjects. However, when the measurements are not made simultaneously a difference of 10 mm Hg or more in systolic pressure is observed in 20% of normotensive and 30% of hypertensive individuals, and a difference in diastolic pressure of 10 mm Hg or more is observed in 10% of normotensive and 15% of hypertensive subjects. Although diastolic pressure is similar in the arms and thighs, systolic pressure is 10 to 40 mm Hg higher in thighs than in arms. The Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure defines systolic and diastolic pressures less than 120 and 80 mm Hg, respectively, as

114 • CHAPTER 8

normal.1 The guideline committee of the European Society of Hypertension—European Society of Cardiology defines systolic and diastolic pressures gross) Intestinal obstruction Renal Hematuria—microscopic Hematuria—gross Proteinuria Other Orchitis Pulmonary CNS

Prevalence of Findings (%) 100 74–82 51–73 63 18–33 1 40–54 26–47 99th percentile) and an aortic graft large enough to accommodate adult blood flow can be used (∼1.8 cm).58 Medical management has not been studied, however, the effects of blocking signaling at the angiotensin type II receptor on down regulating TGF-␤ signaling suggests that it may have a role to play in preventing the development of vascular complications.39

•

ARTERIAL TORTUOSITY SYNDROME

Arterial tortuosity syndrome is a rare condition which manifests as extreme blood vessel tortuosity, particularly of the major branches of the aorta. Other clinical manifestations including joint laxity, contractures, hyperelastic skin, and arachnodactyly are also frequent and consistent with an underlying connective tissue abnormality.60 The underlying genetic basis appears to be a mutation in the SLC2A10 gene on chromosome 20q13.1.61 This gene encodes the GLUT10 glucose transporter. GLUT10 deficiency shares with MFS and LDS an increase in TGF-␤ signaling. Interestingly the manifestations are primarily of tortuosity, although aneurysm formation has been documented.60 Histologically, the changes that have been described in the aorta include a wall thickness that was twice normal and an enlarged and fragmented elastic membrane.62 The elastic and muscular arteries were elongated and spiraled in

242 • CHAPTER 15

appearance. The walls of the muscular arteries were also thickened by intimal fibrosis, disruption of elastic fibers in the medial layer and fragmentation of the internal elastic membrane resulting in diminished luminal diameter.63 Inheritance is autosomal recessive with most cases described in the literature from consanguineous families. It is likely that as more extensive imaging becomes available that additional cases will be identified.

•

FIBROMUSCULAR DYSPLASIA

Fibromuscular dysplasia (FMD) is a noninflammatory nonatherosclerotic vascular disorder that typically presents with complications of stenotic lesions, however, aneurysms and dissection may also be part of more complex lesions. It is characterized by disorganization of the structural components of the wall of muscular arteries. The renal and the carotid arteries are the most common sites of involvement, however, it has been described in nearly every arterial bed.64 Pathogenesis The clinical manifestations are the result of disordered organization of fibers within the vessel walls resulting in intermittent narrowing of the vascular lumen. An underlying genetic substrate for this abnormality has not yet been determined. Familial cases have been described suggesting an inheritable cause, although a putative gene has not been identified.65−68 The majority of the cases, however, these appear to be sporadic. The inheritance pattern in familial cases suggests an autosomal dominant mechanism with variable inheritance. Clinical Manifestations FMD most frequently presents as occlusive and stenotic lesions of the medium sized arties. The renal and carotid arteries are most frequently involved with involvement in 89% and 26%, respectively. Other arteries include mesenteric arteries in 9%, subclavian arteries in 95 and iliac arteries in 5% of cases.69 Age of presentation is typically between 15 and 50 years of age. There is a strong female predominance among afflicted individuals with female to male ratios between 5:1 and 9:1.65,67 Aneurysms and dissections may also be manifestations of FMD.70−72 Involvement of the renal arteries is one of the major causes of secondary hypertension, particularly in patients under the age of 50, accounting for approximately 10% of all cases.73 Occlusion of renal arteries, however, is uncommon. Cerebrovascular involvement typically presents with symptoms of arterial insufficiency in the region supplied by the involved vessel. The symptoms may be nonspecific such as light-headedness or headache, but more specific neurological symptoms such as transient ischemic attacks, strokes or amaurosis fugax are reported.

Diagnosis The beaded appearance of the affected blood vessels is the key diagnostic feature of FMD (see Figure 15-7A). This is most easily appreciated on angiography, but may also be visualized on CT74 and MRI75 (Figure 15-7B). Threedimensional reconstructions or curved planar reconstructions of CT images may also be helpful in recognizing the characteristic appearance (Figures 15-7C and D). Medial hyperplasia is characterized by regions with thickened dysplastic media alternating with regions with thin media. Intimal, perimedial and adventitial are characterized by abnormal collagen deposition in the respective layers of the blood vessel wall.64,76−79 Pathological Findings The beaded angiographic pattern reflects the alternating zones of luminal stenosis and normal vessel diameter and is confirmed at the time of surgical repair. In addition to fibrointimal proliferation the affected vessels show medial and adventitial changes and disorganization of elastic fibers in the medial layer. Three patterns have been described: medial, intimal and adventitial forms with the medial type accounting for the vast majority of cases. The medial form exhibits medial hyperplasia with replacement of some of the medial smooth muscle cells by fibrous connective tissue and fibroblastic cells and close spatial positioning of internal and external elastic membranes. In the intimal form, invaginating buds of fibrointimal tissue create luminal narrowing. Medial dissection and rupture have been reported in the medial type of FMD. Management Management is targeted at the vascular abnormalities. The stenotic lesions respond well to angioplasty and stenting with low risk of restenosis. In the renal arteries the initial success rate of angioplasty is between 82 and 100%.73 Restenosis occurs in less than 11% to 23% of patients.80,81 Revascularization of patients with hypertension caused by FMD results in amelioration or cure in nearly all cases. Surgical intervention has also proven to be successful treatment modality. With the current success of percutaneous approaches it is usually reserved for cases where either percutaneous intervention has failed or is not feasible. When the stenosis is not flow limiting, prophylactic antithrombotic treatment with aspirin is likely prudent, however, there are no clinical data as yet to support this approach.

•

PSEUDOXANTHOMA ELASTICUM

Pseudoxanthoma elasticum (PXE) is an inherited condition characterized by premature vascular atherosclerosis, gastrointestinal bleeding as a result of vessel fragility in the gastrointestinal tract, angioid streaks in the eye and characteristic skin changes.

CONNECTIVE TISSUE DISORDERS IN PERIPHERAL ARTERIAL DISEASE • 243

A

B

C

D

• FIGURE 15-7.

The clinical diagnosis of FMD is most frequently made based on the characteristic beaded appearance of the affected vessels. It is most easily recognized on angiography as shown on the digital subtraction angiogram of (A) an affected renal artery. (B) The beaded appearance can also be seen on contrast CT scan axial images, however, full appreciation of the extent of the beaded appearance may be enhanced by (C) curved planar reconstructions or (D) 3-D reconstructions of the axial CT images.

Pathogenesis The underlying genetic abnormality is caused by mutations in the ABCC6 gene on chromosome 16p13.1, which belongs to the C subfamily of the ATP binding cassette (ABC) genes.82−85 ABC proteins are transmembrane proteins that

act as active pumps for a variety of substrates. Interestingly, ABCC6 is primarily expressed in the liver and kidney, with little expression in the tissues where PXE manifests itself clinically. This suggests that the mutation in ABCC6 results in the lack of or accumulation of substances that interact

244 • CHAPTER 15

with extracellular matrix synthesis and maintenance.86 The altered extracellular metabolism results in the characteristic pathologic findings of elastic fiber fragmentation and mineralization. Inheritance appears to be predominantly autosomal recessive, however, reports of autosomal dominant inheritance exist.87 Clinical Manifestations The vascular manifestations of PXE include premature arterial narrowing and occlusion and mucosal bleeding. The occlusive lesions typically involve small and medium sized arteries and may present with coronary artery disease, peripheral claudication or cerebrovascular disease.88,89 Stenotic lesions develop slowly leading to extensive collateral formation. Histologically, the atheromatosis may be indistinguishable from that because of the traditional risk factors such as smoking and hypertension but occur at an earlier age and affect the arteries of the upper extremities. Mucosal bleeding most frequently occurs in the gastrointestinal tract.90 The precise mechanism of bleeding is unknown, but may relate to defective vasoconstriction. However, there is no evidence of vascular fragility.91 The skin manifestations of PXE are the clinical feature that typically leads to diagnosis, although it need not be uniformly present. The lesions typically consist of yellowish papules ranging in size from 1 to 5 mm. As they coalesce they may form patches that leads to the characteristic “plucked chicken skin” appearance. The lesions typically first become apparent on the lateral aspect of the neck and progress to involve the flexural regions, for example, the axillae, the antecubital, and popliteal fossa. The loss of elasticity of the tissue frequently results in redundant skin folds. The disruption of the elastic fibers in Bruch’s membrane within the eye leads to the characteristic angioid streaks on fundoscopic examination. Although the angioid streaks do not directly affect vision, the proliferation of brittle

choroidal neovessels with subsequent retinal bleeding may lead to blindness. Diagnosis PXE should be suspected when the typical skin findings or unexplained vascular calcification is found. Confirmation by skin biopsy is easily available. Inherited hemoglobinopathies, for example, ␤thalassemia can mimic all of the findings of PXE, skin, cardiac, and ocular, however, they typically occur at an older age.92 Therefore, exclusion of hemoglobinopathies is appropriate when considering the diagnosis of PXE. Pathological Findings The cardiovascular changes in PXE include endocardial plaques in the atria and occasionally on the leaflets of atrioventricular valves. The endomyocardial biopsy can be helpful in documenting the thickened endocardium composed of fragmented, thickened and calcified elastic fibers. The aorta is rarely affected; medium sized vessels are the primary site of involvement. These intimal changes produce luminal stenosis or aneurysmal dilatation and account for the accelerated atherosclerosis.93 Management There is no specific treatment to prevent the vascular manifestations of PXE. Revascularization in the setting of coronary disease seems to be beneficial, however, the internal mammary artery should be used as a conduit only with care since it may also be involved in PXE.94 Aggressive management of the usual risk factors for atherosclerosis such as hyperlipidemia, smoking, and diabetes also makes sense; however, there are no studies to support such an approach. The risk of mucosal bleeding makes the use of antithrombotic agents such as aspirin and clopidogrel somewhat problematic and the risk benefit ratio should be assessed individually.

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7. Germain DP. Ehlers-Danlos syndrome type IV. Orphanet J Rare Dis. 2007;2:32. 8. Gelse K, Poschl E, Aigner T. Collagens—structure, function, and biosynthesis. Adv Drug Deliv Rev. 2003;55(12):15311546. 9. Pope FM, Martin GR, Lichtenstein JR, et al. Patients with Ehlers-Danlos syndrome type IV lack type III collagen. Proc Natl Acad Sci U S A. 1975;72(4):1314-1316.

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10. Pepin M, Schwarze U, Superti-Furga A, et al. Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type. N Engl J Med. 2000;342(10):673-680. 11. Pyeritz RE. Ehlers-Danlos syndrome. N Engl J Med. 2000;342 (10):730-732. 12. Schwarze U, Schievink WI, Petty E, et al. Haploinsufficiency for one COL3A1 allele of type III procollagen results in a phenotype similar to the vascular form of Ehlers-Danlos syndrome, Ehlers-Danlos syndrome type IV. Am J Hum Genet. 2001;69(5):989-1001. 13. Oderich GS, Panneton JM, Bower TC, et al. The spectrum, management and clinical outcome of Ehlers-Danlos syndrome type IV: a 30-year experience. J Vasc Surg. 2005;42(1):98106. 14. North KN, Whiteman DA, Pepin MG, et al. Cerebrovascular complications in Ehlers-Danlos syndrome type IV. Ann Neurol. 1995;38(6):960-964. 15. Barabas AP. Ehlers-Danlos syndrome type IV. N Engl J Med. 2000;343(5):366. 16. Nishiyama Y, Manabe N, Ooshima A, et al. A sporadic case of Ehlers-Danlos syndrome type IV: diagnosed by a morphometric study of collagen content. Pathol Int. 1995;45(7):524529. 17. Crowther MA, Lach B, Dunmore PJ, et al. Vascular collagen fibril morphology in type IV Ehlers-Danlos syndrome. Connect Tissue Res. 1991;25(3-4):209-217. 18. Casana R, Nano G, Dalainas I, et al. Endovascular treatment of hepatic artery aneurysm in a patient with Ehlers-Danlos syndrome. Case report. Int Angiol. 2004;23(3):291-295. 19. Kurata A, Oka H, Ohmomo T, et al. Successful stent placement for cervical artery dissection associated with the EhlersDanlos syndrome. Case report and review of the literature. J Neurosurg. 2003;99(6):1077-1081. 20. Sugawara Y, Ban K, Imai K, et al. Successful coil embolization for spontaneous arterial rupture in association with EhlersDanlos syndrome type IV: report of a case. Surg Today. 2004;34(1):94-96. 21. Uchiyama D, Koganemaru M, Abe T, et al. Successful transcatheter arterial embolization for spontaneous rupture of the posterior tibial artery in a patient with Ehlers-Danlos syndrome type IV. J Vasc Interv Radiol. 2006;17(10):17161717. 22. Tonnessen BH, Sternbergh WC III, Mannava K, et al. Endovascular repair of an iliac artery aneurysm in a patient with Ehlers-Danlos syndrome type IV. J Vasc Surg. 2007;45(1): 177-1779. 23. Schievink WI, Piepgras DG, Earnest FT, et al. Spontaneous carotid-cavernous fistulae in Ehlers-Danlos syndrome Type IV. Case report. J Neurosurg. 1991;74(6):991-998. 24. Horowitz MB, Purdy PD, Valentine RJ, et al. Remote vascular catastrophes after neurovascular interventional therapy for type 4 Ehlers-Danlos Syndrome. AJNR Am J Neuroradiol. 2000;21(5):974-976. 25. Freeman RK, Swegle J, Sise MJ. The surgical complications of Ehlers-Danlos syndrome. Am Surg. 1996;62(10):869-873. 26. Chuman H, Trobe JD, Petty EM, et al. Spontaneous direct carotid-cavernous fistula in Ehlers-Danlos syndrome type IV: two case reports and a review of the literature. J Neuroophthalmol. 2002;22(2):75-81.

27. Hollands JK, Santarius T, Kirkpatrick PJ, et al. Treatment of a direct carotid-cavernous fistula in a patient with type IV Ehlers-Danlos syndrome: a novel approach. Neuroradiology. 2006;48(7):491-494. 28. Vakonakis I, Campbell ID. Extracellular matrix: from atomic resolution to ultrastructure. Curr Opin Cell Biol. 2007;19(5): 578-583. 29. Dietz HC, Cutting GR, Pyeritz RE, et al. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature. 1991;352(6333):337-339. 30. Sakai LY, Keene DR, Engvall E. Fibrillin, a new 350-kD glycoprotein, is a component of extracellular microfibrils. J Cell Biol. 1986;103(6, pt 1):2499-2509. 31. Reinhardt DP, Keene DR, Corson GM, et al. Fibrillin-1: organization in microfibrils and structural properties. J Mol Biol. 1996;258(1):104-116. 32. Ramirez F, Gayraud B, Pereira L. Marfan syndrome: new clues to genotype-phenotype correlations. Ann Med. 1999;31(3): 202-207. 33. Mizuguchi T, Collod-Beroud G, Akiyama T, et al. Heterozygous TGFBR2 mutations in Marfan syndrome. Nat Genet. 2004;36(8):855-860. 34. Kainulainen K, Karttunen L, Puhakka L, et al. Mutations in the fibrillin gene responsible for dominant ectopia lentis and neonatal Marfan syndrome. Nat Genet. 1994;6(1):6469. 35. Faivre L, Collod-Beroud G, Loeys BL, et al. Effect of mutation type and location on clinical outcome in 1,013 probands with Marfan syndrome or related phenotypes and FBN1 mutations: an international study. Am J Hum Genet. 2007;81(3):454466. 36. Aoyama T, Francke U, Dietz HC, et al. Quantitative differences in biosynthesis and extracellular deposition of fibrillin in cultured fibroblasts distinguish five groups of Marfan syndrome patients and suggest distinct pathogenetic mechanisms. J Clin Invest. 1994;94(1):130-137. 37. Judge DP, Biery NJ, Keene DR, et al. Evidence for a critical contribution of haploinsufficiency in the complex pathogenesis of Marfan syndrome. J Clin Invest. 2004;114(2):172181. 38. Matyas G, Alonso S, Patrignani A, et al. Large genomic fibrillin-1 (FBN1) gene deletions provide evidence for true haploinsufficiency in Marfan syndrome. Hum Genet. 2007; 122(1):23-32. 39. Habashi JP, Judge DP, Holm TM, et al. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science. 2006;312(5770):117-121. 40. Aburawi EH, O’Sullivan J. Relation of aortic root dilatation and age in Marfan’s syndrome. Eur Heart J. 2007;28(3):376379. 41. Silverman DI, Burton KJ, Gray J, et al. Life expectancy in the Marfan syndrome. Am J Cardiol. 1995;75(2):157-160. 42. Nawa S, Ikeda E, Ichihara S, et al. A true aneurysm of axillarysubclavian artery with cystic medionecrosis: an unusual manifestation of Marfan syndrome. Ann Vasc Surg. 2003; 17(5):562-564. 43. Savolainen H, Savola J, Savolainen A. Aneurysm of the iliac artery in Marfan’s syndrome. Ann Chir Gynaecol. 1993;82(3): 203-205.

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45. de Virgilio C, Cherry KJ Jr, Schaff HV. Multiple aneurysms and aortic dissection: an unusual manifestation of Marfan’s syndrome. Ann Vasc Surg. 1994;8(4):383-386.

62. Beuren AJ, Hort W, Kalbfleisch H, et al. Dysplasia of the systemic and pulmonary arterial system with tortuosity and lengthening of the arteries. A new entity, diagnosed during life, and leading to coronary death in early childhood. Circulation. 1969;39(1):109-115.

46. Latter DA, Ricci MA, Forbes RD, et al. Internal carotid artery aneurysm and Marfan’s syndrome. Can J Surg. 1989;32(6): 463-466.

63. Pletcher BA, Fox JE, Boxer RA, et al. Four sibs with arterial tortuosity: description and review of the literature. Am J Med Genet. 1996;66(2):121-128.

47. Schievink WI, Parisi JE, Piepgras DG, et al. Intracranial aneurysms in Marfan’s syndrome: an autopsy study. Neurosurgery. 1997;41(4):866-870; discussion 871.

64. Stanley JC, Gewertz BL, Bove EL, et al. Arterial fibrodysplasia. Histopathologic character and current etiologic concepts. Arch Surg. 1975;110(5):561-566.

48. Conway JE, Hutchins GM, Tamargo RJ. Marfan syndrome is not associated with intracranial aneurysms. Stroke. 1999;30 (8):1632-1636.

65. Grimbert P, Fiquer-Kempf B, Coudol P, et al. Genetic study of renal artery fibromuscular dysplasia. Arch Mal Coeur Vaiss. 1998;91(8):1069-1071.

49. De Paepe A, Devereux RB, Dietz HC, et al. Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet. 1996; 62(4):417-426.

66. Rushton AR. The genetics of fibromuscular dysplasia. Arch Intern Med. 1980;140(2):233-236.

44. Flanagan PV, Geoghegan J, Egan TJ. Iliac artery aneurysm in Marfan’s syndrome. Eur J Vasc Surg. 1990;4(3):323-324.

50. Roberts WC, Honig HS. The spectrum of cardiovascular disease in the Marfan Syndrome: a clinico-morphologic study of 18 necropsy patients and comparison to 151 previously reported necropsy patients. Am Heart J. 1982;104:115-135. 51. Shores J, Berger KR, Murphy EA, et al. Progression of aortic dilatation and the benefit of long-term beta-adrenergic blockade in Marfan’s syndrome. N Engl J Med. 1994;330(19):13351341. 52. Gott VL, Greene PS, Alejo DE, et al. Replacement of the aortic root in patients with Marfan’s syndrome. N Engl J Med. 1999;340(17):1307-1313. 53. Tambeur L, David TE, Unger M, et al. Results of surgery for aortic root aneurysm in patients with the Marfan syndrome. Eur J Cardiothorac Surg. 2000;17(4):415-419.

67. Pannier-Moreau I, Grimbert P, Fiquet-Kempf B, et al. Possible familial origin of multifocal renal artery fibromuscular dysplasia. J Hypertens. 1997;15(12, pt 2):1797-1801. 68. Perdu J, Boutouyrie P, Bourgain C, et al. Inheritance of arterial lesions in renal fibromuscular dysplasia. J Hum Hypertens. 2007;21(5):393-400. 69. Luscher TF, Keller HM, Imhof HG, et al. Fibromuscular hyperplasia: extension of the disease and therapeutic outcome. Results of the University Hospital Zurich Cooperative Study on Fibromuscular Hyperplasia. Nephron. 1986;44(suppl 1): 109-114. 70. Bonardelli S, Vettoretto N, Tiberio GA, et al. Right subclavian artery aneurysms of fibrodysplastic origin: two case reports and review of literature. J Vasc Surg. 2001;33(1):174-177.

54. Kim SY, Martin N, Hsia EC, et al. Management of aortic disease in Marfan Syndrome: a decision analysis. Arch Intern Med. 2005;165(7):749-755.

71. Kojima A, Shindo S, Kubota, K, et al. Successful surgical treatment of a patient with multiple visceral artery aneurysms due to fibromuscular dysplasia. Cardiovasc Surg. 2002;10(2):157160.

55. Milewicz DM, Dietz HC, Miller DC. Treatment of aortic disease in patients with Marfan syndrome. Circulation. 2005; 111(11):e150-e157.

72. Radhi JM, McKay R, Tyrrell MJ. Fibromuscular dysplasia of the aorta presenting as multiple recurrent thoracic aneurysms. Int J Angiol. 1998;7(3):215-218.

56. Singh KK, Rommel K, Mishra A, et al. TGFBR1 and TGFBR2 mutations in patients with features of Marfan syndrome and Loeys-Dietz syndrome. Hum Mutat. 2006;27(8):770-777.

73. Safian RD, Textor SC. Renal-artery stenosis. N Engl J Med. 2001;344(6):431-442.

57. Loeys BL, Chen J, Neptune ER, et al. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet. 2005;37(3):275-281. 58. Loeys BL, Schwarze U, Holm T, et al. Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med. 2006;355(8):788-798. 59. Lee RS, Fazel S, Schwarze U, et al. Rapid aneurysmal degeneration of a Stanford type B aortic dissection in a patient with Loeys-Dietz syndrome. J Thorac Cardiovasc Surg. 2007; 134(1):242-243. 60. Wessels MW, Catsman-Berrevoets CE, Mancini GM, et al. Three new families with arterial tortuosity syndrome. Am J Med Genet A. 2004;131(2):134-143. 61. Coucke PJ, Willaert A, Wessels MW, et al. Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome. Nat Genet. 2006;38(4): 452-457.

74. Sabharwal R, Vladica P, Coleman P. Multidetector spiral CT renal angiography in the diagnosis of renal artery fibromuscular dysplasia. Eur J Radiol. 2007;61(3):520-527. 75. Willoteaux S, Faivre-Pierret M, Moranne O, et al. Fibromuscular dysplasia of the main renal arteries: comparison of contrastenhanced MR angiography with digital subtraction angiography. Radiology. 2006;241(3):922-929. 76. Harrison EG Jr, McCormack LJ. Pathologic classification of renal arterial disease in renovascular hypertension. Mayo Clin Proc. 1971;46(3):161-167. 77. Bragin MA, Cherkasov AP. Morphogenesis of fibromuscular dysplasia of the renal arteries (an ultrastructural study). Arkh Patol. 1979;41(2):46-52. 78. Begelman SM, Olin JW. Fibromuscular dysplasia. Curr Opin Rheumatol. 2000;12(1):41-47. 79. Vuong PN, Desoutter P, Mickley V, et al. Fibromuscular dysplasia of the renal artery responsible for renovascular hypertension: a histological presentation based on a series of 102 patients. Vasa. 2004;33(1):13-18.

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80. Plouin PF, Darne B, Chatellier G, et al. Restenosis after a first percutaneous transluminal renal angioplasty. Hypertension. 1993;21(1):89-96. 81. Birrer M, Do DD, Mahler F, et al. Treatment of renal artery fibromuscular dysplasia with balloon angioplasty: a prospective follow-up study. Eur J Vasc Endovasc Surg. 2002;23(2):146152. 82. Struk B, Cai L, Zach S, et al. Mutations of the gene encoding the transmembrane transporter protein ABC-C6 cause pseudoxanthoma elasticum. J Mol Med. 2000;78(5):282286. 83. Bergen AA, Plomp AS, Schuurman EJ, et al. Mutations in ABCC6 cause pseudoxanthoma elasticum. Nat Genet. 2000; 25(2):228-231. 84. Le Saux O, Urban Z, Tschuch C, et al. Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum. Nat Genet. 2000;25(2):223-227. 85. Ringpfeil F, Lebwohl MG, Christiano AM, et al. Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter. Proc Natl Acad Sci USA. 2000;97(11):6001-6006. 86. Le Saux O, Bunda S, VanWart CM, et al. Serum factors from pseudoxanthoma elasticum patients alter elastic fiber formation in vitro. J Invest Dermatol. 2006;126(7):14971505. 87. Plomp AS, Hu X, de Jong PT, et al. Does autosomal dominant

pseudoxanthoma elasticum exist? Am J Med Genet A. 2004; 126(4):403-412. 88. Pavlovic AM, Zidverc-Trajkovic J, Milovic MM, et al. Cerebral small vessel disease in pseudoxanthoma elasticum: three cases. Can J Neurol Sci. 2005;32(1):115-118. 89. Khan MA, Beard J. Peripheral vascular disease in an individual with pseudoxanthoma elasticum. Eur J Vasc Endovasc Surg. 2007;34(5):590-591. Epub 2007 May 31. 90. McCreedy CA, Zimmerman TJ, Webster SF. Management of upper gastrointestinal hemorrhage in patients with pseudoxanthoma elasticum. Surgery. 1989;105(2, pt 1):170-174. 91. Chassaing N, Martin L, Calvas P, et al. Pseudoxanthoma elasticum: a clinical, pathophysiological and genetic update including 11 novel ABCC6 mutations. J Med Genet. 2005;42 (12):881-892. 92. Aessopos A, Farmakis D, Loukopoulos D. Elastic tissue abnormalities resembling pseudoxanthoma elasticum in beta thalassemia and the sickling syndromes. Blood. 2002;99(1):3035. 93. Mendelsohn G, Bulkley BH, Hutchins GM. Cardiovascular manifestations of Pseudoxanthoma elasticum. Arch Pathol Lab Med. 1978;102(6):298-302. 94. Iliopoulos J, Manganas C, Jepson N, et al. Pseudoxanthoma elasticum: is the left internal mammary artery a suitable conduit for coronary artery bypass grafting? Ann Thorac Surg. 2002;73(2):652-653.

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16

History and Physical Examination Jessica A. Sutherland, MD / Ferdinand S. Leya, MD / Robert S. Dieter, MD, RVT

•

HISTORY TAKING

Importance of History Taking A thorough history is essential in all fields of medicine. It has often been said that a majority of all diagnosis are suggested or made by the history, even more when aided by a careful physical examination. Although technology has greatly advanced and it is tempting to order a battery of tests to aid in diagnosis, the history remains the most valuable source of information concerning the patient’s illness. The history serves as the primary source for data gathering and should include both the patient’s perspective and account of symptoms as well as information obtained from directed questioning by the examiner. The patient should be allowed to talk without interruption regarding their primary concern, and should also be able to voice an opinion about what he or she believes may be the underlying problem. When more information is needed, the examiner should use nonleading questions to collect further details and permit the patient to answer each question fully before moving on to the next. If the patient is acutely ill, however, it is reasonable for the examiner to limit the patient’s time for response in order to allow for prompt evaluation and treatment. When possible, the examiner should speak with family members or close friends in order to better understand the extent of disability and the impact of illness not only on the patient but also on those around the patient. Additionally, the time spent during the history allows the patient and examiner to develop a bond that will aid in future diagnosis and therapy. Maintaining eye contact and intent listening will demonstrate the clinician’s compassion and understanding. Asking key questions in words the patient understands and using a nonjudgmental tone will enhance communication, instill confidence, and facilitate a trusting relationship that will lend support to acceptance of therapy and compliance with treatments.

Finally, the history serves as a way to organize the examiner’s thoughts, maximize clinical reasoning, and create a comprehensive differential diagnosis. This in turn leads to a more proficient physical examination, appropriate use of diagnostic aids, and prioritization of therapeutic interventions. Analysis of a Symptom Often the patient will present with a main symptom or complaint for which they seek assistance. In accurately evaluating each symptom, it is important to recall the characteristics of symptom analysis (see Table 16-1). Using each attribute to further define an index symptom is fundamental in recognizing disease patterns and developing a detailed differential diagnosis. Location. In determining location of a symptom, it is important to be as specific as possible. Patients will often include a location in their chief complaint such as “I have leg pain,” etc., however, more precision is needed. For example, is the pain anterior, posterior, hip, thigh, calf, foot, left-sided, right-sided? In addition, does the pain radiate or change location? Some symptoms such as fatigue or weakness may not have a specific location, and this is valuable to document as well. Quality. For some symptoms, more descriptive adjectives

are easily applied. Regarding a chief complaint of pain, one could use words such as burning, pressure, heaviness, sharp, dull, or cramping for further qualification. With other symptoms, like dizziness, patients may have more difficulty expanding on their sensation without the examiner assisting with a question such as “Could you tell me more about what that was like for you?” Sometimes even the patient’s inability to describe the symptom may be a clue in

250 • CHAPTER 16

TABLE 16-1. Characteristics of Symptom Analysis Characteristic Location Quality Quantity (severity) Timing Setting Alleviating/aggravating factors Associated manifestations

itself. Patient facial expressions and gestures can also be of support. Quantity or Severity. Quantification of a symptom may

use well-known units such as number of pillows for orthopnea, or teaspoons of sputum. An analogue scale from 0 to 10 can be used to evaluate severity for symptoms in which a numerical unit cannot be applied such as with pain. Occasionally quantification can be made in terms of how the symptom is affecting daily activities such as walking to the bathroom or carrying bags of groceries. Timing. In evaluating the timing of a symptom, the examiner should note the onset, duration, and frequency. When was the symptom first appreciated or how long has it been taking place? In the case of an intermittent symptom, how long does it persist in terms of seconds, minutes, hours, or days when it does arise? Is the symptom a daily occurrence, twice a week, or maybe only once every few weeks? Setting. Determining the setting of a symptom can be thought of as an expansion on its timing in that the examiner looks to identify when the symptom occurs. Using leg pain as an example, is it related to certain activities such as walking up stairs or prolonged periods of standing? Does it occur at specific times for example upon first waking and getting out of bed or during the night while sleeping? Were there any precipitating factors or events such a fall or car accident? Alleviating and Aggravating Factors. Often the patient will have already made attempts to stop the symptom when it occurs or preempt it from happening altogether. Inquiries should be made as to anything the patient feels may help relieve the symptom including positional changes or medications, both over-the-counter and prescription. In addition, are there things that make the symptom worse or does the patient avoid certain actions in order to prevent the symptom from happening? Associated Symptoms. Finally, the examiner should ex-

plore whether the patient’s complaint is a lone symptom, or if there are other sensations that transpire along with

it. Patients may not even be aware of additional symptoms until questioned. Documentation of a lack of associated symptoms is helpful as well.

•

VASCULAR HISTORY

Peripheral arterial disease can involve the ascending aortic arch and its branches, the descending aorta and its branches, and all muscular arteries. Symptoms produced by peripheral arterial disease are often governed by the location of the lesion, the severity or chronicity of the lesion, and the status of collateral flow. Several questionnaires have been developed to assess the presence and severity of lower extremity peripheral arterial disease. The Rose Questionnaire was initially developed in 1962 to diagnose both angina and peripheral arterial disease in epidemiological surveys but was limited by low sensitivity. Modifications, including the Edinburgh Claudication Questionnaire and the San Diego Questionnaire, have been created and validated to be more sensitive and specific in comparison to a physician’s diagnosis based on walking distance, walking speed, and nature of symptoms.1−3 Most recently, the Walking Impairment Questionnaire has proven to be a validated instrument even after modification for self-administration (see Figure 16-1).4 In evaluating a patient’s symptoms, the examiner must keep in mind risk factors that would yield a vascular etiology to be more likely and assess for them as well. Peripheral arterial disease may be a manifestation of systemic atherosclerosis and therefore shares similar risk factors. Major nonreversible risk factors for atherosclerosis consist of age, male sex, and family history of premature disease. Modifiable risk factors for the development and/or progression of atherosclerotic disease include tobacco smoking, dyslipidemia, diabetes mellitus, hypertension, hyperhomocysteinemia, and elevated C-reactive protein (see Table 16-2).1,5 Common Vascular Symptoms Extremity Pain. The term claudication stems from the

Latin verb claudicare, which means to limp. Intermittent claudication is one of the most common vascular complaints and is defined as a reproducible discomfort in a particular muscle group brought on by exercise and is relieved with rest (see Table 16-3). The actual muscle discomfort can vary from patient to patient, leading to variable descriptions of which the examiner must be aware including pain, cramping, tightness, burning, weakness, heaviness, or fatigue. The description offered by the patient may be helpful in quantifying the extent of ischemia; terms such as “heaviness” and “tiredness” typically represent minimal ischemic changes, but “pain” and “cramping” usually indicate more extensive disease.6 The quantity of discomfort is proportional to the amount and vigorousness of exercise, so questions should be directed so as to determine not only the distance a patient can walk but also at what speed or incline. It is important to note that symptoms of joint or bone pain or those brought on by prolonged standing are

HISTORY AND PHYSICAL EXAMINATION • 251

1.

Please place a  in the box that best describes how much difficulty you have had walking due to pain, aches, or cramps during the last week. The response options range from“No Difficulty” to “Great Difficulty.” During the last week, how much difficulty have you had walking due to:

Slight Some No Difficulty Difficulty Difficulty

Much Great Difficulty Difficulty

a. Pain, aching, or cramps in your calves?

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b. Pain, aching, or cramps in your buttocks?

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For the following questions, the response options range from “No Difficulty” to “Unable to Do.” If you cannot physically perform a specified activity, for example walk 2 blocks without stopping to rest because of symptoms such as leg pain or discomfort, please place a  in the box labeled “Unable to Do.” However, if you do not perform an activity for reasons unrelated to your circulation problems, such as climbing a flight of stairs becuse your home is one level or your apartment has an elevator, please place a  in the box labeled “Don’t Do for Other Resons.” 2. Please place a  in the box that best describes how hard it was for you to walk on level ground withot stopping to rest for each of the following distances during the last week. During the last week, how difficult was it for you to: a. Walk indoors, such as around your home?

Slight Some Much No Difficulty Difficulty Difficulty Difficulty

Unable to Do

Did not Do for Other Reasons

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b. Walk 50 feet? c. Walk 150 feet? (1/2 block)? d. Walk 300 feet? (1 block)? e. Walk 600 feet? (2 blocks)? f. Walk 900 feet? (3 blocks)? g. Walk 1500 feet? (5 blocks)?

• FIGURE 16-1.

Walking Impairment Questionnaire modified for self-administration.

(Continued)

Reproduced, with permission, from Coyne KS, Margolis MK, Gilchrist KA, et al. Evaluating effects of method of administration on walking impairment questionnaire. J Vasc Surg. 2003;38:296-304.

typically not claudication and another etiology should be sought (see Table 16-4). The location of the discomfort gives clues to the arterial system compromised. Most often patients report calf pain which can be attributed to disease in the superficial femoral or popliteal artery; however, patients can also have foot pain from tibial–peroneal disease, gluteal, and thigh pain caused by aortoiliac disease, or arm pain secondary to subclavian involvement. While the occlusive process can be at multiple levels, the initial site of claudication usually reflects the most distal significant lesion or the area with the poorest collateral flow.7 Occlusive arterial disease is often bilateral, although patients will frequently report only unilateral symptoms caused by varying degrees of hemodynamically significant obstruction.

Progression of arterial insufficiency can result in rest pain, especially at night when reclined. Often patients will provide a history of past claudication that had progressed, but will now deny claudication due to self-imposed sedentary lifestyle.6 Rest pain is classically described as stabbing, burning, or stinging, and can be associated with coldness, numbness, or parasthesias of the toes. Patients will commonly relate that relief is only obtained by placing the feet on the floor, dangling them off the side of the bed, or sleeping in a seated position. This dependent posture permits gravity to assist with perfusion pressure and improve the transport of blood supply to the painful extremities. Seventy to eighty percent of patients presenting with acute peripheral syndromes have suffered an embolic event, with acute thrombosis or mechanical compression

252 • CHAPTER 16 3. Please place a  in the box that best describes how hard it was for you to walk one city block on level ground at each of these speeds without stopping to rest during the last week. Please not 1 block is roughly equivalent to 300 feet.

During the last week, how difficult was it for you to:

No Slight Some Much Difficulty Difficulty Difficulty Difficulty

a. Walk 1 block slowly?

Unable to Do

Did not Do for Other Reasons

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b. Walk 1 block at average speed? c. Walk 1 block quickly? d. Run or jog 1 block?

4. Please place a  in the box that best describes how hard it was for you to climb stairs withour stopping to rest durign the last week. Please note 1 flight of stairs is roughly equal to 14 steps.

During the last week, how difficult was it for you to: a. Climb 1 flight of stairs?

No Slight Some Much Difficulty Difficulty Difficulty Difficulty

Unable to Do

Did not Do for Other Reasons

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b. Climb 2 flights of stairs? c. Climb 3 flights of stairs?

• FIGURE 16-1.

(Continued )

occurring much less frequently.8 The patient with acute arterial occlusion classically demonstrates the six p’s: pain, pallor, pulselessness, parasthesias, poikilothermia, and paralysis. Acute arterial occlusion can cause sudden and severe pain that is continuous for the first few hours followed by a period of numbness as ischemic damage progresses. The often-excruciating pain is unrelated to physical exertion and is not relieved by rest or position changes. Chest Pain. When a patient reports any form of chest

pain, the heart is generally considered the most probable as well as the most worrisome source. Varying degrees of chest discomfort, however, can originate from several other noncardiac intrathoracic vascular sources and can be just as serious. The diagnosis and differentiation from myocardial ischemic pain requires careful symptom analysis, including location, radiation, quality, severity, timing, and aggravating or alleviating factors. Sudden onset of severe chest pain is the single most common presenting symptom for acute aortic dissection, reported in 63% of type B dissections and 79% of type A dissections based on the International Registry of Acute Aortic Dissection (IRAD).9 Patients will classically describe the quality of pain as “ripping,” “stabbing,” or “tearing” that often radiates to the back. The intensity of the pain is at its maximum at inception and is often unrelenting in na-

ture; it is not associated with physical activity nor is it relieved by rest or change in body position, although patients have been known to writhe in agony or pace relentlessly in an effort to find some relief. Location and radiation of the pain can be helpful in determining the origin and/or path of the dissection. Anterior chest pain with radiation to the neck, jaw, or face is strongly indicative of involvement of the ascending aorta and one or more arch vessels, whereas chest pain with radiation to the intrascapular or lower back correlates with descending aortic dissections.10 Other clues to the diagnosis include a history of hypertension or connective tissue disorder such as Marfan’s syndrome, and clinical manifestations depending on the branch arteries involved. Noncardiac chest pain that is gradual in onset or of a more chronic nature can result from vascular etiologies such as aneurysms of the thoracic aorta (both ascending and arch) and pulmonary arterial hypertension. Although rare, pain secondary to nondissecting thoracic aneurysms is often related to mass effect on neighboring structures, the chest wall, or erosion into adjacent bones and has been described as a deep and steady, dull discomfort, unaffected by exertion or change in position. Substernal chest pain related to pulmonary hypertension, in contrast, is usually described as a pressure sensation, aggravated by effort and associated with dyspnea, cough, or wheeze.

HISTORY AND PHYSICAL EXAMINATION • 253

TABLE 16-2. Modifiable Risk Factors for Peripheral Arterial Disease Risk Factor

Estimated Relative Risk

Cigarette smoking Diabetes mellitus Hypertension Hypercholesterolemia (per 40–50 mg/dL increase in total cholesterol) Fibrinogen (per 0.7 g/L increase in fibrinogen) C-reactive protein Hyperhomocysteinemia

2.0–5.0 3.0–4.0 1.1–2.2 1.2–1.4

1.35 2.1 2.0–3.2

Reprinted with permission from Creager MA, Libby P. Peripheral arterial diseases. In: Zipes DP, Libby P, Bonow RO, Braunwald E, eds. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. 7th ed. Philadelphia, PA: Elsevier Saunders; 2005:1437-1461.

Dyspnea. Dyspnea is the medical term for a range of

patient complaints including shortness of breath, feelings of breathlessness, or difficulty breathing. As it is often a slowly progressive symptom over months or years, it may also represent a gradual decrease in exercise tolerance or the increasing need for “breaks” while completing daily activities. Most often dyspnea is related to cardiac decompensation or intrinsic pulmonary disease, however, vascular conditions such as pulmonary arterial hypertension, vascular compression of the left mainstem bronchus, or severe generalized vascular disease that limits oxygen delivery to metabolically active muscles can also result in difficulty breathing. Like cardiac dyspnea, vascular conditions may have associated symptoms such as cough, wheeze, or weakness and may be provoked by exertion. However, vascular dyspnea should not be initiated or made worse by change in body position.

Abdominal Pain. Vascular sources of abdominal pain, including aortic dissection, aneurysmal disease of the aorta and abdominal viscera, visceral ischemia, and celiac compression syndrome can have devastating consequences if not diagnosed quickly and accurately. While the majority of abdominal aortic aneurysms are asymptomatic and discovered incidentally, patients will occasionally complain of a steady, gnawing pain in the lower abdomen or back for hours or days at a time. Although movement does not usually affect aneurysm pain, some patients will note relief in certain positions, like lying supine with the legs drawn up. The development of new or worsening pain suggests expansion or impending rupture; it is classically described as severe and constant with possible radiation into the groin, buttocks, or legs. Actual rupture produces severe, diffuse abdominal pain and tenderness with hemodynamic compromise, although a rupture or leak contained by the retroperitoneum may localize the pain to the flank or groin. Like aortic aneurysms, visceral aneurysms may remain asymptomatic until discovered by incidental imaging or they expand and impede upon nearby structures. When pain exists, it tends to be greatest over the region of the abdomen near the abdominal visera affected until rupture when it becomes more diffuse with associated tenderness. The location of the pain induced by acute visceral ischemia may vary based on which arterial branch is occluded, however, symptoms are often nonspecific. With mesenteric disease, symptoms may begin with a very focal area of cramping pain or tenderness that progresses in severity as the duration of ischemia extends. Patients will report difficulty in finding a comfortable position to lie, and will frequently have associated bouts of nausea, vomiting, and bloody bowel movements. Typically, the abdominal examination will lag behind the patient’s complaints of severe pain (i.e., pain out of proportion to the examination findings) which can delay diagnosis. Splenic artery occlusions may be accompanied by epigastric or left upper quadrant discomfort, whereas hepatic artery occlusions are either asymptomatic or present with right quadrant pain. Renal artery occlusions are most often silent, but may

TABLE 16-3. Classification of Peripheral Arterial Disease Fontaine Stage

Rutherford Clinical

I IIa IIb

Asymptomatic Mild claudication Moderate-to-severe claudication

III IV

Ischemic rest pain Ulceration or gangrene

Grade

Category

0 I I I II III III

0 1 2 3 4 5 6

Clinical Asymptomatic Mild claudication Moderate claudication Severe claudication Ischemic rest pain Minor tissue loss Major tissue loss

Reprinted with permission from Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FGR. Inter-society consensus for the management of peripheral arterial disease (TASC II). Eur J Vasc Endovasc Surg. 2007;33:S1-S75.

254 • CHAPTER 16

TABLE 16-4. Differential Diagnosis of Intermittent Claudication Condition

Location

Symptoms

Calf claudication

Calf muscles

Cramping, aching

Thigh/buttock claudication

Buttocks, hip, thigh

Cramping, aching

Foot claudication

Foot arch

Severe pain

Chronic compartment syndrome Venous claudication Nerve root compression

Calf muscles

Tight, bursting pain

Entire leg, worse in calf Radiates down leg

Tight, bursting pain

Effect of Exercise and Rest

Sharp, lancinating pain

Baker’s cyst

Behind knee, down calf

Swelling, tenderness

Hip arthritis

Lateral hip, thigh

Aching discomfort

Spinal stenosis

Bilateral buttocks, posterior leg

Pain and weakness

Reproducible onset; quickly relieved with rest Reproducible onset; quickly relieved with rest Reproducible onset; quickly relieved with rest After much exercise (jogging); subsides very slowly After walking; slowly subsides Induced by sitting, standing or walking; may be present at rest Worse with exercise; often present at rest and not intermittent After variable degree of exercise; not quickly relieved with rest May mimic claudication; variable relief, can take a long time to recover

Effect of Position None

None

None

Relief with elevation

Relief speeded by elevation Worse with sitting, improved by change in position or lying supine None

Improved when not bearing weight Relief by lumbar spine flexion, worse with standing or extending spine

Modified from Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FGR. Inter-society consensus for the management of peripheral arterial disease (TASC II). Eur J Vasc Endovasc Surg. 2007;33:S1-S75.

eventually evolve into sharp back or flank pain associated with nausea, vomiting, and hematuria. Although all acute occlusions can incur without precipitating factors, the examiner’s suspicion should be raised in patients with recent aortic instrumentation such as takes place with angiography. Patients with chronic visceral ischemia may also complain of varying pain syndromes. Mesenteric disease again causes a cramping pain, although this pain usually only occurs 15 to 30 minutes after ingestion of a meal and may not be associated with a change in bowel habits. Over time, the pattern of colicky pain becomes so severe that the patient may shun eating altogether in an effort to diminish or avoid the expected abdominal discomfort. Consequently, significant weight loss may be reported by the patient as well. Celiac compression syndrome (also referred to as median arcuate ligament syndrome, Dunbar syndrome, and celiac axis syndrome) produces abdominal pain through extrinsic compression of the vessels at the celiac axis origin by fibers of the median arcuate ligament of the diaphragm. Symptoms may include weight loss and postprandial pain, which is often augmented by full expiration. Despite many case reports, celiac compression syndrome’s contribution to

chronic abdominal pain and mesenteric ischemia remains uncertain given the rich supply of collaterals between the celiac axis and mesenteric arteries, the presence of compression in a significant proportion of asymptomatic patients, and the failure for surgical correction to reliably relieve symptoms. Other etiologies such as involvement of the splanchnic nerve plexus or delayed gastric emptying have been suggested, however, the diagnosis often remains one of exclusion. Skin Changes. Because of its highly vascular nature, both

acute and chronic occlusive arterial disease can lead to alterations in skin temperature, color, or integrity. A common office complaint is cold hands or feet and is often attributable to an individual’s basic vasomotor tone; however, generalized coolness of an extremity can be related to more serious conditions. When temperature differences are asymmetric or involve only one limb, suspicion is higher for an occlusive process. Disease states resulting in an effective ischemia such as poor cardiac output, hemorrhage, or shock will lead to generalized coolness of all extremities. Skin color varies with blood flow, and therefore can be affected by temperature, physical activity, and emotional

HISTORY AND PHYSICAL EXAMINATION • 255

• FIGURE 16-2.

Livedo reticularis.

Reprinted with permission from Beckman JA, Creager MA. The history and physical examination. In: Creager MA, Dzau VJ, Loscalzo J, eds. Vascular Medicine: A Companion to Braunwald’s Heart Disease. 1st ed. Philadelphia, PA: Elsevier Saunders; 2006:135-145.

stimuli. Patients with Raynaud’s phenomenon will note pale and often painful fingers or toes when exposed to cooler weather, and those with Chilblain lupus (also known as Pernio lupus) report reddish-blue skin nodules occurring in the cold. A violaceous discoloration or cyanosis of a digit or limb that may or may not blanch with pressure is indicative of ischemic disease. Vascultis or atheroembolic disease are common causes of livedo reticularis, a lace-like pattern in the skin consisting of reddish-blue superficial vessels surrounding a central area of clearing sometimes exacerbated by cold exposure (see Figure 16-2). Patients with ischemic rest pain who maintain their feet in a dependent position may develop persistent redness of the toes and feet known as dependent rubor. In some cases of arterial occlusive disease or emboli, chronic ischemia contributes to hair loss and tissue breakdown. Nonhealing and tender ulcerations are often found in distal areas of limbs such as the toes, heel, or fingertips. Patients with peripheral neuropathy are especially at risk for formation of ulcers in areas of trauma. If ulcerations have developed, the patient often requires significant analgesia to combat the pain. Without proper treatment, ischemic ulcers may progress to tissue necrosis and gangrene, resulting in areas of dead tissue that blackens and sloughs.

Neurologic Manifestations. The majority of patients with significant stenoses of the carotid and vertebrobasilar arteries are asymptomatic; however, when symptoms do occur, they are mainly categorized by duration. Transient ischemic attacks (TIAs) are characteristically temporary episodes of spontaneous neurologic dysfunction, lasting from a few minutes to less than 4 hours (though, by definition up to 24 hours). When multiple attacks occur within a short period of time, the syndrome is known as crescendo TIAs. Reversible ischemic neurologic deficits are those that require greater than 24 hours for full recovery. Symptoms that persist for longer periods are generally related to cerebral infarction and are diagnosed as a stroke in evolution or a complete stroke.11 In addition to duration of symptoms, the examiner should note location, setting, quality, and degree of disability when evaluating neurologic complaints to ascertain the affected vascular bed (see Table 16-5). In many instances, it is helpful to have family or friends provide the details of any neurologic manifestation associated with vascular events as confusion or sometimes even loss of consciousness may be a prominent feature. A range of both motor and sensory symptoms might result from embolization of carotid or proximal aortic disease. Amaurosis fugax, or fleeting blindness, occurs when a plaque travels from the proximal aorta or internal carotid artery to the ipsilateral ophthalmic artery. Patients will frequently report monocular vision loss that begins as haziness in the upper fields and progresses downward, like “a veil” or “a shade being drawn.” The vision loss is painless, often without a precipitating factor and usually only lasts for a few seconds or minutes. If both eyes are involved, the cause is rarely carotid artery disease although a vascular etiology should not be completely ruled out. Embolic showers from the proximal aorta or an atheromatous carotid artery to the ipsilateral cerebral hemisphere result in deficits on the side opposite the involved area of the brain. Symptoms will differ based on the area of cerebral cortex supplied by the occluded vessel and can vary from a minor problem, as with a focal parasthesia, to more profound deficits such as aphasia or hemiparesis (see Figures 16-3 and 16-4). The larger the vascular territory, the more widespread is the dysfunction which may occur. Vertebrobasilar disease can also produce parasthesias, dysarthria, or hemiparesis; however, the more likely expressions of ischemia for this arterial system include complaints of confusion, nausea, vomiting, vertigo, dizziness, and ataxia. One of the most frightening symptoms may be “drop attacks” in which patients relate suddenly finding themselves on the floor as a result of an unexpected loss of lower extremity motor function. Because of the anatomic pattern of the vertebral, basilar, subclavian, and innominate arteries, symptoms rarely arise when only one side is occluded. Even when significant bilateral disease is present, patients may remain asymptomatic as a result of the maintainance of adequate blood flow by the communicating arteries in the posterior circulation. Vasculitis of the cranial branches of the arteries arising from the aortic arch may also cause neurologic symptoms.

256 • CHAPTER 16

TABLE 16-5. Carotid Versus Vertebral-Basilar Symptoms Symptoms and Signs Symptoms (attacks of)

Carotid System

Vertebral-Basilar System

Weakness Numbness Aphasia Loss of Vision

One side of face or limbs One side, usually limbs If dominant hemisphere is involved In one eye on side of ischemia (amaurosis fugax) No —

Limbs in any combination One or both sides of body No Homonymous or bilateral hemianopsia Yes Dysarthria, dysphagia, vertigo, ataxia of gait, or limbs

In involved carotid artery Decreased on involved side Retinal arterioles on involved side Over involved carotid artery bifurcation or over globe of eye on involved side, occasionally over opposite carotid artery

In subclavian artery — No Over subclavian artery or back of neck

Diplopia Other Physical signs (inconsistent) Diminished pulsation Change of pressure in ophthalmic artery Retinal emboli Bruits

Reprinted with permission from Siekert RG, Whisnant JP, Sundt TM Jr. Ischemic cerebrovascular disease. In: Juergens JL, Spittell JA Jr, Fairbairn JF, eds. Peripheral Vascular Diseases. 5th ed. Philadelphia, PA: W.B. Saunders Company; 1980:351-380.

Temporal arteritis, also known as giant-cell arteritis, is characterized by a myriad of symptoms which may be gradual or abrupt in onset. The development of a new headache, especially over one or both temporal regions with associated temporal artery tenderness, is the most common complaint

reported in almost two-thirds of patients. Jaw pain secondary to claudication occurs in up to one-half of patients diagnosed with temporal arteritis. Patients may also report impaired vision as an early manifestation of the disease with the most common visual complaints being diplopia or

Shoulder

Head

Arm

Neck

Elbow

Trunk

Forearm

Hip

Wrist

Leg

Hand

Foot

Little finger

Toes

Ring finger

Genitalia

Middle finger Index finger Thumb Eye Nose Face Lips Teeth Gums Jaw Tongue

Anterior cerebral artery

Pharynx

Middle cerebral artery

Intra-abdominal

Posterior cerebral artery Choroidal and striate artery

• FIGURE 16-3.

Sensory homunculus with approximated vascular territories of the main cerebral arteries in the coronal section. The block line stemming from each body part roughly corresponds to the proportion of the sensory cortex devoted to it.

HISTORY AND PHYSICAL EXAMINATION • 257

Shoulder Trunk Hip

Elbow Wrist Hand Little finger Ring finger

Knee Ankle Toes

Middle finger Index finger Thumb Neck Brow Eyelid Eyeball Face Lips Jaw Tongue

Anterior cerebral artery

Swallowing

Middle cerebral artery Posterior cerebral artery Choroidal and striate artery

• FIGURE 16-4.

Motor homunculus with approximated vascular territories of the main cerebral arteries in the coronal section. Again, the block line stemming from each body part roughly corresponds to the proportion of the motor cortex devoted to it.

sudden monocular vision loss. Although complete vision loss in both eyes is rare—if left untreated approximately 15% to 20% of patients will progress to partial or complete vision loss in one or both eyes—sometimes in as quickly as a few days.12 Syncope. Syncope, described as transient and complete

loss of consciousness, and its less complete variants presyncope, lightheadedness, and dizziness, have multiple etiologies and require careful symptom analysis to distinguish vascular from nonvascular causes. Details relating to the setting, duration, aggravating factors, and associated symptoms are important to identify; in addition, eyewitness accounts from family and friends can also lend important clues. Common nonvascular causes to exclude are cardiogenic syncope, epilepsy, hypoglycemia, or reflex syncope. Vasomotor syncope, although associated with vascular events such as bradycardia and peripheral vasodilatation, is not truly related to cardiac or vascular disease. Patients often described this type of syncope as being predictable, recurrent, and precipitated by features like pain, visually shocking sights (i.e., the sight of blood or a needle), fatigue, warm environments, prolonged standing, fasting, fear, or anxiety. Vascular sources, namely cerebrovascular arterial insufficiency, are often part of a larger pattern of neurologic manifestations of arterial disease and can be attributed to occlusive embolic and thrombotic events or vasospasm within the cerebral or arch vessels. Stenosis of the subclavian artery by atherosclerosis or thoracic outlet obstruction can also

lead to subclavian steal syndrome, in which retrograde flow of the vertebral artery to supply the ipsilateral subclavian artery leads to symptoms of vertebrobasliar insufficiency including syncope and presyncope. Peripheral Edema. Edema, the accumulation of interstitial fluid, is often described by patients as “swelling” or “stiffness” in the legs or arms, however, it can also occur around the eyes, face, and sacrum. Patients may relate more subtle symptoms like the inability to fit in their shoes by the end of the day, or that their rings or watch no longer fit comfortably. Although edema is most often related to cardiac dysfunction, renal failure, or abnormalities of the peripheral venous circulation, it may also be a secondary manifestation of peripheral arterial disease. Patients with extremity pain caused by ischemia will often develop lower extremity edema as a result of maintenance of their feet in a dependent position in an attempt to find relief for their discomfort. Important clues to help distinguish between these causes may lie in how the patient tries to alleviate the edema. Cough and Dysphagia. Although the complaint of cough

is more often related to respiratory conditions, it may also be associated with vascular diseases including aortic aneurysms and pulmonary arterial hypertension. As a vascular symptom, cough is typically described as dry, nonproductive, and most often occurring at night. Vascular etiologies are mainly mechanical in nature. Thus, a dilated

258 • CHAPTER 16

TABLE 16-6. Vascular Rings Name

Description

Complete vascular rings Double aortic arch

Right aortic arch

Retroesophageal descending aorta Aberrant right subclavian artery (arteria lusoria) Incomplete vascular rings Pulmonary artery sling Innominate artery compression syndrome

Paired dorsal embryonic aortic arches persist forming a ring around both the trachea and esophagus, with the right arch usually being larger and more cephalad in its course. The left arch distal to the left subclavian may become atretic and there is commonly a left ligamentum arteriosum or a ductus arteriosus present. Right aortic arch with a left ductus or ligamentum arteriosum connecting the left pulmonary artery and the upper part of the descending aorta. May have an aberrant left subclavian artery arising from a structure known as the diverticulum of Kommerrell, causing compression of the airway. Presence of either a left aortic arch with a right descending aorta and right ductus, or a right aortic arch with a left descending aorta and left ductus. Artery runs posterior to the esophagus, but only forms a ring if there is an associated right-sided ductus or ligamentum present. Left pulmonary artery arises from the right pulmonary artery and passes between the trachea and the esophagus prior to entering the left lung. Innominate or brachiocephalic artery originates later along the course of the transverse arch, resulting in a more leftward takeoff than normal. Tracheal compression may occur if the aberrant artery passes anterior to the trachea.

ascending aorta exerting pressure on the trachea and bronchi may stimulate a cough reflex. Hoarseness or a cough response may also result from irritation of the recurrent laryngeal nerve by an aortic arch aneurysm. Additional complaints of hemoptysis, dyspnea, and/or chest pain are the most commonly associated symptoms and frequently suggest increased pulmonary arterial pressures as the underlying pathology. Peripheral arterial disease is a rare cause of dysphagia, however, several vascular abnormalities have been described in the literature. The term vascular ring encompasses several aortic arch or pulmonary artery malformations that exhibit an abnormal relation with the esophagus and trachea. The most common vascular ring is produced by a double aortic arch, in which both the right and left fourth embryonic aortic arches persist. Other vascular rings include a right aortic arch with a left ductus or ligamentum arteriosum, an anomalous origin of the right subclavian artery (arteria lusoria), retroesophageal descending aorta, and pulmonary artery sling (see Table 16-6).13 Although patients may remain asymptomatic, complaints of dysphagia, stridor, and cyanosis, especially while eating, are not uncommon. The severity of symptoms produced by vascular rings depends upon the tightness of the anatomical constriction, which may explain why some patients are not diagnosed until much later in life.

•

PHYSICAL EXAMINATION

General Considerations A thorough history can establish a basis for presumptive arterial disease, and when followed by a precise physical examination, the accurate detection of a number of vascu-

lar processes is remarkably improved. Both efficiency and effectiveness of the examination are enhanced by the sequence of assessment techniques as well as the implications each technique has for the others. It is with this in mind that the examiner should minimize deviations from the planned approach and maintain proper examination procedures. When done carefully, a detailed examination will lead to the more appropriate application of diagnostic techniques, imaging, and therapeutic interventions. The arterial vascular examination essentially consists of three parts: inspection, palpation, and auscultation. The inspection serves as more than a simple “once-over,” but as a careful screen for both overt and subtle physical manifestations of vascular disease. Palpation of arterial and venous pulsations, pulsatile masses, heaves, thrills, edema, and surface temperature offers a mechanism for obtaining valuable information regarding adequacy of perfusion, the size, movements and functioning of several cardiac structures, and the hemodynamics of blood flow. Auscultation of the heart, peripheral arteries, and veins may confirm previous findings and offer additional insights into cardiac function, arterial pressures, and blood flow hemodynamics. Palpation. To maximize detection, it is essential that proper palpation technique be employed. An examiner should use the pad of the fingertips to evaluate pulsations and edema, the palmar aspect overlying the distal metacarpals to detect vibrations, and the dorsal aspects of the fingers to recognize temperature variations. When palpating arterial pulses, the method for accurate palpation involves several key steps3 :

1. Both the patient and the examiner should maintain a relaxed posture.

HISTORY AND PHYSICAL EXAMINATION • 259

2. Use the surface area of three or four fingers when possible. 3. Control and relax the nearby joint with the other hand. 4. Begin with light pressure; increasing or varying pressure as needed. 5. Avoid the use of the thumb to prevent transmission of the examiner’s own pulse. When in doubt, Doppler signals should be used to determine whether a pulse is absent or merely obscured. Several methods are commonly used to describe a pulse. For example, the examiner’s recording of a pulse may be simply as “present” or “absent.” More specific portrayals utilizing qualitative grading scales of either 0 to 2 or 0 to 4, however, will enhance the clinical usefulness of the examination (see Table 16-7). Detection of a vibration, or thrill, may indicate some degree of vascular stenosis or the presence of a fistula. Size of the pulse should also be noted, as a dilated or expansive pulse may suggest ectatic or aneurysmal changes. When feasible, bilateral pulses should be assessed simultaneously for detection in delay or amplitude that may suggest some type of occlusion in the affected extremity. Auscultation. Complete auscultation is a technically de-

manding skill requiring significant practice and focus. For arterial blood pressure determination, accuracy is dependent on proper equipment and technique. When recording blood pressure measurements, it is important to recall that readings can be affected by a multitude of factors: patient position, limb position, cuff size and placement, stethoscope placement, the length of time the artery is occluded, and the rate of cuff deflation.6 As with palpation, bilateral readings should be obtained to assess for asymmetry, using a Doppler device if necessary.

TABLE 16-7. Qualitative Grading of Arterial Pulse by Palpation Grade 0–2 Scale

Pulse Character

0 1 2

Pulse absent Pulse diminished Normal pulse

0–4 Scale 0 1 2 3 4

Pulse absent Pulse markedly diminished Pulse moderately diminished Pulse slightly diminished Normal pulse

The bell of the stethoscope should be used in auscultation of arterial blood flow for the detection of bruits representing turbulent blood flow caused by occlusive disease or vessel tortuosity. All bruits should be characterized as to location, pitch, timing (systolic, diastolic, or both), intensity, and configuration. Low-pitched bruits are common to larger vessels such as the aorta and the carotid or proximal limb arteries, while bruits generated by smaller vessels or a high-grade stensosis are higher-pitched. Low-grade stenoses typically produce early systolic bruits, whereas high-grade stenoses create holosystolic or systolic/diastolic bruits. Once a critical narrowing has been reached, however, an audible bruit may disappear. Pancyclic murmurs may also indicate arteriovenous malformations or shunts. Arterial bruits are located at the site of arterial narrowing, but can be audible for several centimeters downstream; therefore, it is important to listen proximal to the initial place of detection to try to pinpoint the actual site of narrowing. When auscultating, care must be taken to exert minimal pressure with the stethoscope to avoid vessel compression and the creation of an artificial bruit in an otherwise normal vessel. In addition, bruits may also be detected in normal vessels during high-flow states such as anemia, severe aortic insufficiency, and hypothyroidism. Auscultation can also be used to evaluate the hemodynamics of blood flow in peripheral veins. Like its arterial counterpart, a venous hum should be evaluated for location, pitch, and timing. A typical venous hum is a low-pitched, continuous sound heard throughout the cardiac cycle. Although most are physiological in nature with no clinical significance, their presence should still be documented. General Appearance Assessment and recording of the patient’s vital signs, including blood pressure, heart rate, and respiratory rate comprise the initial step in any comprehensive physical examination. Ideally, the blood pressure should be recorded in both arms, preferably in the supine, seated and standing positions. Height and weight should be recorded and the individual’s body mass index calculated. The patient’s general appearance is then appraised; observations of body habitus and conformations, posture, gait, nourishment, demeanor, and vocalizations can provide important clues that will further guide the examination. Head and Neck

Adapted from Lanzer P. Peripheral vascular disease. In: Lanzer P, Topol EJ, eds. Panvascular Medicine: Integrated Clinical Management. 1st ed. New York, NY: Springer-Verlag Berlin Heidelberg; 2002:388-396, with kind permission of Springer Science and Business Media.

Inspection of the head and neck should commence with the possible observation of head bobbing, also known as de Mosset’s sign, which can indicate aortic regurgitation or a widened pulse pressure that may be associated with an ascending aortic aneurysm or dissection. Facial asymmetries should also be noted, as they can be a sign of cranial nerve paralysis secondary to cerebrovascular disease in the form of a TIA, stroke in evolution, or completed stroke. Evidence of temporal wasting can be used to assess overall nutritional status. Observations of telangiectasias on the lips are

260 • CHAPTER 16

associated with pulmonary arteriovenous fistulae, whereas blue-tinged lips suggest central cyanosis and the presence of intrapulmonary or intracardiac right-to-left shunting. Inspection of oral mucous membranes may aid with the determination of a patient’s fluid status. External inspection of the eyes should note the presence or absence of lid xanthelsmae or a corneal arcus as possible manifestations of atherosclerotic disease. Corneal arcus is also known as arcus senilis because of its association with aging. When seen in men younger than 50 years, however, it is referred to as arcus juvenilis and has been linked to increased plasma cholesterol and low-density lipoprotein cholesterol levels as well as increased risk for having type IIa dyslipoproteinemia.14,15 Blue sclera and dislocation of the lens are common features of Marfan’s syndrome, and exophthalmia may indicate thyrotoxicosis and its associated cardiovascular manifestations. Fundoscopic examination is useful as a visualization of the arteriolar changes caused by hypertension (arteriovenous nicking, cotton wool patches, flame hemorrhages, papilledma), diabetes mellitus (neovascularization, microaneurysms), atherosclerosis (exudates, beading of the retinal artery), and atheromatous embolization (Hollenhorst plaques) (see Figure 16-5). Inspection of the neck should include observations of both carotid arterial and jugular venous characteristics. Three features should be noted for carotid arterial pulsations: intensity (or amplitude), rate, and cadence. Intensity, when decreased, may reflect low-cardiac-output states, occlusive disease of the aortic arch, carotid arterial occlusions,

• FIGURE 16-5.

Cholesterol emboli in the retinal arterioles of a patient with atherosclerotic disease of the ipsilateral carotid artery.

Reprinted with permission from Spittell JA Jr. Occlusive peripheral arterial disease. In: Spittell JA, ed. Peripheral Vascular Disease for Cardiologists: A Clinical Approach. 1st ed. New York, NY: Blackwell Publishing, Inc./Futura Division; 2004:1-29.

or hypotension. Variable amplitudes may signify arrhythmias or congestive heart failure. Rate and cadence, as timing characteristics of the pulsations, may reveal other abnormal electrical patterns that can be further defined later in the examination or with additional diagnostic testing. Although jugular venous analysis is considered more predictive of cardiac than peripheral arterial disease, assessment of jugular venous filling as well as notation of the pattern of venous waveforms is part of a complete vascular examination. These observations are best made using the right internal jugular vein with the patient in the supine position on the examination table, their neck slightly extended and rotated to the left. The examiner should gradually raise the head of the table until he or she observes pulsations. In patients with normal central venous pressure, maximal visibility of venous pulsations should be observed just above the medial end of the clavicle with a 30- to 40-degree elevation of trunk. At this level, the amplitude of both the “a” and “v” waves and also the depths of the “x” and “y” troughs following these waves should be noted. Further elevation of the table to 90 degrees allows for measurement of the degree of venous distension. In normal patients, both the internal and external jugular veins are collapsed with no visible distension or pulsation. Dilated jugular veins may suggest arteriovenous fistulae, congestive heart failure, or proximal venous occlusion (e.g., superior vena cava syndrome). Pulse palpation should begin with the temporal artery, located just anterior to the tragus of the ear. The strength of the pulse should be assessed, and the artery should be examined for thickening or dilatation, which may be signs of inflammation found with temporal arteritis or possible aneurysm. Palpation of the carotid artery should be low in the neck by hooking the fingers around in front of the sternocleidomastoid muscles. Care should be taken not to palpate the bifurcation of the artery higher in the neck, as this is the most common area for dislodgement of an atheromatous emboli or induction of marked bradycardia and/or asystole caused by a hypersensitive carotid sinus reflex. For the latter reason it is also not advisable to palpate both carotid arteries simultaneously. The carotid pulse provides the most accurate representation of the central aortic pulse.16−18 Its classification by volume and contour can help identify changes in left ventricular stroke volume and ejection velocity (see Table 16-8). The subclavian pulse is most readily palpated just behind the clavicle in the anterior medial corner of the supraclavicular fossa. Unlike palpation of other arteries, it may be helpful for the examiner to use his or her thumb to reach the vessel, with the remaining fingers braced behind the neck. Prominent systolic pulsations in this region may be secondary to sublcavian or aortic root aneurysms. A bruit heard with the bell over the globe of the eye suggests a possible intracranial carotid artery stenosis. The examination for carotid artery bruits should begin as high in the neck as possible, getting up under the mandible then slowly progressing down the course of the common carotid artery to the base of the neck. The sensitivity and specificity

TABLE 16-8. Carotid Pulse Contours Name

Description

Normal pulse

Feels smooth and rounded, and the notch on the descending slope of the pulse wave is not palpable.

Bounding pulse

Feels strong or exaggerated with a rapid rise, brief peak, and rapid fall. Causes include high cardiac output states (anemia, hyperthyroidism, fever, pregnancy, patent ductus, A-V fistulas), bradycardia, and decreased compliance of arterial walls because of age and atherosclerosis.

Pulsus alternans

Rhythm feels regular with alternating strong and weak pulses. Indicative of left ventricular failure.

Bisferiens Pulse

Two systolic peaks (percussion and tidal waves) separated by a distinct mid-systolic dip. Most commonly caused by aortic regurgitation or the combination of aortic regurgitation and stenosis. Can also be felt with hypertrophic cardiomyopathy, but this is less likely to be palpable.

Pulsus bigeminus

Alternating strong and weak pulses in an irregular rhythm, where the weak beat always follows a shorter interval. Caused by a normal beat alternating with a premature contraction.

Dicrotic pulse

Two peaks, with the second being in diastole as an exaggerated wave following aortic valve closure. Usually seen in cases of cardiac tamponade, severe heart failure, or hypovolemic shock

Corrigan pulse (water-hammer pulse)

Abrupt upstroke (percussion wave) followed by a rapid collapse later in systole. Suggests aortic regurgitation.

Pulsus parvus et tardus

Initial upstroke feels slow and peak is late in systole. Seen with a fixed left ventricular outflow obstruction such as aortic stenosis.

Pulsus paradoxus

Reduction in strength of the pulse during quiet inspiration. It is a characteristic finding with pericardial tamponade, but also occurs with chronic constrictive pericarditis, chronic lung disease (emphysema and bronchial asthma), pulmonary embolus, and hypovolemic shock.

Example

I

Expiration

I

Inspiration

I

261

262 • CHAPTER 16

of a carotid bruit for the presence of a stenosis varies widely, ranging from 50% to 79% and 61% to 91% accordingly.3,19 In addition, the presence or absence of a bruit has been shown to be unreliable in determining the significance of carotid artery disease, with several studies reporting only half of all patients with a carotid artery stenosis of at least 50% as having a detectable bruit on examination, and numerous cases of patients found to have a bruit despite the absence of any identifiable stenotic disease.19,20 Vertebral artery bruits are best appreciated in the area posterior to the sternocleidomastoid muscles, while bruits of arteriovenous malformations may be loudest posteriorly in the neck and occipital areas. Bruits originating from the subclavian artery are best detected in the supraclavicular fossa. It should be noted that patients undergoing hemodialysis typically have supraclavicular bruits ipsilateral to their dialysis access. Using transient brachial artery occlusion while auscultating can differentiate a true stenosis from a dialysis-induced murmur—manual pressure on the brachial artery for less than 5 seconds will cause the latter to disappear.21 When auscultating the vessels of the neck, the examiner should ask the patient to take short breath holds so the breath sounds will not obscure the vascular sounds. In cases where the origin of a bruit may not be clear, a few simple maneuvers can assist the examiner. If a subclavian artery bruit is transmitted to the carotid artery area, it will disappear upon digital compression of the subclavian artery. Similarly, the bruit of a venous hum will disappear with light compression of the external jugular vein. Ausculation at the aortic and pulmonic areas of the chest will help determine whether or not neck bruits might be transmitted from the heart; usually the murmur of aortic stenosis or sclerosis will be transmitted equally to all the neck vessels and will decrease in intensity as the stethoscope is moved up the neck. Chest The examiner should evaluate the chest with the patient in the upright and supine positions, noting general contour, sternal, and spinal deformities, and anterior chest motions. Patients with coarctation of the aorta may exhibit a heavy muscular thorax with collateral arteries visible in the axillae and lateral chest wall contrasting to less developed lower extremities. Both pectus excavatum, posterior displacement of the sternum, and pectus carinatum, in which the sternum is displaced anteriorly, are common manifestations of Ehlers-Danlos syndrome and Marfan’s syndrome. Lack of normal of kyphosis of the thoracic spine should be noted, as this may be associated with pulmonary artery prominence. Cutaneous abnormalities, such as dilated veins on the anterior chest wall, suggest obstruction of the superior or inferior vena cava. Observations of pulsations throughout the precordium should be noted using a tangential light source. Usually only the point of maximal impulse (PMI) can be seen as a single impulse during systole at the apex of the heart. Prominent pulsations of the supraclavicular region are often associated with a dilated or dissecting ascending

aorta, tortuous innominate artery, or right-sided aorta. Visible pulsations in the right second intercostal space (aortic area) may suggest aortic regurgitation, poststenotic dilatation of the ascending aorta, or ascending aortic aneurysms. Diseases associated with pulsations in the left second intercostal space (pulmonic region) include conditions causing pulmonary artery dilatation such as pulmonary arterial hypertension and pulmonary embolus. Enlargement of one or more cardiac of the chambers is suggested by pulsations over the left parasternum or a laterally displaced cardiac apex. A subxiphoid or epigastric pulsation may occur with right ventricular enlargement or a descending aortic aneurysm. Severe valvular regurgitation or large left-toright shunts, especially a patent ductus arteriosus, can cause “shaking” of the entire precordium. Palpation of the chest should take place with the examination table elevated at 30 degrees, with the patient both supine and in the partial left lateral decubitus position. The cardiac apex should be identified by palpation of the PMI, noting location, size, and duration of thrust. Left ventricular enlargement is suggested by an enlarged and laterally-displaced PMI, whereas hypertrophy causes a persistant thrust also known as a heave or lift. Anterior systolic movement over the left parasternal and/or subxiphoid region usually represents right ventricular enlargement or hypertrophy. This, combined with a prominent palpable pulsation of the pulmonary trunk in the second left intercostal space, reflects increased pulmonary arterial hypertension. The suprasternal notch should be palpated, as aneurysms of the ascending aorta or aortic arch may cause palpable systolic impulses in this area. In addition, the examiner should use the flat of the hand to identify any thrills, which are the palpable manifestations of severe valvular stenosis. While the full cardiac auscultory examination is beyond the scope of this chapter, there are several key components that will aid in the diagnosis of peripheral arterial disease. When auscultating the chest, the examiner should be sure to place both the diaphragm and bell of the stethoscope at each of the four basic topographical areas: right second intercostal space (aortic area), left second intercostal space (pulmonic area), left lower sternal border (tricuspid area), and cardiac apex (mitral area). Each area should be examined while the patient is seated upright, supine, and in the left lateral decubitus position. The basic heart sounds, S1 (mitral valve closure) and S2 (aortic valve closure), are identified, making note of intensity and normal versus abnormal splitting. Next is the detection of any “extra” heart sounds such as an S3, S4, opening snap, click, or rub. Finally, if a murmur is appreciated, it should be characterized by location, intensity, pitch, configuration, quality, timing, and direction of radiation. Several abnormal cardiac findings may be related to underlying peripheral arterial disease. The intensity of the A2 component is increased when the aorta is closer to the anterior chest wall, which may occur with aortic root dilation, transposition of the great vessels, or pulmonary atresia. A narrow yet fixed splitting of S2 and a loud P2 component are both associated with pulmonary arterial hypertension.

HISTORY AND PHYSICAL EXAMINATION • 263

Paradoxical splitting of S2 can be heard with left-to-right shunts such as a patent ductus arteriosus. Heart murmurs are generally classified by timing into three categories: systolic, diastolic, or continuous. Aortic systolic murmurs associated with peripheral arterial disease include those caused by supravalvular obstruction such as coarctation of the aorta, and those caused by dilatation of the ascending aorta and root, including aneurysm, atheroma, and aortitis. Early diastolic murmurs such as new onset aortic regurgitation are worrisome for aortic dissection, while pulmonic regurgitation caused by dilatation of the valve ring may be secondary to Marfan’s syndrome. Increased flow across a nonstenotic mitral valve caused by a patent ductus arteriosus may cause a mid-diastolic murmur. Continuous murmurs, generated by flow from a vascular bed of higher resistance to one of lower resistance without phasic interruption between systole and diastole, are generally of four types: an aortopulmonary connection, (patent ductus arteriosus), an arteriovenous connection (coronary arteriovenous fistulas, bronchial collaterals), a disturbance of flow patterns in arteries (coarctation, systemic-to-pulmonary arterial collaterals), and a disturbance of flow patterns in veins (cervical venous hum). Abdomen Examination of the abdomen is performed as the patient lies supine on the examination table with legs outstretched. Visual inspection of the abdomen should identify any engorged superficial veins which may suggest obstruction of the inferior vena cava. In addition, prominent pulsations may be associated with dilated or aneurysmal vessels such as the descending aorta, renal and iliac arteries. Although difficult in obese patients, palpation of the descending and abdominal aorta should be attempted in all patients to assess the intensity of aortic pulsation as well as the diameter. Using the fingers of both hands, the examiner should identify each side of the aorta by its pulsation, starting superficial and gradually increasing pressure to achieve deepest palpation. Diminished pulsations may be associated with atherosclerotic disease or possible coarctation of the aorta. Pulsations that seem laterally expansile (in addition to physiologic anterior motion) or those that can be identified to the right of midline are suspicious for a dilated aorta or possible aortic aneurysm. In addition, palpation of pulsations below the normal position of the umbilicus suggests extension of the process into the common iliac arteries. Some mild patient discomfort is to be expected during deepest palpation, however, significant tenderness should suggest recent expansion or even contained rupture. All four quadrants of the abdomen should be auscultated for the presence of bruits. A venous hum may be audible in the epigatric or right upper quadrant in cases of hepatic cirrhosis. Anterior bruits found by pressing the bell of the stethoscope deep into the abdomen at or just above the level of the umbilicus are suggestive of aortic, mesenteric, or renal artery disease. The three can usually be differen-

tiated by utilizing a combination of pitch and radiation. As the abdominal aorta is a large and central vessel, aortic bruits are low-pitched and nonradiating. In contrast, the smaller mesenteric and renal arteries will have bruits of higher pitch, yet only true renal vascular bruits will radiate laterally to the flanks. Murmurs auscultated over either of the lower abdominal quadrants suggest iliac artery disease. Extremities The upper extremity examination should begin with inspection of the fingers for signs of impaired perfusion. Transient or patchy findings like successive pallor, cyanosis, or rubor may be apparent with Raynaud’s phenomenon, especially if there are fluctuations of color with ambient temperature. Careful study may also reveal evidence of chronic occlusive or microembolic disease such as shiny or atrophic skin, ulcerations, and other localized gangrenous changes at the fingertips and edges of nail beds. Other abnormalities to recognize include the arachnodactyly associated with Marfan’s syndrome, clubbing secondary to chronic hypoxemia, and capillary pulsations in the nail beds suggestive of significant aortic regurgitation or a widened pulse pressure. On the dorsal aspect of the hand, the examiner should make note of any extensor tendon xanthomas which may be linked to systemic atherosclerotic disease. Finally, the limbs should be examined for symmetry, evidence of venous distension, edema, traumatic injuries, and iatrogenic scars such as those representing the creation of an arteriovenous fistula for hemodialysis. Lower extremity examination should include both static and dynamic inspection. Static inspection begins after the patient has dangled both lower extremities over the side of the examination table for several minutes. Color variations, specifically cyanosis and pallor should be noted, as well as distribution of hair growth and the general condition of the skin. If need be the room temperature should be adjusted to avoid induction of cyanosis from peripheral vasoconstriction. Taught, shiny skin, thickened nail plates, the absence of hair growth, and atrophy of underlying soft tissue and muscle all indicate arterial insufficiency. Careful attention should be paid to the “pressure points” of the feet and ankles, as these are the areas most prone to develop arterial ulcerations. Ulcers in these areas, the tips of the toes, dorsum of the feet, metatarsal heads, heel, and malleoli, tend to be painful, have sharp borders and flat, pale bases which may be covered by an eschar. These differ from venous ulcerations, which are usually found on the medial aspect of the lower calf and have poorly demarcated edematous borders and hyperpigmented bases often covered with purulent inflammatory secretions. As with the upper extremities, the lower limbs should also be examined for edema, venous distension, traumatic injuries, and iatrogenic scars such as those secondary to saphenous vein harvest for bypass surgery. Dynamic inspection requires the patient to lie supine for at least 10 minutes with both legs exposed to room temperature. After noting the color of the extremities, the

264 • CHAPTER 16

examiner then passively elevates both legs at a level above the heart (approximately 60 degrees) for 1 minute, and again notes the color for grading of elevation pallor. Although it is normal to have slight pallor upon elevation, occlusive arterial disease is present if there is significant elevation pallor within 30 seconds or less. If elevation pallor is observed, the legs are then lowered to the flat position and the time to return to baseline color is measured. In normal individuals, color should return within 10 seconds; those with significant arterial insufficiency will have a reperfusion time of greater than 45 seconds. If elevation pallor is not observed, the maneuver should be repeated after the patient actively exercises the legs by flexing and extending the feet for up to 1 minute. Another variation involves the patient quickly sittingup after determination of elevation pallor so that his or her legs dangle over the edge of the examination table. The length of time it takes the first vein to fill on the dorsum of the foot is then recorded, known as the venous filling time. With normal arterial circulation, the first veins should fill within 15 seconds. Venous filling times of 20 to 30 seconds suggest moderate ischemia, and those greater than 40 seconds indicate the presence of severe ischemia. Further observation for the development of dependent rubor should follow with more significant disease producing more significant rubor. Confirmation of poor arterial perfusion can be accomplished by assessment of capillary refill, in which the examiner induces blanching of the toes or distal feet by compression of the skin for a few seconds and then measures the time for return of color. Normal capillary refilling time is generally considered to be less than 2 seconds. Palpation of the peripheral vasculature should proceed in stepwise fashion, minimizing patient movement, exposure, and discomfort. Using the fingertips, the examiner should grade the strength of the pulse and identify the presence or absence of aneurysmal dilatation. Subtle differences may be more easily detected by palpating symmetrical pulses simultaneously. When possible, the vessel should also be assessed for deformability as a vessel that is stiff, noncompressible, or rolls away from the examiner’s fingertips suggests the presence of sclerosis. In addition, the presence of a radial-femoral delay, an examination finding highly indicative for coarctation of the aorta, should be ruled out by concurrent palpation of the ipsilateral radial and femoral pulses. Finally, the examiner should palpate the skin to evaluate for temperature differences, especially over symptomatic areas. Although coolness is an insensitive sign for ischemia, asymmetry between limbs may suggest chronic arterial insufficiency. Palpation usually begins with examination of the pulses of the upper extremities with the patient sitting in the upright position. The radial artery is often the easiest to locate, while the ulnar artery may be obscured by a well-developed wrist. In both cases, the examiner’s second hand should be used to relax the patient’s flexor tendons by cupping the patient’s wrist or using the “handshake position” to induce partial flexion. The brachial artery is found in the antecu-

bital fossa while the elbow is partially flexed and the examiner’s free hand supports the forearm. The patient should then be asked to lay supine with the arm stretched outward and elbow bent so the hand is behind the head. In this position, the axillary artery should be more easily accessible although deep palpation is still required. For examination of the lower extremities, the patient should remain supine with the legs outstretched and uncrossed to avoid interference by tense muscles. The distal portion of the external iliac artery and the common femoral artery can be palpated just above and below the inguinal ligament. To palpate the popliteal artery, the examiner should cradle a slightly flexed knee in both hands so that all eight fingers may explore the popliteal crevice. The pulse should be felt directly below the lateral aspect of the patella, and often deep pressure is needed. The posterior tibial artery is found beneath and behind the medial malleolus and may be easier to palpate if the examiner uses the contralateral fingertips (i.e., use the left hand to examine the patient’s right foot and right hand to examine the patient’s left foot) and applies passive dorsiflexion with the free hand. On the dorsum of the foot in line with the second metatarsal bone approximately 2 to 3 inches distal to the joint crevice is where the dorsalis pedis artery pulse should be found, although it may not be palpable in up to 10% of the population because of an abherant course or being congenitally absent.3,16,22 If any color changes, edema or complaints of diffuse arm or hand pain are present, thoracic outlet maneuvers should be done to assess the arterial flow patterns of the proximal vasculature. Although the sensitivity and specificity of these tests are relatively low, between 46% and 62%, they can be helpful if they reproduce the patient’s symptoms in addition to a diminished pulse or bruit.23,24 For the hyperabduction maneuver to assess for subclavian artery compression, the patient sits upright with the head looking forward. The examiner braces the patient’s shoulder with one hand as the other hand continuously palpates the radial pulse while abducting and externally rotating the patient’s arm. Alternatively, the examiner may use the first hand to auscultate the supraclavicular area for development of a subclavian artery bruit during the same maneuver. If the pulse is not diminished, a bruit is not induced, or symptoms are not produced in this position, the patient should then be asked to look to both the ipsilateral followed by the contralateral side with the chin extended (Adson’s maneuver). If the test is still negative, the patient’s arm or neck should be passively moved and the pulse amplitude assessed to evaluate for positional compression of the axillary or subclavian arteries on the affected side. Finally, the costoclavicular maneuver evaluates for compression of the neurovascular bundle between the clavicle and first rib by having the patient stand at exaggerated military attention with the shoulders thrust backward and downward. Because many asymptomatic patients can have positive results, interpretation of all these tests must be made cautiously. If occlusion of the vasculature distal to the wrist is suspected, an Allen test should be done to assess the patency

HISTORY AND PHYSICAL EXAMINATION • 265

• FIGURE 16-6.

Allen test. (A) Open hand at baseline. The patient should then make a fist while the examiner compresses the radial and ulnar arteries. (B) After making a fist, the open hand remains blanched with both arteries occluded. (C) Checking patency of the radial artery. (D) Checking patency of the ulnar artery.

of the radial, ulnar, palmar arch, and digital arteries (see Figure 16-6). As the patient tightly clenches his or her fist, the examiner simultaneously compresses both the radial and ulnar arteries using firm pressure of one or two fingers. Once the fist blanches, the patient opens the hand, taking care to maintain a relaxed posture. The examiner then releases one of the arteries and evaluates the rate of color return. If the hand returns to normal color within a few seconds, the released artery is patent and the test is considered negative. If the hand remains pale, however, occlusion

of the released artery is confirmed. The maneuver is then repeated for evaluation of the opposite vessel. When only part of the palm or certain digits fail to return to normal color, occlusion, or spasm of the palmar arch or a digital vessel is diagnosed. It is important to note a false-positive test may be induced by overextension of the fingers or wrist, as tense ligamentous structures compress an otherwise normal artery. However, even when done properly, the Allen test can have variable diagnostic accuracy, therefore should only be used for screening purposes.25,26

266 • CHAPTER 16

Auscultation for altered blood flow in the extremities should be attempted for the brachial, iliac, femoral, and popliteal arteries. One should not have difficulty identifying the affected vessel when a bruit is heard over the brachial or popliteal area, however, as a bruit detected in the inguinal region can have several sources, the examiner should attempt to localize the obstruction using a few simple techniques. First, the examiner should listen both proximal and distal to the area where the bruit is first auscultated. An iliac artery bruit should decrease in intensity as the examiner moves distally into the femoral region. On the other hand, a bruit that is louder in the femoral area and softer in the iliac fossa is likely secondary to disease of the common femoral artery, the superficial femoral artery and/or the profunda femoral artery. Further distinction among these sources can be made by compressing the superficial femoral artery near the apex of the femoral triangle. If the bruit disappears or decreases in intensity, a stenosis is more likely to be present in the common or superficial femoral artery. A bruit caused by a lesion in the profunda femoral artery will instead become louder with compression. One last bedside maneuver that is helpful in assessing severity of presumed lower limb arterial ischemia is the determination of the ankle-brachial index (ABI). In this vertical assessment of arterial blood flow, the Doppler sys-

tolic pressure of either the dorsalis pedis or posterior tibial artery (whichever is higher among the two) is divided by the highest Doppler systolic pressure of the brachial arteries. In normal vessels, the Doppler systolic pressures at both sites should be nearly equal, resulting in an ABI of greater than or equal to 1.0. In order to allow for any intra- and interobserver variability, however, the normal range for an ABI is often extended down to 0.90. An ABI of less than 0.90 is usually indicative of some degree of arterial occlusive disease within the iliac, the femoral, or the popliteal artery. The lower the ABI, the greater is the severity of arterial insufficiency present. It is important to note that in order for an ABI measurement to be valid, the arteries must be compressible. Patients with heavily calcified or hardened vessel walls can often have a normal, near normal, or supranormal (>1.3) ABI despite the presence of severe occlusive disease. In addition, patients with bilateral subcalvian artery stenosis may also have false elevation of their ABI because of lower than normal brachial artery pressures.

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ACKNOWLEDGMENTS

The authors would like to thank Joshua Liberman, MD and Ravi K. Ramana, DO for their assistance in the completion of this chapter.

REFERENCES 1. Creager MA, Libby P. Peripheral arterial diseases. In: Zipes DP, Libby P, Bonow RO, Braunwald E, eds. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. 7th ed. Philadelphia, PA: Elsevier Saunders; 2005:1437–1461. 2. Caralis DG. Claudication: clinical diagnosis and differential diagnosis. In: Caralis DG, Bakris GL, eds. Lower Extremity Arterial Disease. 1st ed. Totowa, NJ: Humana Press; 2005:1–21. 3. Beckman JA, Creager MA. The history and physical examination. In: Creager MA, Dzau VJ, Loscalzo J, eds. Vascular Medicine: A Companion to Braunwald’s Heart Disease. 1st ed. Philadelphia, PA: Elsevier Saunders; 2006:135–145.

ed. New York, NY: Springer-Verlag Berlin Heidelberg; 2002: 388–396. 9. Tsai TT, Nienaber CA, Eagles KA. Acute aortic syndromes. Circulation. 2005;112:3802–3813. 10. Spittell JA Jr. Occlusive peripheral arterial disease. In: Spittell JA, ed. Peripheral Vascular Disease for Cardiologists: A Clinical Approach. 1st ed. New York, NY: Blackwell Publishing/Futura Division; 2004:1–29. 11. Dilley RB. The history and physical examination in vascular disease. In: Berstein EF, ed. Vascular Diagnosis. 4th ed. Chicago, IL: Mosby-Year Book; 1993:7–13.

4. Coyne KS, Margolis MK, Gilchrist KA, et al. Evaluating effects of method of administration on walking impairment questionnaire. J Vasc Surg. 2003;38:296–304.

12. Aiello PD, Trautmann JC, McPhee TJ, Kunselman AR, Hunder GG. Visual prognosis in giant cell arteritis. Ophthalmology. 1993;100:550–555.

5. Bordeaux LM, Reich LM, Hirsch AT. The epidemiology and natural history of peripheral arterial disease. In: Coffman JD, Eberhardt RT, eds. Peripheral Arterial Disease: Diagnosis and Treatment. 1st ed. Totowa, NJ: Humana Press; 2003:21–34.

13. Pifarre R, Dieter RA Jr, Niedballa RG. Definitive surgical treatment of the aberrant retroesophageal right subclavian artery in the adult. J Thorac Cardiovasc Surg. 1971;61:154– 159.

6. Arnold GJ. Peripheral vascular assessment: history taking and physical examination of the arterial and venous systems. In: Abela GS, ed. Peripheral Vascular Disease: Basic Diagnostic and Therapeutic Approaches. 1st ed. Philadelphia, PA: Lippincott William and Wilkins; 2004:37–52.

14. Farjo QA, Sugar A. Conjunctival and corneal degenerations. In: Yanoff M, Duker JS, Augsburger JJ, et al., eds. Ophthalmology. 2nd ed. St. Louis, MO: Mosby; 2004:446– 453.

7. Joyce JW. Examination of the patient with vascular disease. In: Loscalzo J, Creager MA, Dzau VJ, eds. Vascular Medicine: A Textbook of Vascular Biology and Diseases. 2nd ed. New York, NY: Little, Brown and Company; 1996:397–413. 8. Lanzer P. Peripheral vascular disease. In: Lanzer P, Topol EJ, eds. Panvascular Medicine: Integrated Clinical Management. 1st

15. Segal P, Insull W, Chambless LE, et al. The association of corneal dyslipoproteinemia with corneal arcus and xanthelasma. The Lipid Research Clinics Program Prevalence Study. Circulation. 1986;73:I108–I118. 16. Braunwald E, Perloff JK. Physical examination of the heart and circulation. In: Zipes DP, Libby P, Bonow RO, Braunwald E, eds. Braunwald’s Heart Disease: A Textbook of Cardiovascular

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Medicine. 7th ed. Philadelphia, PA: Elsevier Saunders; 2005: 77–106. 17. Vlachopoulos C, O’Rourke M. Genesis of the normal and abnormal pulse. Curr Prob Cardiol. 2000;25:303–367. 18. Perloff JK. The physiologic mechanisms of cardiac and vascular physical signs. J Am Coll Cardiol. 1983;1:184–189. 19. Magyar MT, Nam E, Csiba L, Ritter MA, Ringelstein EB, Droste DW. Carotid artery auscultation – anachronism or useful screening procedure? Neurol Res. 2002;24:705– 708. 20. Sauve JS, Thorpe KE, Sackett DL, et al. Can bruits distinguish high-grade from moderate symptomatic carotid stenosis? The North American symptomatic carotid endarterectomy trial (NASCET). Ann Intern Med. 1994;120:633–637.

21. Sapira JD. Arteries. In: Orient JM, ed. The Art and Science of Bedside Diagnosis, Philadelphia, PA: William and Wilkins; 1990:331–354. 22. Barnhorst DA, Barner HB. Prevalence of congenitally absent pedal pulses. N Engl J Med. 1968;278:264–265. 23. Dale WA, Lewis MR. Management of thoracic outlet syndrome. Ann Surg. 1975;181:575–585. 24. Conn J Jr. Thoracic outlet syndromes. Surg Clin North Am. 1974;54:155–164. 25. Jarvis MA, Jarvis CL, Jones PR, Spyt TJ. Reliability of Allen’s test in selection of patients for radial artery harvest. Ann Thorac Surg. 2000;70:1362–1365. 26. Levinsohn DG, Gordon L, Sessler DI. The Allen’s test: analysis of four methods. J Hand Surg. 1991;16:279–282.

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17

Noninvasive Arterial Imaging Kevin P. Cohoon, DO / John E. Gocke, MD, RVT / Susan Bowes, RVT / Robert S. Dieter, MD, RVT

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FUNCTIONAL MECHANICS OF NORMAL AND ABNORMAL VASCULAR FLOW

Describing pulsatile fluid systems mathematically is very complex. Hemodynamics can be defined as the physical factors that influence blood flow which is based on fundamental laws of physics, namely Ohm’s law: Voltage (V) equals the product of current (I ) and resistance (R), i.e.,

quirements of the tissue. Flow velocity increases as the pressure gradient increases and flow volumes are relatively preserved, only to a point though. Osborne Reynolds determined how viscosity, vessel radius, and pressure/volume relations influenced the stability of flow through a vessel: Reynolds number = [2(velocity)(density)(diameter)]/ viscosity

V = I × R. In relating Ohm’s law to fluid flow, the voltage is the pressure difference between two points (P ), the resistance is the resistance to flow (R), and the current is the blood flow (F ): F =

P . R

Resistance to blood flow within a vascular network is determined by the length and diameter of individual vessels, the physical characteristics of the blood (viscosity, laminar flow versus turbulent flow), the series and parallel arrangements of vascular network, and extravascular mechanical forces acting upon the vasculature. This is expressed in Poiseuille’s law: 4

Q = (␲Pr )/(8␩L). Poiseuille’s Law relates the rate at which blood flows through a small blood vessel (Q) with the difference in blood pressure at the two ends (P ), the radius (r ) and the length (L) of the artery, and the viscosity (␩) of the blood. Of the above factors, changes in vessel diameter are most important quantitatively for regulating blood flow as well as arterial pressure within an organ. Changes in vessel diameter, either by constriction or dilatation, enable organs to adjust their own blood flow to meet the metabolic re-

Density and viscosity are relatively constant, therefore the development of turbulence depends mainly on the velocity and size of the vessel. Density is defined as mass per unit volume and viscosity is defined as a measure of the resistance of a fluid to being deformed by either shear stress or extensional stress. A Reynolds number >2000 causes turbulence and vessel wall vibration producing a bruit. High velocities cause turbulence and hinder volumes flow, creating eddies.

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TYPES OF VASCULAR ULTRASOUND

Basics of Vascular Ultrasound Ultrasonic waves entering human tissue are absorbed, reflected, and scattered to produce images of anatomic structures. The transmission properties of the sound waves depend on the density and elasticity of the tissues. Density and speed of propagation of ultrasound waves determine a tissue’s acoustic impedance. The larger the differences in acoustic impedance between tissues, the more ultrasound waves are reflected. The reflection further depends on the angle of insonation. Strong reflective interfaces, such as air or bone, prevent imaging of weaker echoes from deeper tissue and cast shadows behind them. Tissues that strongly reflect ultrasound are termed hyperechoic, whereas poorly reflective tissues are termed hypoechoic.

270 • CHAPTER 17

The transducer repeatedly emits pulses of sound at a fixed repetition frequency. A detector records echoes originating from interfaces and scatterers in the sound beam. Echo signals are then amplified and processed into a format for display. If ultrasound is continuously transmitted along a particular path, the energy will also be continuously reflected back from any source in the path of the beam, making it difficult to predict the depth of the returning echoes. With pulse-echo techniques, it is possible to predict the distance of a reflecting surface from the transducer if the time between the transmission and reception of the pulse is measured and the velocity of the ultrasound along the path are known. When the ultrasound pulse returns to the transducer, it causes the transducer to vibrate and will generate a voltage across the piezoelectric element. The amplitude of the returning pulse depends on several factors, including the proportion of the ultrasound reflected to the transducer and by which the signal has been reflected along its path. The amplitude of the pulse received back to the transducer can be displayed (A-mode) against time and then can be calibrated to time, thus showing the depth of the boundary in the tissue. The varying amplitude of the signal can be displayed as a spot of varying brightness. This type of display is known as a B-mode scan. B-Mode Imaging Structures imaged by B-mode, or brightness mode, are displayed proportionally to the intensity of returning echoes. The ultrasonic beam scanning through a tissue plane produces a two-dimensional gray-scale image. In clinical practice, the beam is swept quickly through the field of view, and the image is continuously renewed, allowing visualization of the underlying tissue anatomy. B-mode ultrasound takes reflected signals and converts them to a series of dots on a display. A transducer, whose resonant frequency is between roughly 2 and 10 MHz, is used to transmit a short pulse of sound into a patient. The sound is reflected from a tissue interface where there are differences in acoustic impedance. The reflected pulse is received by the ultrasound instrument and the pulse amplitude is encoded as brightness and depth on a monitor. The time that is required for the pulse to travel from the transducer to the interface and back is directly proportional to its depth. The acoustic velocity is 1540 m/s. As the sound pulse propagates through tissue, it is attenuated and this would darken the parts of the image that correspond to regions further from the probe. In order to compensate for this attenuation, echoes originating from deeper tissues are amplified more than echoes originating near the probe. Because different tissues have different attenuation coefficients, the amplification can be varied as a function of depth. The exact manner in which the amplification depends on depth is usually displayed on the ultrasound instruments monitor as a depth-gain curve or time-gain curve. Usually, 100 to 200 separate ultrasound beam lines are used to construct each image.

Doppler Display Modes Doppler ultrasound is a technique for recording noninvasive velocity measurements. The difference in frequency between emitted and returning ultrasonic echoes is the Doppler frequency shift.1 As the blood is moving, the sound undergoes a frequency (Doppler) shift that is described by the Doppler equation2,3 : F = 2[(F0 )(v)(cos ␪)]/c, where c is the acoustic velocity in blood, 1540 m/s; F0 is the transmitted frequency; ␪ is the Doppler angle; v is the velocity of the blood. The shift is measured only for the component of motion occurring along the ultrasound beam. Therefore, absolute velocity measurements require that a correction be made for the angle (␪) between the vessel and the beam as follows: v = (F × c)/(2F0 cos ␪). Color Doppler Imaging Color Doppler ultrasound is a technique for visualizing the velocity of blood within an image plane. Color is superimposed on a conventional gray-scale image to enhance the image of the Doppler frequency shift. A color Doppler instrument measures the Doppler shifts in a few thousand sample volumes located in an image plane. For each sample volume, the average Doppler shift is encoded as a color and displayed on top of the B-mode image. The way in which the frequency shifts are encoded is defined by the color bar located to the side of the image. By convention, positive Doppler shifts, caused by blood moving toward the transducer, are encoded as red and negative shifts are encoded as blue. Color Doppler images are updated several times per second, thus allowing the flowing blood to be easily visualized. In healthy individuals, arterial flow is pulsatile and laminar, whereas stenoses, angles, or elevated velocities may cause the laminar flow pattern to be distrupted.4 Additionally, turbulence at the stenosis and distal to the area causes an increase in the rage of flow velocities known as spectral broadening.2 As the degree of stenosis progresses, flow velocities increase at the point of maximum narrowing. In very stenotic areas, marked reductions in the residual lumen cause flow velocities to fall, leading to flow cessation with complete lumen obliteration. Doppler insonation proximal to an occluded vessel assumes a stump flow pattern. Continuous Wave Doppler Continuous wave Doppler uses two piezoelectric crystal transducers where one crystal continuously emits toward the region of interest and the other continuously receives reflected echoes. Flow toward the transducer produces an increase in the received frequency, whereas flow away from the transducer causes a drop. Continuous Doppler does not provide information about the depth of the tissue.

NONINVASIVE ARTERIAL IMAGING • 271

Power Doppler TABLE 17-1. Indications for Noninvasive Physiologic Testing

Power Doppler ultrasonography emphasizes the display of amplitude information rather than the relative velocity or direction of flow. This method of display has some advantages in that the power Doppler display is not dependent on the angle of insonation and has better sensitivity when compared with conventional Doppler frequency. Advantages of power Doppler include independence from the angle of insonation, absence of aliasing, and the ability to detect very low flows.

•

NONINVASIVE DIAGNOSTIC IMAGING OF LOWER EXTREMITY PERIPHERAL ARTERIAL DISEASE

Lower extremity peripheral arterial disease (PAD) is associated with an amplified risk of cerebrovascular and cardiovascular morbidity and mortality, including stroke, myocardial infarction, and even death. The prevalence of PAD in North America and Europe is currently estimated to affect approximately 27 million people.5 Noninvasive tests are preformed to confirm and define the extent of obstruction in patients with suspected lower extremity PAD based upon the history (e.g., symptoms of intermittent claudication) or in patients with risks factors for vascular disease (e.g., older age, smoking, diabetes mellitus).6 The establishment of successful patient stratification in vascular medicine is through a thorough clinical evaluation and accurate noninvasive testing. In this chapter, the focus is on the functional mechanics of normal and abnormal vascular flow, types of noninvasive imaging, limitations of noninvasive imaging, and recommendations and guidelines in lower extremity, carotid, renal artery, cerebral, mesenteric, upper extremity, and vertebral vascular diseases. A variety of noninvasive examinations are available to provide an objective diagnostic tool to assess the presence and degree of PAD. The noninvasive vascular evaluation includes ankle and toe brachial index, exercise treadmill test, segmental limb pressures (SLPs), segmental volume plethysmography, and color duplex imaging. These examinations allow the clinician to objectively determine the presence of disease, localize lesions, and establish the severity of disease to determine the progression or its response to therapeutics. This section will review the evidence-based benefits, limitations, quality assurance, and guidelines of each of these vascular diagnostic techniques.

•

r Exercise-related limb pain r Abnormal ratio of ankle-to-brachial arterial systolic blood pressure r Extremity ulcer/gangrene r Assessment of healing potential r Cold sensitivity r Arterial trauma and aneurysms r Absent peripheral pulses r Digital cyanosis or limb pain at rest

LOWER EXTREMITY ARTERIAL VASCULAR TESTING

Patients should be evaluated for PAD if they are at increased risk from their age, presence of atherosclerotic risk factors, have leg pain suggestive of ischemia, or have distal limb ulceration (Table 17-1). Many vascular practices use various algorithms for the diagnosis of PAD; however a thorough historical review of symptoms and atherosclerotic risks factors, physical ex-

This material was originally published in Guidelines for noninvasive vascular laboratory testing: a report from the American Society of Echocardiography and the Society of Vascular Medicine and Biology. J Am Soc Echocardiogr. 2006;19:955-972 and is reproduced with the permission of the copyright holder, the American Society of Echocardiog raphy www.asecho.org. Inclusion of this information does not necessarily imply endorsement of this product.

amination, and the use of noninvasive vascular tests are paramount in diagnosing PAD. The most cost-effective tool for lower extremity PAD detection is the ankle-brachial index (ABI) and should be performed in every patient suspected of having lower extremity PAD (Figure 17-1).8 Many vascular practices simultaneously obtain ABIs, SLPs, and pulse volume recordings (PVRs) in patients with suspected PAD as initial diagnostic tests.

•

ANKLE-BRACHIAL INDEX

The ABI is a relatively simple, inexpensive, and reproducible method to confirm the clinical suspicion of arterial occlusive disease. Despite the increasing use of more sophisticated diagnostic tests, the ABI has been shown through epidemiology studies to predict future cardiovascular ischemic events. This has led to increasing use of the ABI examination in office practice. The sensitivity and specificity associated with an ABI threshold of 0.90 or less have ranged from a sensitivity of 79% to 95% and specificity of 96% to 100% compared with contrast angiography. Fowkes et al.9 demonstrated that with an ABI diagnostic threshold of 0.90, the sensitivity of the ABI was 95% and specificity was 100% compared with angiography. Feigelson et al.10 demonstrated using only posterior tibial measurements in assessing the ABI, that with an ABI diagnostic threshold of 0.8, the sensitivity of the ABI was 89% and specificity was 99% with a overall accuracy of 98% compared with angiography. Lijmer et al.11 evaluated the ABI by using a receiver operating characteristic (ROC) to determine its diagnostic accuracy depending on the localization of the disease. This study demonstrated patients with significant PAD (lesions ≥50%), that with an ABI diagnostic threshold of 0.91, the sensitivity of the ABI was 79%, and specificity was 96%. Multiple investigations have also evaluated the interobserver variability of the ABI measurement. Endres et al.12 tested the variability of a measured ABI with six angiologists, six primary care physicians, and six trained medical

272 • CHAPTER 17

Individual at risk of PAD (no leg symptoms or atypical leg symptoms): Consider use of the Walking Impairment Questionnaire

Perform a resting ABI measurement

ABI 0.91 to 1.30 (borderline and normal)

ABI greater than 1.30 (abnormal)

Pulse volume recording Toe-brachial index (Duplex ultrasonography*)

Normal results: No PAD

Abnormal results

ABI less than or equal to 0.90 (abnormal)

Measure ABI after exercise test

Normal postexercises ABI: No PAD

Decreased postexercise ABI

Evaluate other cause of leg symptoms†

Confirmation of PAD diagnosis

• FIGURE 17-1.

Diagnosis of asymptomatic PAD and atypical leg pain. ABI, ankle-brachial index. ∗ Duplex ultrasonography should generally be reserved for use in symptomatic patients in whom anatomic diagnostic data is required for care. † Other causes of leg pain may include lumbar disk disease, sciatica, radiculopathy; muscle strain; neuropathy; compartment syndrome. It is not yet proven that treatment of diabetes mellitus will significantly reduce PAD-specific (limb ischemic) endpoints. Primary treatment of diabetes mellitus should be continued according to established guidelines. Adapted with permission from Hiatt WR. Medical treatment of peripheral arterial disease and claudication. N Engl J Med. 2001;344:1608-1621 (179a).

office assistants. They performed two ABI measurements: each measurement on six individuals from a group of 36 unselected subjects aged 65 to 70 years and found mean differences between the ABI measurements very close to zero.12 Several studies have shown that the ABI is associated with functional capacity, even in asymptomatic patients. The Women’s Health and Aging Study evaluated disabled women 65 years or older and used the ABI as a measure of lower extremity function. The results showed that decreasing ABI values were associated with worsening functional scores, even after adjustment for age, race, smoking status, and comorbidities.13 Even lower ABI scores in the asymptomatic women in this study correlated with slower walking velocities, poorer standing balance scores, slower time to rise, and fewer blocks walked per week.13 In the Study of Osteoporotic Fractures, 1492 women 65 years or older

were evaluated to compare the relationship between ABI (≤0.90) and extremity function.14 This study showed patients with an ABI greater than 0.90 had significantly higher hip abduction force, knee extension force, walking velocity, and number of blocks walked than those with ABI of less than 0.90. Studies have also shown that an abnormal ABI is predictive of both cardiovascular and cerebrovascular disease. Newman et al.15 has shown an inverse relation between cardiovascular disease and ABI. For example, participants with an ABI 75%) stenosis and arterial occlusion (97% and 98%, respectively), with excellent sensitivity (92% and 89%, respectively).21 Other studies have reported CTA sensitivity at 72% to 99% and specificity at 92% to 99% relative to DSA for detection of ≥50% stenosis.22−27

•

CTA FOR CAROTID DISEASE

Indications The main indications for CTA of the extracranial circulation include atherosclerosis, fibromuscular dysplasia, aneurysms/pseudoaneurysms, and dissection involving the carotid, subclavian, vertebrobasilar system, and aorta. Additional indications include cervical tumors (carotid body) and follow-up after carotid stenting. Technique When scanning cervicocranial arteries, the patient is in supine position with upper arms along the body. The right

CT ANGIOGRAPHY • 333

reveal improved arterial enhancement or visualization using concentrations of 350–400 mg I/mL when compared with both disparate and equal iodine loads using 300 mg I/mL, infused at the same rate. Breath-holding of the patient should be used as the scan typically covers the aortic arch, which moves with respiration. Diagnostic Performance of CTA for Carotid Disease Early studies with 4-slice CT have demonstrated a high rate of accuracy for total occlusions and severe stenosis when compared with DSA. In addition, MDCT was helpful in distinguishing the underlying pathology such as dissection, thrombosis, and calcification (Figure 19-7). The diagnostic performance of CTA using modern 64-slice scanners has not been prospectively evaluated in the context of a large clinical trial comparing this to state of the art MR methodologies or 3-D DSA techniques. The limitations of CTA include the inability to assess luminal patency in arteries with extensive calcification. CTA can be used in the stented patient to assess restenosis. The caliber of the stent and the stent material determine the ability to assess lumen.

•

CTA FOR THORACIC AORTIC DISEASE

Indications CT and MRI are the preferred modalities for comprehensive evaluation of the aorta. Acute aortic syndromes (dissection, penetrating ulcer, and intramural hematoma), atherosclerotic disease, aneurysmal disease (diagnosis, follow-up, postsurgical or intervention (endoleak assessment), assessment of inflammatory aortic disease (immune, infectious), collagen vascular disease (Marfans and Ehlers Danlos syndromes), and congenital abnormalities (coarctation) are common indications (Figures 19-8 and 19-9).

• FIGURE 19-6.

Technique

antecubital vein is the preferred site for the venous access and contrast infusion to avoid “streak artifacts” related to high concentration of contrast media in the left subclavian vein. The imaging volume is planned based on the topogram, with the duration of scan determining the contrast medium bolus duration. The use of thin collimation (0.5–1 mm) is preferable when imaging the cervicocranial arteries to assure high spatial resolution. For imaging the cervicocranial vessels, pitch values of 1500 mosm/kg). They cause significant pain and are generally not tolerated well by patients undergoing peripheral angiography. Low-osmolar ionic ratio-3 agents have three atoms of iodine for every one ion and are low osmolality agents. Their osmolality is roughly twice that of blood, e.g., Ioxaglate (Hexabrix, Mallinckrodt). Low-osmolar nonionic ratio-3 agents are water-soluble and do not have any ions, e.g., Iopamidol (Isovue, Bracco), Iohexol (Omnipaque, Nycomed), Ioversol (optiray, Mallinckrodt). Their osmolality is also twice that of blood and cause burning in many patients. Iso-osmolar nonionic ratio-6 agents have osmolality equal to that of blood (290 mosm/kg). They are very well tolerated by patients. Most commonly used is Iodixinol (Visipaque, Nycomed). It has fewer incidences of allergic

• FIGURE 20-2.

Micropuncture kit.

reactions than Ioxaglate and has shown no major increase in adverse coronary events like intravascular thrombosis, vessel closure, or perioperative myocardial infarction.61 There is also some data suggesting less nephrotoxicity with them. In all patients with renal dysfunction, intravenous hydration with normal saline at 1 mL/kg/h along with Nacetylcysteine (mucomyst) 600 mg orally twice a day should ideally be started 12 to 24 hours prior to the procedure. Gadolinium contrast or CO2 angiography is another option in such patients. Diagnostic Catheters and Guide Wires Vascular access is commonly obtained with an 18-gauge needle that will accommodate most 0.038 inch or smaller wires. A smaller 21-gauge needle with a 0.018-inch wire is available in “micropuncture kit” (Cook, Bloomington, IN) that can be used for difficult femoral, brachial, radial, or antegrade femoral approaches (Figure 20-2). For a nonpalpable pulse Doppler, integrated needle (smart needle) can be used. Wires are available in 0.012 to 0.052 inch in diameter. Most commonly used are wires of 0.035 and 0.038 inch. In a standard guide wire, a stainless steel coil surrounds

PERIPHERAL ANGIOGRAPHY • 347

• FIGURE 20-3.

Angiography selective catheters.

a tapered inner core. A central safety wire filament is incorporated to prevent separation in case of fracture. Typically they are 100 to 120 cm in length but can also be 260 to 300 cm. Wires are available when wire position needs to be maintained for catheter exchanges. Long wires are frequently required in peripheral angiography, more so than in coronary angiography and their use is encouraged when in doubt. The tip of the wires can be straight, angled, or J-shaped. Some wires have the capability of increasing their floppy tip by having a movable inner core. Varying degrees of shaft stiffness, e.g., extra support, to provide a strong rail to advance catheters in tortuous anatomy versus extremely slick hydrophilic with low friction for complex anatomy have made peripheral vascular angiography and interventions a viable and many times a preferred treatment of PAD. Every angiographic suite should have an inventory of such wires. The 0.035-inch wires used in our laboratory are standard J-shaped, Wholey, Straight and Angled Glide, Amplatz Super Stiff, and Supracore. Among the 0.018-inch wires inventory are the Steel Core and V18 Control. In addition to 0.014-inch coronary wires, we frequently use Sparta Core wire in renal and other peripheral vascular interventions. Glide wire (Terumo wire) is very useful in

tracking most vessels but carries the risks of vessel dissection and perforation. It should not be used to traverse needles because of the potential of shearing. Numerous catheters are available (Figures 20-3 to 20-5) and every operator should develop his own skill and “feel” of catheters he uses in peripheral angiography. An “ideal catheter” should be able to sustain high-pressure injections, to track well, be nonthrombogenic, have good memory, and should torque well.62 Catheters are made of polyurethane, polyethylene, Teflon or nylon. They have a wire braid in the wall to impart torquibility and strength. They are available in different diameters and lengths. They can have an end hole, side holes, or both end and side holes. When using the femoral approach, short-length catheters (60–80 cm) are adequate for angiography of the structures below the diaphragm, whereas long catheters (100–120 cm) are needed for carotid artery, subclavian artery, or arm angiography. Five- to six-French catherter (1-F catheter = 0.333 mm) diameter catheters are most commonly used. Three- to four-French catheters are used for smaller vessels. Side-hole catheters are safe and allow large volume of contrast at a rapid rate with power injectors, e.g. pigtail, Omniflush, Grollman. They are commonly used for angiography of ascending aorta, aortic arch, and abdominal aorta.

348 • CHAPTER 20

• FIGURE 20-4.

Angiography selective catheters.

End-hole catheters are very useful in selective angiography using manual hand injections. For DSA, 5-F catheters are sufficient. Omniflush catheter can be advanced over the wire beyond the aortic bifurcation and then pulled back to engage the contralateral common iliac artery for selective angiography of the leg. For type-1 aortic arch, a 5 F JR4 will be adequate for carotid, vertebral, subclavian artery angiography, and for nonangulated renal arteries. Simmons, Vitek, SOS, and Amplatz catheters are very useful in certain situations but require added skills and careful manipu-

lation. Heparin should be used with the use of these latter catheters. Simple curved catheters, e.g., Berenstein, Cobra, and Headhunter, are also useful in angulated renal arteries and vertebrals. Vascular Access Meticulous technique to achieve vascular access is essential for a successful angiographic procedure. In patients with PAD, the success or failure of a procedure will significantly depend on the correct choice of access site. Every effort

PERIPHERAL ANGIOGRAPHY • 349

• FIGURE 20-5.

Angiography selective catheters.

should be made to learn the vascular anatomy and direction of blood flow if the patient had previous bypass graft. Prior noninvasive studies like MRA, CTA, and Duplex ultrasonography (US) should be reviewed prior to the angiography. Peripheral bypass grafts in general should not be punctured for 6 to 12 months after surgery. Most common vascular sites are common femoral artery (CFA) and brachial artery (BA).63,64 Fluoroscopy should be routinely used to identify bony landmarks to avoid puncturing the artery too low or too high. Femoral Approach CFA is ideally suited because of its large caliber that can accommodate up to 14-F sheaths percutaneously and its central location, enabling access to all vascular territories. When compared to the arm approach, there is less radiation exposure but more incidence of bleeding and delayed ambulation. Both retrograde (toward the abdomen) and antegrade (toward the feet) CFA punctures are routinely done. For the antegrade approach, micropuncture technique using 21-gauge needle with 0.018-inch wire is recommended. It should always be done under fluoroscopy and should not

be done in very obese patients. It limits arteriography to the ipsilateral leg, but provides a better platform for interventions if needed. Patients are typically placed in reverse with the feet facing the head-end of the table, allowing maximum mobility of the image intensifier around the limbs. The skin puncture is made at the top of the femoral head. A less acute, less than 45-degree angle is usually required for smooth insertion of the sheath and catheters. Long tapered introducer-sheath instruments are sometimes needed. A short 4- to 5-F sheath should be introduced first and a cine angiogram performed to confirm access in the CFA, and wire position in the superficial femoral artery (SFA) before inserting the larger and longer sheaths and initiation of anticoagulation65 (Figure 20-6). An ipsilateral 30 to 50 degrees angulation will open up the superficial and deep femoral artery (DFA) bifurcation. Anticoagulation can be reversed at the end of the procedure for early removal of sheath and to decrease the incidence of bleeding. Brachial and Radial Approach For radial artery (RA) and 5- to 6-F sheaths and for brachial artery 5- to 7-F sheaths can be used. The biggest

350 • CHAPTER 20

A

B

• FIGURE 20-6.

(A) Antegrade femoral artery access technique under direct flouroscopy using micro puncture needle and wire. The wire is in the deep femoral artery. (B) The wire is directed under flouroscopy into the superficial femoral artery.

advantage with these approaches is less bleeding and early ambulation.66−68 There are however more ischemic complications.69 These approaches require crossing the great vessels of aorta and great care should be exercised to avoid causing embolic strokes. For BA approach, the arm is abducted and the puncture is made at the site of maximum pulsation. Micropuncture technique is recommended. When using this approach, one should be aware of the need for longer length catheters if angiography and intervention of the lower extremities is anticipated. Left brachial approach has approximately 100 mm greater reach than the right brachial approach. Wholey wire, glide wire, and other soft wires should be used with these approaches to minimize trauma and spasm of the vessels. For RA approach,70 more skill is required. RA is superficial and lies against the bone. It has no major veins or nerves in the vicinity. Its smaller size, however, limits the use of some devices and larger stents. Hydrophilic sheaths and guiding catheters of upto 6- to 7-F are now available and can be used with this approach. They can accommodate most current balloons and stents. There is approximately a 3% incidence of RA occlusion postprocedure. Allen’s test71 should be performed prior to cannulating RA to confirm the ulnar artery patency (Figure 20-7). There is, however, some controversy regarding the absolute value of Allen’s test. The success rate of this approach is 95%.72 The

wrist is extended and the arm abducted in supine position. Using micropuncture technique, puncture is made 1 to 2 cm proximal to the wrist crease. After sheath insertion, the arm is brought back in the adducted neutral position. Right arm is preferred to preserve left RA for future bypass surgery if needed. Minimal local anesthesia is administered. Five F long hydrophilic sheath is a good choice. Heparin 2500 to 5000 units should be given directly in the sheath. Radial arteries are very prone to spasm and vasodilators should be used. Nitroglycerin 100 to 200 mg and Verapamil 1 to 2 mg is directly given through the sheath. A short cineangiogram should be performed to look for any

Radial artery

Ulnar artery

• FIGURE 20-7.

Atretic ulnar artery in a patient with equivocal Allen’s test.

PERIPHERAL ANGIOGRAPHY • 351

anomalous arteries. One should look for radial recurrent artery. The sheath should be removed immediately after the procedure. Activated clotting time (ACT) check is not necessary. Compression straps, e.g., Hemoband (Hemoband Corp., Portland, OR) are placed directly over the puncture site. Pressure is maintained for approximately 90 minutes for diagnostic and 180 minutes for interventional procedures. Access site complications are very uncommon. Other Vascular Access Sites PA is uncommonly accessed. The patient has to lie prone. Puncture is performed under fluoroscopy and micropuncture technique is recommended. Axillary approach is more popular among interventional radiologists. Left axillary artery is preferred. The patient needs very close monitoring for bleeding after axillary artery puncture because even a medium-sized hematoma can cause nerve compression. BA cut down is very uncommon now. It is used in less than 10% of cases and should be performed only by experienced operators. Lumbar aortic punctures are again sometimes used by radiologists in patients who have extensive PAD.73 Patient is placed prone. This site is only used as a last resort because in case of bleeding complications direct pressure cannot be applied and patient will likely require open surgical repair of the bleeding vessel. Local Vascular Complications Society for Cardiac Angiography and Interventions (SCAI) has reported an incidence of 0.5% to 0.6% local vascular complications. These complications comprise vessel thrombosis, dissection (Figure 20-8), bleeding, which can be free hemorrhage, retroperitoneal bleeding, or access site hematoma, arteriovenous fistula (Figure 20-9), distal embolization, or false aneurysm (pseudo aneurysm). The operator should be well versed in the diagnosis and management of these complications. Adequate specialty care should be readily available at the facility where such procedures are performed. Thoracic Aorta and Aortic Arch Angiography Noninvasive modalities like MRA and three-dimensional CTA should be performed if available prior to invasive imaging. Angiography provides 2D imaging and may underestimate the tortuosity of various vessels (Figure 20-10). CTA and MRA will also provide information about the type of aortic arch, and anomalous origin of any vessel from the arch (Figure 20-11). Thoracic Aorta Commonly approached via right CFA utilizing 4- to 6-F sheath and diagnostic catheters. Pigtail or tennis racquet catheter is advanced over a soft J-tip guidewire under fluoroscopy. In cases of coarctation of the aorta, anteroposterior and lateral views are obtained with the contrast

• FIGURE 20-8.

Catheter-induced abdominal aortic

dissection.

injected proximal to the coarctation. For cases of patent ductus arteriosus, selective aortic angiography is very sensitive in demonstrating small shunts and supercedes the sensitivity of right heart catheterization with stepwise oximetry. In cases of thoracic aortic aneurysms (TAA), MRA and CTA are again very useful initial tools (Figure 20-12), but catheter angiography is still considered essential to delineate the aneurysm and its relationship to the branches in the chest and abdomen. If endovascular thoracic aneurysm repair (ETAR) or open surgical repair is planned, then coronary, brachiocephalic, visceral, and renal arteriography should also be performed. For the diagnosis of thoracic aneurysms, angiography is performed in the ascending thoracic aorta above the aortic valve using 30 to 40 mL of iodinated contrast at 15 to 20 mL/s using power injection. TAA is less common than abdominal aortic aneurysm (AAA) but the incidence is increasing as the median age of the population is also increasing. It also has a higher incidence of rupture than AAA. Untreated, the mortality is greater than 70% within 5 years of diagnosis.74 Open surgical repair has a mortality of 10% to 30%, spinal cord injury 5% to 15%, respiratory failure 25% to 45%, myocardial infarction 7% to

352 • CHAPTER 20

A

B

• FIGURE 20-9.

(A) Arteriovenous fistula between left CFA and vein. (B) Repair of arteriovenous fistula with a covered stent.

20%, and renal dysfunction 8% to 30%.75 Chronic obstructive pulmonary disease (COPD) and renal failure are strong predictors of rupture. In one series,76 the rupture rate was high for aneurysms greater than 6 cm. In another series, no rupture was reported in aneurysms less than 5 cm. Mean size for rupture was 5.8 cm. With ETAR, the mortality and the morbidity has been reported to be much less.77 In cases of thoracic aortic dissection, angiography has a sensitivity of 80% and specificity of 95%. Noninvasive modalities like CTA, MRA, and transesophageal echocardiography have taken over as the initial diagnostic tools; however, cardiothoracic surgeons will still require an angiogram for additional information about coronary and branch vessel involvement and the competence of the aortic valve prior to aortic repair. A pigtail or tennis racquet catheter is advanced over a soft wire typically via the right CFA approach. Most of the aortic tears are at the greater (outer) curve and to avoid entry into the false lumen, the catheter is used to direct the wire toward the inner curve. Frequent contrast injections should be utilized to check the catheter position. Entry into the false lumen is not uncommon and if that occurs, the catheter should be gently retracted and advanced into the true lumen.

radial approaches can be used in cases of suspected aortic dissection and in patients with severe ileofemoral or abdominal aortic atherosclerotic disease. A pigtail catheter is positioned above the sinus of valsalva and 40 to 60 mL of nonionic iso-osmolar contrast at the rate of 20 cc/s is injected with a power injector. Both cine and DSA imaging can be used. For a cine angiogram, 30 FPS and for DSA, 4 to 6 FPS are commonly used. LAO at 45 degrees angle opens up the aortic arch and the great vessels in most cases. DSA allows a lower contrast load of 30 mL injected at 20 cc/s. Carotid and Cerebrovascular Angiography Catheter angiography is the gold standard for aortic arch, cervical, and cerebral angiography. A major drawback for angiography in this territory has been the risk of strokes. There was 1.2% incidence of stroke in the hands of radiologists in the ACAS78 trial. In a later study79 performed by cardiologists, the risk was 0.5%. Proper patient selection and the procedural volumes and the technical skill of the operator are important predictors of this risk. Carotid Artery

Aortic Arch Catheter angiography is still considered the gold standard, but 3D CTA and MRA are excellent for imaging the aortic arch and should be considered prior to considering arch angiography. CFA is the most common access site. Brachial or

Many patients with carotid artery disease are asymptomatic. History and physical examination are therefore not very sensitive in detecting carotid artery disease. Carotid duplex ultrasound, CTA, and MRA should be utilized as the initial diagnostic tools (Figure 20-13). Invasive angiography

PERIPHERAL ANGIOGRAPHY • 353

• FIGURE 20-11.

CTA showing extremely tortuous carotid arteries making endovascular intervention an undesirable option in such cases.

CTA nicely showing a “bovine” aortic arch. There is also severe stenosis of the left internal carotid artery and the aortic arch is also “type 3” making carotid artery stenting an unsuitable option in this case.

Courtesy: Robert Falk MD, 3-DR Louisville, KY.

Courtesy: Robert Falk MD, 3-DR Louisville, KY.

• FIGURE 20-10.

remains the gold standard in patients considered for carotid artery stenting (CAS). The landmark North American Symptomatic Carotid Endarterectomy Trial (NASCET), European Carotid Artery Surgery (ECAS), and Asymptomatic Carotid Artery Stenosis (ACAS)78,80,81 trials were all based on angiography. Brachiocephalic (BC) artery arises as the first great vessel from the aortic arch and divides into right subclavian (RSC) and right common carotid arteries (RCCA). RCCA almost always arises from the BC and rarely as a separate branch from the aorta. It may come from a single common carotid trunk that also gives rise to left common carotid artery (LCCA). RCCA further divides into right internal carotid artery (RICA) and right external carotid artery (RECA) at the fourth cervical vertebra. The angle of the mandible is a good bony landmark for the bifurcation of the CCA. ECA gives numerous branches (Figure 20-10). LCCA arises 75% of the time as a separate branch from aorta, 10% to 15% of the time as a common origin with the BC, and approximately 10% of the times from the BC (bovine origin) (Figure 20-11). ICA can be divided into four segments82 (Figure 20-11). a. Prepetrous (cervical). Between the CCA bifurcation and the petrous bone. This segment does not give rise to any

• FIGURE 20-12.

CTA showing thoracic aortic aneurysm.

Courtesy: Robert Falk MD, 3-DR Louisville, KY.

354 • CHAPTER 20

• FIGURE 20-14. • FIGURE 20-13.

CTA of carotid arteries showing patent stent in the right common and internal carotid arteries (arrows).

Courtesy: Robert Falk MD, 3-DR Louisville, KY.

major branches and is the most common site of carotid stenosis involving the ostial and the proximal portion of the artery. b. Petrous. This segment courses through the petrous bone and makes a 90-degree L-shaped angle on angiogram. c. Cavernous. This is the part through the cavernous sinus. d. Supraclinoid. This segment gives ophthalmic, posterior communicating, and anterior choroidal branches before terminating as the middle and anterior cerebral arteries. Ophthalmic artery supplies the ipsilateral retina and optic nerve and is a source of important collateral route between ICA and ECA. Posterior communicating branch connects ICA with posterior cerebral artery to provide communication between the anterior and posterior circulation. The area supplied by ACA and MCA is referred to as “carotid territory of the brain.” Angiography Angiography is considered to be the gold standard for the diagnosis of extracranial and intracranial carotid artery disease. For complete cerebrovascular circulation, carotid angiography should be done in conjunction with aortic arch and selective vertebral angiography. Knowledge of arch anatomy and presence of proximal AS and tortuosity are crucial in the appropriate selection of the catheters for selective angiography. For Type-I or Type-II arch, 5 F JR4, Davis, HH (Meditech Watertown, MA), or Berenstein catheters are adequate. In patients with bovine arch Vitek catheter is often needed. For Type-III arch (elon-

Venous phase of cerebral angiogram.

gated), reverse curve catheters like Simmons (Angiodynamics, Queensbury, NY) or Vitek are often required. Simmons catheter can be very useful as it “travels up” the carotid artery and does not get dislodged. Its use, however, requires more skill. Meticulous technique and double flushing is recommended once the catheter is beyond the aortic arch. Diluted low- or iso-osmolar contrast is injected at 4 to 6 mL/s for a total of 8 mL for CCA angiography using DSA at 4 to 6 FPS. Cerebral circulation imaging should be continued into the venous phase to rule out any venous anomaly (Figure 20-14). Multiple projections and angulation are sometimes needed for optimal visualization. In most cases, a straight AP and lateral or 30 to 40 degrees ipsilateral angle will open up the bifurcation to assess the lesion (Figures 2015 and 20-16). RAO projection opens up the bifurcation of the BC artery. In patients who are undergoing carotid or vertebral interventions, cerebral angiography should be performed before and after the intervention, for comparison, in the event of suspected embolic stroke. It also provides information about intracranial aneurysms and atherosclerotic disease. A straight PA cranial view to bring the petrous bone at the base of the orbit (Towne’s view) will nicely outline the cerebral circulation in most cases (Figure 20-17). For assessment of the severity of carotid stenosis, the methodology used by NASCET investigators is most popular. This method compares the stenotic area with the most normal appearing artery distal to the stenosis. Vertebral Artery Left vertebral artery originates as the first branch of subclavian artery. In 3% to 5% of cases, it may arise directly from the aorta between LCCA and LSCA. Very rarely, it may originate distal to LSCA. Right vertebral artery can

PERIPHERAL ANGIOGRAPHY • 355

• FIGURE 20-16.

Severe right carotid artery stenosis in a patient with previous carotid endarterectomy.

Courtesy: John Laird MD, Washington Hospital Center, Washington, DC.

• FIGURE 20-15.

Severe stenosis of right internal carotid

artery.

A

B

• FIGURE 20-17. (Towne’s view).

(A) Right and (B) and lateral view of cerebral angiography in AP

356 • CHAPTER 20

Angiography

• FIGURE 20-18.

Subclavian and vertebral artery angiography is commonly performed from the CFA approach. For patients with severe lower extremity PAD with no femoral access or who have Type-III aortic arch ipsilateral brachial approach can also be used. Unfractionated heparin (3000–5000 units) are given when using the brachial approach. RA can also be used for angiography and in addition to heparin vasodilators should also be given with this approach. AP, RAO, and LAO projections will open up the SCA and VA. RAO cranial angle will show the origin of internal memory artery (IMA). JR4 catheter is usually adequate for straight aortic arch. For elongated aortic arch, Vitek, Head Hunter, or Simmons 1 or 2 are used (Figure 20-19). For vertebral artery, 3 to 4 mL/s for a total of 6 mL of contrast is generally sufficient. Nonselective angiography with a blood pressure cuff inflated on the ipsilateral arm will improve the visualization of ostial disease. Ostia are also better seen in the contralateral oblique projections and V2 and V3 segments are better seen in PA and lateral views or ipsilateral oblique views. Intracranial segments are best seen in steep 40 degrees PA cranial (Towne’s) view and crosstable view. CTA showing “Circle of Willis.”

Courtesy: Robert Falk MD, 3-DR Louisville, KY.

originate from RCCA and duplication of vertebrals can occur at any level. It originates from the superior and posterior aspect of the RSCA. The two vertebrals converge to form the basilar artery at the base of the pons (Figure 20-18). It can be divided into four segments83 : V-1: From the origin to the transverse foramen of the fifth and sixth cervical vertebrae. V-2: Its course within the vertebra until it exits at C2 level. V-3: Extracranial course between the transverse foramen of C2 and base of skull where it enters foramen magnum. V-4: Intracranial course as it pierces the dura and arachnoid maters at the base of skull and ends as it meets the opposite vertebral artery (Figure 20-14). Intracranial part gives anterior and posterior spinal branches; penetrating branches and posterior inferior cerebellar artery (PICA), which gives supply to dorsal medulla and cerebellum. Left vertebral artery is usually dominant and stenosis of the dominant vertebral is likely to cause symptoms. AS is the dominant pathology involving the ostium and proximal extracranial segment of the VA. Surgical revascularization carries significant mortality and morbidity approaching 20%.84 With rapidly improving skills and technology, endovascular revascularization is becoming a very attractive option for these patients.

2

4

1

• FIGURE 20-19.

3

Selective angiography of left subclavian artery (1) using a Simmons catheter. (2) A normal left vertebral artery, (3) a small internal mammary artery, and (4) thyrocervical trunk are also seen.

PERIPHERAL ANGIOGRAPHY • 357

• FIGURE 20-20.

CTA of brachial, radial, and ulnar

arteries.

Courtesy: Robert Falk MD, 3-DR Louisville, KY.

Subclavian, Brachiocephalic, and Upper Extremity This vascular bed constitutes approximately 15% of symptomatic extracranial cerebrovascular disease. Right subclavian artery (RSCA) arises from BCA on the right and LSCA is the last major branch from the aorta on the left. In 0.5% population, RSCA arises as the terminal branch from the descending thoracic aorta and courses over to the right toward its normal distribution to the right upper extremity. Rarely, RSCA and RCCA may have separate origins from the aorta instead of a BCA. It gives vertebral, IMA, and thyrocervical trunk (TCT) from its first segment. TCT gives inferior thyroid, suprascapular, and transverse cervical branches. SCA becomes axillary artery at the lateral margin of the first rib that in turn becomes BA at the anatomic neck of the humerus. Opposite to the neck of radius, BA divides into ulnar and radial arteries (Figure 20-20). In approximately 1.3% of cases, RA originates from the axillary artery and in 15% to 20% of cases from the upper BA. Ulnar artery helps to form the superficial palmar arch and the RA the deep palmar arch (Figure 20-21). Angiography Angiography is generally needed in patients presenting with arm claudication, and in other causes of arm ischemia, e.g., blue digit syndrome, severe digital ischemia, and blunt and penetrating trauma with vascular injury to these vessels. CTA and MRA are useful to delineate arch anatomy. Step-

• FIGURE 20-21.

CTA of hand arteries.

Courtesy: Robert Falk MD, 3-DR Louisville, KY.

wise angiography with iso-osmolar contrast is preferred. Contrast of 5 to 10 mL with hand injection using DSA will give good visualization of these vessels. JR4 catheter is routinely used (Figures 20-22 and 20-23). Vitek or Simmons catheter maybe required depending on the take off of SCA or BCA. Vitek catheter is advanced under fluoroscopy and positioned in the descending thoracic aorta with the curve facing the right side of the arch and the tip facing north. Catheter is gently advanced and each great vessel is selectively engaged. After completion of the angiogram, the catheter is removed over a wire. Simmons catheter is reshaped in the ascending thoracic aorta and is gently withdrawn to engage each vessel selectively. It is also removed after straightening with a wire. Orthogonal oblique views will visualize SCA and its branches. LAO for RSCA and RAO for LSCA will give good views of these vessels (Figures 20-24 and 20-25). Patient’s arm should be adducted to the neutral position during angiography. For axillary artery and BA angiography, catheter is advanced into distal SCA. Usually a long 300 cm Wholey, Magic Torque or a Stiff Shaft Angled Glide wire is used to exchange the JR4, Vitek, or Simmons catheter for a straight 4- to 5-F Glide catheter or a multipurpose catheter. Axillary artery is angiographed in adducted arm position and BA in an abducted position with forearm supine. For the forearm and hand angiogram, the diagnostic catheter is further advanced into the distal BA. Forearm should be supine, fingers splayed and thumb abducted. PA projection

358 • CHAPTER 20 5 F JR4

100% occluded left subclavian artery

6 F long shuttle sheath

• FIGURE 20-22.

Hundred percent occluded left subclavian artery. Dual injection technique is demonstrated with 5-F JR4 catheter in the subclavian artery and 6-F long shuttle sheath in the ascending aorta.

Courtesy: John Laird MD, Washington Hospital Center, Washington, DC.

• FIGURE 20-24.

Critical stenosis of the origin of innonimate artery seen on angiogram performed via right radial artery. Aortic arch is not clearly opacified due to the stenosis. Right common carotid artery is patent (arrow head).

Courtesy: John Laird MD, Washington Hospital Center, Washington, DC.

is adequate. Vasodilators are given intraarterially due to the spasmodic nature of these arteries. For borderline lesions a translesional gradient can be measured using a 0.014-inch pressure wire or simultaneous measurement of pressure between 4- and 5-F catheter tip placed distal to the lesion and the side port of a long 6-F sheath positioned in the distal aorta. Vasodilators can be used to augment the gradient. A gradient greater than or equal to 15 mm Hg in SCA and BCA is considered significant. Abdominal Aorta

• FIGURE 20-23.

Left subclavian artery widely patent

after stenting.

Courtesy: John Laird MD, Washington Hospital Center, Washington, DC.

Atherosclerotic disease is very common with more involvement of the infrarenal abdominal aorta. Abdominal aorta starts at the level of the diaphragm (T12) and continues anterior to the spine and to the left of inferior vena cava. It bifurcates at L4 level into the right and left common iliac artery.85 AA is 15 to 25 mm in diameter and larger in males and older populations.86 It gives rise to the celiac trunk at T12–L1, superior mesenteric artery (SMA) at L1–L2, and inferior mesenteric artery (IMA) at L3–L4 level. Renal arteries originate posterolaterally at L1–L2 level below the origin of the SMA. Four pairs of lumbar arteries originate below the renals. Abdominal aorta is considered to be aneurysmal when the anteroposterior diameter is 3 cm. Diagnosis is based

PERIPHERAL ANGIOGRAPHY • 359

• FIGURE 20-25.

Innonimate artery is widely patent after stenting with opacification of aortic arch.

Courtesy: John Laird MD, Washington Hospital Center, Washington, DC.

on formulas that adjust for age or body surface area or by calculating the ratio between the normal and dilated aortic segments.87−90 The prevalence of AAA increases with age. In a necropsy study,91 incidence was 5.9% in men aged 80 to 85 years and 4.5% in women who were older than 90 years of age. Based on U.S. studies, the prevalence for AAA 2.9 to 4.9 cm is 1.3% for men aged 45 to 54 years and up to 12.5% for men aged 75 to 84 years. Comparable prevalence for women is 0% to 5.2%. Common iliac artery aneurysms are usually also found in association with AAA. One-third to one-half are bilateral and 50% to 85% are asymptomatic when diagnosed.92,93 Rupture occurs when they are more than 5 cm. For the diagnosis, a history of abdominal and back pain and presence of a pulsatile mass are important indicators of the presence of AAA. Plain X-ray film of the abdomen may show curvilinear aortic wall calcification as an incidental finding. US or nuclear scan of abdomen may show AAA as an incidental finding. Similarly, during unrelated arteriography, slow or turbulent flow in the aorta may suggest presence of AAA. US has a specificity of nearly 100% and sensitivity of 92% to 99% for the diagnosis of infrarenal AAA.87 For suprarenal AAA, the accuracy is much less. CTA and MRA are the

• FIGURE 20-26.

CTA of abdominal aorta and iliac arteries showing infrarenal abdominal aortic aneurysm and accessory bilateral renal arteries.

Courtesy: Robert Falk MD, 3-DR Louisville, KY.

current gold standard for the diagnosis of AAA.94 Spiral contrast-enhanced CTA with 3D reconstruction is now the standard preop evaluation to look for vessel calcification, thrombus, and anatomy of the aneurysm for optimal stent graft placement (Figure 20-26). In addition to previously described limitations, CTA tends to overestimate the diameter of the neck and underestimate the length of the neck of the aneurysm. MRA is inferior to spiral contrastenhanced CTA in spatial resolution and not very good for detecting vessel wall calcification. MRA is slower than CTA but not inferior in the diagnosis. It is considered superior to catheter angiography for defining the proximal extent of the AAA, venous anatomy, intraluminal thrombus and iliac aneurysms.95 Renal arteries can also be imaged accurately with the new scanners. Standard MRA protocols for AAA are not available everywhere. Catheter angiography is always done at the time of endovascular aneurysm repair (EVAR). Pelvic angiography is also done at the same time to visualize iliac arteries, which are also frequently involved with abdominal aortic aneurysm. It also helps in the optimal visualization of collateral or variant arterial anatomy.96,97 Contrast angiography, however, is not accurate in estimating the diameter of the AAA due to presence of thrombus that is usually present in the aneurysms. CTA or MRA are thus needed

360 • CHAPTER 20

• FIGURE 20-27.

Large abdominal aortic aneurysm (arrows), only partially visualized on contrast angiogram. The rest of the sac is filled with thrombus.

in conjunction prior to EVAR (Figures 20-27 and 20-28). Prior to open or endovascular repair the maximum transverse diameter of the aneurysm, its relationship to the renal arteries, presence of iliac artery or hypogastric artery aneurysm, stenosis of renal or iliac arteries, and presence of horse-shoe kidneys, etc., must be defined. The diagnostic modality must provide measurement of the neck and body of the AAA and of the iliac arteries. CTA is also excellent in defining the type of endoleak after EVAR before angiography to repair the endoleak (Figure 20-29). Femoral approach is most common using 4- to 6-F pigtail or Omniflush catheter. Radial, brachial, or axillary approaches are also used. As a last resort, translumbar puncture can be done. For AAA, the pigtail or Omniflush catheter is positioned such that the tip is at T12-L1 level so that the side holes are at L1-L2 level. Contrast of 30 to 50 cc is injected. For abdominal or thoracic aortic stenosis, a translesional gradient can be measured as previously described. A gradient greater than 10 mm Hg is considered significant (Figure 20-17). Visceral Artery Aneurysms Open or endovascular repair has a class I indication for aneurysms greater than 2 cm in women of child-bearing age or in men or women undergoing liver transplant. They have Class IIa indication in men or in women who are beyond the child-bearing age. Splenic and hepatic artery aneurysms are not very common.98,99 Most are found incidentally during imaging for other reasons. Most are asymptomatic but a rupture in pregnant women carries a very high mortality that may approach 70% for the mother and >90% for the

• FIGURE 20-28.

CTA of an abdominal aortic aneurysm showing a large thrombus in the aneurysm not likely to be visible on a catheter angiogram.

Courtesy: Robert Falk MD, 3-DR Louisville, KY.

fetus.100 In general population the rupture carries a mortality of 10% to 25% SMA has 6% to 7% of all visceral aneurysms. Lower extremity aneurysms generally do not rupture but pose a danger of thromboembolism or vessel thrombosis. PA carries up to 70% of all LE aneurysms. CTA and MRA are the tests of choice. Renal Artery Renal artery stenosis (RAS) is a very common and progressive disease in patients with PAD. It is a relatively uncommon cause of hypertension.101−103 A duplex US study of patients older than 65 years showed an incidence of 9.1% in men, 5.5% in women, 6.9% in white population, and 6.7% in black population.102 In another series of 395 patients with abdominal aortic and ileofemoral disease, the incidence of RAS greater than 50% was 33% to 50%.104 The incidence of significant RAS in patients who were undergoing coronary angiography who also underwent renal angiography was approximately 11% to 18%.105−107 Conversely, the incidence of clinically significant CAD was 58% in patients with atherosclerotic RAS.108 In 24% patients

PERIPHERAL ANGIOGRAPHY • 361

• FIGURE 20-30.

(A and B) MRA of renal and mesenteric arteries showing normal vessels and abdominal aorta.

Courtesy: Robert Falk MD, 3-DR Louisville, KY.

Angiography

• FIGURE 20-29.

CTA of an abdominal aortic endograft showing an endoleak via a collateral between Internal iliac and inferior mesenteric arteries (arrow).

Courtesy: Robert Falk MD, 3-DR Louisville, KY.

with end-stage renal disease (ESRD) and in need for dialysis, there was severe atherosclerotic RAS.109 AS is by far the most common pathophysiological mechanism approaching 90% in patients with RAS. Fibromuscular dysplasia is found in approximately 10% of patients with RAS. There is also significant progression of RAS. In patients with less than 60% RAS, progression was 20% per year and in those with greater than 60% stenosis, there was complete occlusion in 5% cases at 1 year and 11% at 2 years.110−112 Bilateral RAS is also common. In six different studies including 319 patients, it was found in 44% of cases.113 renal atrophy and ESRD can develop in patients with RAS and RA occlusion.114−116 Renal arteries arise at L1–L2 level from the posterolateral aspect of the abdominal aorta. Right RA typically originates slightly higher than the left. Accessory renal arteries are also quite common and found in 25% to 35% of the general population. These usually supply the lower poles of the kidneys. They can arise anywhere from suprarenal aorta down to the iliac and are generally smaller in caliber. Main renal artery further branch into segmental, interlobar, arcuate, interlobular, and arterioles.

MRA has an ACC/AHA Class I indication as a screening tool for RAS (Figure 20-30). Similarly, CTA has Class I indication in patients with normal renal function. When the clinical suspicion is high and when the noninvasive tests are inconclusive, catheter angiography has Class 1 indication for the diagnosis of RAS (Figure 20-18). MRA with gadolinium compared to catheter angiography has a sensitivity 90% to 100% and specificity of 76% to 94% in atherosclerotic RAS. For patients who have FMD, the accuracy of MRA is less.117 MRA is the most expensive test diagnostic tool and other limitations are as discussed before. CTA has a sensitivity of 92% and specificity of 95% when compared to DSA.118 Use of CTA is limited because of a risk of CIN. CTA with the old scanners had a sensitivity of 59% to 96% and specificity of 82% to 99% when compared to catheter angiography.119−124 With the new scanners, they have improved to 91% to 92% and 99%, respectively. Currently, catheter angiography is reserved for those patients whose diagnosis is not clear by noninvasive testing. It is also recommended in patients who are undergoing coronary or peripheral angiography in whom there is a high suspicion of RAS. For contrast angiography, CFA approach is most common using 5- to 6-F short sheath. In severely tortuous ileofemoral vessels, a long 6 F sheath should be used. Brachial approach is used in patients with poor femoral approach or if the renal arteries are acutely downward angulated. Nonselective angiography is done first with a pigtail or

362 • CHAPTER 20

• FIGURE 20-31.

Bilateral renal artery stenoses on flush angiography of abdominal aorta utilizing pigtail catheter.

Omniflush catheter positioned at L1-L2 level in AP view to look for ostia of the renal arteries and also to look for accessory renal arteries. DSA at 4 FPS with 30 mL nonionic iso-osmolar contrast at the rate of 15 mL/s is usually injected (Figure 20-31). For selective renal angiography 4 to

• FIGURE 20-32.

Selective left renal artery angiography utilizing Judkin’s right coronary catheter showing significant stenosis.

• FIGURE 20-33.

Selective right renal artery angiography utilizing Cobra catheter.

5 F JR4, renal double curve, Cobra, IMA, SOS, or Hockey stick catheters can be used (Figures 20-32 to 20-34). For downward-angulated renals, reverse curve catheters, for example, Simmons or Omniselective can be utilized from the femoral approach or a straight MP catheter from the brachial approach. Contrast of 5 to 8 mL at 5 mL/s using DSA at 4 FPS will give excellent images. Usually an ipsilateral 15 to 30 degree oblique view will display the ostium and proximal renal artery. Another useful technique is to modify the LAO/RAO angulation under fluoroscopy while the catheter is engaged until the tip of the diagnostic

• FIGURE 20-34.

Selective right renal artery angiography showing in-stent restenosis utilizing Judkin’s right coronary catheter.

PERIPHERAL ANGIOGRAPHY • 363

catheter is maximally opened. Cranial and caudal angulation can be used to open up the bifurcation lesions. Cineangiogram is prolonged until the nephrogram phase to assess the kidney size and regional perfusion of the kidney to optimize revascularization strategy.

2

No Touch Technique Abdominal aorta frequently is severely atherosclerotic and there is risk of visceral or distal embolization of atheroma during manipulation of catheters. With this technique, a 0.14-inch wire is advanced through the catheter beyond the renal arteries. The catheter is manipulated toward the renal ostia without touching them, thus avoiding the scraping of the aortic intima. In borderline lesions, a translesional gradient should be measured. A 0.014-inch pressure wire is most accurate. Alternatively, a 4 F diagnostic catheter is advanced beyond the lesion and gradient measured between the catheter and a 6 F sheath in the aorta. A systolic gradient greater than or equal to 20 mm Hg or a mean gradient of 10 mm Hg is considered significant. Vasodilators, for example, nitroglycerin 100 to 300 mg or Papaverine 20 to 30 mg intravenously can be used to augment the gradient. Intravascular ultrasound (IVUS) is also a very useful imaging modality in renal arteries to accurately assess the artery size and disease involvement of the ostia. CIN is a significant risk and can be as high as 20% to 50% in patients with both chronic kidney disease and diabetes mellitus.125,126 Iso-osmolar contrast agent Iodixinol showed less nephrotoxicity than low-osmolar agent Iohexol in one randomized trial.127 In patients with creatinine clearance less than 60 mL/min and serum creatinine greater than 1.2 mg/dL, Mucomyst 600 mg twice a day decreased the incidence of CIN in patients undergoing coronary angiography.128 In patients with renal insufficiency, CO2 angiography can be done injecting 40 to 50 mL of CO2 delivered by hand injection while the patient is holding breath using DSA. This will allow visualization of renal ostia to facilitate selective renal angiography. Gadolinium contrast or iodinated contrast in a 50:50 ratio with normal saline can also be used in patients with renal dysfunction. Mesenteric Arteries AS involvement of these arteries is common but mesenteric ischemia is uncommon. Mesenteric ischemia can also be caused by nonobstructive arterial disease in cases of low flow states. Two-thirds of the patients with intestinal ischemia are women with a mean age of 70 years and most have preexisting CAD.129−131 Postprandial abdominal pain is almost always present as a symptom. Celiac artery arises from the anterior surface of the aorta at T12 level. It travels inferiority for 1 to 3 cm before dividing into common hepatic, splenic, and left gastric arteries. SMA arises at the L1–L2 level and gives rise to middle colic and pancreatoduodenal arteries. IMA arises at L3–L4 level and gives rise to left colic and superior rectal arteries (Figure 20-35).

1 4

3

• FIGURE 20-35.

Mesenteric vessel arteriogram showing (1) patent spenic, (2) common hepatic, (3) superior mesenteric, (4) and right renal arteries. Left renal artery is absent.

These vessels have rich collateral pathways. meandering mesenteric artery allows communication between SMA and IMA. Pancreatoduodenal artery communicates between celiac artery and SMA while IMA has collateral communications with the EIA. Occlusion of one of these arteries generally does not cause intestinal ischemia. Classical teaching was that severe stenosis or occlusion of two of the three of these arteries has to be present to cause this syndrome, but this is not considered entirely true now.132,133 Single vessel disease, virtually always of the SMA, can cause intestinal ischemia (Figure 20-36). Patients in whom collateral circulation has been interrupted by prior surgery are especially prone to intestinal ischemia by single vessel involvement. Duplex ultrasound, CTA, MRA with gadolinium enhancement, and catheter angiography with lateral abdominal aortography where noninvasive testing is not available or indeterminate, all have Class I indication in the diagnosis. In many cases, US is not very helpful because of the presence of bowel gas or patient body habitus. CTA and MRA are good for detecting proximal artery lesions. CTA, however, requires intravenous contrast. In case of acute intestinal ischemia, catheter angiography is the best test but it is limited by the time it may require in such emergencies. It can differentiate between occlusive versus nonocclusive disease. Sometimes the patient is not stable to undergo the procedure. Immediate laparotomy and surgical revascularization is the best approach in such cases. Chronic intestinal ischemia is rare and almost always caused by AS.134 Buerger’s disease, FMD, and aortic dissection are very rare causes.

364 • CHAPTER 20

1

2

• FIGURE 20-36.

Angiogram in a lateral projection showing critical stenosis of (1) celiac trunk and (2) 100% occlusion of SMA in a patient with severe mesenteric angina.

• FIGURE 20-37.

Selective angiography of celiac trunk utilizing reverse curve Simmons catheter.

Courtesy: John Laird MD, Washington Hospital Center, Washington, DC.

Catheter angiography has ACC/AHA Class I indication in patients with suspected nonocclusive intestinal ischemia whose condition does not improve rapidly with the treatment of the underlying disease, e.g., circulatory shock. It can also confirm vasospasm and vasodilator agents can be administered.135−137 CFA approach is most commonly used. Arm approach can be used if femoral approach is not feasible. A 4 to 5 F pigtail or Omniflush catheter is placed at T12-L1 level and 30–40 cc of contrast injected via power injector using DSA at 15 cc/s at 4 to 6 FPS. Lateral view will best visualize these vessels (Figures 20-37 and 20-38). An AP view should also be done to visualize the mesenteric circulation and the presence of any collateral vessels. “Arc of Riolan” (an enlarged collateral vessel connecting the left colic branch of the IMA with SMA) is an angiographic sign of proximal mesenteric arterial obstruction that is visible on the AP view. Pelvis and Lower Extremity Infra renal aorta and ileofemoral vessels are amongst the most commonly involved in atherosclerotic PAD. Ileofemoral involvement is more common in patents that have history of hypertension and smoking while below the knee, disease is commoner in diabetic population. Surgical

• FIGURE 20-38.

Selective angiography of superior mesenteric artery utilizing reverse curve Simmons catheter.

PERIPHERAL ANGIOGRAPHY • 365

revascularization in the ileofemoral region has a patency of >80%138−140 but it is associated with significant mortality and morbidity. Endovascular revascularization is rapidly taking over as the first line of treatment in these cases. AA bifurcates into common iliac arteries (CIA) at the L4-L5 level. CIA divides at L5-S1 junction into internal iliac artery (IIA) and external iliac artery (EIA). IIA courses posteromedially and EIA anterolaterally and exits the pelvis posterior to the inguinal ligament to become the CFA. The IMA takes off medially at the junction of EIA and CFA. The deep iliac circumflex artery takes off laterally and superiorly. CFA originates at the inguinal ligament and bifurcates at the lower part of the head of the femur into SFA anteromedially and DFA posterolaterally. DFA has two major branches, lateral and medial circumflex femoral arteries. These arteries along with the first perforating branch connect with the IIA via the superior and inferior gluteal and obturator arteries. Distally, its branches provide collaterals to the network around the knee, thus communicating with the popliteal and tibial vessels. Therefore, in cases of occlusion of SFA, the DFA becomes a very important source of collateral circulation. The SFA becomes the popliteal artery (PA) as it enters the adductor canal (Hunters canal). PA runs posterior to the femur and gives sural and geniculate branches. Below the knee, the PA divides into anterior tibial artery (AT) that runs anterior and lateral to the tibia and continues into the dorsum of the foot as the dorsalis pedis artery (DP). After the takeoff of the AT, the PA continues as the tibioproneal trunk (TPT) that divides into posterior tibial and peroneal arteries. The peroneal artery runs between the AT and PT. It joins the PT above the ankle via its posterior division and the AT via its anterior division. PT runs behind the medial malleolus and gives medial and lateral plantar branches. The lateral plantar and distal DP joins to form the plantar arch.

• FIGURE 20-39.

CTA of abdominal aorta and pelvic arteries showing severe calcification of distal aorta, common and internal iliac arteries. Celiac trunk, superior mesenteric, and renal and inferior mesenteric arteries are patent.

Courtesy: Robert Falk MD, 3-DR Louisville, KY.

Angiography CTA and MRA are very good tools to delineate the anatomy (Figures 20-39 to 20-41). Compared to DSA, the MRA has shown a sensitivity of 97% and specificity of 99.2%.141 Interest in this technology is growing as the sole diagnostic tool prior to surgical revascularization.142 MRA in fact can be a better imaging modality than CTA and catheter angiography for below the knee vasculature (Figure 20-42). CTA is also excellent in the diagnosis but limited by CIN and radiation hazard.143 Contrast angiography is considered to be the gold standard (Figures 20-43 to 20-45). It should be reserved for the patients being considered for revascularization and should not be done for diagnostic purposes only if CTA or MRA facility is available. Initially a nonselective angiogram should be done. CFA, brachial, or radial approaches are used. Sheaths and catheters of 4 to 6 F are used. A PT or OF catheter is positioned at L4–L5 and 30 mL of contrast at 15 mL/s is injected with a power injector. DSA at 4 to 6 FPS should be utilized. In cases of known iliac artery obstruction, the catheter should be placed just below the renal

• FIGURE 20-40.

CTA showing aortobifemoral and left femoral–distal bypass graft.

Courtesy: Robert Falk MD, 3-DR Louisville, KY.

366 • CHAPTER 20

A

B

• FIGURE 20-41.

“Thick maximal intensity projection” CTA of (A and B) left lower extremity arterial circulation and (C) bilateral ileo femoral arteries.

Courtesy: Robert Falk MD, 3-DR Louisville, KY.

arteries to look for collaterals from the lumbar branches. Selective iliac angiogram is typically done from the contralateral side using 4 to 5 F IMA or JR4 catheter. Other catheters, e.g., Simmons, Omniflush, or SOS, can be used as needed. An exchange length of 200 to 360 cm angled glide wire is advanced under flouro into the CFA or more distally and the catheter exchanged for a straight 4 to 5 F

glide or MP catheter. A selective stepwise angiogram of the leg is performed. A 10 to 15 cc contrast is used at each step. For optimal below the knee angiogram, the catheter should be advanced to the distal SFA and vasodilators used. Interactive bolus chase technique as described before can also be used for nonselective angiography of both the legs.

• FIGURE 20-42.

MRA of below the knee arteries showing 100% occlusion of right posterior tibial artery (solid arrow) and 100% occlusion of all three arteries on the left (dashed arrows).

Courtesy: Robert Falk MD, 3-DR Louisville, KY.

• FIGURE 20-43.

Arteriogram of aorto bifemoral graft with the sheath inserted into the right limb of the graft (arrow).

PERIPHERAL ANGIOGRAPHY • 367

1

2

• FIGURE 20-44.

(1) Hundred percent occlusion of left superficial femoral artery. (2) Collateral vessels reconstituting popliteal artery.

Another technique to engage the common iliac artery is to advance the angled glide wire in the catheter (usually pig tail) already in the abdominal aorta that was used for initial angiogram. The tip of the catheter is faced toward the contralateral iliac. The wire is advanced to “open up” the catheter and the catheter gently pulled down toward the aortic bifurcation. The glide wire will drop down into the common iliac artery as the catheter hooks the ostium of the common iliac. The catheter is then exchanged for the straight catheter as described above. This technique saves an extra step of engaging the contralateral iliac with another catheter first. After the angiogram of the contra lateral leg is completed, the catheter is pulled just a few inches proximal to the tip of the insertion sheath in the ipsilateral leg and angiogram completed in a stepwise fashion. This can also be done with the sheath alone but a smaller catheter has less risk of causing dissection during angiography. Power injector, hand injection, or an “assist device” can be used. Contralateral angle of 30 to 40 degrees will open up the iliac artery bifurcation and 30 to 40 degrees ipsilateral angles will open up the vessels below the EIA. Lesions with greater the 50% diameter stenosis and translesional systolic gradient greater than 10 mm Hg are considered significant. If femoral approach is not feasible, then a brachial or radial approach utilizing straight catheters can also be used for selective angiography of each leg. Vasodilators, for example, NTG 100 to 300 mg, Papavarin 30 to 60 mg, or Tolazoline 12.5 to 25 mg can be used to optimize below the knee imaging and also to augment translesional radiant.144

• FIGURE 20-45.

Hundred percent occlusion of right SFA with extensive collateral vessels from deep femoral artery connecting with the popliteal artery in the same patient. This “mirror imaging” of AS frequently seen in the thigh vessels.

High success rate with endovascular treatment has now encouraged most experienced operators to tackle below the knee PAD that was long thought to be only fit for surgical therapy. Patients with CLI who are being subjected to amputation should be given an option for peripheral vascular intervention even if it helps in the short-term healing of their infections and to prevent more proximal amputation.

•

VENOUS CIRCULATION

With improvement in technology, enthusiasm is gaining momentum in the endovascular treatment of venous occlusive disease (VOD). The most common causes of VOD are coagulopathies, extrinsic compression from tumors, and thrombosis from iatrogenic catheters and wires. Venous enhanced subtracted peak arterial (VESPA) magnetic resonance venography is comparable to conventional venography in the diagnosis of femoral and iliac deep venous thrombosis.145 CTA and MRA are both useful in the diagnosis of upper extremity and central VOD, stenoses, extrinsic masses, and pulmonary embolism. Venous system parallels arterial system. The superficial veins in the infrainguinal region drain into the small saphenous vein, which drains into the popliteal vein, and into the greater saphenous vein that drains into the common femoral vein (CFV). The deep veins converge on the CFV that continues as the external iliac vein and combines with

368 • CHAPTER 20

the internal iliac vein to form the common iliac veins which drain into the IVC that further drains into the right atrium of the heart. Superficial upper extremity veins drain into the lateral cephalic and medial basilic veins that run along the arm. Cephalic vein empties into the axillary vein and basilic vein drain into the brachial vein. Deep veins drain into the brachial vein that continues as the axillary and subclavian veins. Each subclavian vein unites with the internal jugular vein to form the right and left innominate veins. They join together on the right side to form the superior vena cava (SVC) that empties into the right atrium. Venous drainage from the pelvic area flows to internal iliac vein that joins with external iliac vein to form the common iliac vein. Venous drainage from abdominal viscera goes to IVC. The azygous and hemiazygous system of veins form an important link between IVC and SVC. The hemiazygous vein and accessory hemiazygous vein is located along the left side of thoracic vertebrae and receives blood from the left chest wall and lung and drain into the azygous vein. In two-thirds of cases, the hemiazygous vein communicates directly with the left renal vein. Azygous vein is located on the right side of the thoracic vertebrae and drains into the SVC at the level of T4. Distally, it connects to the IVC at the level of the renal vein. Venogram This is still considered the gold standard for VOD. Small amount of contrast through peripherally inserted catheters will provide visualization of the veins. Raising the arm improves central filling. For lower extremity angiography, venous access is obtained in the dorsum of the foot. DSA is used. For iliac veins 5 to 6 F sheath is inserted in the CFV and angiogram is obtained by hand injection of the contrast. For IVC, a pigtail or Omniflush catheter is inserted in CIV and 40 mL of contrast is injected. For pulmonary angiogram a 6 F angled pigtail or a Grollman catheter is advanced in the main pulmonary artery through a sheath in the CFV or IJ vein. Contrast at 30 mL at 15 mL/s is injected, and angiography acquired in AP and lateral views for each lung. If pulmonary artery pressure is high, then selective right and left pulmonary artery angiogram is obtained. Care should be taken in patients with preexisting LBBB because the catheter may cause RBBB, thus, causing complete heartblock.

•

INTRAVASCULAR IMAGING

There are other intravascular imaging techniques that are less commonly used in routine catheter peripheral angiography. They can however be very useful in cases of ambiguous situations or where a decision to intervene is not clear cut.146 IVUS is the most widely available. IVUS catheter uses reflected sound waves to image vascular walls and structures in a two-dimensional tomographic format. Compared to cardiac echocardiogram, the catheters used in peripheral imaging have a much higher frequency, 20 to 40 MHz versus 2 to 5 MHz. Most new IVUS catheters are compatible with 6 F sheaths and guiding catheters. Over the wire and rapid exchange systems are available. In our center we use Boston Scientific Corp. system (Natwik, MA), unfractionated heparin at 70 units/kg is given intravenously during IVUS procedures. Intracoronary nitroglycerin is given prior to delivering the catheter at the area of interest. Automated pullback is done at 0.5 to 1 mm/s. Interpretation is based on recognition of blood–intima and media–adventitia interface. Lumina and adventitia are much brighter than the media creating a bright–dark–bright image. Angioscopy is not FDA-approved in the United States for clinical use. It is probably the best technique for imaging intravascular thrombus. It provides real-time color images of vascular surfaces and also gives information about atherosclerotic plaque and dissection flaps. Optical coherence tomography (OCT) generates real-time tomographic images from backscattered reflection of infrared light. It can be conceptualized as an optical analog of IVUS. It has 10 times higher resolution than conventional ultrasound. Imaging procedure is similar to IVUS; however, saline or contrast media must displace blood. There is only one system that is commercially available (Light bulb Imaging Inc., Westford. MA). A 0.014-inch imaging wire is inserted in the vessel distal to the occlusion balloon. The diagnostic accuracy of OCT for plaque characterization is confirmed by an ex vivo study of 3007 human AS specimens from aorta, carotid, and coronary arteries.147 The complications of this procedure appear to be comparable to IVUS and angioscopy. However, data are lacking.

•

ACKNOWLEDGMENT

We wish to thank and acknowledge all who have allowed us to reproduce their figures and tables.

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123. Kawashima A, Sandler CM, Ernst Rd, et al. CT evaluation of renovascular disease. Radiographics. 2000;20:1321–1340. 124. Lufft V, Hoogestraat-Lufft L, Fels LM, et al. Contrast media nephropathy: intravenous CT angiography versus intra-arterial digital subtraction angiography in renal artery stenosis: a prospective randomized trial. Am J Kidney Dis. 2002;40:236–242. 125. Rihal CS, Textor SC, Grill DE, et al. Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation. 2002;105:2259– 2264. 126. Parfrey PS, Griffiths SM, Barrett BJ, et al. Contrast materialinduced renal failure in patients with diabetes mellitus, renal insufficiency or both. A prospective controlled study. N Engl J Med. 1989;320:143–149. 127. Aspelin P, Aubry P, Fransson SG, et al. Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med. 2003;348:491–499. 128. Kay J, Chow WH, Chan TM, et al. Acetylcysteine for prevention of acute deterioration of renal function following elective coronary angiography and intervention: a randomized controlled trial. JAMA. 2003;289:553–558. 129. Ottinger LW, Austin WG. A study of 136 patients with mesenteric infarction. Surg Gynecol Obstet. 1967;124:251– 261. 130. Hertzer NR, Beven EG, Humphries AW. Acute intestinal ischemia. Ann Surg. 1978;44:744–749. 131. Bergan JJ. Recognition and treatment of intestinal ischemia. Surg Clin North Am. 1967;47:109–126. 132. Mikkelsen WP. Intestinal angina: its surgical significance. Surg Gynecol Obstet. 1957;94:262–267; discussion, 267–269. 133. Buchardt Hansen HJ. Abdominal angina: results of arterial reconstruction in 12 patients. Acta Chir Scand. 1976;142: 319–325. 134. Fisher DF Jr, Fry WJ. Collateral mesenteric circulation. Surg Gynecol Obstet. 1987;164:487–492. 135. Kawauchi M, Tada Y, Asano K, et al. Angiographic demonstration of mesenteric arterial changes in postcoarctectomy syndrome. Surgery. 1985;98:602–604. 136. Siegelman SS, Sprayregen S, Boley SI. Angiographic diagnosis of mesenteric arterial vasoconstriction. Radiology 1974;112:533–542. 137. Nalbandian H, Sheth N, Dietrich R, et al. Intestinal ischemia caused by cocaine ingestion: report of two cases. Surgery. 1985;97:374–376.

PERIPHERAL ANGIOGRAPHY • 373

138. Vitale GF, Inahara T. Extra peritoneal endarterectomy for iliofemoral occlusive disease. J Vasc Surg. 1990;12:409–413; discussion 414–415. 139. van den Dungen JJ, Boontje AH, Kropveld A. Unilateral iliofemoral occlusive disease: long-term results of the semiclosed endarterectomy with the ring-stripper. J Vasc Surg. 1991;14:673–677. 140. de Vries SO, Hunink MG. Results of aortic bifurcation grafts for aortoiliac occlusive disease: a meta-analysis. J Vasc Surg. 1997;26:558–569. 141. Cambria RP, Yucel EK, Brewster DC, et al. The potential for lower extremity revascularization without contrast arteriography: experience with magnetic resonance angiography. J Vasc Surg. 1993;17:1050–1056. 142. Sueyoshi E, Sakamoto I, Matsuoka Y, et al. Aortoiliac and lower extremity arteries: comparison of three-dimensional dynamic contrast-enhanced subtraction MR angiography and conventional angiography. Radiology. 1999;210:683– 688.

143. Poletti PA, Rosset A, Didier D. Subtraction CT angiography of the lower limbs: a new technique for the evaluation of acute arterial occlusion. AJR Am J Roentgenol. 2004;183:1445–1448. 144. Legemate DA, Teeuwen C, Hoeneveld H, Eikelboom BC. Value of duplex scanning compared with angiography and pressure measurement in the assessment of aortoiliac arterial lesions. Br J Surg. 1991;78:1003–1008. 145. Fraser DG, Moody AR, Davidson IR, et al. Deep venous thrombosis: Diagnosis by using venous enhanced subtracted peak arterial MR venography versus conventional venography. Radiology. 2003;226(3):812–820. 146. Honda Y, Fitzgerald PJ, Yock PG. Intravascular Imaging techniques. In: Baim DS, Grossman W, eds. Cardiac Catheterization, Angiography and Intervention. 7th edition; Philadelphia, PA: Lippincott Williams & Wilkins; 2006:371–391. 147. Yabushita H, et al. Characterization of human atherosclerosis by optical coherence tomography. Circulation. 2002;106: 1640–1645.

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chapter

21

Intravascular Ultrasound in Peripheral Arterial Disease Daniel H. Steinberg, MD / Esteban Escolar, MD / Robert A. Gallino, MD / Neil J. Weissman, MD

•

INTRODUCTION

Intravascular ultrasound (IVUS) has become a standard imaging technique in high volume, experienced interventional laboratories, but most of its use is relegated to the coronary arteries. While conventional angiography provides a single-plane “shadow” of the vascular lumen, it has limited ability to accurately and reproducibly measure vessel stenosis and characterize plaque morphology. The highdefinition, cross-sectional images of the arterial lumen and the arterial wall provided by IVUS allow a far more detailed analysis of the target vessel and peripheral interventional success. Nonetheless, IVUS has not enjoyed wide deployment in the peripheral interventional arena. This chapter will provide the information needed to utilize IVUS during peripheral interventions by reviewing the fundamentals of IVUS technology, image interpretation and standardized measurements, its general application during peripheral vascular interventions, and some specific considerations for each vascular territory.

•

HISTORICAL PERSPECTIVE

One of the first IVUS catheters was designed in 1972s by Bom et al.1 with the purpose of exploring the intracardiac chambers and cardiac structures. During the early and mid-1980s, new catheters were designed in order to evaluate and characterize the arterial structures. Because of their size and catheter stiffness, early clinical studies with IVUS in the late 1980s were done primarily in the periphery. In the early 1990s, rapid technical improvement in catheter design, transducer technology, and subsequently imaging quality produced clinically useful catheters. The standard IVUS catheter was reduced to 3.5 to 4.3 F catheter, which

led to marked growth of their use in coronary interventional cardiology research and practice. In the last 10 years, IVUS has moved from being solely a research tool to an established modality in clinical practice. While the use in the coronaries remains more common than in the peripheral arteries, the primary techniques, diagnostic utility, and therapeutic benefits remain similar. IVUS serves three important clinical purposes— diagnosis, guiding the interventional strategy, and optimizing the interventional result. Starting with diagnosis, IVUS is the gold standard method to assess intermediate stenosis, ambiguous lesions, bifurcations, unusual lesion morphology (aneurysms, calcium, thrombi), in-stent restenosis, and any other unusual angiographic finding.2 From an interventional perspective, IVUS has been utilized extensively as a guide to the procedure, aiding in selection of optimal strategy, adjuvant device utilization (rotational atherectomy, predilation, etc.) as well as selection of stent diameter and length.3 Additionally, IVUS imaging enables optimization of stenting procedures, maximizing expansion and apposition, and identifying poststenting complications such as vessel rupture and dissection.

•

TECHNOLOGY

Two different IVUS transducer technologies are currently available—solid state (or phase array) and mechanical (Figure 21-1).4 Solid-state configuration has 64 transducer elements arranged as a collar around the catheter. The backscattered ultrasound information received from each transducer element is sent to a computer that performs realtime image reconstruction to formulate a cross-sectional image of the artery. The advantage of this catheter is that there are no mobile parts and therefore, no motion artifacts

376 • CHAPTER 21

A

B

• FIGURE 21-1.

IVUS transducers. (A) Phased array. (B)

Mechanical.

Reproduced with permission from Yock PG, Fitzgerald PJ, Honda Y. Intravascular ultrasound. In: Topol EJ, ed. Interventional Cardiology. Philadelphia, PA: WB Saunders; 1999:801-818.

in the image. The principal disadvantage is a slightly lower spatial and temporal resolution than mechanical transducers and a “ring-down artifact,” which is characterized by the appearance of bright halos around the IVUS catheter. This creates a small zone of uncertainty in the immediate area around the catheter and requires an additional corrective step in the calibration process5 (Figure 21-2). The second technology is a mechanical transducer, with a single rotating transducer mounted on a drive cable that allows a spinning transducer to build a tomography picture in real time. The resolution and dynamic ranges (gray scale) are superior with this method and clearer images can often be obtained. The disadvantage of a mobile drive shaft and transducers is the potential for an image artifact known as nonuniform rotational distortion (NURD). NURD (Figure 21-2) results from mechanical binding of the spinning transducer,6 which can occur as a result of catheter kinking, excessive tightening of the hemostatic valve, or excessive vessel tortuosity.5 With coronary imaging, the transducers are typically between 30 and 40 MHz. This provides optimal resolution at a depth of penetration necessary for coronary arteries

A

B

• FIGURE 21-2.

and for small peripheral vessels such as the renal or infrapopliteal lower extremity arteries. The frequency of the catheters used in peripheral arteries range from 10 to 40 MHz transducers, depending on the size of the vessel being imaged and the necessary depth of penetration. There are currently two principal IVUS manufactures: Boston Scientific Corporation, Inc. (Maple Grove, MN) and Volcano Therapeutics (VT) (Rancho Cordova, CA). Both systems provide either a portable unit that can be wheeled from room to room of the catheterization laboratory or a permanent unit that is fully integrated into the catheterization laboratory (Figures 21-3A and 21-3B). Boston Scientific CorR PV Periphporation (BSC) has recently released Atlantis eral Imaging Catheter, mainly designed for aortic imaging (of aneurysms) with a wide field of view. It is an over-thewire catheter requiring 8 F catheter introducer sheath and has a 15-MHz transducer capable of 25-cm pullback with 1 cm graduated markers for measurements. For other peR UltraTM catheters ripheral territories, BSC offers Sonicath ranging from 9 to 20 MHz as well as its coronary catheters, which are useful in renal and distal femoral arterial beds. VT has two catheters designed for peripheral vascular imaging. The detailed technical specifications of these catheters are summarized in Tables 21-1 and 21-2.

•

IMPLEMENTATION, ACQUISITION, IMAGE INTERPRETATION, AND ANALYSIS

The important principles and steps necessary to integrate IVUS into the clinical setting are summarized in Table 123. Essentially, designation and training of appropriate IVUS technologists and interpreting physicians will allow for a seamless bridge between image acquisition, interpretation, and application. Once established, it can be expected that IVUS should add no more than a few minutes to the procedure time. A basic IVUS image acquisition protocol that can be used in a busy clinical lab is summarized in Table 12-4. The important point is that early identification for IVUS use allows the machine and catheter to be prepared so that imaging becomes a simple catheter exchange at the

C

IVUS artifacts. (A) NURD that is unique to mechanical systems. (B) Catheter defect producing artifact as bright straight lines around the catheter (arrow). (C) Ring-down artifact, seen as bright halos around the catheter (arrow).

INTRAVASCULAR ULTRASOUND IN PERIPHERAL ARTERIAL DISEASE • 377

IVUS Monitor

Motor Drive Unit Tableside Controller

Copyright © 2005 Bosten Scientific Corporation, All rights reserved.

Radiopaque tip

2.5 cm tip to transducer

8.0F entry profile .035" guidewire compatible

Dual lurmen design

8.0F imaging window profile

A

B

• FIGURE 21-3.

IVUS Equipment. (A) Boston Scientific and (B) Volcano Therapeutics.

appropriate time. Motorized pullbacks are very useful in coronary arteries but can become time consuming in long peripheral lesions. If a long lesion is being imaged, a slow manual pullback often is sufficient as long as care is taken not to move “back and forth” and the rate of withdrawal is kept relatively slow and constant. If lesion length mea-

surements (or volume measurements) are needed, then a motorized pullback is required. Successful IVUS image interpretation is dependent on understanding the fundamentals of the image formation and the anatomy of the arterial structure. IVUS image formation is based on the same principles as standard

378 • CHAPTER 21

TABLE 21-1. Boston Scientific Catheters for Peripheral Vascular Disease R Sonicath TM Ultra Catheters

Transducer frequency (MHz) Maximal penetration (mm) Usable length (mm) Sheath compatibility (F) Guide catheter compatibility (F) Typical use

3.2 20 10 135 6 7 Renal

R Atlantis

Atlantis PV 15 30 95 8 NA Aorta/Iliac

NA, not applicable.

TABLE 21-2. VT Catheters for Peripheral Vascular Disease

Transducer frequency (MHz) Maximal penetration (mm) Usable length (mm) Sheath compatibility (F) Guide catheter compatibility (F) Typical use

Visions PV 8.2

Visions PV .018 F/X

10 60 90 9 9

20 24 135 6 6

Aorta/Iliac

Smaller arteries

TABLE 21-3. Starting an IVUS Program in the Catheterization Laboratory 1. Designate a specific IVUS technologist responsible for all practical aspects of IVUS imaging (equipment and catheter setup, image optimization, proper recording of IVUS imaging runs, patient, and procedure logs). 2. Designate a principle operator to be trained in IVUS image interpretation. With the time, this physician will pass the necessary knowledge to the rest of the operators allowing them to work independently with the help of the IVUS technologist. 3. Appropriate digital labeling: On screen labels should contain the timing of IVUS imaging (pre-, during-, or postprocedure), the procedure being performed, the target vessel, and location. 4. Modern equipment to the IVUS images in CD/DVD using the DICOM platform. Depending on the compression and quality use to save the data, up to eight patients with complete studies can be saved in a DVD.

TABLE 21-4. IVUS Image Acquisition 1. Verify that the catheter is compatible with the guide catheter and wide wire. 2. Flush the catheter free of air as air in the closed system produces black images that complicate image interpretation and continue flushing the catheter as it is introduced through the haemostatic valve. 3. Consider nitroglycerine 10–200 ␮g through the guide catheter in order to avoid vasospasm. (While this an essential step in coronary imaging, it may not be as important in larger peripheral vessels such as the aorta and iliac arteries). 4. Advance the catheter 3 or 5 cm distal to the segment to be interrogated. The catheter should advance smoothly without being forced. If the catheter is stuck in a lesion, it is generally due to an anatomic cause of interest. Turn the transducer on, as it will provide information useful for an interventional strategy (usually 360-degree calcification requiring plaque modification). 5. Connect catheter to automatic pullback device and initiate pullback. We recommend automatic pullback at rate of 1 mm/s in peripheral arteries as it provides improved image quality and increases accuracy of intended measurements. Upon completion the operator can readvance manually to further evaluate a particular area of interest. 6. Upon obtaining the image, the technologist can provide off-line information regarding lesion length, severity and morphology as well as reference diameters and landmarks. 7. Pull the catheter out, flush free of blood and store without bending to ensure catheter integrity for postprocedural use. 8. Repeat steps 1 to 7 with the same IVUS catheter for procedural and postprocedural guidance.

ultrasound imaging. An abrupt change in density (acoustic impedance) between adjacent tissue layers produces a strong reflection, resulting in an apparent boundary on the ultrasound image displayed on the screen. Applying this to vascular anatomy, the IVUS catheter is in the lumen where there is normal flowing blood, which reflects little to no sound and will appear black with a slight “speckle” from the blood cells. If blood cells are stagnant and have rouleaux formation, there will there be a substantial interface for the ultrasound to “bounce off.” In this situation, blood appears bright on the screen. When ultrasound waves hit a very reflective object (such as a calcified plaque) most of the sound waves are reflected back toward the catheter, and the image obtained will be very bright (white) on the screen. Objects between these two extremes are displayed on a gray scale, with darker gray representing tissues with higher water or lipid content and lighter gray representing tissue that is more fibrous.

INTRAVASCULAR ULTRASOUND IN PERIPHERAL ARTERIAL DISEASE • 379

A

B

• FIGURE 21-4.

Vessel layers. (A) IVUS image. (B) Corresponding color codes. Black denotes the IVUS catheter in the lumen. Red depicts the lumen with its outer border at the intimal border. Yellow depicts black and media with its outer border at the EEM. Outside the yellow circle is the adventitial layer.

Figure 21-4 depicts the normal three layers of the arterial wall depicted by IVUS. From the innermost to the outermost are the intima, media, and adventitia. The intima is composed of the endothelial cell layer and the underlying basal membrane with the internal elastic membrane representing external boundary of this layer. The media is composed of smooth muscle cells, elastin, and collagen and encircled by the external elastic membrane (EEM) representing the outer layer of the vessel. The adventitia is mainly composed of fibrous tissue. As can be seen in Figure 21-4, each of the arterial layers has different acoustic properties and each appears different (distinct) on the ultrasound screen. The intima reflects ultrasound and appears brighter than the blood in the lumen. The media, made mostly of homogenous smooth muscle cells, does not reflect a lot of ultrasound and is dark. The adventitia has “sheets” of collagen serving as several layers of interface for the ultrasound to be reflected off and is therefore very bright. While these layers are always present in muscular arteries, young people free of disease will have an intimal thickness below the resolution of IVUS and thus the three layers may be difficult to visualize (and it will appear as a “monolayer” with the blood apparently against the adventitia). Standard IVUS measurements are shown in Figure 215. There are two primary interfaces: (1) the lumen-intima interface and (2) the media-adventitia interface. From these two “circles,” virtually all required measurements can be obtained. The area enclosed by the lumen–intima interface is the luminal area. The area between the two interfaces is the plaque (or sometimes referred as the plaque and media or atheroma) area. The area enclosed by the media–adventitia interface is the vessel area (or media or EEM) area. Diameters are obtained by going through the center of the

• FIGURE 21-5.

IVUS measurements obtained in abdominal aorta. Red: minimum lumen diameter. Yellow: maximum lumen diameter.

380 • CHAPTER 21

A

B

C

• FIGURE 21-6.

Plaque morphology with angiographic appearance. (A) Fibrofatty. (B) Mixed. (C) Calcified.

image. These measurements are performed at the lesion and at the proximal and references. Furthermore, length measurements can be performed based on the amount of time it takes to get from one location to the next with a known pullback speed. Thus, the reported measures include reference lumen area and diameter, lesion area and minimal lumen diameter, and lesion length. These standard measurements can also be applied to stents (by adding another “circle” that follows the contour of the stent), enabling one to assess the stent deployment. In 2001, Mintz et al.5 published the ACC consensus document on IVUS. Although this document refers primarily to coronary imaging, the principles outlined and the direct and derived measurements reviewed also pertain to peripheral imaging. Plaque morphology can also be assessed by IVUS. Based on the degree of echogenicity, plaque can be characterized as soft (fatty), hard (fibrous), calcified, or mixed (Figure 21-6).5,7−10 For instance, fatty plaque has a low echogenicity, where calcific plaque has high echogenicity and appears bright. Fibrous plaque has an intermediate echogenicity and mixed plaque contains more than one subtype.5 Intraluminal thrombus and dissection represent two additional tissue characteristics that can be seen by IVUS. Thrombus (Figure 21-7) is visualized as a mass in the lumen that often has a layered appearance. It is relatively echolucent and can occasionally be confused with atheroma or with stasis.5,11 Dissection (Figure 21-8) is visualized as a discontinuity in the luminal wall with blood speckle be-

hind it. Five categories of dissection are intimal, medial or adventitial (depending on the depth to which a dissection penetrates), intramural hematoma, and intrastent.5 When IVUS is utilized to assess stents, standard luminal measurements apply. However, additional information should also be obtained including apposition, expansion, edge disease and, if present, intimal hyperplasia. Apposition (Figure 21-9) refers to whether the stent struts abut the vessel wall, with good stent apposition defined by stent struts in close-enough proximity to the vessel wall such that no flow between the stent strut and the wall occurs.5,12 Expansion (Figure 21-10) refers to the stent minimum CSA compared to that of the reference segment5 with adequate expansion (associated with a low risk of restenosis).13 Stent edge issues include those of edge stenosis or dissection (both placing a particular vessel at higher risk for restenosis. Finally, neointimal hyperplasia (Figure 21-11) refers to the intimal growth within the stent.

•

CLINICAL APPLICATION

IVUS is an imaging tool that is used for diagnosis, to guide intervention, and to assess for interventional success or complications. The following section provides an overview of the clinical applications of IVUS starting with a general clinical discussion and then addressing specific issues within each arterial bed. It is important to note that IVUS provides similar information regardless of the artery visualized. Specifically, IVUS gives the clinician information about

INTRAVASCULAR ULTRASOUND IN PERIPHERAL ARTERIAL DISEASE • 381

A

B

• FIGURE 21-7.

Thrombus. (A) Angiography reveals minimal filling defect (arrow) corresponding to possible plaque or dissection. (B) IVUS confirms thrombus (arrowhead) from 6:00 to 11:00 around the catheter. Clearly visualized underneath thrombus are the intimal, medial, and adventitial layers.

vessel and lumen size, lesion composition, and lesion length, which helps guide the intervention. After the intervention, IVUS can be used to detect poststent complications such as stent underexpansion or malapposition, residual plaque, dissection, thrombus, hematoma, and rupture.

A

• FIGURE 21-8.

Diagnosis As compared to angiography, IVUS provides high resolution, cross-sectional images of both the lumen and plaque. Thus, IVUS can more accurately determine the degree of luminal stenosis and the pattern/composition of the

B

Intimal SFA dissection post-PTCA. (A) Angiographic evidence of dissection (arrow). (B) IVUS confirms medial dissection (red color marks, blood flow within dissection plane).

382 • CHAPTER 21

B

A

• FIGURE 21-9.

Incomplete stent apposition. (A) IVUS image. (B) The yellow-shaded area denotes incomplete stent apposition to the vessel wall.

B

A

• FIGURE 21-10.

Stent underexpansion. (A) Poststenting IVUS run demonstrating asymmetric underexpansion (arrows). (B) After high-pressure postdilation, symmetric/ complete expansion is noted.

INTRAVASCULAR ULTRASOUND IN PERIPHERAL ARTERIAL DISEASE • 383

A

B

• FIGURE 21-11.

Neointimal hyperplasia. (A) IVUS image. (B) The border of the green circle denotes the stent borders, the yellow circle denotes the lumen, and the green area represents neointimal hyperlasia.

stenotic lesion. For instance, a short and focal severe lesion is often readily apparent on angiography but diffuse disease may also be present; this could potentially alter the plan for treatment. Additionally, calcification and ulceration, two lesion characteristics that might require specific attention at the time of treatment, are readily visualized on IVUS imaging but not always apparent by angiography. As an example of the importance of plaque morphology imaging, IVUS can easily determine whether a renal artery stenosis is caused by fibromuscular dysplasia or atherosclerotic disease. The echogenic characteristics of both the intima and the media with fibromuscular dysplasia and the absence of discrete plaque make it easily distinguishable from atherosclerotic disease. The stenosis from fibromuscular dysplasia can be treated with balloon dilation alone, without adjunctive stenting, whereby atherosclerosis may need stenting. Guide to Intervention When planning an interventional strategy, optimal results will more likely be obtained if there is a comprehensive understanding of lesion characteristics (including reference vessel diameter, lesion length, lesion composition, eccentricity, and calcification). Recognition of these characteristics enables the operator to deploy appropriately sized stents and use adjunctive equipment (such as atherectomy devices) when necessary.

While conventional angiography can provide clues to the above factors, IVUS imaging consistently provides this important information in a reliable fashion. With coronary interventions, preintervention IVUS can alter the strategy planned solely on the angiogram by as much as 40%.3 Although not as robust, similar data in the peripheral literature exists for multiple arterial territories.14,15 A representative case example is seen in Figure 21-12. In this case, fluoroscopy and angiography together demonstrate a complex, heavily calcified lesion in the SFA of this 61-year-old patient with known peripheral arterial disease and right lower extremity claudication at rest (Figure 21-12A). IVUS analysis revealed a heavy 270-degree concentric rim of calcium (Figure 21-12B). This lesion was debulked with a 2.5-mm Turbo Laser (Spectranetics, Colorado Springs, CO) revealing angiographic and IVUS results seen in Figure 2112C. Specifically, the rim of calcium has been significantly fragmented thus allowing facilitated stent expansion. Finally, this lesion was stented at high pressure, yielding excellent angiographic and IVUS results as seen in Figure 21-12D. With reference to stent sizing, IVUS can remove the guesswork implicit in choosing a stent based on luminal measurements. General consensus is to employ a stent diameter based on IVUS that corresponds to the larger of the proximal and distal reference lumens. This often leads to a significant upsizing of stents compared to conventional sizing with a goal of achieving a stent lumen of 80% to 90% of the average reference lumen.16 Some experts, however,

384 • CHAPTER 21

A

C

B

D

• FIGURE 21-12.

Complex calcified lesion. (A) Angiography. (B) IVUS demonstrating a complex/severe lesion with a 270-degree rim of calcium. (C) Postlaser IVUS demonstrates that the calcification is more fragmented, permitting (D) full stent expansion.

base a stent size on “media-to-media” measurements, and therefore upsize even further. Optimizing Final Results and Addressing Complications Postintervention IVUS analysis provides an operator with the ability to evaluate procedural adequacy to a greater extent than angiography alone. For instance, thrombus (Figure 21-7) and vessel dissection (Figure 21-8) represent two complications often requiring further intervention that can be subtle on angiography but are obvious on IVUS. Additionally, stent malapposition (Figure 21-9) and underexpansion (Figure 21-10) are readily seen in vessels on which the corresponding angiogram reveals seemingly adequate results. Regarding dissection, not only can IVUS imaging identify angiographically innapparent dissection but can aid in its treatment by allowing appropriate balloon sizing in order to tack down the dissection flap. An example of this is

shown in Figure 21-13. In this case, a 62-year-old man with right lower extremity claudication underwent diagnostic angiography revealing severe disease of the right SFA (Figure 21-13A). Post-PTCA, a large dissection flap was noted on IVUS imaging (Figure 21-13B). IVUS analysis of the proximal reference segment demonstrated a vessel diameter of 6 mm (Figure 21-13C) and with a 6-mm balloon the dissection was subjected to prolonged inflation with excellent angiographic and IVUS results depicted in Figure 21-13D. This case illustrates the utility of IVUS not only for detecting a significant procedural complication, but also its ability to guide appropriate resolution and optimize final results.

•

CONSIDERATIONS IN SPECIFIC ARTERIAL TERRITORIES

Renal Artery (Table 21-5) In 1991, Sheikh et al.17 demonstrated the feasibility of IVUS imaging of the renal arteries, comparing it to contrast

INTRAVASCULAR ULTRASOUND IN PERIPHERAL ARTERIAL DISEASE • 385

A

D

B

C

• FIGURE 21-13.

Angioplasty complicated by dissection. (A) Pre-PTCA angiography on IVUS of a right SFA lesion in a 62-year-old man with right lower extremity claudication at rest. (B) Post-PTCA. A large dissection flap is noted on both angiography and IVUS (arrows). (C) In order to select a balloon with appropriate size to tack down the dissection, IVUS dimensions of the proximal reference vessel are obtained. In this case, the proximal reference diameter is 6 mm. (D) After a 6-mm balloon is inflated for 3 minutes, the proximal lumen cross-sectional area (top) has increased to 15.3 mm and the dissection flap (bottom) has been tacked down.

386 • CHAPTER 21

TABLE 21-5. Summary of Renal Artery IVUS Studies N

Study Shiekh et al.

17

8

Leertouwer et al.19 Dangas et al.15

Purpose

Principal Findings

Diagnostic

Accurate angiographic and IVUS measurements. Postangioplasty dissection apparent on IVUS. Additional treatment necessary in 6/18 patients with postangioplasty IVUS. Not seen on angiography. Angiographic success in 100%. Post-IVUS led to additional dilation in 23.5%.

22

Interventional

131

Interventional

angiography. In this small series, IVUS measurements and digital angiography demonstrated high correlation with regard to lumen diameter (r = 0.81) and cross-sectional area (r = 0.83). Furthermore, by directly imaging all three layers of the arterial wall, IVUS could identify the mechanism of the renal arterial stenosis (RAS) as either fibromuscular dysplasia or atherosclerotic disease (an example of atherosclerosis and fibromuscular dysplasia is shown in Figure 21-14.18 ) Finally, IVUS imaging diagnosed postangioplasty dissection in three patients apparent by angiography in only one of the three.17 As a guide to intervention, Leertouwer et al.19 reported on an initial experience of 22 patients with atherosclerotic RAS. After predilation, IVUS images were obtained in nine patients, resulting in selection of larger balloon sizes in five patients. In 18 patients, IVUS was performed poststenting, and led to additional interventional treatment in six patients (one for incomplete apposition, three for stent underexpansion, and two for distal lesions not seen on angiography). Additionally, vessel injury was noted in five patients (four dissection, one rupture) by IVUS, seen in only two patients by angiography.19 Investigators from the Washington Hospital Center evaluated IVUS-guided renal artery stenting in 131 patients

A

B

with atherosclerotic RAS.15 Interventions were performed on 153 renal artery segments. Angiography and IVUS demonstrated strong correlations between preintervention reference vessel (r = 0.71, p < 0.0001) and lesion minimal lumen diameter (MLD) (r = 0.72, p < 0.0001), lesion length (r = 0.6, p < 0.0001) and postintervention MLD (r = 0.63, p < 0.0001). However, while angiographic success was seen in all patients, IVUS analysis led to additional balloon dilatation in 36 (23.5%) cases. Factors leading to further intervention included incomplete stent apposition or expansion in 22 cases, dissection in 8 cases, and incomplete ostial stent coverage in 6 cases (incomplete ostial stent coverage is difficult to assess by angiography alone and carries a high risk of restenosis). In seven cases, findings on IVUS led to additional stenting.15 Additionally, case reports have demonstrated the utility of IVUS imaging as a guide to treatment of in-stent restenosis. In one case, IVUS evaluation revealed restenosis as a result of significant intimal hyperplasia and facilitated cutting balloon angioplasty of the segment with an excellent angiographic result confirmed by IVUS.20 Another, more recent report, describes IVUS-guided deployment of 3.5 mm coronary paclitaxel-eluting stent to a proximal renal artery demonstrating severe in-stent restenosis with

C

• FIGURE 21-14.

Renal artery stenosis. Atherosclerosis and fibromuscular dysplasia. (A) Normal renal artery. (B) Atherosclerotic aorto-ostial renal artery stenosis characterized by a mildly calcific eccentric plaque. (C) Fibromuscular dysplasia characterized by a fixed, eccentric, and discrete membrane.

Reproduced with permission from Gowda MS, Loeb AL, Crouse LJ, Kramer PH. Complementary roles of color-flow duplex imaging and intravascular ultrasound in the diagnosis of renal artery fibromuscular dysplasia: should renal arteriography serve as the “gold standard”? J Am Coll Cardiol. 2003;41: 1305-1311.

INTRAVASCULAR ULTRASOUND IN PERIPHERAL ARTERIAL DISEASE • 387

excellent immediate and 6-month results confirmed by IVUS.21

Aorta

Because of the risk of embolization, many operators have been somewhat hesitant to perform IVUS within the carotid vasculature. Safety, feasibility, and utility have since been demonstrated in more than 100 patients.22−25 The largest published experience with carotid IVUS imaging was in 98 consecutive patients,26 No complications directly attributable to IVUS occurred in this series. While IVUS demonstrated excellent correlation with QCA of the reference vessels, a significantly smaller minimal lumen diameter was noted by IVUS as compared to angiography. Despite angiographic success in all patients, IVUS imaging identified the necessity for further intervention in 10% of patients. Furthermore, IVUS findings were found to be a predictor of complications; the IVUS-detected degree of superficial calcium was noted to be an independent and significant predictor of CVA at the time of the procedure.26 The same investigators recently reported on in-stent restenosis in carotid stents utilizing IVUS.27 Of the patients included in the initial IVUS—carotid artery stent study,26 50 patients underwent 6-month IVUS follow-up. In those patients, a smaller minimum stent area and stent underexpansion was associated with increased intimal hyperplasia and restenosis. Again, no complications related to IVUS were noted.27

When applied to aortic aneurysms and dissections, IVUS analysis is capable of providing real-time anatomic definition above that of computed tomography (CT) and angiography alone. In 1999, van Essen et al.28 demonstrated consistent agreement between CT and IVUS with regards to both length (r = 0.99, p < 0.001) and diameter (r = 0.93, p < 0.001) measurements of the aneursym and proximal/ distal neck (r = 0.99, p < 0.001) in a series of 16 patients with abdominal aortic aneurysms, although IVUS tended to slightly underestimate these dimensions compared to CT. In a series reported by Garret et al.,14 IVUS altered the procedure in 28% of 78 cases by identifying, when compared to CT, differences in proximal neck diameter and lesion length. Additionally, IVUS analysis allowed endovascular repair in four patients who by CT were thought to have anatomy unsuitable for the procedure. In their series, although a causal relationship cannot be attributed to IVUS alone, there were no type I endovascular leaks at the conclusion of the procedure or at 20-month follow-up.14 Other authors have reported on the usefulness of IVUS to accurately define aneurysm neck anatomy and optimally size aortic stent-grafts at the time of the procedure.29−31 For endovascular treatment of type B aortic dissections, IVUS was useful in identifying true versus false lumen as well as sites of entry and reentry within the dissection.32 As illustrated by Koschyk et al.,33 IVUS imaging can prove vital in excluding dissections that extend into the thorax

A

B

Carotid Artery

• FIGURE 21-15.

Aortic dissection. (A) Side branch seen clearly in the true lumen—in this case, it is the right renal artery (arrow). (B) Entry point between the true and false lumen (arrow).

Reproduced with permission from Koschyk DH, Nienaber CA, Knap M, et al. How to guide stent-graft implantation in type B aortic dissection? Comparison of angiography, transesophageal echocardiography, and intravascular ultrasound. Circulation. 2005;112:I260-1264.

388 • CHAPTER 21

TABLE 21-6. Summary of Iliofemoral IVUS Studies N

Purpose

Findings

44 (109 stents)

Interventional

Buckley et al.38

52 (71 limbs)

Interventional

Gussenhoven et al.40

39

Interventional

Despite angiographic success, 28 lesions underwent further intervention (underexpansion, malapposition, dissection, thrombus, migration). IVUS led to further intervention in 40% of limbs treated. In follow-up 100% of IVUS cases were free of repeat procedure vs. 77% of arteriography alone patients. After balloon angioplasty, decreased free lumen area and increased extent of dissection predicted restenosis.

Study Navarro et al.

37

procedure (postdilation) in 7 patients.33 The authors concluded that IVUS played an essential role in optimizing their results. An illustration of IVUS facilitated identification of entry site and side branches is provided in Figure 21-15.

from the abdomen and correctly identifying all entry sites between the true and false lumen. In this series, IVUS led to significant modification before the procedure in 5 of 25 dissections (4 with thoracic extension and 1 with a second angiographically unapparent entry site) and after the

A

B

E

C

F

• FIGURE 21-16.

D

G

IVUS facilitated subintimal reentry. (A) The IVUS probe is in the subintimal layer with the needle at 12-o’clock position (arrow) and the true lumen, represented in real-time by red color Doppler, from 3- to 8-o’clock position. (B, C, and D) With gradual rotation of the catheter, the true lumen is centered at the 12-o’clock position. (E) Needle puncture into the true lumen. (F and G) Guidewire advancement into the true lumen.

INTRAVASCULAR ULTRASOUND IN PERIPHERAL ARTERIAL DISEASE • 389

• FIGURE 21-17.

Virtual histology. In this example from a superficial femoral artery, spectral analysis enables color-coding of the various components of plaque. Green: fibrous; white: calcified; red: necrotic; yellow: lipid.

Additionally, IVUS has been utilized to help treat post stent-graft intermittent claudication. In this situation, the false lumen essentially supplies a distal arterial bed, and once excluded by the stent graft, these arterial beds receive inadequate blood supply. Cases have been reported in which IVUS-guided fenestrations are placed within the graft to supply the false lumen and distal vessels with adequate blood flow and relief of claudication symptoms.34 Iliofemoral Arteries (Table 21-6) In the mid-1990s, a few series on angioplasty with or without IVUS established the feasibility of IVUS in the iliac and infrailiac vessels. At the time of these studies, however, balloon angioplasty alone was standard. While angiographic vessel measurement correlate quite well with IVUS preintervention, it is well established from both the coronary and peripheral literature that the angiographic evaluation of postangioplasty vessels often overestimates lumen area and correlates poorly with IVUS measurements. Therefore, authors postulated that postangioplasty IVUS might influence one to use a stent in cases of residual stenosis.35 With the move toward routine stenting of iliac arteries, Arko et al.36 demonstrated on prestenting IVUS that angiography alone underestimated vessel diameter in 25 of 40 aortoiliac occlusive lesions. Furthermore, poststenting IVUS revealed underexpansion in 40% of cases, necessitating postdilation.36 Navarro et al.37 reported on 44 patients undergoing IVUS-guided implantation of 109 stents. Despite angiographic success in all cases, 29 (27%) of these stents were found on postprocedural IVUS to be subop-

timally deployed (20 underexpanded stents, 3 malapposed stents, 4 arterial dissections, 1 thombosis, and 1 stent migration). Twenty-eight of these patients underwent modification with either further balloon dilation or repeat stenting. Successful angiographic and IVUS results were noted in 26 patients.37 In 2002, Buckley et al.38 first reported a favorable effect on outcomes with IVUS in their study of 22 limbs treated with arteriography alone and 49 limbs treated with adjunctive IVUS. These investigators noted that despite angiographic success and a similar improvement in anklebrachial indices, 40% of patients in the IVUS group underwent further balloon dilation because of stent malapposition. More importantly, in the angiography only group, early restenosis or occlusion occurred in four (18%) patients, all of whom at follow-up examination were documented by IVUS to have underexpanded stents. Secondary procedures were performed in none of the patients who underwent IVUS and 23% of those undergoing angiography alone ( p < 0.05).38 In 1992, The et al.39 investigated IVUS in SFA angioplasty, describing the mechanism of angioplasty (stretching) and commenting that overstretching was associated with dissection. Three years later, the EPISODE investigators reported on 39 patients undergoing IVUS-guided SFA angioplasty. They noted that while no characteristics on predilation IVUS appeared to influence 6-month outcomes, free lumen area and extent of dissection seen on IVUS significantly predicted 6-month failure.40 In SFA and popliteal arteries, IVUS has the same utility to guide interventional procedures as it does in the carotid, renal, and iliac arteries.

390 • CHAPTER 21

A particularly interesting niche for IVUS in the iliac and femoral arteries pertains to the treatment of chronic total occlusion (CTO). Subintimal canalization is quite common while crossing a CTO, and when true-lumen reentry beyond the occlusion proves difficult, a number of reentry devices incorporating IVUS can aid in identification and reentry of the true lumen. In 2004, Casserly et al.41 reported on two cases in which the CrossPoint TransAccess catheter (now called Pioneer, Medtronic Inc, Minneapolis, MN) was used to facilitate true lumen reentry and successfully revascularize the SFA. Investigators from St. Louis University recently reported on 87 chronic total occlusions and 24 in which the true lumen could not be re-entered with standard techniques (20 iliac, 4 femoral). In 21 of these cases, the Pioneer catheter was used to facilitate true-lumen reentry with technical success in all cases and continued patency at a mean of 5.8-month follow-up.42 IVUS-guided true lumen reentry represents an important modality in treating

iliac and femoral CTO. An example of this technique is depicted in Figure 21-16.

•

SUMMARY

IVUS is a unique, real-time, cross-sectional imaging modality that provides a view of the artery unlike any other conventional imaging technique. Because of its ability to visualize the lumen, plaque, and arterial structures, it can assist peripheral artery diagnostic dilemmas and guide interventions to optimize results. Furthermore, IVUS can play an important role as a predictor, early identifier, and guide treatment for peripheral vascular interventional complications. In the future, enhanced software reconstruction including, for example, Virtual Histology (utilizing spectral analysis based on ultrasound to determine plaque composition, Figure 21-17)43 may further enable tissue characterization and provide important guidance in both diagnostic and therapeutic arenas.

REFERENCES 1. Bom N, Lancee CT, Van Egmond FC. An ultrasound intracardiac scanner. Ultrasonics. 1972;10:72–76. 2. Di Mario C, Gorge G, Peters R, et al. Clinical application and image interpretation in intracoronary ultrasound. Study Group on Intracoronary Imaging of the Working Group of Coronary Circulation and of the Subgroup on Intravascular Ultrasound of the Working Group of Echocardiography of the European Society of Cardiology. Eur Heart J. 1998;19:207– 229.

10. Nishimura RA, Edwards WD, Warnes CA, et al. Intravascular ultrasound imaging: in vitro validation and pathologic correlation. J Am Coll Cardiol. 1990;16:145–154. 11. Siegel RJ, Ariani M, Fishbein MC, et al. Histopathologic validation of angioscopy and intravascular ultrasound. Circulation. 1991;84:109–117. 12. Nakamura S, Colombo A, Gaglione A, et al. Intracoronary ultrasound observations during stent implantation. Circulation. 1994;89:2026–2034.

3. Mintz GS, Pichard AD, Kovach JA, et al. Impact of preintervention intravascular ultrasound imaging on transcatheter treatment strategies in coronary artery disease. Am J Cardiol. 1994;73:423–430.

13. Moussa I, Moses J, Di Mario C, et al. Does the specific intravascular ultrasound criterion used to optimize stent expansion have an impact on the probability of stent restenosis? Am J Cardiol. 1999;83:1012–1017.

4. Yock PG, Fitzgerald PJ, Honda Y. Intravascular ultrasound. In: Topol EJ, ed. Interventional Cardiology. Philadelphia, PA: WB Saunders; 1999:801–818.

14. Garret HE Jr, Abdullah AH, Hodgkiss TD, Burgar SR. Intravascular ultrasound aids in the performance of endovascular repair of abdominal aortic aneurysm. J Vasc Surg. 2003;37:615–618.

5. Mintz GS, Nissen SE, Anderson WD, et al. American college of cardiology clinical expert consensus document on standards for acquisition, Measurement and Reporting of Intravascular Ultrasound Studies (IVUS). A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2001;37:1478–1492. 6. ten Hoff H, Korbijn A, Smith TH, Klinkhamer JF, Bom N. Imaging artifacts in mechanically driven ultrasound catheters. Int J Card Imaging. 1989;4:195–199. 7. Hodgson JM, Reddy KG, Suneja R, Nair RN, Lesnefsky EJ, Sheehan HM. Intracoronary ultrasound imaging: correlation of plaque morphology with angiography, clinical syndrome and procedural results in patients undergoing coronary angioplasty. J Am Coll Cardiol. 1993;21:35–44. 8. Metz JA, Yock PG, Fitzgerald PJ. Intravascular ultrasound: basic interpretation. Cardiol Clin. 1997;15:1–15. 9. Mintz GS, Douek P, Pichard AD, et al. Target lesion calcification in coronary artery disease: an intravascular ultrasound study. J Am Coll Cardiol. 1992;20:1149–1155.

15. Dangas G, Laird JR Jr, Mehran R, Lansky AJ, Mintz GS, Leon MB. Intravascular ultrasound-guided renal artery stenting. J Endovasc Ther. 2001;8:238–247. 16. Nissen SE, Yock P. Intravascular ultrasound: novel pathophysiological insights and current clinical applications. Circulation. 2001;103:604–616. 17. Sheikh KH, Davidson CJ, Newman GE, Kisslo KB, Schwab SJ. Intravascular ultrasound assessment of the renal artery. Ann Intern Med. 1991;115:22–25. 18. Gowda MS, Loeb AL, Crouse LJ, Kramer PH. Complementary roles of color-flow duplex imaging and intravascular ultrasound in the diagnosis of renal artery fibromuscular dysplasia: should renal arteriography serve as the “gold standard”? J Am Coll Cardiol. 2003;41:1305–1311. 19. Leertouwer TC, Gussenhoven EJ, van Overhagen H, Man in ‘t Veld AJ, van Jaarsveld BC. Stent placement for treatment of renal artery stenosis guided by intravascular ultrasound. J Vasc Interv Radiol. 1998;9:945–952.

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20. Otah KE, Alhaddad IA. Intravascular ultrasound-guided cutting balloon angioplasty for renal artery stent restenosis. Clin Cardiol. 2004;27:581–583. 21. Kakkar AK, Fischi M, Narins CR. Drug-eluting stent implantation for treatment of recurrent renal artery in-stent restenosis. Catheter Cardiovasc Interv. 2006;68:118–122. 22. Reid DB, Diethrich EB, Marx P, Wrasper R. Intravascular ultrasound assessment in carotid interventions. J Endovasc Surg. 1996;3:203–210. 23. Wilson EP, White RA, Kopchok GE. Utility of intravascular ultrasound in carotid stenting. J Endovasc Surg. 1996;3:63–68. 24. Weissman NJ, Canos M, Mintz GS, et al. Carotid artery intravascular ultrasound: safety and morphologic observations during carotid stenting in 102 patients [abstract]. J Am Coll Cardiol. 2000;35(suppl A):10A. 25. Weissman NJ, Mintz GS, Dangas G, et al. Intravascular ultrasound lesion calcium predicts adverse clinical events after carotid artery stenting. J Am Coll Cardiol. 2000;35(suppl A):7A. 26. Clark DJ, Lessio S, O’Donoghue M, Schainfeld R, Rosenfield K. Safety and utility of intravascular ultrasound-guided carotid artery stenting. Catheter Cardiovasc Interv. 2004;63:355– 362. 27. Clark DJ, Lessio S, O’Donoghue M, Tsalamandris C, Schainfeld R, Rosenfield K. Mechanisms and predictors of carotid artery stent restenosis: a serial intravascular ultrasound study. J Am Coll Cardiol. 2006;47:2390–2396.

ison of angiography, transesophageal echocardiography, and intravascular ultrasound. Circulation. 2005;112:I260–1264. 33. Koschyk DH, Meinertz T, Hofmann T, et al. Value of intravascular ultrasound for endovascular stent-graft placement in aortic dissection and aneurysm. J Card Surg. 2003;18:471–477. 34. Husmann MJ, Kickuth R, Ludwig K, et al. Intravascular ultrasound-guided creation of re-entry sites to improve intermittent claudication in patients with aortic dissection. J Endovasc Ther. 2006;13:424–428. 35. Vogt KJ, Rasmussen JG, Just S, Schroeder TV. Effect and outcome of balloon angioplasty and stenting of the iliac arteries evaluated by intravascular ultrasound. Eur J Vasc Endovasc Surg. 1999;17:47–55. 36. Arko F, McCollough R, Manning L, Buckley C. Use of intravascular ultrasound in the endovascular management of atherosclerotic aortoiliac occlusive disease. Am J Surg. 1996;172:546–549. 37. Navarro F, Sullivan TM, Bacharach JM. Intravascular ultrasound assessment of iliac stent procedures. J Endovasc Ther. 2000;7:315–319. 38. Buckley CJ, Arko FR, Lee S, et al. Intravascular ultrasound scanning improves long-term patency of iliac lesions treated with balloon angioplasty and primary stenting. J Vasc Surg. 2002;35:316–323. 39. The SH, Gussenhoven EJ, Zhong Y, et al. Effect of balloon angioplasty on femoral artery evaluated with intravascular ultrasound imaging. Circulation. 1992;86:483–493.

28. van Essen JA, Gussenhoven EJ, van der Lugt A, et al. Accurate assessment of abdominal aortic aneurysm with intravascular ultrasound scanning: validation with computed tomographic angiography. J Vasc Surg. 1999;29:631–638.

40. Gussenhoven EJ, van der Lugt A, Pasterkamp G, et al. Intravascular ultrasound predictors of outcome after peripheral balloon angioplasty. Eur J Vasc Endovasc Surg. 1995;10:279– 288.

29. van Essen JA, Gussenhoven EJ, Blankensteijn JD, et al. Threedimensional intravascular ultrasound assessment of abdominal aortic aneurysm necks. J Endovasc Ther. 2000;7:380–388.

41. Casserly IP, Sachar R, Bajzer C, Yadav JS. Utility of IVUSguided transaccess catheter in the treatment of long chronic total occlusion of the superficial femoral artery. Catheter Cardiovasc Interv. 2004;62:237–243.

30. Tutein Nolthenius RP, van den Berg JC, Moll FL. The value of intraoperative intravascular ultrasound for determining stent graft size (excluding abdominal aortic aneurysm) with a modular system. Ann Vasc Surg. 2000;14:311–317. 31. Slovut DP, Ofstein LC, Bacharach JM. Endoluminal AAA repair using intravascular ultrasound for graft planning and deployment: a 2-year community-based experience. J Endovasc Ther. 2003;10:463–475. 32. Koschyk DH, Nienaber CA, Knap M, et al. How to guide stent-graft implantation in type B aortic dissection? Compar-

42. Jacobs DL, Motaganahalli RL, Cox DE, Wittgen CM, Peterson GJ. True lumen re-entry devices facilitate subintimal angioplasty and stenting of total chronic occlusions: initial report. J Vasc Surg. 2006;43:1291–1296. 43. Vince DG, Nair A, Klingensmith JD, Kuban BD, Margolis MP, Burgess V. Radiofrequency-tissue characterization and virtual histology. In: Waksman R, Serruys PW, eds. Handbook of the Vulnerable Plaque. London, UK: Taylor and Francis; 2004:327–342.

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22

Arterial Diseases of the Eye Robert J. Barnes, MD

The eye is proverbially the window to the soul, and literally a window into the vascular system. Evaluation of the retinal vasculature gives insight into multiple systemic diseases affecting the patient. Simply by evaluating the retina, one can determine diseases such as severe hypertension, diabetes mellitus, embolic disease, lupus, infection, and extended abdominal trauma.

•

REVIEW OF OPHTHALMIC BLOOD SUPPLY

The eye is fed by the first branch of the internal carotid artery. This ophthalmic artery then branches off into the central retinal artery, the posterior ciliary arteries, and the muscular branches. The venous system is comprised of the posterior vortex veins, which drain into the superior and inferior orbital veins which then drain into the cavernous sinus; and the central retinal vein, which drains the retina and the optic nerve directly into the cavernous sinus.1

•

HYPERTENSIVE RETINOPATHY

Systemic hypertension is diagnosed when the blood pressure is greater than 140 systolic and 90 diastolic measured on three separate occasions separated by at least 2 weeks. High blood pressure is extremely common to the industrialized countries. The ocular signs in hypertension are directly related to the rate and degree of systemic blood pressure. Atherosclerosis is a common finding in systemic hypertension. It can also occur in the normal aging population. The retinal changes seen in hypertension may overlap with those found in other retinal vascular diseases such as diabetes (Figure 22-1).2 Systemic hypertension is one of the most common diseases affecting patients throughout the world. The most common ocular manifestations include focal constriction and dilation of retinal arteries, narrowing and irregularity of the retinal arteries, AV nicking, blot retinal hemorrhages,

microaneurysms, and cotton-wool spots. Several classification schemes have been used to stage hypertensive retinal changes. The most commonly accepted are the KeithWagener-Barker classification (Table 22-1) and the Scheie classification (Table 22-2). With these classification systems, one is able to evaluate the degree of hypertension systemically and begin therapy. The treatment of hypertensive retinopathy consists of blood pressure control. No specific ocular therapy exists to reverse the changes. In case of accelerated hypertension or malignant hypertension, systemic diseases must be ruled out such as renal disease, polycystic kidney, renal stenosis, pheochromocytoma, and pregnancy.4

•

RETINAL ARTERY OBSTRUCTION

Retinal artery obstructions are divided into two main types: central and branch, depending on the location of the obstruction. Central retinal artery occlusion is an acute stoppage of blood flow through the central retinal artery, leading to ischemia and nonperfusion of the retina. This is an abrupt, painless, severe loss of vision heralded by a cherryred spot in the macula area. The peripheral retina becomes ischemic and white. The macula remains red secondary to choroidal blood flow. This is commonly referred to as an amaurosis fugax and is a term used to describe the situation with a painless loss of vision occurring. Emboli are seen only approximately 25% of the time. It is an indicator of carotid vascular disease approximately one-third of the time as opposed to giant cell arteritis, which is only found 5% of the time. Branch retinal artery occlusions have a similar presentation commonly associated with carotid vascular disease, cardiac valvular disease, or systemic clotting (Figure 22-3).5 Central retinal artery obstruction is rare. It is estimated to be seen in one patient out of 10 000 who visits to an ophthalmologist. Men are more common than women at a

394 • CHAPTER 22

TABLE 22-2. Scheie Classification Grade 0 Grade 1 Grade 2 Grade 3 Grade 4

• FIGURE 22-1.

Hypertensive retinopathy.

ratio of 2:1 with the onset being around 60 years of age. The majority of central retinal artery obstructions are caused by thrombus formation just proximal to the lamina cribrosa and are therefore not seen on ophthalmic examination. Atherosclerosis is the cause in most cases, although congenital anomalies of the central retinal artery, systemic coagulopathies, or low blood flow states may also be seen. In only 25% of the cases, an emboli is visible in the central retinal artery or one of its branches, suggesting that an embolic cause is not very common. Other diseases besides emboli that can lead to central retinal or branch retinal artery occlusion include shingles, optic neuritis, or mucormycosis. Systemic coagulopathies may be associated with both central and branch retinal artery obstructions. Other causes of obstructive retinopathy include radiation retinopathy, emboli associated with depot medication, injections such as steroids around the eye, and IV drug use.6 The hallmark of ocular manifestation of acute central retinal artery obstruction is an abrupt, painless loss of vision. Pain is unusual and if found is associated with ocular ischemic syndrome. Amaurosis fugax is seen in approximately 10% of the patients. In rare situations, a patient may have a patent cilioretinal artery which perfuses the fovea and the patient may

No changes. Barely detectable arterial narrowing. Obvious arterial narrowing with focal irregularities. Retinal hemorrhages exudates. Same as group 3 plus papilledema3 (Figure 22-2).

have normal central vision. The ophthalmic manifestation on clinical examination, the hallmark is a cherry-red spot of the macula, will not be seen in a patient with a ciliary retinal artery. When a central retinal branch artery occlusion is found, systemic disease associated includes 60% of the time systemic hypertension, 25% of the time diabetes, and 50% of the cases have no definitive cause for the obstruction. Potential embolic sources are found less than 40% of the time in any type of arterial occlusion. The most common association is significant ipsilateral carotid artery disease, which is present in approximately one-third of the patients. An embolic source from the heart is present in less than 10% of the cases. Other rare systemic diseases include blood-clotting abnormalities such as antiphospholipid antibodies, protein S deficiency, protein C deficiency, and antithrombin III deficiency.7 Common systemic conditions associated with central retinal artery obstruction include atherosclerotic cardiovascular disease such as carotid plaques or dissection, aortic plaques or dissection, cardiac disease such as valvular rheumatic fever, VSD (ventriculoseptal defects), cardiac myxoma, mural thrombus, and subacute bacterial endocarditis. Cancers including metastatic tumors, leukemia, and lymphoma have also been associated with vascular obstructive diseases.

TABLE 22-1. Keith-Wagener-Barker Classification Group 1 Group 2 Group 3

Group 4

Moderate narrowing or sclerosis of the artery. Marked narrowing of the artery, exaggeration of the light reflex, and AV nicking. Arterial narrowing and focal constriction, retinal edema, cotton-wool spots, and hemorrhages. Same as group 3 plus papilledema.

• FIGURE 22-2.

Papilledema.

ARTERIAL DISEASES OF THE EYE • 395

cal findings include retinal hemorrhaging; dilated, tortuous veins in affected quadrants; disk edema; macular edema; and cotton-wool spots. Central retinal vein occlusions can be broken down into nonischemic versus ischemic. Both involve hemorrhages throughout the retina in all four quadrants. However, with the ischemic version, approximately two-thirds of the patients go on to develop anterior segment neovascularization usually within 3 months, which then leads to neovascular glaucoma. Workup for venous occlusions would include a complete eye examination, blood pressure, complete blood count, partial thromboplastin time, antinuclear antibody, protein electrophoresis, and sedimentation rate.10 Patients with branch retinal vein occlusions have a similar prognostic fate and require a similar workup.

• FIGURE 22-3.

• Macular degeneration.

Medical procedures such as angiography, angioplasty, chiropractic neck manipulation, and cortical steroid injections around the eye have also been found to lead to vascular obstructive diseases. Systemic vasculitides such as temporal arteritis, Wegener’s granulomatosis, inflammatory bowel disease, Kawasaki syndrome, systemic lupus, and polyarteritis nodosa have also been associated with retinal artery obstruction. Systemic infections such as syphilis—the great masquerader—have also been found associated with this syndrome. Miscellaneous other diseases leading to vascular obstruction include amniotic fluid emboli, IV drug use, cocaine abuse, oral contraception, pregnancy, and migraines.

•

VENOUS OBSTRUCTION OF THE RETINA

Venous obstruction of the retina is a relatively common finding second only to diabetes, more commonly affecting patients 50 years of age or older. Retinal vein obstructions are classified as whether they are central or branch. Although classified commonly together, they have significant differences leading to various outcomes for the eye. Specifically, ischemic venous obstructive diseases can lead to neovascular glaucoma of the eye and eventual blindness.8 Central retinal vein occlusion is 90% of the time in patients 50 years of age or older, more common in men than women. It is often associated with diabetes, hypertension, and atherosclerotic disease. Sedimentation rate elevation appears to be a risk factor in women only. Open-angle glaucoma is a relatively common finding in patients who have had a central retinal vein occlusion. Patients with a history of glaucoma are five times more likely to have a central retinal vein occlusion than those who do not. An acute angle-closure glaucoma may precipitate a central retinal vein occlusion.9 The exact pathogenesis of a central retinal vein occlusion seems to involve a thrombus at the central retinal vein near the lamina cribrosa, and why this occurs is unknown. Clini-

DIABETIC RETINOPATHY

Diabetes mellitus is another very common disease affecting our patients today, and the best predictor of diabetic retinopathy is the duration of the disease. Patients who have had insulin-dependent diabetes for less than 5 years rarely show signs of diabetic retinopathy; however, of those who have had the disease from 5 to 10 years, approximately one-third will go on and develop retinopathy, and those of who have had diabetes for longer than 10 years, 70% to 90% will develop diabetic retinopathy. After 20 to 30 years, the incidence of diabetic retinopathy rises to 95%. Key features include microaneurysms, retinal hemorrhages, cotton-wool spots, lipid exudates, retinal edema, and retinal neovascularization. Diabetes mellitus is the leading cause of blindness in the western world and in the United States specifically.11 Diabetic retinopathy is divided into two main categories: nonproliferative phase and proliferative phase. The nonproliferative phase involves microaneurysm as the first detectable change. Macular edema and retinal thickening is commonly seen where capillaries leak fluid and blood, and lipid is deposited and is a leading cause of permanent blindness (Figure 22-4). Proliferative diabetic retinopathy involves neovascularization of the retinal vessels which leads to increased leakage, lipid formation, and nonperfusion and eventual ischemia, which then leads to neovascularization. The ischemia associated with diabetic retinopathy leads to nonperfusion of the retina and eventual loss of function and blindness (Figure 22-5). Cotton-wool spots often referred to as soft exudates of the nerve fiber layer are white, fluffy lesions of the nerve fiber layer caused by ischemia. Diagnosis of nonperfusion and diabetic retinopathy involve fluorescein angiography. Fluorescein angiography will demonstrate areas of nonperfusion and areas of neovascularization requiring laser photocoagulation. The Early Treatment Diabetic Retinopathy Study (ETDRS) found that intraretinal microvascular abnormalities, multiple retinal hemorrhages, venous beading, and loops seen on angiography are all significant risk factors for the development of proliferative retinopathy

396 • CHAPTER 22

• FIGURE 22-4.

Background diabetic retinopathy.

(Figure 22-6). Treatment for severe diabetic retinopathy is panretinal photocoagulation (PRP). The Diabetic Retinopathy Study demonstrated that patients with highrisk eyes for developing diabetic retinopathy have a significant improvement with treatment with PRP. The exact mechanism by which PRP works remains unknown; however, the theory most advocate is that laser burns reduce the ischemic stimulation of the retina and release of vasoactive proteins. Focal laser also will seal off any leaky blood vessels, reducing lipid formation and hemorrhaging.12 The goal of panretinal photocoagulation is to cause regression of neovascularization in those patients having advanced proliferative phase (Figure 22-7). The ETDRS found that PRPs significantly retarded the development of neovascularization and reduce the amount of macular edema. Another therapy that has previously been used was peripheral retinal cryotherapy that, again, causes a focal scar

• FIGURE 22-5.

Central retinal vein occlusion.

• FIGURE 22-6.

Macular edema (fluorescein

angiography).

formation of the peripheral retina and therefore less oxygen demand and ischemic release of vasoproliferative substances. The final prognosis for most diabetic retinopathy is still poor despite the early treatment options that have been discovered by large studies. However, based on the Diabetic Retinopathy Study and the ETDRS, severe visual loss can be reduced by 95% by aggressive early intervention.13

•

PROLIFERATIVE RETINOPATHIES

Proliferative retinopathies are a group of diseases associated with preretinal or optic nerve neovascularization. This group can be divided into two categories: one with associated systemic disease and the other associated with retinal or ocular disease. Those associated with systemic disease include diabetes, as previously discussed, hyperviscosity syndrome; aortic arch syndrome; carotid cavernous

• FIGURE 22-7.

Diabetic retinopathy.

ARTERIAL DISEASES OF THE EYE • 397

fistula; multiple sclerosis; lupus; sickle cell disease; and sarcoidosis. Diseases with proliferative retinopathy associated with strong hereditary components include sickling hemoglobinopathies such as SC disease, SS disease, and thalassemia. Those diseases associated purely with a retinal vascular or ocular inflammatory disease include Eales’ disease, branch retinal vein occlusion, branch retinal artery occlusion, retinal emboli, retinopathy of prematurity (ROP), acute retinal necrosis, cocaine use, and choroidal melanoma. The number one cause of retinal neovascularization is diabetes mellitus, which has been discussed earlier. Hemoglobinopathies, SS disease, and SC disease are commonly associated with retinal neovascularization. Other diseases that are more uncommon include aortic arch syndrome. Patients with atherosclerosis involving the carotid artery or the aortic arch and patients with arteritis such as Takayasu’s disease or syphilitic aortic involvement may go on and develop peripheral retinal neovascularization. Carotid cavernous fistulas where arterial blood enters the cavernous sinus venous system directly, bypassing the eye, and the consequential ischemia may stimulate retinal neovascularization. Multiple sclerosis has also been shown to develop peripheral venous sheathing and ischemia and may lead to neovascularization. Systemic lupus has also been associated with peripheral retinal neovascularization as well as sarcoidosis.14 Eales’ disease is a bilateral disorder of young men, usually from India. They develop a peripheral retinal phlebitis and retinal nonperfusion. The etiology is unknown; however, frequently neovascularization of the retina is seen. The prognosis is good for this disease, but sometimes retinal photocoagulation is necessary.

•

CHOROIDAL NEOVASCULAR DISEASES

Up to this point, most of the diseases that have been discussed involve retinal vasculature, but as stated earlier, the eye is fed by two branches of the ophthalmic artery, the central retinal artery and the choroidal vasculature. Most of the diseases that have been discussed so far involve the retinal vasculature. At this time, we will discuss abnormalities with the choroidal vasculature. The choroid is a network of blood vessels underlying the retina that supply the outer half of the retinal architecture. The most common disease affecting the choroidal vasculature is macular degeneration or appropriately named agerelated macular degeneration (ARMD). ARMD is the most frequent cause of central vision loss among people aged 50 or older. The majority of the eyes that suffer vision loss are based on the damage from choroidal neovascularization. Choroidal neovascularization is the formation of new blood vessels in the choriocapillaris that erode into the retina, leading to hemorrhagic detachment of the retina, fibrosis, and vision loss. There are other diseases that affect the choriocapillaris and lead to choroidal neovascularizations, which will be discussed further on. ARMD affects severe vision loss on average aproximately

75 years of age. No significant difference is noted between sexes. Drusen or yellow deposits in the retina, which are focal excrescences of Bruch’s membrane, are precursors to ARMD. ARMD is usually divided into non-neovascular or neovascular components. Non-neovascular macular degeneration is the most common form of this disease. It is often called the dry form of macular degeneration. The neovascular form is the growth of choroidal neovascular membranes with presentation of subretinal fluid, macular edema, and diskiform scar. This is frequently called the wet form of macular degeneration.15 Current treatment options for macular degeneration dry form involve vitamin therapy. The wet form at this point has had more significant new advances that are available. Previously, treatment has had more success with laser treatment. Currently, more successful treatment has been with antivascular endothelial growth factor (anti-VEGF) type drugs that are injected directly into the inside of the eye, which have shown vast improvements in the therapeutic options causing shrinkage of the neovascular membrane. Other diseases causing choroidal neovascularization besides ARMD include angioid streaks, Best’s disease, multifocal choroiditis, histoplasmosis, sarcoidosis, and toxoplasmosis (Figure 22-8). Options for treatment for all of these forms of choroidal neovascularization have been improved with the injection of anti-VEGF drugs. Current treatment options for the wet form of macular degeneration involve multiple injections intraocularly of anti-VEGF drugs more than a 2-year period. This reduces the amount of damage from the choroidal neovascularization but does not stop the disease from progressing. Visual prognosis is poor for patients developing choroidal neovascularization. Additional diseases leading to choroidal neovascularization include inflammatory infectious conditions such as histoplasmosis, toxoplasmosis, sarcoidosis, tuberculosis, syphilis, rubella, Candida endophthalmitis, toxocariasis,

• FIGURE 22-8.

Central retinal artery occlusion.

398 • CHAPTER 22

and pseudotumor cerebri. Tumors such as malignant melanoma, metastatic tumor, and choroidal hemangiomas can lead to choroidal neovascularizations. Trauma from choroidal rupture, laser photocoagulation, or surgical trauma can also lead to choroidal neovascularization.

•

RETINOPATHY OF PREMATURITY

Another vascular disease of the eye is seen in premature infants. ROP is a form of a proliferative retinopathy found in premature, low-birth-weight infants featuring abnormal proliferation of developing retinal blood vessels at the junction of vascularized and avascularized areas of the retina. First described in the 1940s was the association between retinopathy in prematurity and oxygen supplementation. ROP is a severe cause of visual loss in infants leading to severe visual impairment. ROP is a proliferative retinopathy that has a paradoxical relationship to oxygen levels. New vessel growth is induced initially by an ischemic avascular retina, but then as an infant of low birth weight receives supplemental oxygen therapy, there is a spurt of neovascularization that occurs, leading to extraretinal proliferation of blood vessels, macular dragging, tractional retinal detachment, retrolental fibroplasia, and glaucoma. The risk and severity of ROP are inversely proportional to birth weight, age, and oxygen use.16 The ocular manifestations of ROP include a classification system developed recently with stage I involving a thin, flat demarcation line between the vascular and avascular retina, stage II a ridge forming along the demarcation line that is elevated and thickened, stage III extraretinal fibrovascular proliferation along this ridge, and stage IV a fibrovascular mass formation and tractional retinal detachment.17 The differential diagnosis of ROP includes retinal blastoma, X-linked retinoschisis, Toxocara, toxocariasis, and Norrie’s disease. Treatment for ROP involves cryotherapy, photocoagulation, and surgical repair of retinal detachments (Figure 22-9).

•

These are unique aneurysms developing in the retinal blood vessels. They are usually localized saccular dilatations of the retinal arterial vessels within the first three branches of the central retinal artery, retinal hemorrhages, protein and lipid exudates, and macular edema. Retinal arterial macroaneurysms tend to occur in older patients, usually older than 60 years, and are commonly associated with hypertension. They may present as a hemorrhage in the vitreous or retina or as an exudative type picture.18 Retinal telangiectasias and a disease named Coats’ disease are a unique group of diseases that are usually unilateral, more common in young men, and present with a white pupil. This is a congenital type anomaly that consists of abnormal telangiectatic segments of the arterial system of the eye. One would see lipid exudates and subretinal fluid. Coats’ disease is a unique condition, and another subset of this is Leber’s miliary aneurysm, which is a localized, less severe form of Coats’ disease. This usually presents between the ages of 8 to 16 years. This is usually a diagnosis of exclusion after other vascular diseases are ruled out. The differential diagnosis would include retinoblastoma, ROP, retinal detachment, persistent hyperplasia of primary vitreous, cataract, toxocariasis, and Norrie’s disease.

•

Toxoplasmosis.

RADIATION RETINOPATHY AND VASCULAR DISORDERS

Radiation treatment to the eye for such diseases as ocular melanoma, retinoblastoma, or metastatic disease can lead to a progressive retinal vasculopathy. This would include retinal hemorrhaging, microaneurysms, exudates, cottonwool spots, and optic nerve swelling. A general rule in patients who receive radiation doses of less than 2500 rads, or 25 Gy, in fractions of 200 rads or less at a time are likely to go on to develop significant retinopathy. Patients who are receiving radiation therapy and develop these retinal vascular disorders must also be ruled out for other diseases such as diabetic disease or vein occlusions.19 In summary, the eye affords us an opportunity to evaluate a patient’s retinal vasculature and gives us great insight into its systemic system. A review of this chapter gives a brief description of a multitude of disease entities that affect a patient’s systemic vascular system that can be easily evaluated and diagnosed by looking at the retinal vasculature.

•

• FIGURE 22-9.

RETINAL ARTERIAL MACROANEURYSMS

ANTERIOR ISCHEMIC OPTIC NEUROPATHY

Anterior ischemic optic neuropathy is a presentation of a group of diseases with a rapid onset of painless unilateral vision loss. Frequently a visual field defect in an altitudinal picture is seen. The optic nerve can be swollen and then go on to develop pallor. In approximately 5% of the cases, an anterior ischemic optic neuropathy may be caused by temporal arteritis. Patients who have temporal arteritis usually

ARTERIAL DISEASES OF THE EYE • 399

have other symptoms associated with it including headache, jaw claudication, and temporal artery tenderness. Patients can also be seen with weight loss, fever, joint pain, and myalgia. Typically the patients, more commonly women, are older than 70 years. Measuring of the erythrocyte sedimentation rate is standard. Usually the sedimentation rate is more than 70 to 120 mm/h. Once an elevated sedimentation rate is discovered, prompt corticosteroid therapy and a confirmatory temporal artery biopsy are necessary. The unfortunate aspect to this disease is that one can have a normal sedimentation rate in an estimated 16% of biopsyproven cases. One can also find elevated sedimentation rates with increasing age and other diseases such as malignancy or inflammatory disease and diabetes and not have temporal arteritis. Therefore, levels of plasma, fibrinogen, and C-reactive protein may aid in differentiation, as they tend to parallel the sedimentation rate only in vasculitis. Biopsies are frequently negative and therefore a minimum of 10 mm of artery must be analyzed, and sometimes, bilateral biopsies are recommended. Also, a negative biopsy does not necessarily rule out arteritis since there are frequently skipped lesions found and therefore an astute pathologist must be looking for these lesions through the complete submitted section.20

•

TRAUMA AND THE EYE

Patients suffering trauma to the head with intracranial bleeding can develop frequently intraocular hemorrhaging. Vitreous hemorrhages can occur in approximately 3% to 5% of patients with intracranial bleeding. Subarachnoid bleeding from a cerebral aneurysm in particular is the most common underlying cause. Terson’s syndrome is an intraocular hemorrhage associated with an acute intracranial bleed. It is bilateral with multiple posterior segment hemorrhages with retinal, intraretinal, and intravitreal locations. This is a term that was coined by Dr. Terson after seeing a patient with subarachnoid hemorrhage developing a vitreous hemorrhage (Figure 22-10).2

• FIGURE 22-10.

Traumatic cataract/implant.

Purtscher’s retinopathy is a retinal infarction with cotton-wool spot associated with severe trauma or other conditions. This is bilaterally seen and has associated retinal hemorrhaging and cotton-wool spots. It can be seen in head trauma, chest trauma, or long-bone injury. It can be seen as an amniotic fluid embolism or pancreatitis.21

•

SHAKEN BABY SYNDROME

Unfortunately, we have seen a rise of child abuse in our society and throughout the world and therefore have been able to diagnose easily from an ocular examination cases of shaken baby syndrome. In this situation, one would see intraocular hemorrhages that can be bilateral or monocular with retinal or vitreous hemorrhage without any associated direct eye trauma. This occurs when a child has whiplashlike abuse. Frequently also associated is intracranial hemorrhaging, usually a subdural, cerebral edema, and other sites of trauma.22

REFERENCES 1. Harris A, Kagemann L. Assessment of human ocular hemodynamics. Surv Ophthalmol. 1998;42(6):509-533.

7. Hayreh SS. Classification of central retinal vein occlusion. Ophthalmology. 1983;90:458-474.

2. Flammer J, Pache M. Vasospasm in the role of pathogenesis to the eye. Prog Retin Eye Res. 2001;20(3):319-349.

8. Recchia FM. Systemic disorders associated with retinal vascular occlusion. Curr Opin Ophthalmol. 2000;11(6):462-467.

3. Scheie HG. Evaluation of ophthalmic changes and hypertension. Arch Ophthalmol. 1953;49:117-138.

9. Sharma S. Systemic evaluation of acute retinal artery occlusion. Curr Opin Ophthalmol. 1998;9(3):1-5.

4. Hayreh SS. Prevalent misconceptions about acute retinal vascular occlusive disorders. Prog Retin Eye Res. 2005;24(4): 493-519.

10. Celia C. Ocular ischemic syndrome. Compr Ophthalmol. 2000;8(1):17-28.

5. Biousse V. Thrombolysis for central and artery occlusion. J Neuroophthalmol. 2007;27(3):215-230. 6. Beatty S. Acute occlusion of retinal arteries, current concepts and recent advances in diagnosis. J Accid Emerg Med. 2000;17(5):324-329.

11. Kosmorsky GS. Sudden painless vision loss: optic nerve and circulatory disturbances. Clin Geriatr Med. 1999;15(1):1-13. 12. Yanko G. Prevalence of retinopathy in middle-aged and early diabetic men. Br J Ophthalmol. 1983;67:759-765. 13. Early Treatment of Diabetic Retinopathy Study Research Group. Fundus photographic risk factors for progression

400 • CHAPTER 22 of diabetic 833.

retinopathy.

Ophthalmology.

1991;98:823-

19. Noble T. Central retinal artery occlusion: the presenting signs in radiation retinopathy. Arch Ophthalmol. 1994;112:14091410.

14. Goldberg M. Sickle cell retinopathy. In: Duane TD, Tasman W, Jaeger EA, eds. Duane’s Clinical Ophthalmology. Philadelphia: JP Lippincott; 1989:1-45.

20. Hayreh SS. Anterior ischemic optic neuropathy. Eye. 1990;4: 25-41.

15. Ciulla TA. Ocular perfusion and age-related macular degeneration. Acta Ophthalmol Scand. 2001;79(2):108-15.

21. Williams DF. Posterior segment manifestations of ocular trauma. Retina. 1990;10:S35-S44.

16. Penn F. The influence of early PAO2 fluctuation on progression of retinopathy of prematurity. Invest Ophthalmol. 1995;1:36-67.

22. Levin AV. Ocular manifestations of child abuse. Ophthalmology. 1990;3:249-264.

17. Pulido. Evaluation of eyes with advanced stages of retinopathy of prematurity using standardized echography. Ophthalmology. 1991;98:1099-1104. 18. Panton. Retinal arterial microaneurysms. Br J Ophthalmol. 1990;74:595-660.

23. Greven V. Retinal artery occlusions of the young. Curr Opin Ophthalmol. 1997;8(3):3-7. 24. Leishman R. The eye in general vascular disease: hypertension. Br J Ophthalmol. 1957;41:641-701. 25. Fineman H. Branch retinal artery occlusion as the initial sign of giant cell arteritis. Am J Ophthalmol. 1996;112:428-430.

chapter

23

Intracranial Arterial Disease Ramachandra P. Tummala, MD / Babak S. Jahromi, MD, PhD / L. Nelson Hopkins, MD

•

INTRODUCTION

All aspects of the management of intracranial arterial disease have undergone major transformations in the past two decades. Alternatives are now available for conditions previously treatable only with a single modality. Moreover, some conditions that would have been considered untreatable in the past now have safe and effective therapies. Although the credit for these advances is attributable to many factors, several fundamental achievements are recognized. First, the advances in noninvasive diagnostic neuroimaging, namely, computed tomographic (CT) and magnetic resonance (MR) imaging and their respective variants have resulted in the increased detection of asymptomatic vascular lesions and improved diagnostic sensitivity. As will be discussed later, this early detection presents a clinical dilemma in determining the appropriate management on the basis of the natural history of specific lesions. Second, the refinement of microneurosurgical techniques has resulted in improved surgical outcomes. This experience has also allowed us to recognize the limitations of cerebrovascular surgery. Third, the advances in neurological critical care have resulted in improved morbidity rates and shorter hospitalizations. Finally, the emergence of neuroendovascular therapy into a multidisciplinary field involving neurosurgeons, neurologists, and radiologists has changed practice patterns dramatically. The ongoing explosion in endovascular advances has allowed for catheter-based therapeutics in virtually every aspect of cerebrovascular disease. In this chapter, the current concepts of the major categories of intracranial vascular disease are reviewed. Given the inherent limitations of covering such a broad subject in one chapter, some discussions are very cursory and superficial. The topics most likely to be encountered in clinical practice, namely, aneurysms, ischemic stroke, and arteriovenous malformations (AVMs), are treated more rigorously.

•

STRUCTURE OF INTRACRANIAL ARTERIES

Histology To gain insight into the numerous pathological conditions of the human intracranial arteries and to develop sound therapies for these disorders, a review of the gross and microscopic structure of normal arteries is necessary. The walls of the cerebral arteries are composed of three regions. From the lumen to the outer surface, these layers are the tunica intima, tunica media, and tunica adventitia. The intima is composed of an endothelial cell layer and the internal elastic lamina. The media is relatively thin and is composed of 4 to 20 smooth muscle layers that account for roughly half the thickness of the artery wall.1 Collagen fibers and fibroblasts mostly comprise the adventitia. Innervation of the cerebral arteries is by myelinated and unmyelinated nerve fibers coursing in the adventitia or between the media and adventitia.2 There are notable differences between the structure of the intracranial and systemic arteries. The internal elastic lamina is extremely convoluted and well developed in the cerebral arteries.3 The internal elastic lamina has long been thought to account for most of the mechanical strength of the artery.4 Cerebral arteries have a smaller wall-to-lumen ratio than their systemic counterparts.5 In contrast to peripheral arteries, intracranial arteries have few elastic fibers within the media. The external elastic lamina is absent, and the adventitia is poorly developed in the cerebral arteries. Unlike the well-developed fibrous layer seen in systemic arteries, the adventitia of intracranial arteries is sparse and composed of a loose network of connective tissue. Cerebral arteries generally do not have vasa vasorum. Instead, the cerebrospinal fluid (CSF) that surrounds these vessels in the subarachnoid space provides nutrients through the porous adventitia.6 The adventitia also contains a distinct

402 • CHAPTER 23

cell type that resembles the interstitial cells of Cajal; these cells may be responsible for rhythmic contraction of the arteries and may play a role in the regulation of cerebral blood flow (CBF).2 The conventional cerebral arterial structure described above becomes disorganized at bifurcation or branching points. Here, the internal elastic lamina is increasingly fenestrated, and the media is thin or absent. The smooth muscle cells are arranged in an organized, circumferential pattern around the lumen in straight segments of the arteries. However, the muscle cell orientation is random and multidirectional at branching points. In addition, asymmetric rings of connective tissue can be found encompassing the lumen at branching sites. Known as “intimal cushions,” these structures are composed of connective tissue matrix and smooth muscle cells. These cushions are common in individuals older than 20 years of age, but their functional significance is unknown. It has been observed that the media layer is attenuated or absent under large intimal cushions.7 Angiographic Anatomy Although cerebral angiography has been supplanted over the past two decades by noninvasive imaging for many diagnostic purposes, it has experienced a revival in recent years with the expansion of endovascular therapy. A thorough understanding of angiographic anatomy is mandatory before proceeding with any cerebrovascular intervention, either surgical or endovascular. In broad terms, the carotid artery and its intracranial branches are referred to as the anterior circulation, and the vertebrobasilar system is known as the posterior circulation. Despite its invasiveness, cerebral angiography can be performed with low risk. More than 5500 diagnostic angiograms have been performed at the authors’ institution during the past 8 years with a complication rate of 0.3% (Hopkins LN, personal communication, July 2007). Cerebral angiography is performed typically through a transfemoral route, although the radial or brachial arteries may be used to gain vascular access in cases of aortoiliac occlusive disease. For a thorough discussion on cerebral angiographic anatomy, refer the comprehensive works by Krayenbuhl and Yasargil,8 Morris,9 and Osborn.10,11 A normal angiogram is shown in Figure 23-1 to serve as a guide for abnormal studies included later in this chapter.

•

COLLATERAL CIRCULATION

In this section, we review briefly the main routes for collateral circulation that are important in the setting of intracranial or extracranial artery occlusion or that of therapeutic intervention. The collateral network of the brain includes anastomoses between the cerebral arteries themselves and between the cerebral arteries and the extracranial vessels. For a comprehensive discussion, refer the texts by Wojak12 and by Marinkovic et al.13 The anastomoses can be grouped into the following six categories based on location: Cervical, extracranial (in the head but outside the

cranium), extracranial–intracranial (EC–IC), intracranial– extracerebral, extracerebral–cerebral, and cerebral. EC–IC Collaterals EC–IC collaterals interconnect branches of the external carotid artery (ECA) and the internal carotid artery (ICA) or branches of the ECA and the vertebral artery (VA). These anastomoses are located primarily in the nasal cavity, orbit, and tympanic cavity. The therapeutic implications are realized when embolization through what seems to be a benign ECA branch leads to a profound neurological deficit. Furthermore, small branches from the ECA territory supply cervical nerve roots and cranial nerves. Branches of the ophthalmic artery (off the ICA) form anastomoses with branches of the ECA, usually in the setting of ICA occlusion (Figure 23-2). Examples include connections between the angular branch of the facial artery and the dorsal nasal branch of the ophthalmic artery, between the frontal division of the superficial temporal artery (STA) (off the ECA) and the supratrochlear branch of the ophthalmic artery, and between the anterior deep temporal artery (off the internal maxillary artery) and the lacrimal branch of the ophthalmic artery.13 The nasal and tympanic branches off the ECA also form anastomotic networks that may be important in chronic ICA occlusion. Persistent embryonic vessels, such as the persistent stapedial or hypoglossal arteries, also belong in the EC–IC category. The ascending pharyngeal artery is a particularly dangerous vessel. The meningeal branch of the ascending pharyngeal artery forms anastomoses with the cavernous and petrous branches of the ICA. Other branches off this artery supply the trigeminal ganglion and lower cranial nerves. These branches have major implications during embolization of skull base tumors, especially those involving the jugular foramen. Rarely, the posterior inferior cerebellar artery may originate directly from the ascending pharyngeal artery rather than the VA.12 The occipital artery forms collaterals with the muscular branches of the VA and may reconstitute the distal VA in the setting of proximal occlusion. This artery may give rise to a stylomastoid branch that supplies the facial nerve as it exits the skull. We have had one case of a complete facial palsy developing after embolization of the occipital artery for a dural arteriovenous fistula (DAVF). The internal maxillary artery forms several potentially dangerous anastomoses with branches of the ophthalmic artery and dural branches of the ICA. The middle meningeal artery, which arises proximally off the internal maxillary artery, is involved in many of these anastomoses. Additionally, the middle meningeal artery supplies the trigeminal ganglion and the first division of the trigeminal nerve.12 Cerebral Anastomoses This group includes connections directly between the cerebral arteries. The circle of Willis is the best-known anastomotic structure in the brain. It provides connections

INTRACRANIAL ARTERIAL DISEASE • 403

Central sulcus Precentral sulcus

Postcentral sulcus

Angular artery Prefrontal artery Temporo occipital artery MCA

Orbitofrontal artery

Hypoplastic ACA

Supraclinoid Ophthalmic Cavernous Laceral Petrous

Ophthalmic artery Cervical

ICA

A

B

Callosomarginal artery

Pericallosal artery

A1

M1

Right A2

Superior M2

A2 Segments

Left A2 Inferior M2

C

D

• FIGURE 23-1.

Normal angiographic anatomy. Right ICA injection—(A) Anteroposterior and (B) lateral intracranial views. In this patient, the right ACA is hypoplastic (a hypoplastic A1 is a common anatomic variant); consequently, the MCA branches can be easily visualized on the lateral projection. MCA branches: orbitofrontal, prefrontal, precentral sulcus, central sulcus, postcentral sulcus, angular, temporo-occipital. ICA segments: supraclinoid, ophthalmic, cavernous, laceral, petrous, and cervical. Left ICA injection—(C) Anteroposterior and (D) lateral intracranial views. Reciprocally, the left A1 is dominant with filling across the anterior communicating artery to supply bilateral A2 segments. ACA segments: right A2, left A2, and A1. MCA segments: M1, superior M2, and inferior M2. (continued )

404 • CHAPTER 23

Calcarine branch of PCA

Posterior temporal branch of PCA

Occipital temporal branch of PCA

L&R P2 segments of PCA

Posterior cerebral artery

L&R P1 segments of PCA

L&R posterior communicating artery

Posterior communicating artery

Superior cerebellar artery

L&R superior cerebellar artery

PICA

Basilar artery L Posterior inferior cerebellar artery

Muscular branch Vertebral artery

Vertebral artery

E

F

Superior temporal artery

Divisions of Superficial temporal artery Anterior Posterior

Occipital artery Middle meningeal artery

Internal maxillary artery

External carotid artery trunk

Occipital artery

Facial artery

Internal maxillary artery

External carotid artery trunk

Lingual artery

G

H

• FIGURE 23-1.

(Continued ) Left VA injection—(E) Anteroposterior and (F) lateral intracranial views. Right ECA injection lateral views—(G) Proximal and (H) distal views.

between the right and left ICA systems through the anterior communicating artery. In addition, the posterior communicating arteries (PCoA) connect the ICA system (anterior circulation) to the vertebrobasilar system (posterior circulation). It has the shape of an irregular polygon and is located mainly at the base of the frontal lobes. There are numerous anatomic variations of the circle of Willis, including agenesis or hypoplasia of certain components (see pp. 135-136 in Ref. 9). Under normal conditions, a hemodynamic balance

exists between the anterior and posterior circulation and between the right and left carotid circulation. A change in the balance, as seen with occlusive cerebrovascular disease, causes redistribution of blood through the circle of Willis. The complexity of these hemodynamic imbalances is responsible for the high frequency of aneurysm formation along branches of the circle of Willis. There are numerous leptomeningeal anastomoses that form on the surface of the brain and that are important

INTRACRANIAL ARTERIAL DISEASE • 405

A

B

• FIGURE 23-2.

External–internal carotid artery collaterals. This patient presented with a right hemispheric transient ischemic attack. A right common carotid artery injection demonstrated ICA occlusion at its origin. (A) Only the ECA branches are filling. (B) An intracranial view shows collaterals between the internal maxillary artery and ophthalmic artery (dotted circle) with resultant filling of the intracranial ICA proximally and distally.

in the setting of large artery occlusions. They occur in every major arterial territory. For example, a middle cerebral artery (MCA) occlusion may activate anastomoses between leptomeningeal branches of the MCA and the leptomeningeal branches of the anterior cerebral artery (ACA) or posterior cerebral artery (PCA). Another example is the anastomosis between the splenial artery (off the PCA) and the pericallosal artery (off the ACA) after occlusion of the ACA or PCA. These collaterals are seen on the lateral surface of the cerebral hemisphere. Connections between the anterior and posterior choroidal arteries occur in the choroid plexus of the lateral ventricle.

•

Histological examination of saccular intracranial aneurysms reveals an absent or discontinuous internal elastic lamina, absence of the media at the aneurysm neck, deficient endothelium in the aneurysm lumen, and atherosclerotic changes in the parent vessel at the origin of the aneurysm. The walls of most small aneurysms are composed of discontinuous endothelium surrounded by fibrous adventitial tissue and no smooth muscle. Large (diameter between 1.0 and 2.5 cm) and giant aneurysms (≥2.5 cm diameter) may have more organized walls consisting of fibrous tissue, foam cells, and deposits of calcium.14,15 It is believed that aneurysms form over a relatively short period of time, and either they rupture or they stabilize and remain unruptured.16

INTRACRANIAL ANEURYSMS

Background

Pathogenesis

The main reason for concern about cerebral aneurysms is the consequences of their rupture and resultant subarachnoid hemorrhage (SAH). The most common cause of SAH is trauma; however, this discussion will focus on aneurysmal SAH. Cerebral aneurysms can be broadly classified by size, location, shape, and etiology. The causes of their formation and rupture are not well known. Unless noted otherwise, most of this discussion will focus on saccular lesions, which are the most common aneurysms by far. Once thought to be congenital, it is widely accepted that these lesions develop later in life.

The reasons for aneurysm development and rupture are not known completely. It has been postulated that aneurysm formation may be related to the intimal cushions and defects of the media at the branching points described above,17 but this has not been proven. Destruction of the internal elastic lamina seems to be the crucial event for aneurysm formation and is likely an early event that weakens the arterial wall.4 Collagen also appears to play a role in aneurysm pathology. Part of the stabilization of the aneurysm is exuberant collagen formation, which leads to thickening of its wall. In fact, unruptured aneurysms have

406 • CHAPTER 23

almost twice the collagen content of normal arteries. It is not known if this increased-collagen formation is a compensatory mechanism for the internal elastic lamina loss. In contrast, ruptured aneurysms have decreased and poorly organized collagen content.18 Unlike normal arteries and unruptured aneurysms, ruptured lesions have a disrupted endothelial lining. Therefore, it has been proposed that endothelial injury may contribute to aneurysm formation and rupture.19,20 The ultimate source of the destruction of the internal elastic lamina and endothelium remains unknown, but an underlying inflammatory cause was proposed as early as the mid-19th century by Virchow.19 T cells (natural killer cells) and macrophages have been found in both ruptured and unruptured aneurysms.19 Additionally, lysosomal granule deposition and increased metalloproteinase activity has been observed within aneurysm walls.21 These and other findings suggest at least a link between inflammation and aneurysm formation and, ultimately, rupture.19 Because inflammatory changes are obligatory features of atherosclerosis,22 aneurysm development may be part of an atherosclerotic spectrum in the parent vessel. Debate continues regarding whether intracranial aneurysm pathogenesis has a genetic, acquired, or combined etiology. Support for a genetic mechanism comes from the association of aneurysms and several inheritable connective tissue disorders. These include autosomal dominant polycystic kidney disease, type IV Ehlers-Danlos syndrome (EDS) (see below), Marfan’s syndrome, ␣1 antitrypsin deficiency, neurofibromatosis type 1, and tuberous sclerosis—to list only a few.23,24 The true incidence of aneurysms caused by these disorders is unknown because of their variable phenotypes. However, it seems these diseases are responsible only for a small percentage of aneurysms. Familial intracranial aneurysms have been described for several decades. However, the pattern of inheritance is unknown. Some studies have shown up to a fivefold increase in aneurysm or SAH incidence in first-degree relatives of patients harboring intracranial aneurysms.25,26 Regardless, the evidence has been sparse, and screening for asymptomatic intracranial aneurysms is not well defined. The yield of screening first-degree relatives and their lifetime risk of SAH are low when only one family member harbors an aneurysm.27,28 The authors’ strategy has been to evaluate first-degree relatives with CT angiography or MR angiography in families with two or more affected members. This is based on evidence that the yield from such screening is roughly 10%.29,30 If the initial screening fails to reveal an aneurysm, we repeat a noninvasive study every 5 years in order to detect any de novo lesions. Acquired risk factors are not well defined for SAH. Cigarette smoking is the one consistent factor identified in all studies to date. The estimated risk of SAH is up to 10 times higher in smokers than in nonsmokers. Smoking accelerates intracranial aneurysm growth, and continued smoking may increase the risk of de novo aneurysm development after an initial SAH.31−34 Many re-

ports have demonstrated the role of hypertension in increasing aneurysm development and rupture.34,35 However, this risk does not seem to be as high as with smoking. While low-level alcohol consumption may lower SAH risk, high-level consumption and binge drinking seem to increase the risk.33 Epidemiology Annual incidence rates of SAH are estimated between 9 and 15 cases per 100 000 persons.36,37 This translates into roughly 30 000 cases of SAH in North America annually. However, there are considerable global variations in these figures. For example, a Finnish study reported an incidence as high as 30 per 100 000 person-years.38 In contrast, a French study reported an incidence of 2.2 per 100 000.39 In most studies, women have a 1.5 times greater incidence of SAH than men, with hormonal factors implicated for the gender inequity.40 Unlike other types of stroke, SAH is unique with its female predilection. Studies from the United States have shown a more than two times greater risk for SAH in blacks than in whites.41,42 The peak incidence of SAH is between 55 and 60 years of age. Indeed, our experience parallels the above figures in that the typical patient with SAH is a middle-aged female smoker. The true prevalence of intracranial aneurysms remains unknown and is difficult to determine. It has been estimated at 5% on the basis of autopsy studies.43 On the other hand, incidental aneurysms were detected in only 1% of cases during a random review of cerebral angiograms.44 Not surprisingly, these studies are criticized for selection bias (e.g., what was defined as an aneurysm) and patient population. A prevalence of approximately 2% is generally assumed, as suggested by a contemporary meta-analysis.45 The outcome from aneurysmal SAH is dismal.46 Approximately one-third of patients with a first SAH will die in the acute phase. One-third will remain with significant neurological disability. Only the remaining third will recover well from the hemorrhage and its sequelae.37 Although there are some variations in these statistics from other studies, the above figures serve as easy reminders that the overall prognosis for SAH remains poor despite advances in initial resuscitation, aneurysm treatment, critical care, and treatment of cerebral vasospasm. Predictors of a good recovery from SAH include young age and good neurological function at presentation.40 Natural History Given the gravity of SAH, knowledge of the natural history of cerebral aneurysms is important to understand the effects of treatment. In this section, the discussion has been limited to the known natural history of unruptured aneurysms. Knowing the natural history is particularly germane now that more aneurysms are being discovered with noninvasive imaging. The natural history of the aneurysm and the life expectancy of the patient must be matched against the risks of treatment.

INTRACRANIAL ARTERIAL DISEASE • 407

Unfortunately, the natural history of intracranial aneurysms is not well established. Historically, the risk of rupture of an aneurysm was believed to be 1% to 2% per year. Of course, this risk can vary, depending on the patient and the aneurysm. Any contemporary discussion on the natural history must include the International Study of Unruptured Intracranial Aneurysms (ISUIA).47,48 For this discussion, we focus on the ISUIA because of its influence on current practice patterns. The ISUIA was the largest systematic study undertaken to evaluate the natural history of unruptured aneurysms and to evaluate treatment risk. The study contained two parts. The first part, published in 1998, had both retrospective and prospective components.47 In the retrospective cohort, 1937 aneurysms in 1449 patients from 53 centers were evaluated. These patients were subdivided into two groups:—those with previous SAH from another aneurysm and those without previous SAH. In the prospective arm, the surgical outcomes of unruptured aneurysms in 1172 patients were analyzed. For patients without previous SAH and with aneurysms 12 mm, and aneurysm location in the posterior fossa. The rupture risk was 2.5% over 5 years for lesions involving the posterior circulation in patients with no previous SAH and 0% over 5 years for anterior circulation lesions. On the other hand, patients with previous SAH had 5-year rupture risks of 1.5% in the anterior circulation and 3.4% in the posterior circulation. The authors of the ISUIA proposed that there was no benefit in treating aneurysms 4 mm, 94% for aneurysms 2 to 4 mm, and 50% for aneurysms 25% of its original diameter) angiographic vasospasm seen in 30% of patients.87,88 Those with more severe hemorrhage suffer from an increased incidence of severe vasospasm, with >50% narrowing seen in 55.9% of grade III to V patients.89 Although vasospasm >50% is generally required before flow restriction results in clinical

412 • CHAPTER 23

A

B

C

D

• FIGURE 23-5.

Aneurysm recanalization. This 41-year-old man underwent coil embolization of a ruptured basilar tip aneurysm at an outside hospital and made a good recovery. He presented for follow-up evaluation and was found (by digital subtraction angiography [DSA]) to have significant recanalization of this (A) wide-necked aneurysm. (B) He underwent placement of a stent that spanned the distal BA and the right PCA (unsubtracted view). (C [DSA] and D [unsubtracted view]) The aneurysm was then coiled without herniation of the coils into either PCA (stent markers are circled).

ischemia,90 other factors, such as location of spasm, collateral supply, and cerebral perfusion pressure, also influence whether ischemic symptoms become manifest. As a result, the incidence of clinical vasospasm is approximately half that of angiographic vasospasm and can be seen in up to one-third of patients.86,89,91

Pathogenesis Extensive evidence points to the presence of subarachnoid blood clot as the chief etiology in cerebral vasospasm. The amount and location of subarachnoid blood predict the subsequent site and degree of cerebral vasospasm,92,93 as

INTRACRANIAL ARTERIAL DISEASE • 413

does the rate of clearance of subarachnoid clot via endogenous means.94 Hemoglobin within red blood cells is a key spasmogen,95,96 although other components of the subarachnoid blood clot also contribute to vasospasm.97 The underlying pathophysiology appears to be prolonged contraction of vascular smooth muscle cells rather than fibrosis or cellular proliferation,98−100 as also evidenced by the ability of intra-arterial (IA) vasodilators such as papaverine and nicardipine to (at least transiently) ameliorate vasospasm. Medical Management Prophylaxis against cerebral vasospasm with oral nimodipine is considered standard of care in the treatment of SAH, because it significantly improves the odds of a good outcome and reduces death and disability owing to vasospasm.101−104 However, once cerebral vasospasm becomes clinically apparent by causing neurological deficit(s), immediate/first-line therapy has traditionally involved the institution of so-called “triple-H” (hypertension, hemodilution, hypervolemia) therapy with use of increased fluids and/or pressors, particularly when access to endovascular treatment is limited or unavailable. Of the three components, induced hypertension is likely the most important,105 with the common denominator of this approach being an increase in cerebral perfusion pressure, thereby enhancing both flow through a vasospastic segment and also collateral supply to the distal ischemic brain. Although never subjected to a randomized trial, outcomes with such treatment appear to be significantly better than the natural history of untreated vasospasm.103,106 Endovascular Management Endovascular therapy for symptomatic cerebral vasospasm is generally undertaken after medical intervention has been deemed unsuccessful. It is important to rapidly maximize medical therapy to determine its efficacy or lack thereof and subsequent need for endovascular treatment because a delay in decision making can lead to fixed rather than reversible cerebral ischemic deficits. Endovascular options may be broadly categorized as IA infusion of vasodilators or balloon angioplasty. The first and most frequently used IA vasodilator drug is papaverine, initially described by Kaku et al.107 and Kassell et al.108 in 1992 for the treatment of vasospasm after aneurysmal SAH. Effects of papaverine are unfortunately short-lasting and include the potential side effects of raised intracranial pressure (ICP) and seizures, prompting renewed interest in IA calcium 2+ channel blockers, such as nicardipine109 or verapamil,110 or the treatment of vasospasm. Although side effects of IA calcium 2+ blockers (raised ICP in particular) are less frequent, their short-term effect has led to the adoption of balloon angioplasty, introduced in 1984 by Zubkov et al.111 for symptomatic cerebral vasospasm. Current techniques with over-the-wire balloons provide a long-lasting, relatively safe treatment for vasospasm, although technical challenges diminish successful application in the ACA as a result of vessel angulation and tortuosity.112,113 IA vasodila-

tors still play a role in the treatment of distal vasospasm (inaccessible to balloon angioplasty) or in the pretreatment of very severe vasospasm in order to permit navigation by angioplasty balloons.

•

ISCHEMIC STROKE

Epidemiology The term “stroke” is all encompassing and includes ischemic stroke, ICH, and SAH. Annually, 15 million people worldwide suffer a stroke.114 Of these, one-third die and onethird are permanently disabled.114 Although the incidence of stroke is declining in industrial countries because of improved control of hypertension and smoking, the absolute numbers of strokes is increasing because of the aging population in these countries. Stroke is the third-leading cause of death in developed countries behind cardiovascular disease and cancer. In 2002, 10% of all deaths worldwide were attributed to stroke.114 Ischemic strokes account for 87% of all strokes. Each year, approximately 700 000 people in the United States suffer a stroke.115 Of these, 500 000 are firsttime strokes. The estimated cost of stroke in the United States will exceed $62 billion in 2007.115 Etiology and Presentation The hallmark feature of stroke is the sudden onset of neurological symptoms and signs. Focal neurological symptoms such as diplopia, weakness on one side, loss of sensation, dysarthria, aphasia, and visual field deficits are suggestive of ischemic stroke. In contrast, presentations of severe headache, seizures, alterations in level of consciousness, and vomiting are more likely to reflect hemorrhage. Ischemic stroke can be classified by the type of vascular lesion or by the mechanism of ischemia. Numerous mechanisms may cause brain ischemia. Severe arterial stenosis or occlusion from atherosclerosis or thrombus may reduce perfusion in a purely hemodynamic fashion. Embolism may originate from a more proximal source and result in arterial occlusion. The small end-arteries in the deep gray matter may be affected by local atherosclerosis or lipohyalinosis. Miscellaneous causes of ischemic stroke include hypercoagulability, arterial dissection, arterial vasospasm, vasculitis, fibromuscular dysplasia, and moyamoya disease. Of all these causes, the four most frequent are large-vessel atherosclerosis, cardioembolism, small-vessel disease, and cryptogenic.116 Extracranial large-arterial atherosclerosis, which is responsible for up to 40% of all ischemic strokes, is beyond the scope of this chapter. Intracranial atherosclerosis will be addressed later in this chapter. Cardioembolism accounts for 15% to 30% of all ischemic strokes.116 The most common cardiac sources of embolism include valvular disease such as mitral stenosis or regurgitation, endocarditis, mural thrombus following anterior myocardial infarction, left atrial appendage from atrial fibrillation, severe cardiomyopathies, and ventricular aneurysms. Less common is embolism from atrial myxoma or paradoxical right to left embolism from a patent foramen ovale.

414 • CHAPTER 23

A cardiac source is presumed when multiple infarcts involving more than one cerebral vascular territory are seen clinically or radiographically. Most embolic obstruction is cleared automatically within 48 hours through the homeostatic processes of recanalization and fibrinolysis. Lacunar strokes also account for 15% to 30% of all ischemic strokes. These strokes involve the small vessels supplying the deep structures of the brain such as the basal ganglia and thalamus. These penetrating arteries can become stenotic or occluded by microatherosclerosis and lipohyalinosis. Uncontrolled hypertension and diabetes mellitus are often implicated with these strokes. Because these vessels are less than 400 ␮m in diameter, angiography is often unremarkable. Most lacunar strokes are diagnosed clinically with pure motor or sensory syndromes. MR imaging may demonstrate a small, deep infarct. Characteristics of Specific Arterial Occlusions In this section, the characteristics of specific large-vessel occlusions are outlined in the broadest terms. More specific descriptions can be found in standard neurology texts. Occlusion of the main trunk of the MCA causes contralateral hemiparesis, contralateral anesthesia, ipsilateral gaze preference, and contralateral hemianopsia. If the dominant cerebral hemisphere is involved, the patient will also suffer from global aphasia. Involvement of the nondominant hemisphere leads to impaired spatial perception. Less severe combinations of these symptoms may occur, depending on occlusions of distal branches rather than the main trunk. Infarction in the ACA territory typically results in paresis and anesthesia in the contralateral lower extremity. Motor neglect and disinclination to use the contralateral extremities may be observed. Bilateral ACA infarction is particularly devastating with resultant behavior and personality changes, severe apathy, incontinence, and muteness. These features are attributed to involvement of both the medial frontal lobes and the limbic structures. Occlusion of the PCA usually causes a contralateral homonymous hemianopsia caused by injury to the occipital lobe. Proximal PCA occlusion may also injure the thalamus and midbrain because of the involvement of perforating branches. This typically results in contralateral loss of sensation, altered mental status, and impaired vertical gaze. There are many brainstem infarction syndromes depending on the level (midbrain, pons, or medulla) and location in the brainstem. For interventional purposes, we have limited this discussion to vertebrobasilar occlusion. Rather than describing the dozens of brainstem syndromes, we will focus on what happens when the VA or BA itself are occluded. Occlusion of the BA or VA is more often the cause of brainstem infarction than occlusion of perforating branches.117 The posterior circulation is easy to overlook as a source of stroke because of the wide spectrum of presentations, many of which are nonspecific. However, failure to recognize a VA or BA occlusion may have disastrous consequences. The

posterior circulation should be considered in patients with bilateral or crossed (e.g., ipsilateral face and contralateral limb) motor and sensory signs, disconjugate eye movements or nystagmus, dysmetria and ataxia, involvement of cranial nerves, and altered levels of consciousness. Malignant Cerebral Infarction Classically, malignant infarction is described for large strokes involving the MCA. It is an emergency that carries a rate of mortality six to eight times higher than seen in other ischemic strokes. By definition, more than 50% of the MCA territory is involved with subsequent brain edema that may result in elevated ICP and eventual herniation and death.118 Malignant MCA infarction may account for up to 10% of all ischemic strokes.118 Besides the focal neurological deficit caused by the stroke itself, a progressive decline in the patient’s level of consciousness is seen at approximately 48 hours after the onset of the stroke. In young patients with no baseline brain atrophy, clinical deterioration may begin as early as 12 hours from the onset.119 Despite maximal medical management of intracranial hypertension, including osmodiuresis, hypothermia, and barbiturate coma, the mortality approaches 80%.120 Mechanical decompression of the edematous cerebral hemisphere through a hemicraniectomy has been performed for decades in numerous settings. Hemicraniectomy is very effective at reducing ICP and may be life-saving. Until recently, level I evidence supporting this procedure has been lacking. Controversial issues in the setting of stroke have been timing of hemicraniectomy and performance of this operation on left-sided lesions. The historical argument against left hemicraniectomy has been that survivors will remain globally aphasic and hemiplegic. In contrast, right-sided lesions may be more compatible with a functional outcome because of the absence of language involvement. One retrospective analysis concluded that hemicraniectomy reduced the mortality from malignant stroke to 24% and that patients with left-sided strokes had similar outcomes to those with right hemispheric strokes.121 Additionally, patients younger than the age of 50 years seemed to have better outcomes. It has also been proposed that early (92%; intubate for airway protection as needed b. Normothermia (or hypothermia in context of neuroprotection trials) c. Continuous cardiac monitoring ≥24 hours; treatment of detected arrhythmias or ischemia d. Blood pressure: i. treat systolic blood pressure >220 mm Hg or diastolic blood pressure >120 mm Hg (185 and 110 mm Hg, respectively, if undergoing any thrombolytic intervention) with IV labetalol, nitropaste, or nicardipine infusion ii. determine underlying cause of and treat hypotension; optimize cardiac output iii. induce hypertension to improve cerebral blood flow in exceptional cases e. serum glucose: avoid hypoglycemia, treat glucose >140 mg/dL (goal 80–140 mg/dL) 3. Baseline diagnostics a. All patients: CT or MR imaging; serum glucose and electrolytes; renal function tests; cardiac enzyme levels; complete blood count; prothrombin time, partial thromboplastin time, international normalized ratio; electrocardiogram; O2 saturation b. Select patients: liver function tests; toxicology screen; blood alcohol level; pregnancy test; arterial blood gas; chest X-ray; lumbar puncture (if SAH suspected); electroencephalogram (if seizure suspected) 4. Thrombolysis a. Rapid and accurate determination of onset, risk factors, and eligibility for treatment b. If eligible: IV and/or IA thrombolytic therapy (see sections on ischemic stroke medical therapy and endovascular therapy) 5. Supportive measures a. Setting: admission to comprehensive acute stroke unit is recommended b. Screening: lipid profile, dysphagia risk c. Prophylaxis: deep vein thrombosis; anticoagulation for atrial fibrillation; aspirin, 325 mg, within 24–48 hours of onset d. Treatment: medical or surgical treatment for brain edema or hemorrhage; antibiotics for urinary or pulmonary infections; avoid indwelling bladder catheters if possible; early mobilization e. Nutrition and hydration: nasogastric, nasoduodenal, or percutaneous endoscopic gastrotomy feedings if unable to swallow safely Adapted from Adams HP Jr, del Zoppo G, Alberts MJ, et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke. 2007;38(5):1655-1711.

416 • CHAPTER 23

TABLE 23-2. Characteristics of Patients with Ischemic Stroke Who Could Be Treated with rt-PA Diagnosis of ischemic stroke causing measurable neurological deficit Neurological signs that are not clearing spontaneously or are not minor and isolated Caution should be exercised in treating a patient with major deficits Stroke symptoms that are not suggestive of SAH Onset of symptoms 7 experienced a 36.4% absolute benefit and a 3.2-fold decrease in risk of poor outcome after IA urokinase, compared with 6.4% absolute benefit and 1.2 risk ratio for those with ASPECTS ≤ 7. A similar dichotomous result for ASPECTS was not found in the NINDS IV rt-PA trial,183 possibly

420 • CHAPTER 23

Area of infarct

Preoperative CBF

Preoperative CBV

Postoperative DWI

Area of infarct

• FIGURE 23-7.

CT Perfusion imaging in acute stroke. An 83-year-old man with paroxysmal atrial fibrillation presented with a right MCA stroke and an NIHSS score >10 at 14 hours after onset. CT perfusion imaging demonstrated large penumbra (decreased CBF but relatively preserved CBV, blue arrows) with a small area of established infarct (markedly decreased CBF as well as CBV, red arrows). Following combination therapy consisting of IA thrombolytic, GP IIb/IIIa inhibitor, mechanical retrieval, and intracranial angioplasty, complete (TIMI 3) revascularization was achieved. As a result, MR imaging several days later demonstrated only small stroke within the areas predicted by the CT perfusion findings; and the patient was discharged home without objective neurological deficit, with an mRS score of 0 at the 3-month follow-up evaluation.

because early CT changes (0–3 hours) may be reversible, whereas the later changes seen in PROACT II (3-6 hours) may represent fixed deficits. Indeed, more recent investigators have shown that early changes represented by focal swelling alone (rather than hypoattenuation) on CT images may represent the increased blood volume seen in salvageable penumbra rather than actual infarcted core.184,185 Use of CT perfusion images rather than noncontrast CT increases prognostic accuracy of the ASPECT score, with final infarct mirroring cerebral blood volume (CBV) or CBF deficits when reperfusion is or is not achieved, respectively.186 Knowledge of regional blood flow in brain ischemia, although until recently not widely available, can be of great benefit to clinical decision making. In primates, reversible ischemia, cessation of electrical activity, and irreversible ischemia occur at 20 to 23, 18, and 10 to 12 mL/100 g per minute, respectively, matching human values for functional penumbra, flat EEG (during carotid artery clamping in endarterectomy studies), and cerebral infarction at thresholds of 14 to 22, 16 to 18, and 5 to 15 mL/100 g per minute, respectively (reviewed in Hoeffner et al.187 and Heiss et al.188 ). With increasing availability of multidetector CT equipment and CT perfusion software packages,

clinicians can now rapidly assess CBF, CBV, and mean transit times (MTT) in ischemic brain. Although various algorithms exist from which to derive perfusion data, all such methods use CT equipment in cine mode to track the arrival and washout of IV contrast bolus and the associated parenchymal enhancement peak in real-time. CT perfusion is much more sensitive for stroke detection than plain CT,179,180,189 and derived flow, volume, and transit time parameters have been well validated against Xenon-CT,190 diffusion–perfusion MR imaging,191 and PET.192 CT perfusion imaging permits differentiation of normal brain from ischemic penumbra (salvageable brain) and infarcted core (dead, unsalvageable brain). CBV appears critical in distinguishing penumbra from infarct: although both penumbra and infarcted core have decreased CBF, relative preservation or increase in CBV is what sets penumbra apart from infarcted core (Figure 23-7). At the simplest level, preserved or increased CBV may reflect the presence of dilated collaterals. Early investigators noted that CBV (rather than CBF or MTT) correlated better with final infarct volume, regardless of whether perfusion data was generated by CT193 or MR194 protocols. Importantly, it is preserved or increased CBV that determines what is salvageable penumbra if reperfusion happens:

INTRACRANIAL ARTERIAL DISEASE • 421

Parsons et al.195 found that with reperfusion of hypoperfused areas, 97%, 41%, and 3% of low, normal, and high CBV areas, respectively, progressed to infarct, whereas without reperfusion of hypoperfused areas, 94%, 63% and 94% of low, normal, and high CBV areas, respectively, went on to infarct. Other authors have suggested the use of relative ratios as more accurate, with CBF reduction beyond 66% (of the normal contralateral side) having 95% PPV for infarction regardless of recanalization.196 Combined analysis of CBF and CBV quantitative values may further increase CT perfusion accuracy. Murphy et al.197 found that in stroke patients who experienced recanalization, CBF progressively decreased from normal to penumbral to infarcted gray matter (37.3 ± 5.0, 25.0 ± 3.82, and 13.3 ± 3.75 mL/100 g per minute, respectively) whereas CBV increased from normal to penumbral tissue but was markedly decreased in gray matter destined for infarction (1.78 ± 0.30 mL/100 g, 2.15 ± 0.43 mL/100 g, 1.12 ± 0.37 mL/100 g). Having noted divergent changes in CBF versus CBV in penumbral tissue, Murphy et al.197 derived a multiplicative cutoff value of 31.3 (CBF × CBV) for ≥97% sensitivity, specificity, and accuracy in distinguishing penumbra from infarcted core. Corresponding values for white matter are generally lower because of decreased metabolic needs.196 CT perfusion imaging is not without pitfalls. Current technology provides less cranial coverage than MR imaging (2–8 slices), although this will likely change with the advent of 256-detector CT. Small lacunar or subcortical strokes may be missed despite excellent accuracy with large territorial strokes.180 Analysis and postprocessing are somewhat dependent on operator choice of arterial or venous region of interest.198 CT perfusion also subjects patients to ionizing radiation. Although the radiation dose incurred by first-generation CT perfusion was roughly similar or less than that of a whole-head noncontrast CT,199 this is not necessarily true with current multidetector CT; and investigators have examined ways of further reducing radiation dose by increasing scan intervals.200 Modern 64-slice CT scanners can provide near-DSA quality images of cervicocerebral vascular anatomy, with “arch-to-vertex” acquisition and analysis time of approximately 5 minutes for CT angiography. Combined CT, CT angiographic, and CT perfusion imaging is therefore now a routine part of a “CT Stroke Protocol” at the authors’ institution, permitting treatment triage with knowledge of both the anatomy and physiology underlying acute cerebral ischemia within 15 minutes and 60% stenosis)

0.6

1.3

3.9

1.2

1.6

4.0

1.9

1.0

1.4

0.4∗

0.2∗

0.5∗

∗

Excludes 1.2% risk of stroke after angiography. Source: North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991; 325:445-453. ‡ Source: Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. NEJM. 1998;339:14151425. § Source: Hobson RW, Weiss DG, Fields WS, et al. Efficacy of carotid endarterectomy for asymptomatic carotid stenosis. The Veterans Affairs Cooperative Study Group. N Engl J Med 1993;328:221-227. ¶ Source: Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for asymptomatic carotid artery stenosis. JAMA 1995;273:1421-1428. †

2. Symptomatic high-grade stenosis (typically >70% by duplex ultrasound) 3. Symptomatic patients with moderate (>50%) carotid stenosis. These lesions are typically associated with deep ulceration and failure of medical (antiplatelet) therapy. With the advent of CAS, CEA has again come “under attack,” despite its proven efficacy and durability in stroke prevention in patients with high-grade stenosis of the internal carotid artery (ICA).8 Proponents of CAS have suggested that the results of NASCET and ACAS are not achievable in general practice outside selected centers of excellence. The question is a reasonable one; if the combined stroke and death rate of CEA in asymptomatic patients were more than 3%, there would be little benefit of operation in the asymptomatic population.9 Both ACAS and NASCET included good-risk patients on the basis of reasonable life expectancy (so as to be available for followup) and exclusion of other potential causes of stroke (such as atrial fibrillation). Exclusion criteria included previous carotid surgery, prior myocardial infarction (MI), congestive heart failure (CHF), renal failure, unstable angina, and those requiring combined CEA and coronary bypass procedures. Tables 24-2 and 24-3 list inclusion and exclusion criteria for several important CEA and CAS trials. A review of 25 CEA studies reporting 30-day stroke and death rates by

Rothwell et al.10 found a mortality rate of 1.3% in asymptomatic patients and 1.8% in symptomatic patients. The combined stroke and death rates were 3% in asymptomatic patients and 5.2% in those presenting with symptomatic carotid stenosis. A number of studies have focused on NASCET and ACAS trial eligibility as they relate to the results of CEA in the general population. Lepore et al.11 from the Ochsner Clinic reviewed 366 CEAs performed at their institution over a 2-year period. Surprisingly, 46% were found to be high risk based on NASCET and ACAS trial-ineligibility. Their cohort included 60% who presented with asymptomatic carotid stenosis; the remaining 40% had focal ipsilateral symptoms at presentation. The overall stroke and death rate (combined stroke and mortality, [CSM]) was 2.5%; trial-eligible “good risk” patients had a CSM of 1.5%, and the remainder (trial-ineligible) had a CSM of 3.6%. While there was a trend toward higher neurologic morbidity in trial-ineligible patients, this difference did not reach statistical significance ( p = 0.17). These authors concluded that ineligibility for NASCET or ACAS should not be employed as a de novo indication for CAS. Illig et al.12 examined the results of CEA at the University of Rochester in 857 patients. Stroke or death at 30 days occurred in 2.1%. Rates were similar in patients excluded from (2.7%) or included in (1.6%) NASCET and ACAS and in patients eligible (3.1%) or ineligible (2.1%) for ARCHeR, a CAS registry in high-risk patients. These rates did not differ according to whether exclusion or inclusion was based on anatomic risk, medical risk, or protocol exclusion; there was a trend, however, toward worse outcome in the high medical risk subgroup. Stroke and death rates were similar according to age, gender, repeat procedure, or the presence of contralateral occlusion. Mozes et al.13 examined the results of 776 consecutive CEAs from the Division of Vascular Surgery at the Mayo Clinic in Rochester, MN. Patients were categorized as “high risk” based on the inclusion and exclusion criteria for the SAPPHIRE trial of CAS with cerebral embolic protection. Of 776 CEAs, 323 (42%) were considered high risk based on the criteria listed in Table 24-4. Clinical presentation was similar in the high- and lowrisk groups (Table 24-5). The overall postoperative stroke rate was 1.4% (symptomatic: 2.9%, asymptomatic: 0.9%). When comparing high- and low-risk CEAs, there was no statistical difference in stroke rate. Factors associated with significantly increased stroke risk were cervical radiation therapy, class III/IV angina, symptomatic presentation and age ≤60 years. Overall mortality was 0.3% (symptomatic: 0.5%; asymptomatic: 0.2%), not significantly different between the high- (0.6%) and low-risk groups (0.0%). NonQ MI was more frequent in the high-risk group (3.1 vs. 0.9%; p < 0.05). Of note, the only MIs that occurred in the entire series were nontransmural (non-Q). A composite cluster of adverse clinical events (death, stroke, and MI) was more frequent in the symptomatic high-risk group (9.3% vs. 1.6%; p < 0.005), but not in the asymptomatic cohort. There was a trend for more major cranial nerve injuries in patients with local risk factors, such as high carotid

TABLE 24-2. Definition of High-Risk CEA: Major Exclusion Criteria of the NASCET/ACAS and Major Inclusion Criteria for Population-Based Studies on High-Risk CEA and for the SAPPHIRE Study Exclusion Criteria

Inclusion Criteria Ouriel et al.15 (2001)

NASCET

ACAS

>79 y -Contralateral CEA 180 systolic, 115 diastolic BP -Fasting glucose >400 -Liver failure -Cancer, target stenosis -Cervical radiation treatment

Age History

Comorbidities Cardiac

Jordan et al.21 (2002)

Gasparis et al.20 (2003)

SAPPHIRE

≥80y

>80 y

-NYHA functional class III/IV -Canadian CVA heart failure functional class III/IV - CABG 4 mm detected by intraoperative ultrasonography was prevalent in 26% of 387 patients selected for follow-up by Schachner et al. after coronary bypass surgery and was associated with an increased risk of late stroke.119 In this same patient population the risk for an ascending aortic wall thickness >4 mm was correlated with age (mean age of patients with atheromas was 70 years), an elevated creatinine, higher EuroSCORE (European system for cardiac operative risk evaluation), and descending aortic wall thickness.120 In the experience of the author, ongoing cigarette smoking is also a significant correlate. Epiaortic ultrasound scanning is therefore recommended to direct modifications in cardiac surgical techniques to prevent atheroembolic strokes in elderly smokers and in those with other atherosclerosis risk factors since it has been shown that inspection and palpation of the ascending aorta is not adequately sensitive in such patients.120

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computed tomography. J Thorac Cardiovasc Surg. 2002;123: 1060-1066.

2. Hager A, Kaemmerer H, Rapp-Bernhardt U, et al. Diameters of the thoracic aorta throughout life as measured with helical

3. Rammos S, Apostolopoulou SC, Kramer HH, et al. Normative angiographic data relating to the dimensions of the aorta

ASCENDING THORACIC AORTA AND AORTIC ARCH • 535

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71. Bauer M, Gliech V, Siniawski H, Hetzer R. Configuration of the ascending aorta in patients with bicuspid and tricuspid aortic valve disease undergoing aortic valve replacement with or without reduction aortoplasty. J Heart Valve Dis. 2006;15: 594-600.

57. Loeys BL, Schwarze U, Holm T, et al. Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med. 2006;355:788-798. 58. Loeys B, Van Maldergem L, Mortier G, et al. Homozygosity for a missense mutation in fibulin-5 (FBLN5) results in a severe form of cutis laxa. Hum Mol Genet. 2002;11:21132118. 59. Hucthagowder V, Sausgruber N, Kim KH, Angle B, Marmorstein LY, Urban Z. Fibulin-4: a novel gene for an autosomal recessive cutis laxa syndrome. Am J Hum Genet. 2006; 78:1075-1080.

72. Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ. Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and EhlersDanlos Support Group (UK). Am J Med Genet. 1998;77:3137. 73. Pepin M, Schwarze U, Superti-Furga A, Byers PH. Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type. N Engl J Med. 2000;342:673-680. 74. Perdu J, Boutouyrie P, Lahlou-Laforet K, et al. Vascular Ehlers-Danlos syndrome. Presse Med. 2006;35:1864-1875.

ASCENDING THORACIC AORTA AND AORTIC ARCH • 537

75. Oderich GS, Panneton JM, Bower TC, et al. The spectrum, management and clinical outcome of Ehlers-Danlos syndrome type IV: a 30-year experience. J Vasc Surg. 2005;42: 98-106. 76. Laporte-Turpin E, Marcoux MO, Machado G, et al. Lethal aortic dissection in a 13-year-old boy with a vascular EhlersDanlos syndrome. Arch Pediatr. 2005;12:1112-1115. 77. Barabas AP. Ehlers-Danlos syndrome type IV. N Engl J Med. [author reply]. 2000;343:366;368. 78. Pyeritz RE. Ehlers-Danlos syndrome. N Engl J Med. 2000; 342:730-732. 79. Wenstrup RJ, Meyer RA, Lyle JS, et al. Prevalence of aortic root dilation in the Ehlers-Danlos syndrome. Genet Med. 2002;4:112-117. 80. Koullias GJ, Ravichandran P, Korkolis DP, Rimm DL, Elefteriades JA. Increased tissue microarray matrix metalloproteinase expression favors proteolysis in thoracic aortic aneurysms and dissections. Ann Thorac Surg. 2004;78:2106, 2110; discussion 2110-2111. 81. Longo GM, Xiong W, Greiner TC, Zhao Y, Fiotti N, Baxter BT. Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms. J Clin Invest. 2002;110:625-632. 82. Ikonomidis JS, Barbour JR, Amani Z, et al. Effects of deletion of the matrix metalloproteinase 9 gene on development of murine thoracic aortic aneurysms. Circulation. 2005;112: I242-1248. 83. Boyum J, Fellinger EK, Schmoker JD, et al. Matrix metalloproteinase activity in thoracic aortic aneurysms associated with bicuspid and tricuspid aortic valves. J Thorac Cardiovasc Surg. 2004;127:686-691. 84. Ihling C, Szombathy T, Nampoothiri K, et al. Cystic medial degeneration of the aorta is associated with p53 accumulation, Bax upregulation, apoptotic cell death, and cell proliferation. Heart. 1999;82:286-293. 85. Schmid FX, Bielenberg K, Schneider A, Haussler A, Keyser A, Birnbaum D. Ascending aortic aneurysm associated with bicuspid and tricuspid aortic valve: involvement and clinical relevance of smooth muscle cell apoptosis and expression of cell death-initiating proteins. Eur J Cardiothorac Surg. 2003; 23:537-543. 86. Schmid FX, Bielenberg K, Holmer S, et al. Structural and biomolecular changes in aorta and pulmonary trunk of patients with aortic aneurysm and valve disease: implications for the Ross procedure. Eur J Cardiothorac Surg. 2004;25: 748-753. 87. Wang X, LeMaire SA, Chen L, et al. Increased collagen deposition and elevated expression of connective tissue growth factor in human thoracic aortic dissection. Circulation. 2006;114:I200-1205. 88. Mckusick VA. The cardiovascular aspects of Marfan’s syndrome: a heritable disorder of connective tissue. Circulation. 1955;11:321-342. 89. Kirsch EW, Radu NC, Gervais M, Allaire E, Loisance DY. Heterogeneity in the remodeling of aneurysms of the ascending aorta with tricuspid aortic valves. J Thorac Cardiovasc Surg. 2006;132:1010-1016. 90. Larson EW, Edwards WD. Risk factors for aortic dissection: a necropsy study of 161 cases. Am J Cardiol. 1984;53:849-855.

91. Lansman SL, McCullough JN, Nguyen KH, et al. Subtypes of acute aortic dissection. Ann Thorac Surg. 1999;67: 1975,1978; discussion 1979-1980. 92. Bahnson HT, Nelson AR. Cystic medial necrosis as a cause of localized aortic aneurysms amenable to surgical treatment. Ann Surg. 1956;144:519-529. 93. Homme JL, Aubry MC, Edwards WD, et al. Surgical pathology of the ascending aorta: a clinicopathologic study of 513 cases. Am J Surg Pathol. 2006;30:1159-1168. 94. Vorp DA, Schiro BJ, Ehrlich MP, Juvonen TS, Ergin MA, Griffith BP. Effect of aneurysm on the tensile strength and biomechanical behavior of the ascending thoracic aorta. Ann Thorac Surg. 2003;75:1210-1214. 95. Koullias G, Modak R, Tranquilli M, Korkolis DP, Barash P, Elefteriades JA. Mechanical deterioration underlies malignant behavior of aneurysmal human ascending aorta. J Thorac Cardiovasc Surg. 2005;130:677-683. 96. Borghi A, Wood NB, Mohiaddin RH, Xu XY. 3D geometric reconstruction of thoracic aortic aneurysms. Biomed Eng Online. 2006;5:59. 97. Hatzaras I, Tranquilli M, Coady M, Barrett PM, Bible J, Elefteriades JA. Weight lifting and aortic dissection: more evidence for a connection. Cardiology. 2007;107:103-106. 98. Bertovic DA, Waddell TK, Gatzka CD, Cameron JD, Dart AM, Kingwell BA. Muscular strength training is associated with low arterial compliance and high pulse pressure. Hypertension. 1999;33:1385-1391. 99. Russo CF, Mazzetti S, Garatti A, et al. Aortic complications after bicuspid aortic valve replacement: long-term results. Ann Thorac Surg. 2002;74:S1773,S1776; discussion S1792S1799. 100. Borger MA, Preston M, Ivanov J, et al. Should the ascending aorta be replaced more frequently in patients with bicuspid aortic valve disease? J Thorac Cardiovasc Surg. 2004; 128:677-683. 101. Bulpitt CJ, Cameron JD, Rajkumar C, et al. The effect of age on vascular compliance in man: which are the appropriate measures? J Hum Hypertens. 1999;13:753-758. 102. Mohiaddin RH, Underwood SR, Bogren HG, et al. Regional aortic compliance studied by magnetic resonance imaging: the effects of age, training, and coronary artery disease. Br Heart J. 1989;62:90-96. 103. McEniery CM, Yasmin, Wallace S, et al. Increased stroke volume and aortic stiffness contribute to isolated systolic hypertension in young adults. Hypertension. 2005;46:221226. 104. Scharfschwerdt M, Sievers HH, Greggersen J, Hanke T, Misfeld M. Prosthetic replacement of the ascending aorta increases wall tension in the residual aorta. Ann Thorac Surg. 2007;83:954-957. 105. Laurent S, Boutouyrie P, Asmar R, et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension. 2001;37:12361241. 106. Farrar DJ, Bond MG, Riley WA, Sawyer JK. Anatomic correlates of aortic pulse wave velocity and carotid artery elasticity during atherosclerosis progression and regression in monkeys. Circulation. 1991;83:1754-1763.

538 • CHAPTER 27 107. Nigam A, Mitchell GF, Lambert J, Tardif JC. Relation between conduit vessel stiffness (assessed by tonometry) and endothelial function (assessed by flow-mediated dilatation) in patients with and without coronary heart disease. Am J Cardiol. 2003;92:395-399. 108. Girerd X, Laurent S, Pannier B, Asmar R, Safar M. Arterial distensibility and left ventricular hypertrophy in patients with sustained essential hypertension. Am Heart J. 1991;122: 1210-1214. 109. Rerkpattanapipat P, Hundley WG, Link KM, et al. Relation of aortic distensibility determined by magnetic resonance imaging in patients > or = 60 years of age to systolic heart failure and exercise capacity. Am J Cardiol. 2002;90:1221-1225. 110. Stefanadis C, Stratos C, Vlachopoulos C, et al. Pressurediameter relation of the human aorta. A new method of determination by the application of a special ultrasonic dimension catheter. Circulation. 1995;92:2210-2219. 111. O’Rourke MF, Safar ME. Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. Hypertension. 2005;46:200-204. 112. Petersen SE, Wiesmann F, Hudsmith LE, et al. Functional and structural vascular remodeling in elite rowers assessed by cardiovascular magnetic resonance. J Am Coll Cardiol. 2006; 48:790-797. 113. Wiesmann F, Petersen SE, Leeson PM, et al. Global impairment of brachial, carotid, and aortic vascular function in young smokers: direct quantification by high-resolution mag-

netic resonance imaging. J Am Coll Cardiol. 2004;44:20562064. 114. Stefanadis C, Vlachopoulos C, Tsiamis E, et al. Unfavorable effects of passive smoking on aortic function in men. Ann Intern Med. 1998;128:426-434. 115. Sokolis DP, Zarbis N, Dosios T, et al. Post-vagotomy mechanical characteristics and structure of the thoracic aortic wall. Ann Biomed Eng. 2005;33:1504-1516. 116. Mills NL, Everson CT. Atherosclerosis of the ascending aorta and coronary artery bypass. Pathology, clinical correlates, and operative management. J Thorac Cardiovasc Surg. 1991;102: 546-553. 117. Amarenco P, Cohen A, Tzourio C, et al. Atherosclerotic disease of the aortic arch and the risk of ischemic stroke. N Engl J Med. 1994;331:1474-1479. 118. Davila-Roman VG, Murphy SF, Nickerson NJ, Kouchoukos NT, Schechtman KB, Barzilai B. Atherosclerosis of the ascending aorta is an independent predictor of long-term neurologic events and mortality. J Am Coll Cardiol. 1999;33: 1308-1316. 119. Schachner T, Zimmer A, Nagele G, Laufer G, Bonatti J. Risk factors for late stroke after coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2005;130:485-490. 120. Schachner T, Nagele G, Kacani A, Laufer G, Bonatti J. Factors associated with presence of ascending aortic atherosclerosis in CABG patients. Ann Thorac Surg. 2004;78:2028-2032; discussion 2032.

28

chapter

Aortic Arch Vessels and Upper Extremity Arteries David C. Cassada, MD / Trent L. Prault, MD

Loss of arm and hand function arguably carries higher morbidity than that of the leg, as there seems to be an unspoken stigma associated with arm or hand loss. Upper extremity function is critical to human interaction within the environment. Hand strength, sensation, and other complex functions protect and provide for human survival and socialization. Vascular disorders of the upper extremities result in symptoms ranging in severity from nuisance to limbthreatening. Patients with arm-related vascular pathology are encountered by physicians with lesser frequency than lower extremity vascular disease, making diagnosis and treatment unfamiliar to many clinicians who are otherwise skilled in the care of vascular disease. It is paramount that the clinician be able to recognize many of the upper extremity arterial disorders to prevent both overly aggressive treatment, as well as treatment omissions that could lead to tissue loss. This chapter serves to provide an overview of the diagnosis and treatment of frequently encountered vascular disease patterns of the arm. The arm’s arterial supply consists of the brachiocephalic vessels of the aortic arch, as well as the run-off arterial anatomy of the upper extremities. The disease processes are broken down into three major groups: arterial occlusive/ embolic disease, arterial inflammatory disease, and aneurysmal disease of the branch vessels and upper extremities. In approximately 92% of the population, the aortic anatomy includes, from right to left, the innominate artery, the right common carotid artery, (succeeded across the arch by the origin of the left common carotid artery), and the left subclavian artery. Depending on congenital formation and obliteration of primordial arches allowing for tortuous changes. Over time, the origins of the great vessels can vary

in their initiation across the curve of the aortic arch. In general, the more proximal the take-off of the great vessels from the ascending aortic arch, the more difficult catheterbased access becomes when endovascular surgery is performed for subclavian and carotid arterial disease (Figure 28-1).1,2 In 2% to 6% of patients, the left common carotid artery takes its origin from the innominate artery. This arrangement termed bovine arch, can increase the complexity of intervention for innominate arterial disease, as the majority of cerebral inflow is dependent upon the innominate artery. In general, the innominate artery is the largest branch arising from the arch of the aorta. Its origin occurs at the upper border of the second right costal cartilage and because of the angulation of the aortic arch, it is found anterior to the left carotid in the anterior–posterior plane. The innominate artery typically gives off no branches but in 1% of patients a thyroidea IMA takes origin and supplies blood to the lower part of the thyroid body.1 The right common carotid artery arises from the innominate artery behind the right sternoclavicular articulation. The left common carotid artery takes its origin from the highest point in the aortic arch. The left common carotid is typically longer than the right carotid, and takes its origin deeper within the thorax. The left subclavian artery occupies the position posteriorly and slightly left and lateral to this.3,4 Anomalies in aortic arch anatomy can occur during developmental obliteration of the six primordial aortic arches. One observed anomaly includes the origin of the right subclavian artery from the lower aortic arch at the level of the aortic isthmus, crossing posterior to the aerodigestive tract as a result of the partial persistence of a right aortic arch.

540 • CHAPTER 28

• FIGURE 28-1.

Great vessels arising far right within the aortic arch present challenges in the endovascular treatment of both occlusive and aneurysmal disease of Axillo-subclavian arterial segments.

Chronic compression by aerodigestive structures can result in subclavian arterial aneurysmal degeneration, manifesting as dysphagia or airway-obstructive symptoms. The number of arch vessels can also be increased from three to four where the right carotid and subclavian arteries arise directly from the aortic arch with the innominate being absent. Based on primordial arch anatomy, this arrangement can be highly variable, and the number of trunks from the arch may be increased to five or six. In such cases, the external and internal carotid arteries can rise separately from the main aortic arch. In rare cases, where six branches are encountered, there are also separate origins of the vertebral arteries directly from the aortic arch. Because of the rare potential variety of arch anatomic configurations, there can be any combination of these anomalies with new challenges presented during the management of aortic arch disease.

•

GIANT CELL ARTERITIS

Giant cell arteritis (GCA) is termed temporal arteritis or cranial arteritis. This is a systemic vasculitis affecting segmental portions of the aortic arch and great vessel anatomy.5−7 Early signs of this disease process can include headache and partial or complete vision loss as a result of dissection or end-arterial obliteration.8,9 Further catastrophic consequences of GCA can include aortic aneurysmal rupture and cerebral or coronary hypoperfusion syndrome. Additionally, the axillary and brachial arteries can be affected resulting in rapid onset of forearm and hand claudication symptoms. The aortic arch and its branches, particularly the medium diameter branches, are the blood vessels most

affected. Rarely, lower abdominal branch vessels including renal, mesenteric, and iliofemoral arteries as well as the coronary arteries can be affected.7 GCA can cause an array of changes to include stenosis, frank occlusion or aneurysmal dilatation. Microscopically the vascular wall is infiltrated with inflammatory cells, particularly monocytes and CD-4 positive T cells, as macrophages are found to penetrate throughout the arterial wall. Multinuclear giant cells are observed and found closely related to the disrupted internal elastic membrane, likely because of the activity of proteolytic enzymes.7,10 Loss of this membrane and medial necrosis can cause formation aneurysms or thickening of the wall acute bouts of arteritis resulting in stenosis or occlusion. Early signs of GCA include headache, poor appetite, muscle pain, loss of weight and febrile status. Within weeks, severe headaches and jaw claudication can occur.5,6,11 If these symptoms are in fact caused by GCA, 40% of untreated patients may proceed to permanent vision impairment to include blindness, ipsilateral to the affected arteries. Many patients with GCA demonstrate underlying polymyalgia rheumatica (PMR). PMR can present as pain in the shoulder and hip girdles with weakness and muscle pain during motion.12 Classic symptoms and presentation are rare, therefore, unilateral headaches, particularly those with visual changes, should prompt consideration of GCA and result in the appropriate testing to include measurement of Westergren sedimentation rate (WSR or ESR) and C-reactive proteins (CRP). A WSR greater than 50 mm/h is of concern for GCA but often can exceed 100 mm/h in patients with severe GCA. CRP is noted to be increased in 92% of patients and although this is a nonspecific test, it can be sensitive in detecting GCA. Elevated white blood cell count, platelet count and liver enzymes occur in roughly 30% of patients with GCA. Occasionally, GCA can also be associated with increased anticardiolipin antibodies, compounding the obliterative process because of the associated thrombophilia.5,7,8,10 Treatment of GCA requires confirmation of diagnosis with arterial biopsy done at a low threshold based upon clinical presentation. In patients in their sixth or seventh decade of life, new onset of severe headaches, jaw claudication, or bilateral arm claudication, with or without systemic signs of inflammation, could indicate GCA. Evaluation should include noninvasive arterial waveform testing, arterial biopsy and occasionally arteriography.6 Duplex evaluation of the temporal artery demonstrates the “halo sign.” Waveform plethysmography of the upper extremities may suggest bilateral proximal axillo-subclavian or brachial artery occlusive disease. Brisk onset of such disease is consistent with acute GCA and may present as arm and hand claudication during performance of tasks (Figure 28-2).7 Unilateral headaches, with or without visual changes and positive ESR and CRP, should prompt vessel biopsy to confirm the diagnosis. Biopsy of the temporal artery should include a minimum 2-cm segment with a longer segment obtained if possible, thereby improving the pathologic

AORTIC ARCH VESSELS AND UPPER EXTREMITY ARTERIES • 541

A

B

• FIGURE 28-2.

(A) GCA can involve segment of the axillary and brachial segments of the upper extremity arterial anatomy. (B) Although the treatment of GCA generally requires the use of steroids to resolve arterial inflammation, occasionally endovascular therapy or surgical bypass can be performed for tissue-threatening occlusive lesions. Here a selfexpanding stent is deployed to improve arm arterial runoff in a patient with hand tissue loss.

sampling of the vessel, as well as the sensitivity and specificity of this clinical test to confirm GCA.10 The acute treatment of GCA includes the administration of corticosteroids. Prednisone can be initiated at a dose of 1 mg/kg per day. However, in those with impending vision loss, prednisone should be administered in a dose of at least 20-mg three times daily. Once the active phase of the disease is controlled, the dose is consolidated to a single daily dose until the vasculitis resolves completely, after which steroid taper is possible. Corticosteroid treatment can be guided by normalization of ESR and CRP. Other medications have included various forms of immunosuppressive drugs, with variable proven clinical efficacy.5∗ Surgical bypass for the complications of GCA is typically not performed in the inflammatory setting of acute vasculitis. Where tissue threat is present, principles of surgery include bypass from normal inflow vessels to relatively healthy target vessels while trying to avoid the inclusion of acutely diseased segments in the anastomotic zones of the revascularization. There seems to be little role for endovascular therapy beyond diagnostic imaging of diseased arteries in planning for medical and/or surgical therapy. However, in those patients with severe comorbidities, angioplasty is a reasonable treatment strategy to avoid tissue loss.

•

RADIATION-INDUCED ARTERITIS

Radiation-induced arteritis is seen increasingly in patients who have undergone radiation in the treatment of malig-

nancies earlier in life. Ionizing radiation tends to injure rapidly dividing cells and is therefore effective in cancer cells. However, adjacent tissue radiation can result in damage to normal mitotic cells and can result in chronic radiation damage of the vascular tree.13 Endothelial cells are exquisitely radiosensitive. Initially there can be swelling and exfoliation of endothelial cells, which can lead to obstruction of small blood vessels by thrombosis as subintimal collagen is exposed to blood cell constituents. Therefore, the acute damage of small diameter cells results in characteristic “sausage segment” with irregular stenotic occlusion of these vessels. In larger diameter vessels, there can also be damage to the vaso vasora with chronic medial fibrosis producing a narrowed arterial lumen which may require revascularization, depending upon its location within the great vessel anatomy.13

•

SMALLER ARTERIAL DISEASES OF THE UPPER EXTREMITY

In the majority of patients with ischemic changes of the hand, there is a relationship to small vessel obstructive disease. The small vessel arterial disease results in symptoms related to vasospasm or obstruction of the small digital arteries of the hand. The vasospastic processes can result in a waxing and waning of ischemic changes, coolness, pain, and numbness. Color changes are often initially observed which may make the patient particularly aware that there is an arterial problem with their digits. Vasospasm can ultimately

542 • CHAPTER 28

lead to loss of portions of the digits if the disease goes unchecked.

•

RAYNAUD’S SYNDROME

Raynaud’s Syndrome (RS) is the most commonly encountered upper extremity arterial disease process. RS manifests as intermittent digital ischemia in response to environmental cooling of the hand. This can be exacerbated by high cat cholinergic states such as during periods of emotional or physical stress. RS has a classic presentation of tri-colored changes proceeding from white to blue to red, although one or more phases of this color progression may be absent. RS is seen in the cooler and damper climates typical to the United States, Great Britain, and Scandinavia.14,15 RS is subdivided into vasospastic and thrombo-obstructive subgroups. Those with vasospastic RS can be observed as having normal plethysmographic waveforms when symptoms are not present. Vasospasms result in a marked increase in the obstructive characteristics of peaked plethysmographic waveforms (“nipple sign”) in the fingertips, correlating with symptoms. A large portion of the patients (approaching 50%) can proceed to obstructive RS as the vasospasm results in intraluminal small vessel obliteration sufficient to overcome systemic pressure distending forces.15 Treatment of RS initially includes major lifestyle modifications including the liberal use of gloves for thermal protection from environmental cold stress. Patients are encouraged to avoid handling cold objects, and to refrain from submerging their hands in cold water. They are also counseled regarding rapid changes in environmental temperatures such as proceeding into an air-conditioned indoor setting from an otherwise warm day. Underlying life stressors are identified and addressed as is appropriate. Initial pharmacological therapy includes the use of calcium channel blocking medications, and antiplatelet medications.14−16 Some physicians recommend medications to alter the rheology of red blood cells to decrease small vessel blood viscosity. Long-acting vasodilators, such as nifedipine (available in a 30-mg slow-release formulation) as well as an antiplatelet medication, can be effective. Patients refractory to these measures can be treated with either needle directed pharmacological sympathectomy or surgical sympathectomy focusing efforts on the second thoracic segment of the sympathetic ganglia. There are also multiple treatment regimens dependent upon pharmacological sympatholytic agents (primarily alpha adrenoceptor blockade) to affect vasodilatation during severe vasospasm.15,17 Connective tissue diseases can be associated with RS although literature review shows a wide variation in association. Most commonly, these diseases include scleroderma, lupus, polymyositis, and rheumatoid arthritis. Many patients with some connective tissue disease will manifest RS during fulminant courses of their disease process; however, an aggressive search for connective tissue diseases will often be nondiagnostic in those patients presenting with RS alone.14

There are other causes for RS as a secondary process related to primary disease or traumatic insult. Ergot derived drug toxicity and ␤-adrenoceptor blocking medications can initiate RS as well as acquired arterial occlusive conditions. Arterial thoracic outlet syndrome can also be complicated by secondary RS and the surgical treatment may include T2 sympathectomy to improve vasodilation after thoracic outlet decompression and revascularization.

•

BUERGER’S DISEASE

Thromboangiitis obliterans or Buerger’s Disease (BD) is characterized by thrombosis of small and medium-sized arteries in the extremities with associated arterial wall leukocyte infiltrate.18,19 A large number of patients suffering from BD will have only upper extremity manifestations; however, 40% of these may also demonstrate lower extremity disease. Patients with BD are predominately men in their fourth decade who often abuse tobacco. The age of onset is especially important in suspicion of this disease, as it almost always occurs before 45 years of age. This is further suggested by noninvasive evidence of the absence disease proximal to the elbow in the upper extremity, and proximal to the knee in the lower extremity. Although strongly suspected, tobacco abuse alone does not constitute a sole risk factor for BD. Arteriographic findings with BD include normal appearing inflow vessels with the presence of “cork screw” changes in the small and medium vessels of the distal extremity and digits. The corkscrew changes result in obliteration of normal arterial lumens as a result of the inflammatory changes within the vessel. Collaterals are formed as the adventitial vaso vasora form large channels to perfuse the distal extremity. As the collaterals form, they are ectatic and irregular, resulting in the “cork screw” appearance. Treatment includes extensive counseling regarding tobacco use, as well as psychological counseling, and the possible use of pharmacologic agents to break habitual smoking. It is still important to refrain from pharmacological nicotine substitutes, as these medications tend to exacerbate peripheral vasospasm, which may worsen the BD.18 There are clinical reports of the use of pharmacologic sympathectomy to treat acute bouts of digital ischemia, and rarely the use of surgical sympathectomy of both the lower and upper extremities to abate the disease process. Up to 40% of patients will proceed to digit loss and/or major portions of extremities. This is likely because of the high recidivism rate of those who attempt tobacco abstinence. There is limited relief after the use of long-acting calcium channel blockers and/or sympathectomy.20

•

OCCUPATIONAL UPPER EXTREMITY VASCULAR DISEASE

Exposure to traumatic or regular use of vibrating instruments such as jackhammers and mortar screws can result in chronic small vessel arterial disease. The initiating factors are thought to be vasospasm especially where cold exposure is involved, followed by arterial obliteration.

AORTIC ARCH VESSELS AND UPPER EXTREMITY ARTERIES • 543

Other traumatic injuries to hand arterial vessels can occur in certain lines of work where the hand is used as a blunt force to move or align objects. As such, pounding of the hypothenar imminence of the hand results in “hyperthenar hammer syndrome” where the distal most segment of the ulnar artery is traumatized at the wrist. This can result in aneurysmal changes with ischemia secondary to thrombosis or distal embolization. Arteriography is often diagnostic and can help plan small vessel repair where incomplete palmar arch anatomy precludes resection and ligation of the diseased arterial segment.

•

AORTIC ARCH RECONSTRUCTION

Management of aortic arch arterial disease requires many considerations. For occlusive disease, the clinician must consider the fact that there is redundancy of cerebral inflow to both the anterior and posterior circulation making even short segment occlusive lesions tolerable by the patient. Therefore, not every occlusion requires treatment. Left subclavian arterial occlusive disease is the most common complete occlusion found in patients with extracranial cerebrovascular disease. This is followed by left common carotid artery disease, and brachiocephalic occlusive lesions. Left subclavian arterial occlusive disease is usually well-tolerated by patients, absent most of which are neurologic symptoms (i.e., although patients may have subclavian steal, they do not have subclvavian steal syndrome). Often there is no reason to treat great vessel disease at this level. Symptoms can include neurologic deficits resulting from arterial embolic phenomenon to include transient ischemic attacks and strokes of the anterior and posterior circulation. Additionally, hemodynamic factors must be considered such as subclavian steal syndrome of posterior circulation, whereby there is observed reversal of vertebral blood flow to supply the upper extremity runoff basin when the resistance of the arm capillary bed is lower than that of the posterior fossa run off. Interestingly, symptoms can sometimes be provoked after deflating a blood pressure cuff on the affected arm. The resultant low resistance to the arm “steals” more blood from posterior circulation—thus, causing symptoms. Radiographic subclavian steal anatomy can be observed absent the symptoms associated with subclavian steal syndrome. Typically, a patient with true subclavian steal syndrome will complain of vertebral-basilar related symptoms such as effort-induced dizziness, dizziness at rest, blurred vision, and even nausea and vomiting. In patients presenting with these symptoms, a pressure gradient between the arms of 20 mm Hg systolic blood pressure can indicate that the anatomy producing subclavian steal syndrome could be present. The “Dieter test” can be useful to provoke symptoms in a patient with borderline symptoms. In this test, a blood pressure cuff is applied to the affected extremity and inflated above the systolic pressure. The cuff is then rapidly deflated. This results in hyperemic flow to the arm and exacerbation of any vertebral artery flow reversal and steal—potentially evoking neurological symptoms. Diagno-

sis can be made with noninvasive imaging such as MRA and CTA with image reconstruction to determine the extent of subclavian artery occlusive disease, as well as proximity to the origin of the ipsilateral vertebral artery. Dyanamic kinking of the proximal subclavian artery during respirations (the “Dieter sign”) has been described; since it represents a pseudostenosis, invasive treatment should be avoided (Figure 28-3). Other considerations for subclavian steal syndrome include the presence of common and internal carotid artery disease, as well as intracranial vascular anatomy, which may play an important role in the presence of subclavian steal syndrome. Despite the subclavian steal syndrome that is observed clinically in select patients, chronic occlusion of the proximal left subclavian artery is surprisingly well-tolerated by a significant number of patients where there is a robust collateral arterial network supplying both the intracranial runoff and the axillo-subclavian segment. It is likely that fewer than 30% of these lesions will ever come to clinical significance and are therefore rarely treated. In symptomatic patients with demonstrated subclavian steal syndrome related to proximal subclavian artery occlusive, it is reasonable to consider catheter-based therapy. The appeal of such therapy includes avoiding the cardiovascular stress of general anesthesia and operative exposure, as well as reducing arterial occlusive times related to crossclamping of the subclavian artery and the ipsilateral common carotid artery. Important to consider is prior coronary revascularization, where the ipsilateral internal mammary artery may provide inflow to the myocardial vessels pending on patent graft function. In this subset of patients, there can be observed subclavian steal with associated anginal symptoms (“coronary subclavian steal syndrome”). Careful consideration is made prior to treating these patients either by endovascular or open technique given the potential for worsened complicating myocardial ischemia and myocardial infarction. Both subclavian and axillary arterial lesions can be approached either antegrade by a femoral artery access or retrograde by brachial or radial artery access.21,22 The best candidates are those patients who have lesions that are not involving the origin of the vertebral or internal mammary artery (Figure 28-4). Whether the antegrade or retrograde approach is planned, aortic arch arteriography is important and is generally performed through a femoral approach, using a pigtail catheter. Imaging of the arch and great vessel origins is important to define the exact location of the vessel ostium, so that ballooning and stenting of these lesions can be done with great precision. Often a guide wire is left positioned against the outer curve of the aortic arch to help determine where the great vessel origin takes place during the variability of the cardiac cycle.23 The best lesions indicated for angioplasty and/or stenting are those which are remote from the subclavian region, both well proximal and isolated from the vertebral artery. A lesion juxtaposed to the vertebral artery may be best treated with open surgery since intervention may result in vertebral artery dissection and compromise vertebral artery

A

B

• FIGURE 28-3.

The Dieter sign represents dynamic subclavian artery obstruction with respiration. (A) With inspiration the artery is straightened. (B) With expiration there is apparent stenosis.

Reproduced, with permission, from Dieter RS, et al. Description of a new angiographic sign: dynamic left subclavian artery obstruction. Vasc Dis Manage. 2006;3:298–299.

B

• FIGURE

A

544

28-4. These images show upper extremity (A) with and (B) without evocative maneuvers that reveal extrinsic compression of the sublcavian and/or axillary artery. Without such maneuvers, these periodic compressive forces would not be evident, and potentially not seen during the evaluation of the patient with arterial thoracic outlet syndrome. Areas of extrinsic compression can represent damage to the arterial wall intima, and are potentially sources for thromboembolic disease of the hand.

AORTIC ARCH VESSELS AND UPPER EXTREMITY ARTERIES • 545

blood flow. Such a complication can have catastrophic consequences, which may not be addressed quickly enough to avoid neurological morbidity using a less invasive procedure. Some have utilized protection strategies for complex lesions involving the vertebral artery. Balloon diameter within the subclavian artery is typically chosen between 6 and 8 mm. The subclavian artery is quite soft and rupture of this vessel can result in acute intrathoracic bleeding which can be fatal. Therefore, computer-assisted measuring of the vessel prior to intervention is critical to treatment planning; others have used IVUS or a marker catheter during angiography for sizing. Once angioplasty is performed, completion angiography is reviewed to look for evidence of recurrent stenosis greater than 20% of the normal luminal diameter of the vessel, or the presence of a subclavian artery dissection. Thereafter, a balloon expandable or selfexpanding stent can be placed to assure wide patency of the treated vessel and also to reapproximate any intimal flaps to prevent ongoing dissection or acute occlusion during the perioperative period.23 There is little long-term data regarding the use of stents in the proximal subclavian arteries. In one study by Peterson et al; there is a report of 20 consecutive brachiocephalic interventions using catheter-based technology for stenosis ranging from 85% to 95% diameter narrowing.22 A technical success rate of 100% is reported as well as a nonincidence of any periprocedural untoward events. Long-term outcomes and restenosis data is incomplete in this series, and cannot be compared to open surgical data. In a separate study, proximal subclavian artery angioplasty and stenting was performed in the treatment of coronary steal syndrome after coronary revascularization using internal mammary artery in 14 patients. Again, this study did not reveal any significant periprocedural morbidity or mortality and a 29month patency was cited at 100%. From this data, it seems that there is clearly a role for angioplasty and/or stenting in the proximal subclavian artery in select patients with symptoms of subclavian steal syndrome or arm claudicating symptoms.21 Other considerations during treatment for axillosubclavian artery occlusive disease include the morphology of the vascular lesion. If there is associated aneurysmal disease or ulceration within the plaque, strong consideration should be made favoring open surgery to provide a more durable repair, potentially avoiding the complication of upper extremity or posterior circulation embolic phenomenon (thoracic outlet syndrome must be ruled out for distal lesions prior to undertaking an endovascular treatment since these lesions are best treated initially with surgical decompression). More recently, there has been clinical experience with the use of embolic protection devices to include occlusive balloons and filter wires to control embolic disease. Given these advances in technology, some authors favor the use of endovascular treatment for proximal subclavian lesions over open surgical technique.22 Open surgical management of proximal arterial occlusive lesions consists of two basic techniques, subclavian to carotid arterial transposition and carotid to subclavian by-

• FIGURE 28-5.

The complete absence of great vessel origins on vascular imaging generally precludes safe endovascular intervention, and surgical bypass become the treatment of choice in those patients with cerebrovascular symptoms or arm ischemic symptoms.

pass, both providing inflow to the upper extremity as well as vertebral or internal mammary arteries (Figure 28-5). Subclavian artery transposition has the adherent advantage of avoiding the use of bypass graft conduit.24,25 In the neck, nonautogenous materials such as polytetrafluoroethylene and modified Dacron polyester seem to have an advantage where dynamic movement in the neck and shoulder girdle can lead to graft kinking. The ridged nature of such manmade materials tends to resist kinking during routine range of motion use of the neck and upper extremity. Subclavian to carotid transposition requires general anesthesia and involves proximal mobilization and transection of the subclavian artery with end-to-side transposition of this vessel to the common carotid artery. Such an operation has challenging technical aspect as the subclavian artery needs to be dissected deep within the thoracic outlet and loss of control of the proximal subclavian artery can lead to intrathoracic and mediastinal hemorrhage which may be difficult to control acutely. The remaining subclavian artery stump needs to be oversewn in a secure fashion using permanent monofilament suture to prevent postoperative bleeding or pseudoaneurysm formation in the remaining stump.26 During the course of subclavian artery transposition, there is occlusion of both the subclavian artery and the common carotid artery so it is important to have knowledge of the intracranial arterial anatomy optimally including a patent and complete circle of Willis. If there is uncertainty as to the extent of collateral circulation, distal common carotid artery stump pressures can be measured

546 • CHAPTER 28

while intraoperative systolic blood pressure is maintained at 150 mm Hg or greater. A pressure of at least 30 mm Hg within the distal stump would indicate adequate collateral blood flow to tolerate the relative ischemic time during the reconstruction. The reconstruction should be brisk, yet meticulous, with excellent communication between the surgeon and anesthesiologist to maintain cerebral perfusion pressures by manipulating the intraoperative blood pressure and maintaining a systolic 150 mm Hg or greater.24 If coronary revascularization exists, based on internal mammary artery bypass, this technique may be unsuitable as proximal subclavian occlusion could precipitate myocardial infarction during the obligate ischemic period of subclavian artery cross-clamping. Carotid subclavian transposition, when done correctly, can demonstrate long-term patency rates exceeding 80%. Perioperative mortality should be less than or equal to 1% with a brief hospital stay. These assumptions are made based on the experience of the surgeon with prior operations and the ability to complete a well-orchestrated operation.24 Carotid to subclavian bypass may be a better option when there is extensive proximal subclavian artery occlusive disease or there is compromised intracranial blood flow, such that two vessel cross clamping cannot be tolerated without unacceptable cerebral ischemia. It can also be a treatment of choice where coronary blood flow is dependent on an IMA bypass graft, as proximal subclavian arterial clamping may not be necessary.24 Access is made to both the common carotid artery and the subclavian artery with close proximal dissection within the thoracic outlet. A short-segment 6- or 8-mm polytetrafluoroethylene or Dacron graft is selected, and placed in such a position as not to compromise the phrenic nerve and also to be resistant to kinking during range of motion.26 Manipulation of the arm should be carried out after conclusion of the operation to assure no graft kinking occurs. More distal extremity revascularizations to the axillary and brachial artery are best done with autogenous material such as reversed or nonreversed greater saphenous vein. The saphenous vein provides a healthy conduit which is relatively resistant to intimal hyperplasia. There is better size matching on the distal vessel and crossing of the shoulder girdle and even the elbow joint can be successfully achieved with reasonable patency rates over time. Primary patency rate of the carotid-subclavian artery bypasses should be in excess of 90%, but major complications can include thoracic duct injury on the left, resulting in limb fistula or chylothorax, Horner’s syndrome, cranial nerve injury, graft infection, or possible phrenic injury. The morbidity of such an operation should be similar to that of carotid-subclavian transposition and is again dependent on the experience of the surgeon performing the operation.24

•

ARTERIAL THORACIC OUTLET SYNDROME

It is important that the clinician pay special attention to arm and hand complaints by sorting out the different vascular

related diseases to prevent morbidity related to arterial disease of the arm. Thoracic outlet syndrome (TOS) is defined by symptoms and clinical findings that can vary in description from one authoritative source to the next. TOS contains references to multiple anatomic sites of neurovascular compression, all generally located around the scalene musculature, and the first thoracic rib and the clavicle, resulting in end-organ dysfunction. Morbidity includes ischemic and embolic arterial disease, venous-occlusive disease, and neuropathic disease.27−29 The vascular components of TOS can have objective measures to specify the diagnosis and describe the pathophysiology, while neurogenic TOS carries the challenge of trying to interpret a location of neurocompression based upon history, symptoms, and often-subjective clinical findings.30 These complicating factors can lead to significant time delay in diagnosing TOS. When arterial compromise results from TOS, delay in treatment can severely compromise functional outcome because of the ongoing arterial damage and thromboembolic events, potentially leading to permanent neurologic damage.31−35 In a review of our own experience with TOS at the University of Tennessee Knoxville, we found the clinical course of arterial TOS is largely determined by correct early identification of those patients at risk for arterial compression (Table 28-1). Unfortunately, because of the confusing nature of symptoms many patients have had prior diagnoses ascribed to explain pain and numbness, and a large subset have even had non-TOS operations that preceded vascular examination.30 As time progresses, further arterial damage occurs with aneurysmal degeneration of the artery, thromboembolism, and permanent loss of runoff vessels to the arm and hand.36 Although technical success is possible in the revascularization after longstanding disease, there can be a loss in function and pain likely related to chronic ischemia. Clinical awareness of TOS is therefore paramount to recognizing and appropriately treating patients early, before permanent arm impairment occurs. The bony boundaries of the thoracic outlet include the transverse processes of the lower cervical vertebrae, the first

TABLE 28-1. Examples of Potential Risk Factors for the Development or Exacerbation of Extrinsic Arterial Compression in TOS, as Seen in the Described Series Review r Shelf stocking r MVC r Repetitive labor r Healthcare r COPD/coughing r Baseball pitcher r Cheerleader r Computer r No identified risk

3 3 5 2 2 1 1 2 3

AORTIC ARCH VESSELS AND UPPER EXTREMITY ARTERIES • 547

• FIGURE 28-6.

Sub-humeral brachial artery compression is seen particularly in athletes where damage to segments under traction can result in aneurysm formation and/or digital thromboembolization.

A

thoracic rib and clavicle.37 This bony framework provides the platform for the musculature that completes the “fixed” points of the thoracic outlet. The transverse processes of C4 through C7 are invested with the tendinous origin of the anterior and middle scalene, which inserts onto the anterior and lateral superior surfaces of the first rib. These muscles have a teleological role in ventilation, and are rarely recruited in the healthy adult during periods of ventilatory exertion as a portion of the “accessory” muscles of breathing. Cervical ribs can exist with variation in size and “completeness,” ranging from complete C7 ribs that insert 3/4 of the length along the first rib to small rudimentary ribs with fibrous bands that connect to the first rib.38 These bony and fibrous elements are well described and raise the floor of the scalene triangle, leading to an increased fulcrum of the artery and lower trunk of the brachial plexus where it exits the interscalene space.37 Where a cervical rib exists with symptoms, there is no opportunity for relief by physical therapy alone, and surgery is needed to eliminate the possibility of ongoing subclavian artery damage. Diagnosis of arm ischemic changes from TOS can be made based upon history and physical examination. Digital plethysmography with the arms placed in positional, evocative maneuvers can help confirm the diagnosis. Compression of the subclavian artery most often occurs at the insertion of the anterior scalene muscle upon the anterior first thoracic rib, and elevation with abduction of the arm

B

• FIGURE 28-7.

(A and B) Evocative maneuvers performed during the course of arteriography may be required to reveal sites of extrinsic arterial compression. This series was obtained during the evaluation of a patient with digital ulceration caused by thromboembolism developed during the course of manual labor requiring overhead arm tasks.

548 • CHAPTER 28

accentuates the extrinsic compression with subsequent pulse waveform dampening. Those patients with a fixed diminution in the pulse or with frank ischemic changes caused by embolism should proceed to arteriography both to confirm the diagnosis and to plan therapy consisting of thrombus clearance with revascularization of the damaged arterial segments.39 This author prefers to avoid percutaneous thrombolytics as morcellation of the thrombus can lead to distal embolization and loss of precious digital runoff vessels. Controlled open thrombectomy of the major burden of thrombus can be performed safely, followed by the administration of urokinase or tissue plasminogen activator to dissolve small residual thrombus debris. In our series of patients, we have observed three separate sites of arterial compression as a cause for arm ischemia either because of the ongoing embolization or arterial occlusion. These include the anterior scalene insertion point on the first rib, (just posterior to the insertion of pectoralis minor on the first rib), and under the humeral head because of traction on the circumflex humeral branch vessels (Figure 28-6). To elucidate the exact location of arterial injury during arteriography, evocative maneuvers should be performed to include Adson’s maneuver and the “military

tuck” position (Figure 28-7). If thrombus is seen, residing in the vessel at any of these shoulder girdle locations, the evocative maneuvers are avoided, and adequate data will include only a runoff sequence to determine the degree of distal embolic disease. In our review of 23 patients undergoing treatment for arterial TOS, 95% had complete resolution of hand emboli, with no further events after surgery. There was 80% technical success for patients undergoing revascularization. A single failure accounts for further loss of runoff and failure of graft patency after surgery in a patient with thrombophilia. This unfortunate patient underwent hand amputation after three failed attempts at thrombectomy and graft revision. Postoperative morbidity was common and included temporary or chronic neuropathic pain, ischemic nerve injury with contracture, temporary phrenic nerve dysfunction, and pneumothorax. The greatest number of complications was encountered in the group undergoing revascularization; however, decompression alone accounted for a significant number of untoward events (Figure 28-8). Patients undergoing revascularization failed to return to gainful employment during the study interval and 63% undergoing decompression alone were able to return to work with physician-guided modifications to their manual responsibilities. In all cases, the surgeon played an active role as patient advocate in obtaining disability leave, interacting with employment safety officers, and providing depositions in the event of worker’s compensation determination. All patients treated by physical therapy alone were eventually able to return to the workforce with specific restrictions imposed, while 60% of those undergoing decompression

Neurovascular compression

Reversible

Digital emboli

Tissue loss

Activity related

Persistent ischemic symptoms

Severe arterial insufficiency

No ischemic changes

Angiography Physical therapy

Angiography

Decompression

Modify lifestyle

Decompression

Revascularization

Antiplatelet

Modify lifestyle

Assist life needs

TIME OF SYMPTOM PROGRESSION

• FIGURE 28-9. • FIGURE 28-8.

Intraoperative exposure of the interscalene space during thoracic outlet decompression for dynamic arterial compression. Although relatively rarely performed, this intervention can help salvage extremities threatened by ongoing arterial injury during the course of every day tasks.

Proposed algorithm for the treatment of arterial TOS. Symptoms and arterial injury can progress in a time-based fashion, requiring more aggressive treatment ranging from physical therapy with antiplatelet pharmacology to complex surgery with the goals of arterial decompression and vessel reconstruction. Although arm salvage is generally the rule, longstanding embolic and ischemic damage can lead to functional destruction of the arm and hand.

AORTIC ARCH VESSELS AND UPPER EXTREMITY ARTERIES • 549

were eventually able to perform an occupation (Figure 28-9). All patients undergoing decompression and revascularization were rendered disabled for the study period. Time to diagnosis seemed to correlate closely with the degree of arterial damage and need for aggressive interven-

tion. The best method of improving outcome in these difficult cases is to generate a wider clinical understanding and awareness of arterial TOS with primary care providers who have the important role of directing patients to the appropriate vascular specialist for treatment.

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37. Ritter A, Sensat ML, Harn SD. Thoracic outlet syndrome: a review of the literature. J Dent Hyg. 1999;73(4):205-207.

35. Davidovic LB, Kostic DM, Jakovljevic NS, et al. Vascular thoracic outlet syndrome. World J Surg. 2003;27(5):545550.

38. Guidotta TL. Occupational repetitive strain injury. Am Fam Physician. 1992;45(2):585-592. 39. Durham JR, Yao JS, Pearce WH, et al. Arterial injuries in the thoracic outlet syndrome. J Vasc Surg. 1995;21(1):57-70.

chapter

29

Descending Thoracic Aorta Daniel Alterman, MD / Raymond A. Dieter III, MD

•

INTRODUCTION

Acute aortic syndrome presents challenging diagnostic and therapeutic disease. Intramural hematoma (IMH), penetrating aortic ulcer, aortic dissection (AD), and aneurysm can all have a similar clinical presentation with advanced disease. Many of these syndromes have undergone significant revision in terms of classification and therapeutic strategy in the last 30 years. The increasing sophistication and speed of computed tomographic (CT) scan has raised it to a prominent role in the evaluation of this disease. The exact role endovascular intervention will play in the treatment algorithms remains to be determined. Despite the benefit of modern imaging and this collective experience, it remains a highly morbid malady.

•

EMBRYOLOGY

The embryonic vascular system begins formation in the third week of gestation. From the primitive aortic sac arise six ventral paired aortic arches. These pass laterally around the primitive gut to terminate in the paired dorsal aortae. Eventually, there is fusion of the paired dorsal aortae. The first pair of aortic arches contributes to formation of maxillary and external carotid arteries. The second pair contributes to formation of the stapedial arteries. The third pair contributes to formation of the common and internal carotid arteries. The left fourth aortic arches contribute to form the aortic arch and the right fourth arch contributes to formation of the right subclavian artery. The fifth pair of aortic arches usually has no anatomic contribution. An association between persistent fifth aortic arch and chromosome 22q11.2 deletion has been described.1 The left sixth aortic arch contributes to formation of the left pulmonary artery and the ductus arteriosus. The right sixth

aortic arch contributes to formation of the right pulmonary artery.

•

ANATOMY

The descending thoracic aorta arises from the aortic arch just after the origin of the left subclavian artery, at the inferior border of the fourth thoracic vertebrae. This point of transition is termed the aortic isthmus. In adults, the average diameter of the descending thoracic aorta is 2.8 cm in men and 2.6 cm in women.2 This narrows as it descends into the abdomen. It terminates as it enters the abdomen via the diaphragmatic aortic hiatus, at the 12th intercostal space. The thoracic aorta descends in the posterior mediastinum to the left of the vertebral column and gradually shifts to the midline at the aortic hiatus. It is surrounded by the thoracic aortic plexus. Anteriorly, the left pulmonary hilum crosses with the left main bronchus and left pulmonary artery being closely associated. Continuing inferiorly, the esophagus, pericardium, and diaphragm are also situated at the anterior border of the thoracic aorta. As the thoracic aorta descends, the esophagus crosses anteriorly and then laterally at the diaphragm. Posteriorly, the hemiazygous vein and anterior vertebral column are associated. Laterally, it is closely applied to the inferior lobe of the left lung. Medially, the esophagus, thoracic duct, and azygous vein are closely associated. There are bronchial, esophageal, intercostal, mediastinal, pericardial, subcostal, and superior phrenic branches of the descending thoracic aorta. The main artery supplying the lower spinal cord (artery of Adamkiewicz) typically arises from a left-sided intercostal artery between the 9th and 12th intercostal spaces. The wall of the aorta is composed of thin inner intima, a thicker middle media, and a thinner outer adventitia containing vasa vasorum. During systole, the elastic laminae

552 • CHAPTER 29

of the robust media distend and create potential energy, which is transmitted during the diastolic phase.

•

THORACIC AORTIC ANEURYSM

Epidemiology The estimated incidence of thoracic aortic aneurysm (TAA) was 0.37/100 000 person-years.3 The incidence has been reported to be rising dramatically in the past 40 years, with a recent estimate of 10.4/100 000 person-years.4 The median age of diagnosis ranges from 64.5 to 68.5 years and the mean 58 to 70.5 years. Men tend to have a higher incidence than women with an average ratio of 1.9:1, but the reported range varies from 0.9:1 to 17:1.5 Several risk factors have a strong association with TAA formation. Of those having TAA, greater than 70% have hypertension and at least 80% are smokers.5 Other associated risks are coronary artery disease, chronic renal failure, cerebrovascular disease, peripheral vascular disease, visceral occlusive disease, chronic obstructive pulmonary disease (COPD), and diabetes mellitus.5 A recent study of TAAs, dissections and pedigrees revealed that 21.5% of non-Marfan syndrome patients had an inherited pattern. Seventy-six percent were transmitted autosomally dominant with a varying penitiance.6 Pathophysiology An aneurysm has been defined as a permanent localized dilation of an artery having at least a 50% increase in diameter compared to the expected normal diameter of the artery. The average diameter of the descending thoracic aorta is 2.8 cm in men and 2.6 cm in women.2 It is more accurate to define the size of aneurysm based on expected size of age, gender, and body surface area (BSA) matched controls. This data is available in the Pearce et al. paper2 (see Figure 29-1). An imbalance of enzymatic degradation as well 30

Levels 1 - Thoracic 2 - Celiac 3 - Renal 4 - Infrarenal 5 - R. Iliac 6 - L. Iliac

28

Diameter (mm)

26 24 22 20 18 16 14 12 10 8

Male Female

0

1

2

3

4

5

6

7

Level

• FIGURE 29-1.

Normal diameter of aorta, tapering from thoracic to iliac levels; male and female.

Reproduced, with permission, from Pearce WH, Slaughter MS, LeMaire S, Salyapongse AN, Feinglass J, McCarthy WJ, Yao JS. Aortic diameter as a function of age, gender, and body surface area. Surgery. 1993;114: 691–697.

as genetically defective structural elements has been implicated in aneurysm formation. Deficiency of other proteins, as occurs with Marfan’s syndrome with deficient fibrillin, is associated with aortic aneurysm also. There is also an association between bicuspid aortic valve and TAA. Turner syndrome is associated with aortic dilation in approximately 6.3% of those affected according to one survey.7 The most common congenital anomaly of the heart is bicuspid aortic valve. Aortic root dimensions were found to be significantly larger in a group of young men with biscup aortic valve.8 Up to 15% to 20% of TAA or AD maybe familial.9 Several specific loci have been identified to be associated with familial syndrome, specifically 16p12.2– p13.3, 5q13–q14, 3p24–p25, and 11q23.2–q24.9 Collagen and elastin contribute significant structural support to the aorta. Elastin allows mobility throughout the cardiac cycle. A paucity of elastin is found in the wall of an aneurysm and can be experimentally depleted by elastase, resulting in dilation of the aortic wall.10 Dilation of the aorta leads to increased wall tension according to La Place’s law T = (P × r )/2t, where T is wall tension, P is distending pressure, r is the radius, and t is the wall thickness. This principle may also explain the well-documented logarithmic growth of TAA. Collagen types I and III are abundant in the wall of the aorta. A deficiency or increased destruction of collagen via collagenase has been implicated in formation of aneurysm.4 Cystic medial degeneration is commonly found in TAA.11 Atherosclerosis is typically found in descending TAA.12 Of TAAs, about 40% involve the descending aorta.11 TAAs are often part of a multifocal aneurysmal disease. In a review of 217 patients operated for TAA by Crawford, 68% of these had multiple aneurysms with the most common association being with infrarenal abdominal aortic aneurysm (AAA). Additionally, of 1076 patients treated for AAA, 12% were found to have additional aneurysms.13 Of patients with thoracoabdominal aortic aneurysm (TAAA), aneurysms of the renal artery occurred an average 2.7% and in peripheral arteries (such as iliac, femoral, or popliteal) an average of 4.2%.5 These data emphasize both the systemic nature of this disease as well as the importance of adequate screening for associated aneurysmal disease upon discovery of one site. Natural History The natural history of descending TAA is one of progressive enlargement with risk of rupture. Both the size of the aneurysm and the rate of expansion have significant impact on development of complications. The natural history of AAAs is more clearly defined than TAA. Part of the reason for this is the heterogeneity in the literature, often included in these series are a mixture of aneurysm extents as well as different acute aortic syndromes. There is a faster expansion of AAA compared with TAA. Masuda found an average expansion of TAA to be 1.3 mm/year compared with 3.9 mm/year of AAA.14 The rate of expansion is influenced by initial aneurysm size, with aneurysms >5 cm having a higher rate of expansion.15 The most common cause of

DESCENDING THORACIC AORTA • 553

death in patients with untreated TAA is aortic rupture.16 A series by Dapunt et al. estimated change in TAA diameter to be 0.43 cm at 1 year with largest rate of expansion in smokers and aneurysm size >5 cm at presentation.15 Coady reported annual aneurysm growth rate of 0.12 cm/year of descending TAA to be greater than ascending TAA of 0.09 cm/year, with a mean size of 5.2 cm at initial presentation.17 While a larger aneurysm carries a higher risk of rupture, smaller TAA (those between 4 and 5 cm) also have a significant risk of rupture and death. Classification The extent of involvement of TAAA is defined according to the Crawford classification18 (see Figure 29-2). Type I extends from above the sixth intercostal space, near the left subclavian artery, to the root of mesenteric vessels but not to the infrarenal aorta. Type II extends from above the sixth intercostal space to the infrarenal aorta and usually to the bifurcation as well. Type III arise below the sixth intercostal space of the thoracic aorta and extend to the infrarenal aorta as type II does. Type IV runs the length of the abdominal aorta from diaphragm to the bifurcation.18 Risk Stratification Predicting the risk of rupture has been evaluated by several authors by proposed formula. As a result of review of 67 patients by Dapunt, a formula was proposed to predict the rate of change of maximal diameter.15 Y = aX b , where Y is the change in diameter, a = 0.0167, X is the initial diameter, and b = 2.1. Juovonen reviewed a series of 114 patients and reported the following factors to be associated with the risk in rupture in descending TAA; maximal aneurysm diameter, older

• FIGURE 29-2.

Crawford classification of thoracoabdominal aortic aneurysm.

Reproduced, with permission, from LeMaire SA, Miller CC 3rd, Conklin LD, Schmittling ZC, Koksoy ¨ C, Coselli JS. A new predictive model for adverse outcomes after elective thoracoabdominal aortic aneurysm repair. Ann Thorac Surg. 2001;71:1233–1238.

age, uncharacteristic pain and history of COPD.19 Based on multivariate risk factor analysis, the following formula was proposed to predict 1-year risk of rupture. ln ␭ = −21.055 + 0.093 (age) + 0.841 (pain) + 18.22 (COPD) + 0.643 (descending diameter in cm), where pain and COPD = 1 if present and 0 if absent. Probability of rupture within 1 year = 1 – e1␭(365) . Descending TAA tend to rupture at a larger size (median diameter 7.2 cm) compared with ascending or arch aneurysms (median diameter 5.9 cm).17 A review of 165 patients with TAA led to proposal of a similar formula to predict risk of rupture. Risk factors identified included aneurysm size, COPD, age, and uncharacteristic pain. A more rapid growth rate was seen with smokers. ln ␭ = −21.055 + 0.0093 (age) + 0.841 (pain) + 1.282 (COPD) + 0.643 (descending diameter in cm), where pain and COPD = 1 if present and 0 if absent. Probability of rupture within 1 year = 1 – e1␭(365) . An attempt was made to validate the above formulae by Schimada et al.16 This review of 88 patients with TAA again demonstrate exponential enlargement over time. When this data was compared with the above formulas, the Coady formula underestimated growth by 0.8 mm while the Dapunt formula overestimated growth by 1.5 mm. The decision to operate will be more straightforward in some patients and will obviate the need for calculation as above. Current indications include presence of symptoms, evidence of dissection, accelerated growth rate (>10 mm/year), or diameter 6 to 7 cm.18,20 Some patients will not be adequately evaluated by the above formula because there are other possible risks such as development of serious cough with associated recurrent laryngeal nerve irritation with rapid aneurysmal expansion. Additionally, comorbidities may dictate the urgency of repair as well. New onset or increasing severity of pain will also lead to earlier repair. Based on recent review of 721 patients with TAA, the mean rate of rupture or dissection of TAA is 2% for aneurysm 8 cm at aortic arch) is about 80% sensitive and 50% specific. Widening of the left paraspinal stripe and deviation of the trachea or esophagus to the right are greater than 80% specific but sensitivity is low.25 Thoracic aortography yields sensitivity almost 100% and specificity of 98% for traumatic aortic injury.25 CT scan is 99.3% specific and about 90% sensitive for detecting aneurysm (Figure 29-3). MRA is almost 100% sensitive and specific for detecting aneurysm.(Figure 29-4).25 An important potential pitfall to be aware of when evaluating cross-sectional imaging is transverse slice through torturous area where the aorta is angulated or curving. This is common in the elderly. This can result in a false-positive read for aneurysm. Plain film chest radiograph is often used as an initial study with chest complaint. Several criteria have been associated with aortic disease on chest radiograph. Widening of the aortic contour, widening of the mediastinal shadow, tracheal shift to the right or distortion of the left main bronchus, displacement of intimal calcification greater than 6 mm into the aortic shadow, kinking or tortuosity of the

• FIGURE 29-3.

CT scan of descending thoracic aorta aneurysm with compression, left bronchus.

aorta, opacification of the pulmonary window, and blurring of the aortic contour. A ratio of mediastinal width to chest width exceeding 0.25 has been used although some sources say up to 0.45 is acceptable.26 Chest radiography has a sensitivity of 64% and specificity of 86% for detecting aortic disease, with the percentage being lower for ascending aortic disease.26 Magnetic resonance imaging (MRI) is an accurate method to image patients with suspected aortic aneurysm or dissection. There is high soft tissue contrast and the ability to finely evaluate the aortic lumen and wall. An advantage when compared with the potentially nephrotoxic and allergenic CT contrast media is that MRI gadolinium-based contrast media are safer and have less renal toxicity.27 Specific considerations apply when evaluating aneurysm disease with MRI/MRA. Accurate measurements of the outer aortic diameter are best obtained without angiographic enhancement. Also, the adventitia is not well visualized on MRA. MRI is also highly accurate for the detection of AD. Because of the length of the study, MRI has limitations in the emergent setting and is restrictive in terms of monitoring equipment. Transesophageal echocardiography (TEE) offers highresolution images as a result of the proximity of the esophagus and thoracic aorta. The ascending aorta and aortic root are directly anterior to the esophagus. From the level of the aortic arch to the diaphragm, the aorta and esophagus are close in their course. The newer biplane probes allow better imaging of the aorta compared with the monoplane transducer. In the evaluation of AD, reported sensitivity ranges from 97% to 99% and specificity from 77% to 100%.28 The sensitivity is higher for dissections of the ascending aorta, however.29 The finding of an undulating intimal flap in the aorta is the most definitive finding for AD.29 This modality also allows assessment of aortic valve function, cardiac

DESCENDING THORACIC AORTA • 555

A

B

• FIGURE 29-4.

MRI images demonstrating descending thoracic aortic aneurism.

function, blood flow in false and true lumens and thrombus, and frequently visualization of coronary ostia. It is advantageous to be able to evaluate the coronary ostia for operative planning in the case of a proximal dissection. Typically, this has been done with preoperative coronary angiography. Compared with MRI or CT, it is not as good at detecting thrombus in the false lumen as well as evaluating the entire length of the aorta.28 The ascending aorta and proximal arch are incompletely evaluated by TEE.30 TEE is a good adjunct to follow TAA, however, as some areas are incompletely visualized. It is very useful for aortic valve assessment with known TAA, which is an important consideration in surgical decision. TEE avoids the potential risks of aortography, which may include embolus with possible stroke, possible retrograde extension of the dissection, and site complications. There are certain patients who will not tolerate a TEE. It is not suitable for those with known esophageal varices, stricture, or tumors. It may produce vasovagal reaction and there is the risk of perforation.29 Medical Treatment Medical management consists of minimizing risk factors for aneurysm growth. Beta blockade is the standard recommendation titrated to a systolic blood pressure of 100 to 120 mm Hg. Long-term beta-blockade therapy has been demonstrated to be effective in slowing the rate of aortic dilatation in patients with Marfan’s syndrome.31 The foundation of this treatment is derived from experimental data of turkeys prone to spontaneous aortic rupture having improved survival when propranolol was added to the

feed.32 In addition to blood pressure control and heart rate control, this also reduces P /t, the so-called antiimpulse therapy.25 Surgical Treatment It is unclear exactly which TAA should be repaired and which should be observed. Distinguishing between the risk of nonoperative and operative treatment is key but often difficult in the absence of clear guidelines for each patient. Careful risk assessment and knowledge of the natural history of TAA will guide this decision. For elective repair, a TAA of 7 cm or larger should be repaired.14 Crawford recommends repairing TAA and TAAA greater than 5 cm in a good-risk patient and in symptomatic patients.33 Lobato and colleagues gathered prospective data on 31 patients with TAA of less than 60 mm and deemed high risk for surgery or who had refused surgical therapy.20 They recommend elective repair when the initial anterior–posterior diameter is 5 cm or greater with an annual growth rate of at least 10 mm. However, during their 47-month follow-up, nine patients with initial aneurysm size of 4 to 4.9 cm had rupture.20 An unanswered question remains what is the best treatment for aneurysms 4 to 5 cm, especially those with a smaller growth rate than 10 mm annually. Operative mortality for type I Crawford TAAA is reported to range between 5% and 8%.5 Endovascular Treatment Endovascular repair (EVAR) of the thoracic aorta has seen increasing utilization. The position of the proximal point

556 • CHAPTER 29

TABLE 29-1. Anatomic Endograft Zones of Thoracic Aorta Zone 0: Ascending aorta to distal innominate artery origin Zone 1: Arch distal innominate artery origin to distal left carotid origin Zone 2: Arch–distal left carotid to distal left subclavian Zone 3: Descending thoracic aorta–distal left subclavian to mid-descending thoracic aorta Zone 4: Distal descending thoracic aorta

of the endograft is defined according to four anatomic divisions of the proximal aorta proposed by Ishimaru.34 These zones (Table 29-1) are based anatomically on a line drawn tangent to the distal side of each of the arch branches (see Figure 29-5). A recent review by Iyer examined their 6-year experience with 70 cases of EVAR of the thoracic aorta. EVAR was used for TAA in 63% and 30-day mortality was 1/70. Other lesions included one aortoesophgeal fistula, seven traumatic rupture, and eight type B dissections. Postoperative endoleak occurred in 23% and endovascular failure in 11%. The majority of these repairs were done with the Tal-

ent self-expanding endograft system and five with Zenith system. Graft access was via common femoral artery, iliac artery via retroperitoneal exposure, or directly to the aorta via laparotomy. Systemic heparin was only used in one case and pharmacologic hypotension was used with graft deployment. For arch lesions, extra-anatomic bypass is used to enlarge the proximal landing zone (as with zone 1 or some zone 2 repairs). When more than one graft component is used, a 4 to 5 cm overlap is utilized. Cerebrospinal fluid drain was placed in 70% of patients and there was only one case of peripheral neuropraxia documented at 30 days with no paraplegia. Acute renal failure and conversion to open occurred in 4%. At 5 years, about 70% of the total treated patients were free from secondary endovascular intervention.35 A similar report by Criado examined their 4-year experience of 47 thoracic lesions with 31 TAA and 16 type B dissections. The mean size of TAA treated was 6.8 cm (4.8 to 10.7 cm). A 4% 60-day mortality was reported. There was no paraplegia or stroke. These report as well as several older reports are adding to the growing body of evidence that may make EVAR of thoracic lesions the procedure of choice in the future. It should be recalled however that the reported 30-year experience of Crawford demonstrated a 30-day survival rate of 92% (1386/1509).22 Long-term results of EVAR have yet to be determined but initial reports are promising. What remains to be answered are what lesions will provide the best long-term outcomes with endovascular approach and which should be treated with open repair. A phenomenon known as postimplantation syndrome has been described after aortic endograft placement.34 This consists of leukocytosis, mild thrombocytopenia, and postoperative fever. This may represent inflammation of the aortic wall to the graft. Conservative treatment with aspirin is recommended and typically resolves spontaneously.

•

THORACIC AORTIC DISSECTION

Epidemiology Incidence of AD has been estimated to be 2.9/100 000/year incidence. Other estimates have ranged from 0.5 to 4.04/ 100 000/year. Average age at dissection is about 63.4 years with a male-to-female ratio 1.55: 1.36,37 Natural History

• FIGURE 29-5.

An anatomical map of each landing zone bordered by lines delineating the distal sides of the branch arteries of the aortic arch. The position of the proximal end of the endograft is classified according to this system. Z, zone; T, thoracic vertebral level.

Reproduced, with permission, from Mitchell RS, Ishimaru S, et al. First International Summit on Thoracic Aortic Endografting: Roundtable on Thoracic Aortic Dissection as an Indication for Endografting. J Endovasc Ther 2002;9:II-98-II-105.)

The physician of King George II, Dr Nicholls, first described AD on autopsy in 1760.38 Despite the significant advances in technology, the mortality of AD remains high. Type A dissection carries a higher rate of complication and mortality. After the acute onset of symptoms of AD, the mortality maybe as high as 1% per hour.39 Predictors of in-hospital death include age >69 years, hypotension or cardiac tamponade, renal failure, and pulse deficits.38 A trend toward improved survival with AD has been seen in recent years.40 Erbel and colleagues reported survival rates of 52% for type I dissection, 69% for type II dissection, and 70% for type III dissection.41 The IRAD data reports mortality of type A

DESCENDING THORACIC AORTA • 557

dissection to be 26% with surgical treatment and 58% without it. Mortality of type B dissection was 10.7% with medical treatment and 31.4% with surgical treatment37 hence, the difference in treatment of ascending versus descending thoracic ADs. Classifcation AD is typically classified based on anatomical location and time from onset. Those involving the ascending aorta are Stanford type A dissection and those not involving the ascending aorta and distal to the left subclavian artery are Stanford type B. DeBakey type I AD involves the entire aorta, type II just the ascending portion, and type III the descending portion (see Figure 29.6). Within 14 days of the initial dissection is designated the acute phase. Presentation after 14 days of the acute phase is designated a chronic dissection (see Figure 29.6). Svensson and colleagues have defined five types of AD, which includes the classically described type and its variants.42 Type 1 involves an intimal tear creating a flap between true and false aneurysm, allowing flow of blood through a false channel. Type 2 is described as an IMH (see following section). Type 3 is an intimal tear without creation of false lumen. Type 4 is a penetrating ulcer to the adventitia. Type 5 is related to iatrogenic cause or trauma, such as injury with endovascular catheter. Mortality of iatrogenic AD is higher than noniatrogenic (35% vs. 24%).8

• FIGURE 29-6.

Etiology for type A iatrogenic AD includes cardiac surgery (69%), coronary angiography or intervention (27%), and renal angioplasty (4%). For iatrogenic aortic type B dissection, coronary angiography or intervention is primarily implicated (87%) and cardiac surgery secondarily (12%).43 Sequelae of iatrogenic AD include myocardial ischemia or infarction (36% and 15%), limb ischemia (14%), and 30day mortality of 35%.43 In addition to endovascular injury, another iatrogenic etiology is the association with cardiac surgery. Type A AD is rare after heart surgery with an incidence of about 0.12%.44 This is frequently attributed to surgical trauma of the aorta and the patients underlying diseased vessels. Off-pump aortocoronary bypass surgery is associated with a higher risk of AD compared with onpump and maybe resulting from a risk of injury associated with aortic sideclamp and the subsequent pulsatile pressure at that site.44 Pathophysiology Mechanisms that weaken the aortic wall can induce aortic dilation, eventually leading to dissection or rupture. The most commonly implicated mechanism for this weakening is hypertension. Risk factors were analyzed in data from the International Registry of Acute Aortic Dissection (IRAD).37 Of 464 patients registered, 72% had history of hypertension, 5% had history of diabetes or Marfan syndrome. Risk factors associated with AD are long-standing

Classification of aortic dissection: DeBakey and Stanford types.

Reproduced, with permission, from Erbel R, Alfonso F, Boileau C, et al. Diagnosis and management of aortic dissection: recommendations of the Task Force on Aortic Dissection, European Society of Cardiology. Eur Heart J 2001;22:1642.

558 • CHAPTER 29

hypertension, connective tissue disorders, bicuspid aortic valve, coarctation, vasculitis, dyslipidemia, cocaine, blunt trauma, genetics, and introgenic injuries.43 The role of various entities such as cystic medial necrosis and atherosclerosis have been discussed as playing a central role in AD but these are found to play a role in only a minority of cases.36

CT scan, MRI, and aortography are discussed in the previous sections. The role for coronary angiography is useful preoperatively to define the coronary anatomy. However, angiography is not without risk and is difficult in this setting and therefore is often not done. Only 25% of patients with acute dissection have significant coronary artery disease.39

Evaluation

Treatment

Up to 55% of patients will die without a correct antemortem diagnosis of aortic dissection.39 A high index of suspicion is necessary as well as rapidly implemented therapeutic plan. The sudden onset of severe chest pain is a cardinal symptom; however up to 20% of patients may not manifest this condition.39 Differential diagnosis of AD includes acute coronary syndromes (ACS), aortic regurgitation, aortic aneurysm, musculoskeletal pain, pericarditis, mediastinal tumor, pleuritis, pulmonary embolus, cholecystitis, and atherosclerotic or cholesterol embolism.41 Common presenting signs and symptoms are intense paroxysmal thoracic pain, syncope, hypotension, congestive heart failure, pulse loss, and evidence of branch obstruction such as cerebrovascular accident or paraplegia. A new onset diastolic aortic insufficiency murmur may also be a key finding. From the IRAD data, only 31.6% had aortic regurgitation and 15.1% had pulse deficit.37 Of presenting symptoms reported, 95% reported abrupt onset of pain to chest and back, severe in nature and typically sharp or tearing in quality. This is contrasted to the pressure or tight sensation of angina. On imaging with chest X-ray, 61.6% had widened mediastinum and 50% had abnormal aortic contour.37 See “Evaluation of TAA” for a discussion of the imaging modalities. Initial diagnostic steps should include an EKG, chest radiograph, and a definitive imaging study, most commonly CT (Figure 29.7). The role and sensitivity of TEE,

The main goal of medical therapy is to decrease the force of left ventricular contraction. The primary treatment of type B AD is medical therapy. Early mortality with medical therapy ranges from 8% to 12%.45 Treatment focuses on halting progression of dissection by decreasing “impulse-force” (P /t). This is accomplished with using beta-blocker, calcium-channel blocker, nitroglycerin, and sodium nitroprusside (in this ascending order) to obtain target systolic blood pressure 90 mm Hg Elevated levels of serum blood urea nitrogen (>40 mg/dL) or Creatinine (>1.5 mg/dL) Evidence of hepatitis B virus infection via serum antibody or antigen serology Characteristic angiographic abnormalities not resulting from noninflammatory disease process A biopsy of small or medium sized artery containing polynuclear cells

∗

Presence of at least 3 of the criteria has a sensitivity and specificity of 82% and 87% for diagnosis of PAN.

are likely to show multiple occlusions with collateralization (“corkscrew collaterals”) around the areas of occlusion. Mesenteric arteries can also be involved in this vasculopathy, leading to mesenteric ischemia. The only proven strategy to prevent disease progression is immediate cessation of smoking in any form. Figure 31.21 illustrates Buerger disease. Churg-Strauss Syndrome. Churg-Strauss syndrome also

affects small- and medium-sized vessels, and present as characteristic triad of allergic rhinitis, asthma, and peripheral eosinophilia.79 Most patients with this disease respond to high-dose steroid therapy. Diagnostic criteria for ChurgStrauss syndrome is enlisted in Table 31.5. Henoch-Schonlein Purpura. Mostly a disease of children, Henoch-Schonlein purpura (HSP) is a small vessel vasculopathy with gastrointestinal involvement in up to 50% of cases. Patients with gastrointestinal involvement may present with colicky abdominal pain, nausea, vomiting, diarrhea, and gastrointestinal bleeding. It is selflimiting, resolving spontaneously in majority of cases, and rarely needs systemic steroids or immunosuppressive agents in recalcitrant cases.80 Diagnosis is confirmed by demonstration of immunoglobulin A (IgA) deposition on skin or kidney biopsy. Takayasu’s Disease. A medium/large vessel vasculopa-

thy of the aorta and its major branch vessels, it typically involves aortic arch branches, although can extend into the mesenteric and renal arteries. Often, because of chronic progression of the disease, collaterals develop in patients with visceral artery involvement, and they remain

MESENTERIC ARTERY DISEASE • 609

• FIGURE 31-21.

Management of CMI. Solid lines indicate accepted management plan. Dashed lines indicate alternate management plan. MRA, magnetic resonance angiography; CT, computed tomography.

Reproduced, with permission, from Brandt LJ, Boley SJ. AGA technical review on intestinal ischemia. Gastroenterology 2001;118:954.

TABLE 31-5. Diagnostic Criteria for Churg-Strauss Syndrome∗ 1. Asthma (a history of wheezing or the finding of wheezing on expiration) 2. Eosinophilia of >10% on differential white blood cell count 3. Mononeuropathy (including multiplex) or polyneuropathy 4. Migratory or transient pulmonary opacities detected radiographically 5. Paranasal sinus abnormality 6. Biopsy containing a blood vessel showing the accumulation of eosinophils in extravascular areas ∗

Presence of 4 or more of the criteria yields a sensitivity of 85% and specificity of 99.7%.

asymptomatic for a long time. Intestinal ischemia maybe brought on by thrombosis of main visceral arteries that propagate into the collateral vessels. Women are predominantly affected mostly in their early ages between 10 and 40 years. The prevalence is very high among the Asians. Gastrointestinal involvement with mesenteric ischemia can occur and manifest as abdominal pain, diarrhea, and bleeding. Diagnostic criteria for Takayasu’s arteritis is listed in Table 31.6.81 Behcet’s Syndrome. A necrotizing vasculitis predominantly affecting young males, it is characterized by uveitis, aphthous stomatitis, and genital ulcers. Meseneteric vessels are rarely involved and cause mesenteric ischemia mostly by occlusion of arteries with organized thrombi. New international criteria82 for diagnosis of Behcet’s disease require the presence of recurrent oral aphthous ulcers (at least three times a year) plus two of the following four criteria: (1) recurrent genital ulcers; (2) uveitis; (3) skin lesions (erythema nodosum, pseudovasculitis, papulopustular lesions, and acneiform nodules); and (4) a positive pathergy test (a papule of 2 mm or more in size developing 24 to 48 hours after oblique insertion of a 20 to 25 gauge needle

610 • CHAPTER 31

• TABLE 31-6. Diagnostic Criteria for Takayasu’s Arteritis 1. Age at onset ≤40 years 2. Claudication of the extremities 3. Decreased pulsation of one or both brachial arteries 4. Difference of at least 10 mm Hg in systolic blood pressure between the arms 5. Bruit over one or both subclavian arteries or the abdominal aorta 6. Arteriographic narrowing or occlusion of the entire aorta, its primary branches, or large arteries in the proximal upper or lower extremities, not caused by atherosclerosis, fibromuscular dysplasia, or other causes ∗

Presence of 3 or more criteria yields a sensitivity and specificity of 90.5% and 97.8%, respectively, for Takayasu’s arteritis.

into the skin). Although the symptoms can wax and wane, systemic disease is typically treated with steroids and immunosuppressive agents such as azathioprine, cyclosporine, or cyclophosphamide. Diagnosis Most patients will have systemic manifestations and will have already been diagnosed before the onset of mesenteric symptoms. Laboratory Testing. Erythrocyte sedimentation rate (ESR) is almost always elevated. Specific serological markers are also helpful in making specific diagnosis such as antinuclear antibody (ANA) and antidouble-stranded DNA antibody for SLE, antinuclear cytoplasmic antibodies (ANCA) for PAN, and antiphospholipid antibody for APS. Tissue biopsies are confirmatory in most of these vasculitides. Imaging Studies. CT scan and barium studies are non-

specific in diagnosing early cases of mesenteric vasculitis. Angiography is useful in diagnosing PAN, Buerger disease, and Takayasu’s arteritis. Endoscopy. Endoscopy at times maybe used for tissue

biopsies if other accessible biopsy sites are not readily available. Endoscopy should be done with extreme caution as there is an increased risk of perforation from this instrumentation. Treatment. Treatment of vasculitides is aimed at treating the underlying systemic disease with aggressive immunosuppressive therapy and corticosteroids. Surgical intervention is indicated in patients with mesenteric infarction or intestinal perforation.

FIBROMUSCULAR DYSPLASIA

FMD is nonatheroclerotic, noninflammatory angiopathy primarily of medium-sized arteries, leading to arterial stenoses and symptoms of ischemia. It is seen in mostly in young women with an incidence of 1%. Although this disease predominantly involves renal and cerebral arteries, mesenteric arteries are involved in about 9% of the total cases.83,84 Table 31.7 enlists the arterial distribution of FMD. Unless severe, FMD may go undiagnosed and less likely to be considered in the differential diagnosis as it maybe mistaken for more commoner pathology such as atherosclerosis, thrombosis, or even vasculitis. Genetics may play a role in the development of FMD, and is most likely to be inherited as an autosomal dominant pattern with variable penetrance. Mechanical factors such as cyclic stretching of arterial smooth muscle cells and trauma to the blood vessel wall may also contribute to the development of FMD. Ischemia of the arterial wall by occlusion of the vasa vasorum may potentially lead to increased accumulation of connective tissue and myofibroblasts as a reparative process leading to FMD. Smoking may also predispose to FMD in a dose–response relationship. FMD can have three different pathological morphologies. Medial fibroplasia is the commonest and has classic “strings of beads” appearance. The beading is larger than the caliber of the normal artery and is confined to the middle to distal portion of the artery. Media is typically involved, whereas the intima, internal elastic lamina, and adventitia are spared. Medial fibroplasia causes thickened fibromuscular ridges alternating with mural thinning and aneurysms. Intimal fibroplasia occurs in less than 10% of patients. Angiographically, it may appear as a focal, concentric stenosis or a long tubular stenosis.

TABLE 31-7. Arterial Involvement in Fibromuscular Dysplasia Arteries Involved Renal arteries Bilateral Extracranial cerebrovascular circulation (carotid or vertebral arteries) Associated intracranial aneurysm Multiple vascular beds Other arterial beds (iliac, popliteal, splanchnic, hepatic, coronary, subclavian, brachial, aorta, superficial femoral, tibial, or peroneal)

Frequency of Involvement (%) 60–75 35 25–30

7–50 28 Uncommon, exact frequency unknown

Fibromuscular dysplasia may be a generalized process; in rare case, it has also been identified in the venous system. Reproduced, with permission, from Olin JW. Thromboangitis obliterans. N Engl J Med. 2000;343: 864-869.

MESENTERIC ARTERY DISEASE • 611

A

• FIGURE

31-22. (A) Pathology and (B) angiograms of Buerger

disease.

Reproduced, with permission, from Olin JW. Thromboangitis obliterans. N Engl J Med. 2000;343:864-869.

Adventitial (periarterial) fibroplasia is the rarest of all varieties of FMD. Angiographically, it may appear as sharply localized, tubular stenosis. Symptoms of mesenteric FMD include nausea, vomiting, abdominal pain, anorexia, and weight loss. Although symptomatic FMD is rare, and because of collateral network, ischemia is uncommon unless two major arteries are severely involved. At times, presence of an abdominal bruit gives clue to the diagnosis. Diagnosis of FMD is challenging. Duplex ultrasonography, CTA, and even MRA are useful imaging modalities in the initial work-up and characteristic appearance on the angiography are further suggestive of the diagnosis. A histopathological diagnosis is needed for confirmation. Symptomatic mesenteric FMD may require revascularization. Focal FMD can be treated by PTA. But FMD is diffuse, majority of patients eventually require surgical revascularization treatment. Data on the outcomes of surgical revascularization are mixed. In one study,85 following revascularization of mesenteric stenosis, patients had resolution of symptoms with minimal postoperative mortality or morbidity. On the contrary, a study by Howard et al.86 had shown poor outcome of surgery of mesenteric arteries for FMD and was complicated by multiorgan failure and death. Patients with diffuse mesenteric FMD become symptomatic at a very advanced stage of the disease

B

and surgery is then poorly tolerated. Figure 31.22 illustrates FMD in renal arteries.

•

MESENTERIC ARTERY ANEURYSMS

Aneurysms of mesenteric arteries are not so uncommon. Based on autopsy reports, the prevalence of mesenteric artery aneurysms is estimated to be up to 10%. About 25% of these aneurysms are complicated by ruptures that carry a mortality rate ranging 25% to 70%.87 Most of the splanchnic aneurysms will require surgical intervention. The use of endovascular coils and stent grafts have been reported and may gain popularity as experience and follow-up develops. Figures 31.23 through 31.26 illustrate the distribution and types of various splanchnic aneurysms. Etiology The causes of mesenteric artery aneurysm are listed in Table 31.8. Splenic Artery Aneurysm. Splenic artery aneurysms are

more prevalent among multiparous women, in patients with splenomegaly such as portal hypertension, and following orthotopic liver transplantation. Increased splenic blood flow is likely to be the contributing factor in the development of splenic artery aneurysms among these patients. Most of the aneurysms occur at the distal third of

612 • CHAPTER 31

A

B

• FIGURE 31-23. C

(A–C) Imaging of fibromuscular dysplasia.

Reproduced, with permission, from Slovut DP, Olin JW. Fibromuscular dysplasia: current concepts. N Engl J Med. 2004;350:1862-1871.

the splenic artery, are saccular, and involve the bifurcation. Risk of rupture is markedly increased among pregnant patients, and with aneurysms larger than 2 cm in diameter. If symptomatic, these aneurysms mostly present as left upper quadrant pain. When ruptured, complications such as hypovolemic shock or gastrointestinal bleeding causes increased mortality, especially among pregnant patients with a 75% maternal and 95% fetal mortality. Elective surgery for splenic artery aneurysm is indicated for symptomatic aneurysms, aneurysms larger than 2 cm, and aneurysms of any size present in pregnant women or in women of childbearing age. Ruptured aneurysms are treated with splenectomy. Percutaneous coil embolization maybe performed for all splenic aneurysms except for those present in the hilum, which are best treated by splenectomy. Proximal artery aneurysms are treated by sim-

ple surgical ligation and midartery aneurysms are treated by aneurysmectomy followed by end to side anastomosis. While elective surgery has minimal surgical mortality, emergency surgery has a mortality rate as high as 40%. Close follow-up of the splenic aneurysms measuring 1 to 2 cm is therefore recommended with an imaging study every 6 months. Splenic aneurysms associated with portal hypertension are treated by transcatheter coil embolization as increased vascularity may make the surgical treatment difficult. Splenic artery pseudoaneurysms are better treated by surgery. Celiac Artery Aneurysm. Celiac artery aneurysm occurs mostly among middle-aged individuals, and has equal occurrence among both sexes. Upper abdominal pain, dysphagia, and gastrointestinal bleeding are common presenting

MESENTERIC ARTERY DISEASE • 613

• FIGURE 31-24.

Distribution of splanchnic artery aneurysms (AA). Prevalence of percentage of all splanchnic artery aneurysms and sites of splanchnic artery aneurysms are indicated.

Reproduced, with permission, from Pasha SF, Gloviczki P, Stanson AW, Kamath PS. Splanchnic artery aneurysms. Mayo Clin Proc. 2007;82:472-479.

symptoms. Celiac aneurysms are usually treated by surgical ligation followed by aortohepatic bypass or direct aortic reimplantation. Ruptured aneurysms are managed by either surgical ligation or percutaneous coil embolization.

Hepatic Artery Aneurysm. Hepatic artery aneurysm accounts for 20% of mesenteric aneurysms. Most of the hepatic aneurysms are pseudoaneurysms, and may follow interventional procedures. Most of the symptomatic hepatic artery aneurysms present as right upper quadrant pain.

Splenicartery aneurysm

SMA aneurysm

• FIGURE 31-25. artery aneurysm.

Angiogram showing an SMA and splenic

• FIGURE 31-26.

Angiogram showing an SMA aneurysm.

614 • CHAPTER 31

TABLE 31-8. Etiology of Splanchnic Artery Aneurysms True aneurysms Common causes Arteriosclerosis Fibromuscular dysplasia Cystic medial necrosis Portal hypertension Uncommon causes Autoimmune /collagen vascular diseases Polyaretritis nodosa Systemic lupus erythematosus Takayasu’s arteritis Ehlers-Danlos syndrome Marfan syndrome Neurofibromatosis Hypertension Congenital Alpha-antitrypsin deficiency Pseudoaneurysms Common causes Inflammatory conditions Pancreatitis Blunt or penetrating abdominal trauma Anastomotic pseudoaneurysms (after orthotopic liver transplantation) Percutaneous intervention of biliary tract Arterial dissection Uncommon causes Infectious diseases Mycotic aneurysms Syphilis Infective endocarditis Tuberculosis Adapted from Pasha SF, Gloviczki P, Stanson AW, Kamath PS. Spalnachnic artery aneurysms. Mayo Clin Proc. 2007;82:472-479.

Obstructive jaundice from compression by the aneurysm of the bile duct, erosion into the biliary tract, or gastrointestinal bleeding following rupture are more serious presentations of hepatic artery aneurysms. Most aneurysms are extrahepatic and occur mostly in men older than 60 years of age. Multiple aneurysms and nonatherosclerotic aneurysms are associated with increased risk of rupture and thus warrant intervention. Surgical ligation with or without vascular reconstruction are the preferred mode of management for these aneurysms although transcatheter coil embolization or endograft stenting are reserved for patients with high surgical risks. Superior Mesenteric Artery Aneurysm. Superior mese-

nteric artery aneursym occurs both in men and women equally. Infective endocarditis, especially with nonhemolytic streptococci, staphylococci, or gram-negative bac-

• FIGURE 31-27.

Angiogram showing a splenic artery

aneurysm.

teria account for most of the SMA aneurysms. These aneurysms occur among young men younger than 50 years of age with a history of intravenous drug use. Nearly 50% of patients present with rupture with a mortality rate of up to 30%. SMA aneurysms are usually symptomatic, and may present with abdominal pain with or without mesenteric ischemia, or gastrointestinal bleeding. Surgical ligation is advised for patients with low surgical risks. Transcatheter coil embolization or endograft stenting are reserved for high surgical risk patients or for patients not willing to have surgery. Beta-blockers may protect against rupture and should be used when these aneurysms are medically managed. Figures 31.21 and 31.27 show SMA and splenic artery aneurysm. Pancreaticoduodenal and Gastroduodenal Artery Aneurysms. Pancreaticoduodenal and gastroduodenal

artery aneurysms are usually the sequelae of pancreatitis or of pancreatoduodenectomy. Epigastric pain is the commonest presentation of these aneurysms. Erosion into the pancreatic duct may cause hemosuccus pancreaticus (bleeding into the pancreatic duct). Erosion into a pancreatic pseudocyst may cause a pulsatile pseudocyst. Either surgical ligation with or without vascular reconstruction or endovascular exclusion with transcatheter coil embolization or stent-grafting is recommended for treatment of these aneurysms. Diagnosis Abdominal plain radiograph may reveal calcification, and often provides early clues to a diagnosis of visceral artery aneurysm. Diagnosis of a splanchnic artery aneurysm is usually made with one of the imaging modalities. Ultrasonography has a very low sensitivity and is compromised by bowel gas and obesity. Computed tomography (CT) helps to even detect small aneurysms with excellent delineation of anatomical details. Magnetic resonance imaging (MRI)

MESENTERIC ARTERY DISEASE • 615

can also provide a great clarity of the splanchnic vessel aneurysms, but is often cumbersome and not readily available. Angiography is the diagnostic study of choice as it provides the elaborative details of the aneurysms, and at the same time offers the scope of catheter interventions if warranted.

•

TABLE 31-9. Complications of Splanchnic Artery Aneurysms 1. Intraperitoneal rupture a. Hemoperitoneum b. Hypovolemic shock 2. Intrahepatic subcapsular rupture 3. Retroperitoneal hemorrhage 4. Gastrointestinal hemorrhage a. Hemobilia b. Hemosuccus pancreaticus c. Herald bleed 5. Arteriovenous fistula formation a. Portal hypertension b. Ascites c. Variceal bleeding 6. Obstructive jaundice 7. Acute mesenteric ischemia

INTESTINAL ARTERIOVENOUS MALFORMATIONS

Arteriovenous malformations (AVMs) of the gastrointestinal tract are rare sources of gastrointestinal bleeding, and are categorized into three clinical groups depending on lesion location and age at presentation. Angiodysplasia is the commonest form of intestinal AVMs, which are solitary and localized lesions usually found in the right colon, and manifest later in life usually after the age of 50 years. Angiodysplasias are common among the elderly, and also among patients with aortic stenosis. Less common are the AVMs of small intestine, usually occurring in younger patients and present as massive bleeding with negative diagnostic workups. Most often, these patients would end up undergoing several blind intestinal resections. Rarest variety of AVMs constitutes hereditary hemorrhagic telengiectasia (HHT) also called Osler-Weber-Rendu syndrome. HHT is an autosomal dominant disorder with varying penetrance. Presence of at least three of the four criteria confirm the diagnosis of HHT: (1) spontaneous and recurrent epistaxis; (2) multiple mucocutaneous telangiectasia; (3) visceral involvement, most commonly of gastrointestinal, pulmonary, cerebral, and hepatic AVMs; and (4) a first-degree relative with HHT. The exact etiology of HHT is not entirely known. However, presence of mutation involving endoglin, a membrane glycoprotein needed for maintaining endothelial integrity on chromosome 9, and mutation of activin-receptor like kinase, ALK-1, a transdermal growth factor ␤ (TGF-␤) receptor on chromosome 12 are implicated in the causation of AVMs seen in HHT. HHT is not present at birth. Epistaxis, the earliest sign, occurs in childhood. Pulmonary AVMs occur at puberty, and gastrointestinal and mucocutaneous signs occur with increasing age. Nearly 30% of HHT will have pulmonary AVMs, 30% with hepatic AVMs, and 10% to 20% with cerebral AVMs. Dyspnea, hemoptysis, and playpnea-orthodeoxia are common symptoms of pulmonary AVMs. Cerebral abscesses, cerebrovascular accidents, or transient ischemic attacks are common neuroembolic manifestations of HHT and occur exclusively in patients with pulmonary AVMs with right to left shunts. Cerebral AVMs may present with headache, seizures, or cerebral hemorrhage. Hepatic AVMs mostly present with high-output cardiac failure (left to right shunt), portal hypertension, biliary disease, and hepatic encephalopathy. Screening of the family members with HHT should be carried out with history, focused physical examination, chest X-ray, contrast echocardiogram, and cerebral MRI.

Reproduced, with permission, from Pasha SF, Gloviczki P, Stanson AW, Kamath PS. Spalnachnic artery aneurysms. Mayo Clin Proc. 2007;82:472-479.

Treatment In some studies, splanchnic artery aneurysms have been found to be more common than the abdominal aortic aneurysms in the autopsy studies. Advancement in imaging technology with the CT, MRI, and digital angiography has led to easier detection of asymptomatic aneurysms as an incidental finding when these tests are ordered for other reasons. Multiple aneurysms maybe detected in one third of these patients. Although mostly asymptomatic, mortality from rupture of a visceral aneurysm is very high (50%–75%) even with an emergency surgery whereas elective repair has a low mortality rate (less than 15%). Close follow-up of the splanchnic aneurysms is therefore required to minimize the rate of rupture and thus to reduce mortality. Although presentations of these aneurysms vary, symptoms of abdominal pain, abdominal bruits, or a pulsatile mass should raise the suspicion of a splanchnic artery aneurysm. Table 31.9 describes the complications of splanchnic artery aneurysms. Surgical repair (aneurysmectomy with or without arterial reconstruction) or percutaneous exclusion (coil embolization or endograft stenting) of the aneurysms are the modalities commonly used to treat these aneurysms. While surgery is commonly preferred, percutaneous treatment is reserved for high surgical risk patients. Symptomatic aneurysms, enlarging aneurysms, or large aneurysms (>2 cm) require prompt interventions.85

•

SEGMENTAL ARTERIAL MEDIOLYSIS

Segmental arterial mediolysis (SAM) is an acute; selflimiting; noninflammatory visceral arteriopathy of unclear etiology that is very rare but affects mainly the mesenteric vasculature.90 Vacuolization and subsequent lysis of the smooth muscle cells of the mesenteric arterial walls leading

616 • CHAPTER 31

to aneurysmal dilation of the arteries are characteristics of this disease. Vacuolization initially starts in the outer media with sparing of the internal elastic lamina and the intima but in the advanced stage, it progresses to be transmural. SAM most commonly presents with painful abdominal distension, intra-abdominal hemorrhage, and hypotension or shock from aneurysmal ruptures of the mesenteric arteries. Pathology remains to be the gold standard for making a diagnosis of SAM; however, digital subtraction angiography or CT angiography demonstrating characteristic arterial involvement while maintaining a high degree of clinical suspicion is probably enough in most cases to clinch a diagnosis of SAM. An estimated mortality of up to 50% may be seen in the acute phase of this disease. Surgical interventions including segmental resection of the diseased segment and end-to-end anastomosis are the mainstay of management. However, transcatheter arterial embolization of the involved artery may be useful and feasible in treatment of SAM, although very close monitoring following coil embolization is imperative for these patients as morphological evolution can ensue very rapidly among these patients.91

•

SMA SYNDROME (OR WILKIE SYNDROME)

SMA syndrome or Wilkie syndrome is characterized by constellation of symptoms resulting from the compression of the transverse part of the duodenum against the aorta by the SMA. Abdominal pain, abdominal distension, nausea, or vomiting may be the manifest presentations of this syndrome as a result of chronic, intermittent, or acute com-

plete or acute partial duodenal obstruction. As the transverse part of duodenum course between the aorta and SMA, any condition that alters this aortomesenteric angle (such as thin body habitus, skeletal deformities, surgical interventions of the spine, etc.) can predispose to this syndrome. Most patients may only need conservative treatment while surgery may be reserved for the nonresponders. Barium X-rays or CT of abdomen is usually helpful in clinching the diagnosis.

•

NUTCRACKER SYNDROME

Nutcracker syndrome, also known renal vein entrapment syndrome, results from the compression of the left renal vein between the abdominal aorta and SMA. This is associated with hematuria, left flank pain, nausea, and/or vomiting. This is diagnosed with left renal venography (the gold standard test), or with CT. Treatment may include endovascular stenting, renal vein reimplantation, or gonadal vein embolization.

•

CONCLUSION

Mesenteric vascular disease is quite a common, yet highly lethal disease. Treatment of this disease should be immediate, aggressive, and accurate. Adequate knowledge of the disease with a high degree of suspicion is a must for prompt and effective treatment of these patients. The decision to perform a mesenteric angiogram in patients with high-risk features of mesenteric arterial disease should not be delayed, and a multidisciplinary approach should be followed in treating these patients.

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76. Lightfoot RW, Michet BA, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa. Arthritis Rheum. 1990;33:10881093. 77. Kobayashi M, Kurose K, Kobata T, Hida K, Sakamoto S, Matsubara J. Ischemic intestinal involvement in a patient with Buerger disease: case report and literature review. J Vasc Surg. 2003;38:170-174. 78. Olin JW. Thromboangitis obliterans. N Engl J Med. 2000; 343:864-869. 79. Masi AT, Hunder GG, Lie JT, et al. American College of Rheumatology 1990 criteria for the classification of ChurgStrauss syndrome. Arthritis Rheum. 1990;33:1094-1100. 80. Blanco R, Martinez-Taboada VM, Rodriguez-Valverde V, et al. Henoch- Schonlein purpura in adulthood and childhood: two different expressions of the same syndrome. Arthritis Rheum. 1997;40:859-864. 81. Arend WP, Michel BA, Block DA, et al. The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheum. 1990;33:1129-1134. 82. Criteria for diagnosis of Behcet’s disease. International study group for Behcet’s disease. Lancet. 1990;335:1078-1080. 83. Slovut DP, Olin JW. Fibromusular dysplasia: current concepts. N Engl J Med. 2004;350:1862-1871. 84. Guill CK, Benavides DC, Rees C, Fenves AZ, Burton EC. Fatal mesenteric fibromuscular dysplasia: a case report and review of the literature. Arch Intern Med. 2004;164:1148-1153. 85. Babu SC, Shah PM. Celiac territory ischemic syndrome in visceral artery occlusion. Am J Surg. 1993;166:227-230. 86. Howard TR, Brooks DL, Flynn TC, Seeger JM. Multiple organ dysfunction after mesenteric artery revascularization. J Vasc Surg. 1993;18:459-460. 87. Pasha SF, Gloviczki P, Stanson AW, Kamath PS. Spalnachnic artery aneurysms. Mayo Clin Proc. 2007;82:472-479. 88. Petrella S, Rodrigues CFS, Sgrott EA, Fernandez GJM, Marques SR, Prates JC. Relationship of the celiac trunk with median arcuate ligament of the diaphragm. Int J Morphol. 2006;24:263-274. 89. Richards WO, Garrard CL, Allos SH, Bradshaw LA, Staton DJ, Wikswo JP. Noninvasive diagnosis of mesenteric ischemia using a SQUID magnetometer. Ann Surg. 1995;221:696704. 90. Slavin RE, Saeki K, Bhagavan B, et al. Segmental arterial mediolysis: a precursor of fibromuscular dysplasia? Mod pathol. 1995;8:287-294. 91. Shimohira M, Ogino H, Sasaki S, et al. Transcatheter arterial embolization for segmental arterial mediolysis. J endovasc Ther. 2008;15:493-497.

chapter

32

Renal Artery Disease Brian Guttormsen, MD / Giorgio Gimelli, MD

Major advancements in vascular imaging techniques have facilitated the diagnosis of renovascular disease, and modern medical therapies as well as surgical and percutaneous interventional techniques offer the clinician a wide array of therapeutic tools in the management of renovascular disease. Despite these developments however, the indications for medical therapy versus surgical or percutaneous revascularization are controversial, and the clinician’s ability to predict the effect of revascularization on clinical outcomes remains limited. Vascular lesions affecting the renal artery can be caused by atherosclerosis, fibromuscular dysplasia (FMD), aneurysms, congenital or traumatic arteriovenous fistula (AVF), extrinsic compression, trauma, and embolization. The overwhelming majority of arterial artery lesions, however, are secondary to either atherosclerosis or FMD, which will be discussed below. A separate section will be dedicated to renal artery aneurysms, arteriovenous malformations (AVMs), and spontaneous renal artery dissections.

•

PREVALENCE AND NATURAL HISTORY

Fibromuscular Dysplasia Often clinically silent and discovered incidentally, FMD accounts for less than 10% of cases of renal artery stenosis (RAS), and although it can affect the intima, in the majority of cases it involves the media, resulting in the typical “string of beads” appearance (Figure 32-1).1 The cause remains largely unknown; however it may have a genetic component and it is more frequent in hypertensive patients and smokers.2 FMD usually affects women between 15 and 50 years of age, but it can be also observed in males and older patients as well.1 It occurs most frequently in the renal artery, but can also involve the carotid and vertebral arteries, sometimes in association with intracranial aneurysms, as well as other visceral vessels.1,3,4

In a series of angiogram of potential renal donors, incidental renal FMD was found in 3.8% patients, 75% of whom were females; in another study of patients with resistant hypertension screened with angiography, 16% had FMD.5,6 Because it is a disease of young patients with few cardiovascular risk factors, FMD is easily distinguishable from atherosclerotic RAS. FMD, unlike atherosclerotic RAS, tends to affect the mid and distal portion of the renal artery, and not the ostium. Its appearance can sometimes resemble vasculitis, but FMD is not an inflammatory process and it lacks the systemic manifestations and abnormal markers typical of vasculitis. The severity of stenosis can be difficult to accurately measure with both noninvasive testing as well as with catheter-based angiography, but progression of disease has been documented in up to 37% of patients.7,8 Atherosclerotic Renal Artery Stenosis Atherosclerosis accounts for approximately 90% of all renovascular lesions, and it usually involves the ostium and the proximal portion of the artery, although occasionally it can extend more distally.9 Atherosclerosis of the renal artery is more prevalent in the elderly, in patients with diabetes, and in patients with evidence of coronary or peripheral vascular disease elsewhere. In elderly white and black patients participating in the Cardiovascular Health Study (CHS), the prevalence of significant (≥60%) RAS detected by renal duplex sonography was 6.8%.10 Renovascular disease was not correlated to ethnicity, but was independently associated with age, hyperlipidemia, and hypertension. In a series of hypertensive patients undergoing coronary angiography, 19% had ≥50% stenosis and 7% had ≥70% stenosis by quantitative angiographic analysis. In a larger series of 3987 patients undergoing coronary angiography, aortography demonstrated ≥75% RAS in 4.8% patients.11 In 3.7% patients, the renal

620 • CHAPTER 32

patients in whom optimal blood pressure control has been achieved with medical therapy.17 RAS can result in decreased renal size. In a series of 204 kidneys in 122 subjects, Caps et al. reported a 2-year cumulative incidence of renal atrophy of 5.5%, 11.7%, and 20.8% in kidneys with normal renal arteries, with 1. Dieter et al. have recently demonstrated that pulse pressure inversely correlates to the outcome of renal artery

interventions. Patients with a high pulse pressure tend not to respond to treatment while those with a more normal pulse pressure have improvements in blood pressure and renal function after intervention on renal artery stenosis (personal communication from the author). Recently, investigators have looked for a possible association between brain type natruretic peptide (BNP) and improvement in HTN control following renal intervention.132 These authors examined a series of 27 patients with RAS and measured BNP before, during, and after intervention. They were able to show that a higher initial BNP and a more significant drop in BNP after intervention were independently associated with improved blood pressure control after intervention. Certainly, this study will need to be performed in a larger group; however it highlights the ongoing quest for a test to identify patients who will benefit from renal revascularization. In summary, the majority of renal revascularizations are performed today using stenting and this technique has been shown to be durable and effective in achieving improvement in renal arterial diameter. Further studies will be required to improve patient selection, choose the most appropriate adjuvant pharmacology, define the role of distal embolic protection devices, and to prevent and optimally treat in-stent restenosis.

•

OTHER CAUSES OF RENOVASCULAR DISEASE

Arteriovenous Malformations and Arteriovenous Fistulas Renal AVMs are anomalous congenital communications between the arterial and venous systems of the kidney, with no intermediate capillary vessels (Figure 32-12).133 Renal AVMs are rare, with an incidence of 1 per 30 000 in a large series of autopsies.133 They can be divided into two types, cirsoid and cavernomatous.134,135 Cirsoid AVMs are the most common type and are formed of multiple spiralshaped arteriovenous communications in the form of a renal mass near the collecting system. Cavernomatous AVMs are instead composed of a cystic cavity with a single artery entering it and draining vein.133,134 AVMs are usually unilateral, but bilateral AVMs have been reported.136,137 Acquired lesions are referred to as AVFs and are much more common than AVMs, representing 75% to 80% of all anomalous renal arteriovenous communications.133,134 AVFs can be caused by trauma, malignant disease, or nephrectomy, but the most common cause is percutaneous renal artery biopsy.133,138 Renal AVMs can be asymptomatic, but usually present with gross hematuria, which is the most common symptom and has been reported in 72% to 80% of cases.139−141 Gross hematuria is more frequent in AVMs than in acquired fistulas.141 Renin-mediated arterial hypertension can be present in both AVMs and AVFs, but more often in AVFs (50% vs. 25%, respectively). Other less common clinical findings include flank pain or tenderness, cardiomegaly with or without congestive

632 • CHAPTER 32

A

B

• FIGURE 32-12.

C

(A, B, and C) Arteriovenous malformation in the left renal artery.

Courtesy of Robert Dieter, MD, RVT.

heart failure, and abdominal bruits.133,139,141 When patients present with gross hematuria, the initial evaluation is usually performed with intravenous pyelography (IVP) and CT scan. IVP can be normal but may show filling defects of the dilated vessels as well as blood clots. Ultrasonography is usually the first diagnostic technique employed when the diagnosis of AVM is suspected.142 Color Doppler ultrasonography can demonstrate the vascular nature of the lesion showing high-velocity turbulent flow. Spiral CT scan with contrast administration may demonstrate a vascular mass and renal vein dilatation, but cannot differentiate AVMs from hypervascular solid lesions.143 MRI and MRA reveal the vascular nature of the lesion, but may fail to differentiate AVMs from aneurysms.141 Angiography remains the standard for the diagnosis of renal AVMs, and demonstrates single or multiple arteriovenous communications and early visualization of the draining renal veins and inferior vena cava, possibly with a decreased nephrogram distal to the AVM, and is necessary to guide therapeutic percutanous interventions.135,141,144 Treatment of AVMs should be tailored to the individual. Asymptomatic patients require no treatment, while more aggressive management is reserved for patients with severe hematuria, intraparenchymal hemorrhage, severe and resistant hypertension, recurrent renal or urethral colics, as well for those with heart failure.135 When treatment is necessary, transarterial embolization should be tried first, while surgery should be reserved when this approach fails or in very large AVMs.135,144,145 Embolization agents used include platinum coils, glue, plastic polymers, gelatin sponges as well as absolute alcohol.145−148 Surgical approaches include nephrectomy and ligation of the feeding vessels; surgical procedures that spare renal parenchyma are preferred and can be performed in conjuction with endovascular techniques.135,144

The causes are not known, and changes in the media and vasa-vasorum are among the possible etiologic factors. Although FMD can coexist with dissecting aneurysms in 9.1% of FMDs, SDRA is probably a separate entity.152 Renal artery dissection can be an incidental finding, and can be found bilaterally in 20% to 25% of the cases.150,153 Patients, however, often present more dramatically with new or accelerated hypertension and impaired renal function, flank pain, and hematuria, as well as with neurological symptoms.150,154−156 The natural history is not known, but severe hypertension can result in target organ damage, encephalopathy, and severe cardiovascular complications including sudden death.153,157 The diagnosis of renal artery dissection is primarily made by angiography, usually performed to rule out renovascular causes of elevated blood pressure. Whereas standard aortography maybe sufficient to outline dissections of the renal artery’s ostium and proximal segment, selective angiography is usually necessary when the dissection extends to the terminal branches of the artery.154 Treatment of SDRA is controversial.151 Medical therapy can be an acceptable first approach when SDRA is accompanied by hypertension, but endovascular or surgical treatment maybe necessary for refractory cases or in severely damaged kidneys. The role of endovascular treatment of SDRA has not been well established, but this approach seems reasonable in ostial and proximal renal artery dissections. For more distal disease, arterial artery reconstruction either in situ or ex situ followed by autotransplantation can achieve restoration of normal arterial anatomy and renal perfusion.154,156 The only indications for nephrectomy are severely damaged kidneys with dissections affecting inaccessible intrarenal branches and severe parenchymal alterations.154 Renal Artery Aneurysm (Figure 32-13)

Spontaneous Dissection of the Renal Artery Spontaneous dissection of the renal artery (SDRA) is a rare disease, and its clinical presentation may vary.149−151

Renal artery aneurysm represents a rare diagnosis with the prevalence in the general population reported at between 0.01% and 1%.158 Renal artery aneurysms represent 22%

RENAL ARTERY DISEASE • 633

• FIGURE 32-13.

Renal artery aneurysm.

Courtesy of Robert Dieter, MD, RVT.

of all visceral artery aneurysms.159 Clinicians will typically encounter this diagnosis as an incidental finding on an imaging study such as CT scan or MRI; however patients can

present with hypertension, renal dysfunction, hematuria, flank pain, and rarely rupture. The most common etiologic agents are atherosclerosis and FMD. The natural history of renal artery aneurysms is unknown, but the incidence of rupture is thought to increase with size. Mortality rates following rupture are reported at 10%.160 Indications for treatment of renal artery aneurysm in symptomatic patients include hypertension, hematuria, flank pain, and pregnancy. The reported incidence of rupture with pregnancy is as high as 80% mandating treatment in pregnant patients.158 The size at which to intervene in an asymptomatic patient is unknown. Some authors have advocated for intervention in aneurysms as small as 1.5 cm if they are increasing in size while others have suggested intervening in those aneurysms >2 cm.160,161 This question will likely remain unanswered given the infrequency with which this diagnosis is encountered. Treatment options include both surgical and percutaneous techniques. Historically, these lesions have been treated with open surgical anuerysmectomy with good operative outcomes. In a series from Michigan, 121 patients were treated operatively for renal artery aneurysms.162 There were no perioperative deaths and all but two grafts remained patent during a mean follow-up of 91 months. Percutaneous treatment is limited to case reports with reported techniques including placement of stent grafts, coiling and exclusion with covered stents.160,163−165 The longterm durability of these techniques with regard to patency and prevention of rupture remains unknown.

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79. Buecker A, Spuentrup E, Ruebben A, et al. New metallic MR stents for artifact-free coronary MR angiography: feasibility study in a swine model. Invest Radiol. 2004;39(5):250253.

65. Elkohen M, Beregi JP, Deklunder G, Artaud D, MounierVehier C, Carre AG. A prospective study of helical computed tomography angiography versus angiography for the detection of renal artery stenoses in hypertensive patients. J Hypertens. 1996;14(4):525-528.

80. Reginelli JPCCJ. Renal artery intervention. In: Wilkins LW, ed. Peripheral Vascular Interventions. Philadelphia, PA; 2005:175.

66. Kim TS, Chung JW, Park JH, Kim SH, Yeon KM, Han MC. Renal artery evaluation: comparison of spiral CT angiography to intra-arterial DSA. J Vasc Interv Radiol. 1998;9(4):553559.

81. Schreier DZ, Weaver FA, Frankhouse J, et al. A prospective study of carbon dioxide-digital subtraction vs standard contrast arteriography in the evaluation of the renal arteries. Arch Surg. 1996;131(5):503-507; discussion 507-508.

67. Fisher JEO, Jeffrey W. Renal artery stenosis. Clinical evaluation. In: Saunders E, ed. Vascular Medicine. Philadelphia, PA; 2006:343.

82. Hawkins IF, Jr., Wilcox CS, Kerns SR, Sabatelli FW. CO2 digital angiography: a safer contrast agent for renal vascular imaging? Am J Kidney Dis. 1994;24(4):685-694.

636 • CHAPTER 32 83. Spinosa DJ, Hagspiel KD, Angle JF, Matsumoto AH, Hartwell GD. Gadolinium-based contrast agents in angiography and interventional radiology: uses and techniques. J Vasc Interv Radiol. 2000;11(8):985-990. 84. Spinosa DJ, Matsumoto AH, Angle JF, et al. Safety of CO(2)and gadodiamide-enhanced angiography for the evaluation and percutaneous treatment of renal artery stenosis in patients with chronic renal insufficiency. AJR Am J Roentgenol. 2001;176(5):1305-1311. 85. Spinosa DJ, Matsumoto AH, Hagspiel KD, Angle JF, Hartwell GD. Gadolinium-based contrast agents in angiography and interventional radiology. AJR Am J Roentgenol. 1999;173(5):1403-1409. 86. Nally JV, Barton DP. Contemporary approach to diagnosis and evaluation of renovascular hypertension. Urol Clin North Am. 2001;28(4):781-791. 87. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001; 285(19):2486-2497. 88. Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): executive summary a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease) endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. J Am Coll Cardiol. 2006;47(6):12391312. 89. Textor SC. ACE inhibitors in renovascular hypertension. Cardiovasc Drugs Ther. 1990;4(1):229-235. 90. Benjamin ME, Dean RH. Techniques in renal artery reconstruction: Part I. Ann Vasc Surg. 1996;10(3):306-314. 91. Cambria RP, Brewster DC, L’Italien GJ, et al. The durability of different reconstructive techniques for atherosclerotic renal artery disease. J Vasc Surg. 1994;20(1):76-85; discussion 86-77. 92. Lawrie GM, Morris GC, Jr., Glaeser DH, DeBakey ME. Renovascular reconstruction: factors affecting long-term prognosis in 919 patients followed up to 31 years. Am J Cardiol. 1989;63(15):1085-1092. 93. Libertino JA, Bosco PJ, Ying CY, et al. Renal revascularization to preserve and restore renal function. J Urol. 1992; 147(6):1485-1487. 94. Hansen KJ, Starr SM, Sands RE, Burkart JM, Plonk GW, Jr., Dean RH. Contemporary surgical management of renovascular disease. J Vasc Surg. 1992;16(3):319-330; discussion 330-333. 95. Novick AC, Ziegelbaum M, Vidt DG, Gifford RW, Jr., Pohl MA, Goormastic M. Trends in surgical revascularization for renal artery disease. Ten years’ experience. JAMA. 1987;257(4):498-501.

96. Cherr GS, Hansen KJ, Craven TE, et al. Surgical management of atherosclerotic renovascular disease. J Vasc Surg. 2002; 35(2):236-245. 97. Bredenberg CE, Sampson LN, Ray FS, Cormier RA, Heintz S, Eldrup-Jorgensen J. Changing patterns in surgery for chronic renal artery occlusive diseases. J Vasc Surg. 1992;15(6):10181023; discussion 1023-1014. 98. Reilly JM, Rubin BG, Thompson RW, Allen BT, Anderson CB, Sicard GA. Long-term effectiveness of extraanatomic renal artery revascularization. Surgery. 1994;116(4):784-790; discussion 790-791. 99. Steinbach F, Novick AC, Campbell S, Dykstra D. Long-term survival after surgical revascularization for atherosclerotic renal artery disease. J Urol. 1997;158(1):38-41. 100. Chaikof EL, Smith RB, 3rd, Salam AA, et al. Ischemic nephropathy and concomitant aortic disease: a ten-year experience. J Vasc Surg. 1994;19(1):135-146; discussion 146-148. 101. Hansen KJ, Wilson DB, Edwards MS. Surgical revascularization of atherosclerotic renovascular disease: state of the art. Perspec Vasc Surg Endovasc Ther. 2004;16(4):281-295. 102. Clair DG, Belkin M, Whittemore AD, Mannick JA, Donaldson MC. Safety and efficacy of transaortic renal endarterectomy as an adjunct to aortic surgery. J Vasc Surg. 1995;21(6): 926-933; discussion 934. 103. Weibull H, Bergqvist D, Bergentz SE, Jonsson K, Hulthen L, Manhem P. Percutaneous transluminal renal angioplasty versus surgical reconstruction of atherosclerotic renal artery stenosis: a prospective randomized study. J Vasc Surg. 1993; 18(5):841-850; discussion 850-852. 104. Xue F, Bettmann MA, Langdon DR, Wivell WA. Outcome and cost comparison of percutaneous transluminal renal angioplasty, renal arterial stent placement, and renal arterial bypass grafting. Radiology. 1999;212(2):378-384. 105. Bettmann MA, Dake MD, Hopkins LN, et al. Atherosclerotic Vascular Disease Conference: Writing Group VI: revascularization. Circulation. 2004;109(21):2643-2650. 106. Gruntzig A, Kuhlmann U, Vetter W, Lutolf U, Meier B, Siegenthaler W. Treatment of renovascular hypertension with percutaneous transluminal dilatation of a renal-artery stenosis. Lancet. 1978;1(8068):801-802. 107. Tegtmeyer CJ, Elson J, Glass TA, et al. Percutaneous transluminal angioplasty: the treatment of choice for renovascular hypertension due to fibromuscular dysplasia. Radiology. 1982;143(3):631-637. 108. Sos TA, Pickering TG, Saddekni S, et al. The current role of renal angioplasty in the treatment of renovascular hypertension. Urol Clin North Am. 1984;11(3):503-513. 109. Webster J, Marshall F, Abdalla M, et al. Randomised comparison of percutaneous angioplasty vs continued medical therapy for hypertensive patients with atheromatous renal artery stenosis. Scottish and Newcastle Renal Artery Stenosis Collaborative Group. J Hum Hypertens. 1998;12(5):329335. 110. Plouin PF, Chatellier G, Darne B, Raynaud A. Blood pressure outcome of angioplasty in atherosclerotic renal artery stenosis: a randomized trial. Essai Multicentrique Medicaments vs Angioplastie (EMMA) Study Group. Hypertension. 1998;31(3):823-829.

RENAL ARTERY DISEASE • 637

111. van de Ven PJ, Kaatee R, Beutler JJ, et al. Arterial stenting and balloon angioplasty in ostial atherosclerotic renovascular disease: a randomised trial. Lancet. 1999;353(9149):282-286. 112. Leertouwer TC, Gussenhoven EJ, Bosch JL, et al. Stent placement for renal arterial stenosis: where do we stand? A meta-analysis. Radiology. 2000;216(1):78-85. 113. Isles CG, Robertson S, Hill D. Management of renovascular disease: a review of renal artery stenting in ten studies. QJM. 1999;92(3):159-167. 114. Rocha-Singh K, Jaff MR, Rosenfield K. Evaluation of the safety and effectiveness of renal artery stenting after unsuccessful balloon angioplasty: the ASPIRE-2 study. J Am Coll Cardiol. 2005;46(5):776-783. 115. Vignali C, Bargellini I, Lazzereschi M, et al. Predictive factors of in-stent restenosis in renal artery stenting: a retrospective analysis. Cardiovasc Intervent Radiol. 2005;28(3):296-302. 116. Lederman RJ, Mendelsohn FO, Santos R, Phillips HR, Stack RS, Crowley JJ. Primary renal artery stenting: characteristics and outcomes after 363 procedures. Am Heart J. 2001;142(2):314-323. 117. Bates MC, Rashid M, Campbell JE, Stone PA, Broce M, Lavigne PS. Factors influencing the need for target vessel revascularization after renal artery stenting. J Endovasc Ther. 2006;13(5):569-577. 118. Nolan BW, Schermerhorn ML, Powell RJ, et al. Restenosis in gold-coated renal artery stents. J Vasc Surg. Jul 2005; 42(1):40-46. 119. Stoeteknuel-Friedli S, Do DD, von Briel C, Triller J, Mahler F, Baumgartner I. Endovascular brachytherapy for prevention of recurrent renal in-stent restenosis. J Endovasc Ther. 2002;9(3):350-353.

stenting under protection: the way for the future? Catheter Cardiovasc Interv. 2003;60(3):299-312. 129. Zeller T, Frank U, Muller C, et al. Predictors of improved renal function after percutaneous stent-supported angioplasty of severe atherosclerotic ostial renal artery stenosis. Circulation. 2003;108(18):2244-2249. 130. Rocha-Singh KJ, Mishkel GJ, Katholi RE, et al. Clinical predictors of improved long-term blood pressure control after successful stenting of hypertensive patients with obstructive renal artery atherosclerosis. Catheter Cardiovasc Interv. 1999;47(2):167-172. 131. Burket MW, Cooper CJ, Kennedy DJ, et al. Renal artery angioplasty and stent placement: predictors of a favorable outcome. Am Heart J. 2000;139(1 Pt 1):64-71. 132. Silva JA, Chan AW, White CJ, et al. Elevated brain natriuretic peptide predicts blood pressure response after stent revascularization in patients with renal artery stenosis. Circulation. 2005;111(3):328-333. 133. Munoz IA, Bustos GA, Pardal AG, et al. Heart failure and severe pulmonary hypertension secondary to a giant renal arteriovenous malformation. J Ultrasound Med. 2006; 25(7):933-937. 134. Kawashima A, Sandler CM, Ernst RD, Tamm EP, Goldman SM, Fishman EK. CT evaluation of renovascular disease. Radiographics. 2000;20(5):1321-1340. 135. Crotty KL, Orihuela E, Warren MM. Recent advances in the diagnosis and treatment of renal arteriovenous malformations and fistulas. J Urol. 1993;150(5 Pt 1):1355-1359. 136. Minetti E, Montoli A. Images in clinical medicine. Bilateral renal arteriovenous malformation. N Engl J Med. 2004; 351(10):e9.

120. Reilly JP, Ramee SR. Vascular brachytherapy in renal artery restenosis. Curr Opin Cardiol. 2004;19(4):332-335.

137. Ullian ME, Molitoris BA. Bilateral congenital renal arteriovenous fistulas. Clin Nephrol. 1987;27(6):293-297.

121. Munneke GJ, Engelke C, Morgan RA, Belli AM. Cutting balloon angioplasty for resistant renal artery in-stent restenosis. J Vasc Interv Radiol. 2002;13(3):327-331.

138. Cho KJ, Stanley JC. Non-neoplastic congenital and acquired renal arteriovenous malformations and fistulas. Radiology. 1978;129(2):333-343.

122. Bax L, Mali WP, Van De Ven PJ, Beek FJ, Vos JA, Beutler JJ. Repeated intervention for in-stent restenosis of the renal arteries. J Vasc Interv Radiol. 2002;13(12):1219-1224.

139. Yazaki T, Tomita M, Akimoto M, Konjiki T, Kawai H, Kumazaki T. Congenital renal arteriovenous fistula: case report, review of Japanese literature and description of non-radical treatment. J Urol. 1976;116(4):415-418.

123. Zeller T, Rastan A, Rothenpieler U, Muller C. Restenosis after stenting of atherosclerotic renal artery stenosis: is there a rationale for the use of drug-eluting stents? Catheter Cardiovasc Interv. 2006;68(1):125-130. 124. Kakkar AK, Fischi M, Narins CR. Drug-eluting stent implantation for treatment of recurrent renal artery in-stent restenosis. Catheter Cardiovasc Interv. 2006;68(1):118-122; discussion 123-124. 125. Krishnamurthi V, Novick AC, Myles JL. Atheroembolic renal disease: effect on morbidity and survival after revascularization for atherosclerotic renal artery stenosis. J Urol. 1999;161(4):1093-1096. 126. Scolari F, Tardanico R, Zani R, et al. Cholesterol crystal embolism: a recognizable cause of renal disease. Am J Kidney Dis. 2000;36(6):1089-1109. 127. Holden A, Hill A. Renal angioplasty and stenting with distal protection of the main renal artery in ischemic nephropathy: early experience. J Vasc Surg. 2003;38(5):962-968. 128. Henry M, Henry I, Klonaris C, et al. Renal angioplasty and

140. Takaha M, Matsumoto A, Ochi K, Takeuchi M, Takemoto M, Sonoda T. Intrarenal arteriovenous malformation. J Urol. 1980;124(3):315-318. 141. Chatziioannou A, Mourikis D, Kalaboukas K, et al. Endovascular treatment of renal arteriovenous malformations. Urol Int. 2005;74(1):89-91. 142. Cisternino SJ, Malave SR, Neiman HL. Congenital renal arteriovenous malformation: ultrasonic appearance. J Urol. 1981;126(2):238-239. 143. Honda H, Onitsuka H, Naitou S, et al. Renal arteriovenous malformations: CT features. J Comput Assist Tomogr. 1991; 15(2):261-264. 144. Kopchick JH, Bourne NK, Fine SW, Jacobsohn HA, Jacobs SC, Lawson RK. Congenital renal arteriovenous malformations. Urology. 1981;17(1):13-17. 145. Takebayashi S, Hosaka M, Kubota Y, Ishizuka E, Iwasaki A, Matsubara S. Transarterial embolization and ablation of renal arteriovenous malformations: efficacy and damages in

638 • CHAPTER 32 30 patients with long-term followup. J Urol.1998;159(3): 696-701.

real reconstruction and autotransplantation1. J Vasc Surg. 2003;38(1):116-122.

146. Bischoff W, Pohle W, Goerttler U. Treatment of arteriovenous angiomas of the kidney: surgical intervention and intraarterial embolization. J Urol. 1979;122(6):825-828.

157. Esayag-Tendler B, Yamase H, Ramsby G, White WB. Accelerated hypertension with encephalopathy due to an isolated dissection of a renal artery branch vessel. Am J Kidney Dis. 1994;23(6):869-873.

147. Beaujeux R, Saussine C, al-Fakir A, et al. Superselective endo-vascular treatment of renal vascular lesions. J Urol. 1995;153(1):14-17. 148. Takebayashi S, Hosaka M, Ishizuka E, Hirokawa M, Matsui K. Arteriovenous malformations of the kidneys: ablation with alcohol. AJR Am J Roentgenol. 1988;150(3):587-590. 149. Beroniade V, Roy P, Froment D, Pison C. Primary renal artery dissection. Presentation of two cases and brief review of the literature. Am J Nephrol. 1987;7(5):382-389. 150. Smith BM, Holcomb GW, Richie RE III, Dean RH. Renal artery dissection. Ann Surg. 1984;200(2):134-146. 151. Edwards BS, Stanson AW, Holley KE, Sheps SG. Isolated renal artery dissection, presentation, evaluation, management, and pathology. Mayo Clin Proc. 1982;57(9):564-571. 152. Harrison EG, Jr., Hunt JC, Bernatz PE. Morphology of fibromuscular dysplasia of the renal artery in renovascular hypertension. Am J Med. 1967;43(1):97-112. 153. Mathieu D, Abbou C, Meunier S, Larde D, Vasile N. Primary dissecting aneurysm of the renal artery. Urol Radiol. 1983;5(1):17-21. 154. Lacombe M. Isolated spontaneous dissection of the renal artery. J Vasc Surg. 2001;33(2):385-391. 155. Gewertz BL, Stanley JC, Fry WJ. Renal artery dissections. Arch Surg. 1977;112(4):409-414. 156. van Rooden CJ, van Baalen JM, van Bockel JH. Spontaneous dissection of renal artery: long-term results of extracorpo-

158. Bulbul MA, Farrow GA. Renal artery aneurysms. Urology. 1992;40(2):124-126. 159. Deterling RA, Jr. Aneurysm of the visceral arteries. J Cardiovasc Surg (Torino). 1971;12(4):309-322. 160. Pershad A, Heuser R. Renal artery aneurysm: successful exclusion with a stent graft. Catheter Cardiovasc Interv. 2004; 61(3):314-316. 161. Hageman JH, Smith RF, Szilagyi E, Elliott JP. Aneurysms of the renal artery: problems of prognosis and surgical management. Surgery. 1978;84(4):563-572. 162. Henke PK, Cardneau JD, Welling TH, III, et al. Renal artery aneurysms: a 35-year clinical experience with 252 aneurysms in 168 patients. Ann Surg. 2001;234(4):454-462; discussion 462-463. 163. Bui BT, Oliva VL, Leclerc G, et al. Renal artery aneurysm: treatment with percutaneous placement of a stent-graft. Radiology. 1995;195(1):181-182. 164. Centenera LV, Hirsch JA, Choi IS, Beckmann CF, Gillard CS, Libertino J. Wide-necked saccular renal artery aneurysm: endovascular embolization with the Guglielmi detachable coil and temporary balloon occlusion of the aneurysm neck. J Vasc Interv Radiol. 1998;9(3):513-516. 165. Tan WA, Chough S, Saito J, Wholey MH, Eles G. Covered stent for renal artery aneurysm. Catheter Cardiovasc Interv. 2001;52(1):106-109.

chapter

33

Lower Extremity Peripheral Arterial Disease Ravi K. Ramana, DO / Bruce E. Lewis, MD / Robert S. Dieter, MD, RVT

•

r review the common and uncommon etiologies of

INTRODUCTION

Lower extremity peripheral arterial disease (LEPAD) is a major cause of poor quality of life, disability, and significant morbidity and mortality in the United States.1−17 In this chapter, LEPAD is used to refer to any arterial disease affecting the lower extremity, including occlusive, aneursymal, and vasculitic disease states. Even when asymptomatic, LEPAD has been shown to decrease mobility and bone mineral density8,9,12,18 ; leads to foot ulcers and amputations8,19 ; and be a strong predictor of subsequent cardiovascular (CV) disease, nonfatal CV events (e.g., myocardial infarction and stroke), and mortality.6,10,20 Standard therapy for LEPAD should include antiplatelet therapy and be directed at control of risk factors including smoking cessation, lipid management, strict diabetic therapy, and control of blood pressure21 in attempts to stop progression of the systemic atherosclerotic process. Current therapy on symptomatic disease includes exercise therapy, antiplatelet medications, and a variety of percutaneous interventional and surgical procedures. Therefore, early diagnosis and appropriate therapy for LEPAD can significant improve quality of life and decrease significant morbidity and CV mortality. This chapter will attempt to concisely r review the epidemiology and determined risk factors

of LEPAD, r discuss the embryologic development and subsequent

normal and variant anatomic features of LE vasculature, r summarize the classification and grading schemata for LEPAD, r discuss the pathophysiology underlying LEPAD and limb ischemia,

LEPAD, r discuss the typical clinical presentation, physical ex-

amination findings, and natural history of LEPAD, r summarize the various diagnostic modalities for

LEPAD, r review the medical and nonpharmacologic therapies

for LEPAD, r discuss the percutaneous and surgical revasculariza-

tion procedures for LEPAD and outline the appropriate clinical indications for use of each therapy, r discuss more specific therapy for critical limb ischemia (CLI), and r summarize the current investigations and future directions in the treatment of LEPAD.

•

EPIDEMIOLOGY

Prevalence It is without question that LEPAD is a common disease process affecting a significant portion of the adult population. There are a reported 413 000 discharges per year with chronic peripheral arterial disease (PAD), 88 000 inpatient lower extremity arteriographies, and nearly 30 000 discharges involving patients who had undergone embolectomy or thrombectomy of the lower limb arterial vasculature.22 Numerous epidemiologic studies have been performed in attempts to accurately quantify the prevalence of LEPAD in the adult population and although these studies have reported a variety of rates, most experts and consensus statements agree that up to 12 million individuals in the United States are affected by PAD. The variability found in these numerous studies evaluating

640 • CHAPTER 33

LEPAD is widely attributable to the differing clinical presentations (namely asymptomatic individuals), clinical definitions, diagnostic modalities, or specific patient subpopulations used in each study. The Framingham Heart Study was the first to address the prevalence of LEPAD in a large population sample in 1948. The initial and long-term follow-up data, which based the diagnosis of LEPAD exclusively on intermittent claudication symptoms, reported the prevalence of LEPAD to be 7.3%. In addition, this study was the first to report the incidence of LEPAD was higher in the elderly, a finding which has been consistently reproduced. However, their data suggesting a higher incidence in males has not been as well validated.16,23,24 However, the overall prevalence rates reported in this cohort study is a gross underestimate, since LEPAD often may present in asymptomatic forms that can only be detected via noninvasive or invasive imaging. Therefore, more recent studies have used other modalities to diagnosis LEPAD in further attempt investigate the prevalence of LEPAD in the general and specific patient populations. These studies have revealed a number of epidemiologic characteristics and disease comorbid risk factors that result in a higher prevalence in certain patient populations. One such study attempted to elucidate the prevalence of large-vessel and small-vessel LEPAD in a small population. Their assessment involved traditional questionnaires, physical examination, and noninvasive testing (segmental blood pressure, flow velocity, postocclusive reactive hyperemia, and pulse reappearance half-time). Results revealed a nearly 12% and 16% prevalence of large- and small-vessel lower extremity disease, respectively. Interestingly, the prevalence of large-vessel disease, but not isolated small-vessel disease, was significantly correlated with patients who were male and older than 60 years of age. These results demonstrate a significant fivefold underestimate of LEPAD when compared to symptoms of claudication, but a twofold overestimate of LEPAD when compared to pulse abnormalities on physical examination.14 A national, community-based PAD detection program (PARTNERS) used 350 local primary care sites to identify patients who were deemed higher risk for PAD: Age more than 70 years, or age more than 50 years with a history of diabetes and/or tobacco abuse. Findings revealed a 29% incidence of PAD, defined as an ankle–brachial index (ABI) less than 0.9.13 Similarly, a European population study evaluating more than 7000 patients, found nearly a 20% frequency of LEPAD in patients 55 years and older, with nearly 60% frequency in men elder than 85 years of age.13,16 Interestingly, in nearly all of the patients diagnosed by abnormal ABIs or other noninvasive imaging in these studies, only 1% to 22% of the patients had self-reported claudication or symptoms by Rose questionnaire.13,16,25−29 This strongly supports the notion that most patients with LEPAD remain either asymptomatic, have limited their activities to avoid claudication symptoms, are limited by other comorbid conditions, or simply attritibute their symptoms to their increasing age. Yet, it is important to note that

nearly 10% of these “asymptomatic” patients have advanced PAD with severe obstruction to blood flow,17 and all carry an increased risk of future CV events.14,16,17,30,31 Risk Factors Numerous risk factors for the development of LEPAD have been identified (Figure 33-1). And since the vast majority of LEPAD is caused by occlusive atherosclerotic disease, risk factors for the development and/or progression of LEPAD are nearly identical to those which can lead to cardiac and cerebrovascular atherosclerotic disease.21 The strongest correlations exist with elderly age and variably male gender (as discussed above). Other comorbidities including tobacco abuse, diabetes mellitus, hypertension, and hyperlipidemia and the relative risk—each of these relays onto the development of LEPAD are discussed below (Figure 33-1). Also, the coexistence of these risk factors relates synergistic effects on the development of LEPAD— one study reported a relative risk increase of 2.3 to 3.3 to 6.3 in patients with one, two, or three risk factors (tobacco abuse, hypertension, and diabetes) present, respectively.32 Tobacco Abuse. The association between smoking and PAD and subsequent claudication symptoms was first

1

Odds ratio 2 3

4

Male gender (cf female)

Age (per 10 years)

Diabetes Smoking

Hypertension

Dyslipidemia

Hyperhomocysteinemia Race (Asian/hispanic/ black vs. white) C-reactive protein

Renal insufficiency

• FIGURE 33-1.

Odd ratios for risk factors developing PAD.

Source: Reprinted with permission from Elsevier in Norgren L, Hiatt WR, Dormandy JA, et al. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg 2007;45(1): S5-S67.

LOWER EXTREMITY PERIPHERAL ARTERIAL DISEASE • 641

described in 1911.33 Tobacco abuse is a strong predictor of the development and progression of LEPAD15 as studies have reported a two- to sixfold risk of development of LEPAD compared to nonsmokers.5,16,34−36 In fact, tobacco abuse has been demonstrated to have a significantly higher relative risk for the development of PAD compared with the traditional atherosclerotic risk factors.34 Also, there is a strong, dose-dependent (i.e., number of packs per day and number of pack-years smoked) predictor of the development of LEPAD, risk of amputation, peripheral graft occlusion, and mortality.33,37−39 Diabetes. Numerous epidemiologic studies have reported a strong association between diabetes and an increased prevalence of PAD.40,41 Specifically, studies have reported that for every 1% increase in hemoglobin A1C levels, there is an associated 26% increased risk of PAD.42 Even patients with insulin resistance (and not diabetes) carry an increased risk of PAD.43 Moreover, other studies have demonstrated a two- to fourfold higher prevalence of LEPAD (defined as ABI 50% RAS > 60% CAS > 50% or RAS > 60% CAS > 50% and RAS > 60%

n

% (95% CI)

47 67 64

28.0 (21.2–34.8) 39.9 (32.5–47.3) 38.1 (30.8–45.4)

25

14.9 (9.5–20.3)

CAS, carotid artery stenosis; RAS, renal artery stenosis; CI, confidence interval. Source: Miralles M, Corominas A, Cotillas J, Castro F, Clara A, VidalBarraquer F. Screening for carotid and renal artery stenoses in patients with aortoiliac disease. Ann Vasc Surg. 1998;12(1):17-22.

coexistence of symptomatic coronary artery disease, PAD, and/or atherothrombotic brain infarctions in their patient population.84 Another study suggest that in patients with known LEPAD, angiographically proven coronary heart disease can be seen in up to 90%.99,100 Similar studies have reported more than one-fourth of patients undergoing coronary angiography prior to elective LEPAD revascularization surgery have severe triple-vessel coronary artery disease.101 Furthermore, an autopsy study which evaluated the coronary arteries in elderly patients (mean age 63 years) who had undergone amputation of at least one lower extremity because of severe LEPAD revealed that 92% of subjects had severe atherosclerotic narrowing (>75% of CSA) of at least one major epicardial vessels.102 Although the association is less dramatic, it appears that in patients with known LEPAD, carotid artery disease is seen in up to 25% of patients.33,102 However, these patients rarely have any history of clinically significant cerebrovascular events (less than 5%).33 In addition, a smaller study of patients undergoing elective aortoiliac surgery revealed nearly 40% of patients showed >60% stenosis in one or both renal arteries as assessed by renal duplex scanning. These patients were more likely to have significant renal artery stenosis if the planned aortoiliac surgery was secondary to obstructive arterial disease rather than abdominal aortic aneurysm (43% vs. 29%), or had an ABI less than 0.5 (73% coprevalence rate).103 Although not yet supported by clinical data, some suggest that in patients with PAD, the presence of significant renal artery stenosis portends a higher mortality rate33 (Table 33-1).

•

ANATOMICAL AREAS OF INTEREST

Embryology. Early in development, the embryologic dor-

sal aorta develops three sets of branches, including the (dorsal and ventral) intersegmental arteries which give rise to vasculature of the head, neck, body wall, vertebral column, and limbs. The median sacral artery is the small continuation of the dorsal aorta beyond the bifurcation at the iliac arteries. The fifth intersegmental artery which be-

comes the lumbar and lateral sacral arteries, together with an axial artery that develops along the central axis of the limb, supply blood to each leg limb bud. This original axial artery, which develops as a continuation of the internal iliac artery, terminates into a plexus where it joins the femoral artery. The axial artery, then progressively degenerates and is represented in the adult only as a small sciatic (ischiatic), inferior gluteal, popliteal, and distal section of the peroneal artery. Thereafter, the majority of the limb blood supply is derived from the external iliac artery. For instance, the obturator artery, tibial arteries, and proximal part of the popliteal artery develop much later in utero104 (Figure 33-3). In vast majority of patients with normal arterial anatomy, the abdominal aorta bifurcates into the common iliac arteries at the level of the fourth and fifth lumbar vertebrae (Figure 33-4). Each common iliac artery travels laterally and caudally and gives rise to small branches to the peritoneum, lumbar musculature, ureters, and occasionally iliolumbar or accessory renal arteries. The common iliac artery terminates by dividing into the hypogastric and external iliac artery, the latter supplying blood to the lower extremity. The hypogastric artery provides blood to the pelvis, buttocks, genitalia, and medial thigh. In addition, the common iliac gives rise to small branches to the peritoneum, lumbar musculature, ureters, and occasionally iliolumbar or accessory renal arteries (Figures 33-5 and 33-6). In addition, there is an extensive collateral circulation present involving the iliac and pelvic vasculature (Figure 33-7). The external iliac artery courses to the inguinal ligament and becomes the common femoral artery (CFA) just distal to the lateral circumflex and inferior epigastric arteries. The first portion of the CFA, which is enclosed in a fibrous sheath (i.e., the femoral sheath), subsequently divides into the deep profunda femoral artery (PFA) and the superficial femoral artery (SFA) (Figures 33-8 to 33-10). From its posterolateral origin at the CFA, the PFA travels deep behind the adductor longus and adductor magnus, feeding blood to the posterior thigh musculature and acts as an important source of collateral flow to the distal vessels. More specifically, the PFA gives off the lateral and medial femoral circumflex, perforating and muscular arteries. As the SFA courses along the upper third and middle part of the thigh, it is contained in the femoral triangle (Scarpa’s triangle) and adductor canal (Hunter’s canal), respectively. Major branches of the SFA include the superficial epigastric, superficial iliac circumflex, superficial and deep external pudendal, and various muscular branches. The SFA ends as it passes into the adductor canal and becomes the popliteal artery. In turn, the popliteal artery gives off blood supply to numerous cutaneous, muscular (to the posterior thigh and lower leg musculature), and genicular arterial branches (Figure 33-11). At the lower border of the popliteus muscle, the popliteal artery divides into the anterior tibial artery and tibioperoneal, which further divides into the peroneal and posterior tibial (PT) arteries. Also, surrounding the knee is a complex network of vessels that constitutes a superficial and deep plexus (Figure 33-12).

644 • CHAPTER 33

• FIGURE 33-3.

Embryologic development of the vasculature of the lower limb.

Source: Reprinted with permission from Elsevier in Larsen WJ, Sherman LS, Potter SS, and Scott WJ. Human Embryology. 3rd ed. Philadelphia, PA: Churchill Livingstone; 1993.

For the majority of its course, the anterior tibial artery travels along the interosseous membrane supplying the front of the leg via the tibial recurrent, fibular, maelleolar, and more muscular artery branches (Figure 33-13). At the lower part of the leg, the anterior tibial artery lies along the tibia and becomes the dorsalis pedis artery. In contrast, the majority of the blood supply to posterior lower leg musculature arises from the PT artery. As the PT artery travels on the tibial side of the leg to the posterior aspect of

the ankle, it gives rise to several branches including malleolar, medial calcaneal, muscular, and the peroneal artery. The peroneal artery travels down the medial side of the fibula and terminates into lateral calcaneal branches. The majority of the blood supply to the foot is from the dorsalis pedis artery, peroneal artery, and the distal branches of the PT artery (Figure 33-14). Initially, the anterior tibial artery gives rise to the anterior (medial and lateral) malleolar arteries that arise above the ankle and travel through

LOWER EXTREMITY PERIPHERAL ARTERIAL DISEASE • 645

• FIGURE 33-4.

Branches of the abdominal aorta.

Source: Reprinted with permission from Elsevier in Standring S, ed. Gray’s Anatomy. The Anatomical Basis of Clinical Practice. 39th ed. Philadelphia, PA: Churchill Livingstone; 2005.

the sides of the ankle, and anastomose distally with the (medial and lateral) plantar arteries (Figure 33-15). Also, the dorsalis pedis artery branches include the tarsal (medial and lateral), arcuate, and deep plantar arteries. The tarsal arteries provide blood supply to the medial and lateral borders of the foot, and anastomose distally with the branches of the malleolar and lateral plantar arteries. The arcuate artery gives off the second, third, and fourth dorsal metatarsal arteries and subsequent digital branches. The dorsalis pedis terminates into the bifurcation of the first dorsal metatarsal and deep plantar artery (Figure 33-16). These arteries mainly supply the halux and sole of the foot, respectively. Lastly, the PT artery gives rise to the calcaneal arteries (supplying the heel) and nutrient artery (supplying the navicular bone). The PT ends at the takeoff of the medial and lateral plantar arteries. The smaller medial plantar artery courses toward the base of the halux and supplies

blood flow to the halux and musculature on the medial portion of the foot. On the other hand, the lateral plantar artery tranverses laterally to join with the deep plantar branch of the dorsalis pedis artery (the plantar arch). This artery acts as the major blood supply of the lateral foot musculature; second, third, and fourth metatarsals; and digits.105 Variant Anatomy. Minor alterations in the above de-

scribed anatomy; considered merely normal variants, occur in the general population. For example, the level of aortic bifurcation varies and may be seen below the level of the iliac crest. Levels of bifurcation and relative lengths of the each of the described arteries can vary. Cases have been reported of patients with absence of the CFA, SFA, and/or PFA106 ; duplication of the SFA and/or PFA107 ; SFA bifurcation again after the origin of the PFA; or the popliteal artery trifurcating directly into the anterior tibial, PT, and

646 • CHAPTER 33

• FIGURE 33-5.

Collateral circulation around the hip and

thigh.

Source: Reprinted with permission from Elsevier in Standring S, ed. Gray’s Anatomy. The Anatomical Basis of Clinical Practice. 39th ed. Philadelphia, PA: Churchill Livingstone; 2005.

peroneal artery106 (Figure 33-17). Also, there appears to be a clear association with some chromosomal abnormality syndromes (e.g., disorganization-like syndrome, campomelic syndrome, congenital abnormalities of the lower limb) and abnormalities in lower leg vasculature.108−110 Other rare causes of LEPAD include gelatinous dystrophy, Leriche-Fontaine aneursymal dystrophy, and anterior tibial hypoplasia.111 Persistence of Sciatic (Ischiatic) Artery. The sciatic

artery is an embryologic continuation of the internal iliac artery into the popliteal–tibial arteries. In early embryologic

development, it serves as the major source of blood supply to the lower limb bud. In normal embryologic development, the sciatic artery involutes once the femoral arteries form and provide the majority of blood to the lower extremity.112 Normal adult remnants of the proximal sciatic artery are the proximal portions of the anterior and superior gluteal arteries, the artery to the sciatic nerve, and the popliteal and peroneal arteries112,113 (Figure 33-18). However, in less than 0.5% of adults, the embryologic sciatic artery persists. In most cases, this occurs when the femoral arterial vasculature (specifically, the SFA) fails to develop properly.112 In these patients, the persistent sciatic artery (PSA) may continue to be the major blood supply to the lower extremity as a continuation from the internal iliac artery to the popliteal artery.114−116 Five types of PSA anomalies have been described in attempt to better compare outcomes from different centers: Type I—complete PSA with continuity from the internal iliac to the popliteal artery with the femoral system ending as the saphenous artery; Type II—complete PSA associated with aplastic external iliac and femoral arteries and normal superficial femoral and popliteal arteries; Type III—incomplete PSA with the femoral system ending as the saphenous and sural arteries; Type IV—incomplete PSA with hypoplasia of the sciatic artery in the thigh with the femoral system as the dominant supply to the lower extremity; and Type V— incomplete PSA with hypoplasia of both the femoral and the sciatic arteries with limb atrophy.117 Of more clinical importance, there is an estimated 44% incidence of aneurysmal dilatation in these persistent sciatic arteries.115 Other vascular findings that can be seen in conjunction with persistent sciatic arteries include abnormal iliac and hypogastric arteries,118−120 and various venous anomalies.119−122 Most commonly, a PSA is an incidental finding. However, patients with this disorder may present with abnormal lower extremity pulses, claudication, sciatic pain (via compression of the adjacent sciatic nerve), a pulsatile mass in the buttocks, or rupture.115,118,122−124 Diagnosis can be readily made by ultrasound, computed tomography (CT), magnetic resonance imaging, or angiography. Treatment is not necessary for asymptomatic patients with persistent sciatic arteries. However, aneursymal sciatic arteries should be occluded by surgical ligation or transcatheter embolization in attempts to prevent distal embolization or rupture.112 In select patients, bypass revascularization from an adequate proximal (femoral) artery to the distal limb vasculature may be necessary.116,125,126

•

CLASSIFICATION

There are two major schemes to characterize PAD: The Fontaine and Rutherford Classifications. The severity of a patient’s disease process is based on symptoms, evidence of tissue damage, and/or tissue loss. The Fontaine classification includes four stages (Table 33-2). Fontaine I represents asymptomatic individuals; Stages IIa and IIb describe individuals with mild and moderate claudication, respectively; Stage III includes patients with ischemic rest pain;

LOWER EXTREMITY PERIPHERAL ARTERIAL DISEASE • 647

• FIGURE 33-6.

Arterial system of the pelvis.

Source: Reprinted with permission from Elsevier in Standring S, ed. Gray’s Anatomy. The Anatomical Basis of Clinical Practice. 39th ed. Philadelphia, PA: Churchill Livingstone; 2005.

and patients with ischemic ulcerations or gangrene are classified as Fontaine Stage IV. Similarly, the newer Rutherford classification divides PAD into five grades (0-IV), which include six categories: Rutherford Grade 0 represents asymptomatic individuals; Grade I signifies claudication symptoms of varying severity; Grade II describes patients with ischemic rest pain; and Grades III and IV include patients with tissue loss, ulceration, or gangrene.33,127

•

ETIOLOGY

The most common cause of LEPAD is systemic, atherosclerotic disease. However, LEPAD may also be caused by degenerative disorders that affect arterial wall structure and subsequent dilation99 including Marfan syndrome, EhlersDanlos syndrome (EDS), and cystic medical necrosis. The disorders that lead to thromboembolic phenomenon or inflammatory changes, in the vessel wall, may also lead LEPAD (Table 33-3). Atherosclerosis The most common cause of asymptomatic and symptomatic LEPAD is atherosclerosis. Studies have shown that

this disease is a complex, chronic, active immunoinflammatory and fibroproliferative process. The atherosclerotic plaques begin with macrophages and cholesterol deposition into intact, but leaky endothelium. These complexes become oxidized and, in turn, become proinflammatory, prothrombotic, and chemotaxic via the MMP, tissue factor and further macrophage recruitment. This inflammatory process promotes further cholesterol deposition and plaque formation. The process continues as smooth muscle cell proliferation occurs in attempt to heal and repair arterial injury. This fibroproliferative process may thicken the plaque’s cap, but also may become voluminous and result in symptomatic stenosis.127,128 These plaques may continue to remain stable or become unstable, the latter often referred to as “vulnerable” plaques. These vulnerable plaques have been defined to have a (1) thin fibrous cap, (2) necrotic; lipid rich core, and (3) dense macrophage infiltration.129 Once a vulnerable plaque ruptures, circulating platelets adhere to the necrotic core and monocytes secrete tissue factor promoting thrombosis or embolization.1 Patients with (and without) underlying atherosclerosis may present with an embolic phenomenon that leads to symptoms of LEPAD. Patients with known atherosclerosis

648 • CHAPTER 33

• FIGURE 33-7.

Extensive collateral circulation of the branches of the aorta and iliac

vessels.

Source: Adapted from Agur, Grant’s Atlas of Anatomy, 9th ed. and S. Meltzer, Medical Class of 1991.

are prone to cholesterol plaque rupture and subsequent thrombosis or distal atheroembolization resulting in thrombosis. Other conditions (e.g., primary prothrombotic diseases, atrial fibrillation, prosthetic valves, aneurysmal disease, ventricular thrombus, or endocarditis) predispose patients to an embolic event that may affect large or medium-sized arterial vessels.99 Embolic events may classically appear on angiography with multiple filling defects,

filling defects at bifurcations, meniscus sign, and/or lack of collateral or notable atherosclerotic disease.33 Abdominal Coarctation of the Aorta Claudication secondary to abdominal (infrarenal) coarctation of the aorta with/without severe hypoplasia of the aortoiliac femoral arterial system has been reported.130−134

LOWER EXTREMITY PERIPHERAL ARTERIAL DISEASE • 649

• FIGURE 33-9.

Arterial system of the profunda femoral

artery.

Source: Reprinted with permission from Elsevier in Standring S, ed. Gray’s Anatomy. The Anatomical Basis of Clinical Practice. 39th ed. Philadelphia, PA: Churchill Livingstone; 2005.

Aneurysmal Disease and Acute Dissection

• FIGURE 33-8.

Arterial system of the gluteal and posterior femoral regions.

Source: Reprinted with permission from Elsevier in Standring S, ed. Gray’s Anatomy. The Anatomical Basis of Clinical Practice. 39th ed. Philadelphia, PA: Churchill Livingstone; 2005.

Typically, these patients present with hypertension, cardiac failure, claudication, or decreased lower extremity pulses.130,131,133−135 Diagnosis can be confirmed with contrast aortography and standard treatment is surgical bypass revascularization.

Diseases of the arterial wall (e.g., atherosclerosis, connective tissue disorders, trauma, nonspecific inflammatory changes, etc.) can lead to local weakening and subsequent aneurysm formation. In the case of atherosclerosis, the exact mechanism of aneurysm formation is unknown. Although it is likely because of a combination of compromise of oxygen and nutrients to the media and aortic wall shear stress from hypertension. This scenario leads to ischemic injury to the media producing local weakening and damage (to the media and elastic membrane) to the vessel wall. Subsequently, this weakening allows dilatation of the aorta that (based on Laplace’s law) results in further wall tension stress and further dilatation of the vessel lumen. This process may be accentuated by an active inflammatory and proteolytic process. Also, these aneursymal lesions are

650 • CHAPTER 33

• FIGURE 33-10.

Arterial system of the superficial femoral

region.

Source: Reprinted with permission from Elsevier in Standring S, ed. Gray’s Anatomy. The Anatomical Basis of Clinical Practice. 39th ed. Philadelphia, PA: Churchill Livingstone; 2005.

predisposed to dissection that may cause distal ischemia via rupture or lumen occlusion. In addition, as a result of nonlaminar flow through the aneursymal segment, blood stasis may occur predisposing the patient to lumen thrombus formation. This thrombus material may embolize distally and produce ischemic symptoms. Aneurysmal disease can be seen in any arterial vascular bed. Most commonly, it affects the aorta with and without combination with more distal peripheral arterial beds. The most commonly occurring peripheral arterial aneurysms are popliteal artery aneurysms (PAAs), which account for up to

• FIGURE 33-11.

Arterial system of the popliteal, PT, and

peroneal region.

Source: Reprinted with permission from Elsevier in Standring S, ed. Gray’s Anatomy. The Anatomical Basis of Clinical Practice. 39th ed. Philadelphia, PA: Churchill Livingstone; 2005.

85% of all peripheral arterial aneurysms, and are most often because of underlying atherosclerosis.135 These aneurysms, defined when the artery is greater than 1.5 cm, are often bilateral and associated with abdominal aortic aneurysms.136 These aneurysms may be asymptomatic if small, but also may present as symptomatic disease (e.g., claudication/rest pain or leg pain/numbness as a result of mass effect and compression). PAAs may present with acute limb ischemia caused by acute vessel thrombosis (Figure 33-19), distal embolization or rupture—all historically carrying a high rate of limb loss.137

LOWER EXTREMITY PERIPHERAL ARTERIAL DISEASE • 651

• FIGURE 33-12.

Arterial anastomoses of the knee joint.

Source: Reprinted with permission from Elsevier in Standring S, ed. Gray’s Anatomy. The Anatomical Basis of Clinical Practice. 39th ed. Philadelphia, PA: Churchill Livingstone; 2005.

In contrast, aneurysms involving the CFA are rare but also are a marker of possibly aneurismal disease elsewhere (Figure 33-20). Common femoral artery aneurysms (CFAA) can be classified anatomically as Type I, in which the aneurysm ends before the bifurcation of the CFA into the superficial femoral and profunda femoris arteries, and Type II, in which the aneurysm involves the orifice of the profunda femoris artery. However, aneursymal disease isolated to the iliac system (IIAA) can be seen in 2% to 7% of patients affected with intra-abdominal aneurysms. Of note, these isolated iliac aneurysms are mostly asymptomatic but do carry a high rate of rupture, embolization, thrombosis, compression of adjacent structures, and significant operative mortality.138,139

Connective Tissue Disorders Ehlers-Danlos Syndrome. EDS is a disorder consisting of

nine distinct subtypes, all of which are characterized by abnormal collagen and subsequent hyperelasticity of the skin and hypermobile joints. The diagnosis of EDS is based on the clinical presentation: Patients typically present in the third decade with hyperplastic and fragile skin, hypermobile joints, or spontaneous rupture of arteries in the legs

with ensuing ecchymosis.140−143 Currently, there is no specific therapy for patients with EDS. Since patients with Type IV and IX (Menkes’ Syndrome) have been found to have an increased risk of arterial aneurysm formation and possible arterial (e.g., popliteal, femoral, iliac, and aorta) dissection or rupture, it would be prudent for these patients to undergo serial ultrasound evaluations for early detection of aneurysm formation. However, surgical repair of detected aneurysms may be complicated by the increased friability of tissues and pseudoaneursym formation.144−146 Elasticum. Pseudoxanthoma elasticum is a rare, inherited connective tissue disorder that results in abnormal elastic fibers. Pseudoxanthoma elasticum most commonly presents in the second to fourth decade of life147 with symptoms related to elastic degeneration of the skin, eyes, gastrointestinal system, or arteries (18% present with intermittent claudication).148−150 All arterial beds may be affected and is manifested as progressive luminal narrowing with severe arterial calcification that may lead to complete occlusion.148−150 Treatment consists of avoidance of dietary calcium and standard (albeit often extensive) revascularization interventions for only symptomatic stenosis.151

Pseudoxanthoma

652 • CHAPTER 33

has been theorized to be attributable to arteritis, previous thigh injury, or thromboembolic events with recanalization of the artery.152 Diagnosis can be made by angiography revealing a classic “string of beads” appearance reflecting diseased, thickened fibromuscular ridges adjacent to thin, less involved arterial wall segments. Treatment consists of PTA or surgical revascularization for symptomatic patients. In addition, these patients presenting with FMD of the lower extremity should be routinely screened for similar disease in the carotid and renal vasculature. Adventitial Cystic Disease. Cystic adventitial disease,

whereas intramural mucin-containing cysts occur between the media and adventitial layers of the vessel wall, has been reported to cause claudication. This condition more commonly affects the popliteal and femoral artery, and presents as sudden calf claudication aggravated by knee flexion.153,154 However, this condition was first described affecting the external iliac artery.155 Diagnosis can be made using Doppler ultrasound, CT, or MR. Also, contrast angiography may depict a smooth, curvilinear stenosis (scimitar sign) or hour-glass narrowing. Treatment may include cyst evacuation or aspiration, patch angioplasty, or surgical resection with vein bypass.154,156,157 Vasculitis Vasculitides consist of a large, variable group of chronic inflammatory disorders that result in damage to the blood vessel structure. These conditions result in a reduced peripheral blood flow caused by endothelial dysfunction and/or vascular obstructions.158 A broad range of vasculitic disease states exists, since any vessel type, vessel size, and vascular bed can be affected. (Of note, limb ischemia may develop acutely with inflammatory processes such as HIV arteriopathy).33 Thromboangiitis Obliterans. Thromboangiitis obliterans

• FIGURE 33-13.

Arterial system of the tibial and dorsal

pedis regions.

Source: Reprinted with permission from Elsevier in Standring S, ed. Gray’s Anatomy. The Anatomical Basis of Clinical Practice. 39th ed. Philadelphia, PA: Churchill Livingstone; 2005.

Dysplasia. Fibromuscular dysplasia (FMD) is a disease affecting medium- and small-sized arteries. It is most commonly seen affecting the renal or carotid arterial vasculature, although there have been reports of isolated abnormalities of the iliac and lower limb vasculature.152 Histologic examination most often reveals medial dysplasia with or without fibrosis of the elastic membrane in the diseased vessel wall. Specifically in isolated cases of lower limb vasculature, the abnormality Fibromuscular

(TO or Buerger disease) is an inflammatory disorder resulting in stenosis and obstruction of medium- and small-sized vessels in the distal arms and legs. The disease typically affects young Asian males (although women and the elderly have been reported) with heavy tobacco use. Although the underlying pathophysiology of TO is unclear, it is suggested that it may be an autoimmune reaction against a component of tobacco. Histologic examination reveals leukocyte and fibroblast infiltration leading to perivascular fibrosis and recanalization. Also, endothelin-1, a potent vasoconstrictor, may be elevated in patients with TO.159−161 Patients with TO often present with claudication or ischemic rest pain in the hand or foot. In more severe cases, ulcerations and gangrene of the fingers and toes may occur. Diagnosis is supported by angiography depicting smooth, tapering segmental lesions in the distal vasculature and/or classic “corkscrew” appearance of arteries resulting from vascular damage at sites of occlusions (Figure 33-21). In contrast to other vasculitidis, TO does not affect arteries outside the limb vasculature (e.g., visceral, pulmonary,

LOWER EXTREMITY PERIPHERAL ARTERIAL DISEASE • 653

• FIGURE 33-14.

Arterial anastomoses of the ankle joint.

Source: Reprinted with permission from Elsevier in Standring S, ed. Gray’s Anatomy. The Anatomical Basis of Clinical Practice. 39th ed. Philadelphia, PA: Churchill Livingstone; 2005.

renal, cerebral vasculature). To date, there has been no data to support the benefit for use of antiplatelet, anticoagulant, or anti-inflammatory medications in these patients. The only effective treatment for Buerger disease is immediate and complete cessation of tobacco use. Results with sympathectomy to control the vasospastic component of the disorder has been have been suboptimal. In end-stage patients, attempts with omentopexy (pedicled omental transplantation) to the affected limb to avoid amputation have been promising with nearly 85% limb-salvage rates.162,163 Takayasu Arteritis. Most commonly, Takayasu’s arteritis (TA) affects the aortic arch and its branches (large- and medium-sized vessels) of young women. The underlying pathophysiology of TA is unclear, but immunopathogenic mechanisms have been suggested. Histologic examination suggests a panarteritis with inflammatory infiltrates, occasional giant cells, marked intimal proliferation and fibrosis, scarring of the media, and degeneration of the elastic lamina.164 Affected patients may complain of fever, fatigue or be noted to have new-onset hypertension, aortic insufficiency, or suffer a cerebrovascular event. In severe cases, patients may present with arm and/or leg claudication. Often, these patients will have evidence of arterial occlusive disease on physical examination with appreciable bruits and significantly dimished (or absent) peripheral pulses. Diag-

nosis can be confirmed by ultrasound and MR (evidenced by thickening of the aortic wall) or contrast angiography (revealing stenosis, poststenotic dilatation, aneurysm formation and occlusion of the aorta with possible involvement of its major branches). Most patients respond to prednisone therapy, but methotrexate may be useful. Additional revascularization via endovascular or surgical bypass revascularization also may be needed for significant stenosis. Giant Cell Arteritis. Giant cell arteritis (GCA or temporal arteritis) is the most common adult type of vasculitis that occurs almost exclusively in the elderly population. This disorder typically affects the carotid artery and its branches, but may affect any large- or medium-sized artery, including, but rarely, the lower extremities. Nearly half of GCA patients are found to have polymyalgia rheumatica. Classic presenting symptoms include headache or scalp tenderness, jaw claudication, proximal muscle pain, fever or blurred vision. If severe and left untreated, it may progress to blindness. The underlying mechanism of this disease is unknown, but likely related to an autoimmune reaction or elevated levels of endothelin-1, a potent vasoconstrictor.159−161 Histologic examination reveals a panarteritis with leukocyte infiltrates in the vessel wall with frequent giant cell formation. Diagnosis is made the clinical scenario, elevated sedimentation rate, and confirmed by biopsy of the temporal

654 • CHAPTER 33

pair is complicated by the diseased delicate vessel walls, which predispose the patient to pseudoaneurysm at the site of anastomosis or thrombosis of the bypass grafts.166−169 Other Etiologies Vasospastic (Raynaud) Disease. Abnormal peripheral vasospasm, first described by Maurice Raynaud in 1862,170 is often caused by increased vascular tone in response to cold or emotional stimuli. Classic presentation occurs in three phases: First, the digits main arterial branches constrict resulting in paleness, numbness, pain or parasthesias; second, the digits become cyanotic and become purple or black in appearance; and third, the blood flow is reestablished with postischemic hyperemia and the digits appear purple. The pathophysiology of this condition is unclear, although many believe it is a result of endothelial dysfunction. The abnormal vascular tone may be a primary (Raynaud disease) or secondary phenomenon (usually because of an underlying collagen vascular disease). The diagnosis of Raynaud disease is entirely based on clinical presentation and there are no laboratory or imaging tests needed for confirmation (although some may be done to rule out other etiologies). Treatment for Raynaud disease includes avoidance of sudden cold exposure, cessation of tobacco use, and avoidance of sympathomimetic medications (e.g., decongestatnts, amphetamies, etc.). Cases that are more resistant may be treated with calcium channel blockers, other vasodilators, sympatholytic agents, and prostaglandins.

• FIGURE 33-15.

Plantar arteries of the foot—superficial

dissection.

Source: Reprinted with permission from Elsevier in Standring S, ed. Gray’s Anatomy. The Anatomical Basis of Clinical Practice. 39th ed. Philadelphia, PA: Churchill Livingstone; 2005.

(affected) artery. The current treatment for TA is prednisone therapy. Smaller studies have reported response to therapy with methotrexate and tumor necrosis factor blockers. Behcet Disease. Behcet disease, presumed to be immune mediated, presents typically as a triad of mouth ulcers, genital ulcers, and eye inflammation. But, in less common instances, it may include a panarteritis affecting even the limb arteries. Vascular symptoms include claudication or a lower extremity mass that can be as a result of aneursymal formation or occlusion of an affected arterial bed. The underlying histopathology reveals fragmentation of the vessel wall’s elastic fibers, degeneration of vasa vasorum with perivascular round cell infiltrate.165,166 Diagnosis can be made with CT or angiography. Treatment usually includes immune-mediated medications and possible surgical resection and/or bypass revascularization. However, surgical re-

Pernio (Chilbain’s Disease). Similar in clinical presentation to Raynaud disease, pernio is an inflammatory condition characterized by raised red and blue, pruritic lesions located on the pretibial area and toes. In severe cases, these lesions may blister or ulcerate. Typically, these lesions last less than 3 weeks. Pernio is caused by an abnormal vasomotor tone response to cold exposure, and therefore most likely to present in the spring and autumn (during cold, damp conditions). Pernio may be idiopathic or secondary to an underlying disorder (e.g., chronic myelomonocytic leukemia, macroglobulinemia, cyroglobulinemia, antiphospholipid antibody syndrome, or anorexia nervosa). A variant of pernio is chilblain lupus erythematosus that manifests as similar lesions over the dorsal interphalangeal joints. These patients often have abnormal serology (antinuclear antibody and/or rheumatoid factor) and a small proportion progress to develop systemic lupus. Diagnosis can be confirmed by lesion biopsy revealing dermal edema, perivascular lymphocytic infiltrate (“fluffy edema” of vessel walls) and epidermal spongiosis or necrosis. Treatment consists of keeping affected areas warm and dry. Several other studies have suggested that vasodilator medications, such as calcium channel blockers, or ultraviolet light therapy may have clinical benefit in treating and preventing episodes. Ergot Toxicity. Rare cases of claudication and digital ischemia may be secondary to ergot toxicity (e.g., St. Anthony’s fire), most commonly seen in younger females being

LOWER EXTREMITY PERIPHERAL ARTERIAL DISEASE • 655

• FIGURE 33-16.

Plantar arteries of the foot—deep dissection.

Source: Reprinted with permission from Elsevier in Standring S, ed. Gray’s Anatomy. The Anatomical Basis of Clinical Practice. 39th ed. Philadelphia, PA: Churchill Livingstone; 2005.

treated with ergot derivatives for migraines. Typical symptoms are a result of an acute vasospastic episode initially occurring in the SFA and progressing distally.171−173 Diagnosis can be made with contrast angiography which classically reveals diffuse and segmental vasospasm seen as a smooth narrowing of the vessels.174 Treatment includes discontinuation of smoking, caffeine intake or any other offending ergot product. Additional vasodilator therapy (nitroprusside or nifedipine) may be necessary in severe or refractory cases. Popliteal Artery Entrapment Syndrome. First described

in 1879, the popliteal artery entrapment syndrome is a rare anatomic abnormality (0.2%–3% of adults) consisting of an anomalous popliteal artery, which courses around the gas-

trocnemius muscle, resulting in intermittent vascular compression (i.e., entrapment) between the muscle and medial femoral condyle.175−177 The compression can lead to vessel wall fibrosis, stenosis, thrombosis, aneurismal dilatation, and distal microembolization.175 This abnormality is caused by abnormal embryologic development of the gastrocnemius and popliteal artery (although cases have been reported following femoropopliteal bypass surgery because of the similar misplacement of the venous graft.175 Based on Insua’s classification, there are four variants of this entrapment syndrome, but most cases are secondary to an abnormal course of the popliteal artery or abnormal insertion site of the medial head of the gastrocnemius.178 In rare cases, acquired entrapment syndrome may occur following surgical procedures.175,177−180

656 • CHAPTER 33

A

B

F

C

G

• FIGURE 33-17.

D

H

E

A, Normal. B, Trifurcating popliteal artery. C, Peroneal artery arising from low anterior tibial artery. D, “Island” popliteal artery (very rare); this pattern was not identified in our series. E, High anterior tibial origin passing superficial to popliteus muscle. F, Same as E with peroneal artery arising from anterior tibial artery. G, Same as E with anterior tibial artery passing deep to popliteus muscle. H, Same as F except anterior tibial artery passes deep to popliteus muscle. I, Absent posterior tibial artery.

I

Anatomic variants of the popliteal artery.

Source: Mauro MA, Jaques PF, Moore M. The popliteal artery and its branches: embryologic basis of normal and variant anatomy. AJR Am J Roentgenol. 1988;150(2):435-437.

Although a rare entity, history of sudden, unilateral calf claudication with parathesia and numbness while walking—but not running—in a young, athletic male should raise the clinician’s suspicion of this disorder. Diagnosis should be confirmed by angiography (performed with leg straight and in flexion), or more recently, by CT of the popliteal fossa.175 The treatment of choice is surgical release of the gastrocnemius muscle, grafting of the damaged artery with a vein graft resulting in normal blood flow to the lower limb.175,181 In addition, there are several case reports of other muscular or surrounding (e.g., Baker’s cyst, bony prominence, or venous aneurysm) structures constricting or compressing large arteries. For example, adductor canal compression syndrome occurs in cases where an abnormal band of tissue, originating from the adductor magnus muscle, courses across the SFA. Patients with this abnormality often are asymptomatic, but may have claudication with exercise as a result of the compression of the artery within the adductor canal. This condition may result in arterial damage and thrombotic events and can be treated with surgical ligation of the compressing tissue bands.182 Other case reports have described the passage of the femoral artery through the sartorius muscle.183 Iliac Artery Entrapment Syndrome. Similarly, patients

with external iliac endofibrosis (iliac artery compression)

may complain of leg pain with exercise—most commonly with high-performance cycling. Initial reports suggested the leg pain was as a result of the compression of the iliac artery at the inguinal ligament (because of the position of a cyclist).184,185 Others suggest the symptoms that occur with exercise are secondary to marked intimal thickening and subsequent significant stenosis. Treatment of symptomatic patients may be PTA/stent, surgical endarterectomy, or surgical bypass revascularization.185 Pseudoocclusion. Some patients who present with

symptoms of lifestyle limiting claudication or ischemic pain and undergo angiography are not found to have severely stenotic or occlusive lesions. Instead, these patients are found to have symptoms as a result of the external compression of arteries. For example, intermittent popliteal occlusion can occur with marked extension of the knee with or without plantar flexion.186,187 In more rare instances, popliteal artery compression can occur with the knee in neutral position. Pseudoocclusion of the popliteal artery must be differentiated from popliteal entrapment syndrome that also often occurs with only extreme dorsal flexion of the ankle. Evidence that might suggest pseudoocclusion as a cause of the symptoms includes normal angiographic appearance with change in position (e.g., knee flexed) (Figure 33-22), angiographic appearance out of proportion to an ABI measurement, lack of contralateral

LOWER EXTREMITY PERIPHERAL ARTERIAL DISEASE • 657

disease or collateral circulation. Patients with pseudoocclusion, and therefore proven normal arterial anatomy, should not undergo mechanical intervention.188 Inferior Gluteal Artery Profunda Femoris Artery Sciatic Artery Superficial Femoral Artery

Miscellaneous. Other causes of LEPAD include trauma

Primitive Arterial Segments Which Regress

Primitive Arterial Segments Which Persist Popliteus Muscle

Popliteal Artery Tibia

Anterior Tibial Artery

Non-Primitive Arterial Segments

Posterior Tibial Artery Peroneal Artery

• FIGURE 33-18.

Diagram showing embryologic

development of PSA.

Source: Mauro MA, Jaques PF, Moore M. The popliteal artery and its branches: embryologic basis of normal and variant anatomy. AJR Am J Roentgenol. 1988;150(2):435-437.

(including iatrogenic), pseudoanueryms (PSA), and arteriovenous fistulas (AVF). A pseudoaneursym is a contained disruption of the intimal and medial layers of a vessel wall. A PA may result from blunt trauma,189 an iatrogenic cause (e.g., arterial puncture), or dehiscence of a surgical anastomosis. Patients with PA located in the lower limb vasculature may remain asymptomatic or complain of swelling, a pulsatile mass, parasthesias, localized pain, or claudication. Symptomatic PA may be successfully treated with ultrasound-guided compression, thrombin injection, endovascular ligation or stent implantation, or via open surgical repair. In addition, these PA may become complicated by infection, most commonly by Staphlyococcus. Patients with infected PA most often present following a percutaneous arterial access or synthetic graft bypass revascularization procedure and require surgical excision and bypass revascularization with (commonly) the superficial femoropopliteal vein.190 Arteriovenous fistulas (AVF) are abnormal communications between an artery and vein, which bypasses the capillary bed. These defects may be congenital or acquired (as a complication to cardiac catheterization, etc.). Other reports have presented patients presenting with claudication because of the spontaneous arteriovenous fistulas of the lower extremities.191 AVFs may be asymptomatic, but can present as a pulsatile mass that may result in chronic venous insufficiency and/or distal ischemia. Duplex ultrasound or angiography can confirm the diagnosis. Treatment of large/symptomatic AVFs include surgical excision. Other modes of trauma injury include penetrating injuries, gunshot wounds or blunt trauma. Patients with traumatic vascular injury may present either hemodynamically stable or unstable. Diagnosis can be made on physical examination (e.g., evidence of distal ischemia, absent or diminished peripheral pulses, or expanding hematoma) or by

TABLE 33-2. The Two Major Schemes to Characterize PAD: The Fontaine and Rutherford Classifications Fontaine Stage

Clinical

I IIa IIb

Asymptomatic Mild claudication Moderate-to-severe claudication

III IV

Ischemic rest pain Ulceration or gangrene

Rutherford Grade 0 I I I II III III

Category 0 1 2 3 4 5 6

Clinical Asymptomatic Mild claudication Moderate claudication Severe claudication Ischemic rest pain Minor tissue loss Major tissue loss

Source: Reprinted with permission form Elsevier in Norgren L, Hiatt WR, Dormandy JA, et al. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg 2007. 45(I):S5-S67.

658 • CHAPTER 33

TABLE 33-3. Differential Diagnosis in the Etiology of LEPAD and Claudication Symptoms Anuerysmal disease Arthritis Atherosclerosis Baker’s cyst Coarctation of the abdominal aorta Chronic compartment syndrome Cystic adventitial disease Ischemic intermittent claudication Emboli Endofibrosis of the external iliac artery FMD Lymphangitis Musculoskeletal Myositis Nerve root compression Neuropathy Phlebetis Popliteal entrapment Reflex sympathetic dystrophy Spinal stenosis Trauma Vasculitis Vascular tumors Venous claudication

preoperative angiography. These patients should be treated with surgical bypass revascularization (utilizing saphenous vein or PTFE grafts) or arteriorrhaphy.192

•

• FIGURE 33-19.

CT images of thrombosis of the left popliteal artery with proximal aneurysal dilatation.

CLINICAL PRESENTATION

Asymptomatic The overwhelming percentage of patients with LEPAD are asymptomatic. On the basis of previous data, nearly 90% of all PAD patients would be missed if ABI testing was reserved only for patients with classic claudication symptoms.193 Therefore, further objective evaluation of high-risk asymptomatic patients is necessary. Claudication The most common presenting symptom in patients with LEPAD are atypical symptoms. However, intermittent claudication, defined as pain in the leg musculature with ambulation which is relieved by a short rest, is the earliest and most common classic presenting symptom in patients with LEPAD affecting 2% to 5% of the Unites States population older than 55 years,21,33 with prevalence of claudication symptoms increasing with age.33 However, the rates of reported intermittent claudication by patients greatly underestimates the prevalence of LEPAD in the general population (Figure 33-23). This is likely a result of many elderly patients who are unable to walk far enough to experience

claudication symptoms caused by other comorbidities including congestive heart failure, chronic obstructive pulmonary disease, and/or osteoarthritis. Yet, less than 25% of patients with claudication will have significant progression of their disease.194 This stabilization of the disease process may be as a result of the development of collateral vessels, metabolic adaptation of ischemic muscle, or change in the patient’s behavioral or activity patterns.33 It is important to realize that not all subjective complaints of leg pain is claudication. Therefore, it is imperative for the clinician to have a thorough understanding of the various causes of leg discomfort (Table 33-3). Critical Limb Ischemia CLI, defined as pain that occurs at rest in the affected limb or impending limb loss, is secondary to a severe reduction of blood flow in the affected tissue bed.99 These patients have tissue perfusion that is inadequate to maintain the resting metabolic needs of the affected limb. In a patient presenting with limb ischemia, it is mandatory that the clinician quickly determine if the disease process is acute or chronic CLI because the diagnostic methodology, therapeutic

LOWER EXTREMITY PERIPHERAL ARTERIAL DISEASE • 659

• FIGURE 33-21.

Contrast angiography depicting smooth, tapering segmental lesions in the distal vasculature and/or classic “corkscrew” appearance in a patient with TO.

• FIGURE 33-20.

CT image of right common femoral

aneurysm.

regimen, and prognosis for each is strikingly different. In general, chronic ischemic disease is defined as the presence of symptoms for more than 2 weeks.33 Chronic CLI The most common symptoms of chronic CLI are rest pain, ischemic ulcers and gangrene. Rest pain as a result of severe, chronic tissue ischemia is most often located in the forefoot or toes and is not easily attenuated by standard analgesics. Since the discomfort is often worsened when the patient is supine or when the limb is elevated, it is very common for the patient to complain of the symptoms at night or while sleeping. On the other hand, ischemic ulcers often originate in patients with an ABI ABI ≥ 0.5 ABI < 0.5*

0.6

0.5 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 Months

• FIGURE 33-26.

Three-year survival and event-free survival rates according to ABI.

Source: Reprinted with permission from Diehm C, Lange S, Darius H, et al. Association of low ankle brachial index with high mortality in primary care. Eur Heart J. 2006;27(14):1743-1749.

are at a 15-fold increase in CV and coronary heart diseaserelated deaths.6 Similar studies have reported that LEPAD patients have been shown to have an increased risk of angina, coronary artery bypass graft surgery, congestive heart failure, and nonfatal or fatal myocardial infarction.196,20,209−217 In addition, LEPAD predicts increased mortality in these patients with acute myocardial infarction218−220 or undergoing percutaneous coronary intervention,221 or coronary artery bypass graft surgery.222 Also, patients with LEPAD are at

increased risk for TIA,196 nonfatal stroke,223 and worse outcomes once a cerebrovascular event occurs.224

•

DIAGNOSTIC MODALITIES

The clinician can initiate an appropriate, focused work-up only after a thorough understanding of the patient’s subjective complaints, medical history, and physical examination. However, the history and standard physical examination alone have a very low accuracy in the diagnosis of LEPAD.

664 • CHAPTER 33

TABLE 33-5. Summary Table of Diagnostic Modalities Angioscopy ABI Bedside Doppler ultrasound CTA Contrast angiography Digital subtraction angiography Doppler velocity waveform analysis Duplex arterial ultrasound Exercise ABI and TBI History and physical examination Intravascular ultrasound Magnetic resonance angiography Optical coherence tomography Pressure gradient wire measurements Pulse volume recording Segmental limb pressure and continuous wave Doppler

In addition to obtaining a standard medical history, the clinician may find a standardized questionnaire to help elucidate symptoms of claudication or LEPAD. Presently, three standardized forms originally created to assess and standardize patients’ symptoms in previous trials regarding LEPAD can be effectively used in clinical practice: The Rose and Edinburgh questionnaires. The Rose questionnaire, developed in 1962, has been shown only to correctly identify 10% patients with an abnormal ABI.20 In addition, numerous epidemiologic studies have shown only moderately sensitivity (∼65%) but high specificity (90%–100%) in detecting intermittent claudication.196 Therefore, in efforts to improve upon the questionnaire’s diagnostic accuracy, the Edinburgh claudication questionnaire (ECQ) was created as a modification of the Rose questionnaire in 1962. In an initial small study of 300 patients, the ECQ had a reported sensitivity of 91% and sensitivity of 99% in the diagnosis of intermittent claudication.225 Thirdly, the San Diego Claudication Questionnaire was developed in order to further evaluate leg-specific symptoms and evaluate thigh, buttock and calf pain.55 Physical Examination

Therefore, many patients require more objective measures of LEPAD be used (Table 33-5). Clinical History and Standard Questionnairres The vast majority of patients with LEPAD are asymptomatic. The lack of symptoms is most likely because of either mild, nonflow limiting obstructive disease, or a sedentary lifestyle which does not induce ischemic symptoms. The most common presenting symptom of LEPAD is intermittent claudication. Other clinical presentations include atypical leg pain, ischemic ulcers, or chronic and acute limb ischemia (see above). Important aspects of any reported symptoms include the timing, symmetry (i.e., symptoms in the contralateral limb), use of potentially vasospastic medications, abuse of nonprescription drugs (especially tobacco), and occupational exposures. Also, one must closely review the comorbid medical conditions that the patient has been, and maybe even has not been, diagnosed with previously. Specifically, one must ascertain if the patient has a known history of atherosclerosis in another vascular bed (e.g., coronary, carotid, or renal). Additionally, a prior history of atrial fibrillation or flutter, severe left ventricular dysfunction, aortic plaqueing, aneursymal disease, or intracardiac shunts (e.g., patent foramen ovale or atrial septal defect)99 raises the probability that thromboembolic disease may be a culprit of any lower extremity symptoms. Other constitutional symptoms, such as fever, weight loss, night sweats, malaise, arthralgias, and myalgias may be indicative of an inflammatory vasculitic process. Any previously diagnosed hematologic, rheumatologic, or malignant diseases raises the suspicion for vasospasm, vasculititis, or hypercoaguable conditions.

In general, a complete physical examination should also focus on evidence of underlying systemic disorders that are risk factors for the development of LEPAD. For example, close attention must be given to determine signs of end-organ damage caused by underlying hypertension (retinopathy, fourth heart sound, abdominal bruits), hyperlipidemia or hyperlipoproteinemia (arcus, hollenhorst plaque, xanthomas, etc.), or diabetes (signs of peripheral neuropathy, diabetic ulcers). Patients with systemic inflammatory, rheumatologic, or vasculitic disease may appear chronically ill or cachetic. These patients also present with synovitis, nail pitting, prominent nailbed capillary loops, and skin lesions (e.g., erythema nodosum, pyoderma gangrenosum, petechial rash, or palpable purpura). However, the constellation of fever, rash, petechiae, and nail findings also warrants the consideration of infective endocarditis with embolization to the lower extremities. Other additional findings of embolization (atheroembolic or endocarditis) underlying the process include hemorrhages near the optic discs with white spots in the center (Roth spots), Osler nodes, Janeway lesions, and splinter hemorrhages under the nail beds. Because of the high prevalence of asymptomatic LEPAD in patients with risk factors for atherosclerosis, it is reasonable to perform an office-based screening for LEPAD in all patients referred to a vascular specialist by assessing pulses, auscultating for bruits, palpating for abdominal aortic aneursyms, and measuring blood pressures in both arms. All central and peripheral pulses should be palpable and symmetric throughout their course. When palpating for arterial pulsations, it is important to assess the volume of the pulse and the apparent condition of the vessel wall. Pulse volume is most commonly reported on a scale of 0 to 2 (0, absent; 1, decreased; 2, normal).226 Pulses that should

LOWER EXTREMITY PERIPHERAL ARTERIAL DISEASE • 665

be appreciable in healthy patients include the femoral, popliteal, dorsalis pedis, and PT arteries. Significant narrowing of the vasculature may manifest as reduced/absent pulses and/or bruits.227 However, patients with isolated occlusion of the internal iliac artery or stenosis of the common or external iliac artery pay have normal femoral and pedal pulses at rest and after exercise, but buttocks claudication and/or impotence in males.33 The femoral artery should be palpated just caudal to the inguinal ligament, halfway between the anterosuperior iliac spine and the pubic symphysis.227 The popliteal artery can be best appreciated with the patient’s hip and knee slightly flexed and the clinician’s fingers tucked into the popliteal fossa.228 The PT artery can be palpated below and behind the medial malleolus.229 Lastly, the dorsal pedis pulse is most often detected with the patient’s foot in slight dorsiflexion and the clinician palpating nearly halfway down the dorsum of the foot, just lateral to the extensor tendon of the first toe.227,219 However, absent pedal pulses can be an indicator of LEPAD with only moderate sensitivity and specificity.230 In less than 10% of patients, pulses may not be present because of congenital absence of the artery—most commonly the dorsalis pedis artery.226 At the same time, ausculatation to appreciate bruits should be performed over the iliac (2 cm lateral from the umbilicus halfway toward the inguinal ligament), common femoral, superficial femoral, and popliteal artery areas.228 The presence of a bruit may indicate the presence of a stenosis, extrinsic compression of the vessel, or other abnormality. Other helpful clues on physical examination include capillary refill time and the Buerger test. Capillary refill can be determined by applying firm pressure for 5 seconds on the plantar aspect of the halux. After releasing pressure in a patient without LEPAD, normal skin color should return in 5 seconds.231 In patients with severe LEPAD, it may take up to 20 seconds for the pallor to dissipate.226 Also, pallor can sometimes be induced on the soles of the feet by elevation of the foot above the level of the heart and repeated dorsiflexion and plantar flexion of the ankle. Then, the leg may be slowly lowered until the reddish hue returns (known as the “angle of circulatory insufficiency”). The test is considered abnormal if the angle of circulatory insufficiency is less than 0 degrees (i.e., patient’s leg needs to hang off the table for baseline color to return).231,232 This maneuver assesses the rate of blood flow, which in turn reflects the severity of stenosis and adequacy of collateral vessels.232 To perform the Buerger test, the patient is placed supine and his leg is raised to 90 degrees or until the clinician notes the development of pallor (known as the “vascular angle”). In cases of CLI, this angle is often less than 30 degrees.226 Then, the leg may be slowly lowered until the reddish hue returns (known as the “angle of circulatory insufficiency”). The test is considered abnormal if the angle of circulatory insufficiency is less than 0 degrees (i.e., patient’s leg needs to hang off the table for baseline color to return).231 Venous refill time may be determined by raising the leg for 30 to 60 seconds and then returned to the horizontal position. An abnormal test, indicative of severe arterial ischemia,

is suggested if the veins take greater than 5 seconds to refill.226 Patients with distal limb segments with chronic ischemia may have distal limb segments that appear purple (dependent rubor), which is attributable to skin capillaries becoming dilated with deoxygenated blood.226 Additonally, the examiner may appreciate noticeable skin color changes, especially when closely compared to the contralateral limb. The most common signs of acute arterial insufficiency are pulselessness, pallor, poikilothermia, pain, parasthesia, and/or polar (coldness). Additional signs of chronic arterial insufficiency include cool skin, noticeable petechiae, persistent cyanosis or pallor, pedal edema resulting from prolonged dependency, smooth and “bronzing” skin, focal hair loss, muscle atrophy, thickened and brittle toenails, and subcutaneous fat atrophy of the digital pads.226,228,232 The development of skin fissures and nonhealing ulcers at areas of minor trauma and digital gangrene may also indicate chronic arterial insufficiency (although they may be seen in acute arterial insufficiency).233 Arterial ulcers typically have a pale base, sharply demarcated borders, a typical “punched out” appearance and usually involve the tips of the toes or the heel of the foot, develop at sites of pressure, and vary in size (3 mm and greater).232 These ulcers, which most commonly occur at the lateral malleolus, tips of the toes, and/or metatarsal heads, can often be differentiated from venous ulcers which occur on the medial malleolus and are usually painless.228 Although the presence of skin ulceration strongly suggests atherosclerotic disease, the clinician still must consider embolic disease, Buerger disease, or vasculitis.99 In cases of atheroembolism, livedo reticularis, a mottled, “fishnet” reticular pattern can be seen on the lower extremities. The discoloration is typically pink or purplish in color that worsens with cold exposure. This finding also is seen in Raynaud syndrome, collagen vascular diseases, and hyperviscosity syndromes.226 Bedside Doppler Ultrasound Following a thorough physical examination, the use of a rapid, bedside Doppler examination of the lower extremity may be helpful in patients in whom the clinician is considering the diagnosis of LEPAD. In a study evaluating more than 200 patients, a “PAD score” was calculated based on the number of ausculatated arterial components, grade of peripheral pulse, and history of myocardial infarction which included the number of auscultated components and grade of palpated pulses of both PT arteries and the history of myocardial infarction. Patients with a score of less than 6 (or less than 4 when only one limb was assessed), made the diagnosis of LEPAD highly more likely (LR 7.80). These investigators suggested using this simple Doppler examination to determine which patients should be referred for ABI testing.234 Ankle–Brachial Index The most commonly used objective measurement for the assessment of LEPAD are ABIs because of its ease of

666 • CHAPTER 33

use, noninvasive nature, high sensitivity and specificity (95% and nearly 100% respectively, when compared to angiography),235,236 and lack of expense. An ABI can be readily calculated by dividing the highest ankle systolic pressure (dorsalis pedis or PT artery measured blood pressure at the level of the malleolus) by the highest brachial systolic pressure.21 Although methods to quantitate systolic pressures vary (including auscultation with a stethoscope, oscillometric, or Doppler ultrasound), no study has shown one method to be more superior. Traditionally, this technique is done using Doppler ultrasound: A suggested method of obtaining ABI includes placing the patient in a supine position, inflating the sphygmomanometer cuff 2 to 3 cm above the point of pulse measurement, and slowly releasing cuff pressure. Then a Doppler ultrasound probe, placed at the point of pulse measurement, is used to determine systolic pressure defined as the systolic pressure during which the Doppler signal returns.235 But, a small study which evaluated the use of automated oscillometry (i.e., “automated ABIs”) compared to standard Doppler ultrasound determined that an automated ABI is a reliable and easier method in diagnosing LEPAD (correlation coefficient 0.78).237 However, it is important that the methodology guiding patients’ serial examinations be consistent over time. An ABI of or = 62 years of age. Am J Cardiol. 1994;74(1):64-65. 85. McDermott MM, Fried L, Simonsick E, Ling S, Guralnik JM. Asymptomatic peripheral arterial disease is independently associated with impaired lower extremity functioning: the women’s health and aging study. Circulation. 2000; 101(9):1007-1012.

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420. Belli AM, Cumberland DC, Procter AE, Welsh CL. Followup of conventional angioplasty versus laser thermal angioplasty for total femoropopliteal artery occlusions: results of a randomized trial. J Vasc Interv Radiol. 1991;2(4):485-488.

406. Zehnder T, von Briel C, Baumgartner I, et al. Endovascular brachytherapy after percutaneous transluminal angioplasty of recurrent femoropopliteal obstructions. J Endovasc Ther. 2003;10(2):304-311.

421. Bolia A, Brennan J, Bell PR. Recanalisation of femoropopliteal occlusions: improving success rate by subintimal recanalisation. Clin Radiol. 1989;40(3):325.

407. Waksman R, Laird JR, Jurkovitz CT, et al. Intravascular radiation therapy after balloon angioplasty of narrowed femoropopliteal arteries to prevent restenosis: results of the

422. Treiman GS, Whiting JH, Treiman RL, McNamara RM, Ashrafi A. Treatment of limb-threatening ischemia with percutaneous intentional extraluminal recanalization: a preliminary evaluation. J Vasc Surg. 2003;38(1):29-35.

700 • CHAPTER 33 423. Nydahl S, Hartshorne T, Bell PR, Bolia A, London NJ. Subintimal angioplasty of infrapopliteal occlusions in critically ischaemic limbs. Eur J Vasc Endovasc Surg. 1997;14(3):212216.

440. Weichmann BaK, SE. Cryoplasty for treating femoropopliteal occlusive disease. Endovascular Today June 2005:76-79.

424. McCarthy RJ, Neary W, Roobottom C, Tottle A, Ashley S. Short-term results of femoropopliteal subintimal angioplasty. Br J Surg. 2000;87(10):1361-1365.

441. Laird J, Jaff MR, Biamino G, et al. Cryoplasty for the treatment of femoropopliteal arterial disease: results of a prospective, multicenter registry. J Vasc Interv Radiol. 2005; 16(8):1067-1073.

425. Dieter RS, Pacanowski JR Jr, Ahmed MH, Mannebach P, Nanjundappa A. FoxHollow atherectomy as a treatment modality for common femoral artery occlusion. WMJ. 2007; 106(2):90-91.

442. Wiedermann JG, Marboe C, Amols H, Schwartz A, Weinberger J. Intracoronary irradiation markedly reduces restenosis after balloon angioplasty in a porcine model. J Am Coll Cardiol. 1994;23(6):1491-1498.

426. Laird JR, Zeller T, Gray BH, et al. Limb salvage following laser-assisted angioplasty for critical limb ischemia: results of the LACI multicenter trial. J Endovasc Ther. 2006;13(1):111.

443. Waksman R, Rodriguez JC, Robinson KA, et al. Effect of intravascular irradiation on cell proliferation, apoptosis, and vascular remodeling after balloon overstretch injury of porcine coronary arteries. Circulation. 1997;96(6):19441952.

427. Laird J. Peripheral Excimer Laser Angioplasty (PELA) Trial Results. In: TCT Annual Meeting; 2002; Washington, DC. 428. Dieter RS, Laird JR. Nonstent endovascular treatment of SFA Occlusions. Endovascular Today. March 2006:59-64. 429. Boccalandro F, Muench A, Sdringola S, Rosales OR. Wireless laser-assisted angioplasty of the superficial femoral artery in patients with critical limb ischemia who have failed conventional percutaneous revascularization. Catheter Cardiovasc Interv. 2004;63(1):7-12. 430. Konig CW, Pusich B, Tepe G, et al. Frequent embolization in peripheral angioplasty: detection with an embolism protection device (AngioGuard) and electron microscopy. Cardiovasc Intervent Radiol. 2003;26(4):334-339. 431. Ansel GM, Sample NS, Botti IC Jr, et al. Cutting balloon angioplasty of the popliteal and infrapopliteal vessels for symptomatic limb ischemia. Catheter Cardiovasc Interv. 2004;61(1):1-4. 432. Rabbi JF, Kiran RP, Gersten G, Dudrick SJ, Dardik A. Early results with infrainguinal cutting balloon angioplasty limits distal dissection. Ann Vasc Surg. 2004;18(6):640-643. 433. Fourrier JL, Bertrand ME, Auth DC, Lablanche JM, Gommeaux A, Brunetaud JM. Percutaneous coronary rotational angioplasty in humans: preliminary report. J Am Coll Cardiol. 1989;14(5):1278-1282. 434. Rubartelli P, Niccoli L, Alberti A, et al. Coronary rotational atherectomy in current practice: acute and mid-term results in high- and low-volume centers. Catheter Cardiovasc Interv. 2004;61(4):463-471. 435. Hoffmann R, Mintz GS, Kent KM, et al. Comparative early and nine-month results of rotational atherectomy, stents, and the combination of both for calcified lesions in large coronary arteries. Am J Cardiol. 1998;81(5):552-557. 436. Simpson JB, Selmon MR, Robertson GC, et al. Transluminal atherectomy for occlusive peripheral vascular disease. Am J Cardiol. 1988;61(14):96G-101G.

444. Fischer-Dzoga K, Dimitrievich GS, Schaffner T. Effect of hyperlipidemic serum and irradiation on wound healing in primary quiescent cultures of vascular cells. Exp Mol Pathol. 1990;52(1):1-12. 445. Mukherjee D, Moliterno DJ. Brachytherapy for in-stent restenosis: a distant second choice to drug-eluting stent placement. JAMA. 2006;295(11):1307-1309. 446. Pokrajac B, Potter R, Maca T, et al. Intraarterial (192) Ir highdose-rate brachytherapy for prophylaxis of restenosis after femoropopliteal percutaneous transluminal angioplasty: the prospective randomized Vienna-2-trial radiotherapy parameters and risk factors analysis. Int J Radiat Oncol Biol Phys. 2000;48(4):923-931. 447. Bonvini R, Baumgartner I, Do DD, et al. Late acute thrombotic occlusion after endovascular brachytherapy and stenting of femoropopliteal arteries. J Am Coll Cardiol. 2003; 41(3):409-412. 448. Krueger K, Zaehringer M, Bendel M, et al. De novo femoropopliteal stenoses: endovascular gamma irradiation following angioplasty—angiographic and clinical follow-up in a prospective randomized controlled trial. Radiology 2004; 231(2):546-554. 449. Waksman R. Results of the PARIS Trial. In: TCT Annual Meeting; 2003; Washington, DC. 450. Kipshidze N, Serruys PW, Moses J, Fareed J, ed. Textbook of Interventional Cardiovascular Pharmacology. 1st ed. London, UK: Informa Healthcare; 2007. 451. Johnson WC, Lee KK. A comparative evaluation of polytetrafluoroethylene, umbilical vein, and saphenous vein bypass grafts for femoral–popliteal above-knee revascularization: a prospective randomized Department of Veterans Affairs cooperative study. J Vasc Surg. 2000;32(2):268-277.

437. Henry M, Amor M, Ethevenot G, Henry I, Allaoui M. Percutaneous peripheral atherectomy using the rotablator: a single-center experience. J Endovasc Surg. 1995;2(1):51-66.

452. Veith FJ, Gupta SK, Ascer E, et al. Six-year prospective multicenter randomized comparison of autologous saphenous vein and expanded polytetrafluoroethylene grafts in infrainguinal arterial reconstructions. J Vasc Surg 1986;3(1):104114.

438. Zacca NM, Raizner AE, Noon GP, et al. Treatment of symptomatic peripheral atherosclerotic disease with a rotational atherectomy device. Am J Cardiol 1989;63(1):77-80.

453. Baldwin ZK, Pearce BJ, Curi MA, et al. Limb salvage after infrainguinal bypass graft failure. J Vasc Surg. 2004;39(5):951957.

439. Lyden SP. Polarcath cryoplasty: 9 month IDE Trial update. In: 31st Global Vascular and Endovascular Issues, Techinques and Horizon; 2004; Cleveland, OH.

454. de Vries SO, Hunink MG. Results of aortic bifurcation grafts for aortoiliac occlusive disease: a meta-analysis. J Vasc Surg. 1997;26(4):558-569.

LOWER EXTREMITY PERIPHERAL ARTERIAL DISEASE • 701

455. Hunink MG, Wong JB, Donaldson MC, Meyerovitz MF, Harrington DP. Patency results of percutaneous and surgical revascularization for femoropopliteal arterial disease. Med Decis Making. 1994;14(1):71-81. 456. Oskam J, van den Dungen JJ, Boontje AH. Thromboendarterectomy for obstructive disease of the common iliac artery. Cardiovasc Surg. 1996;4(3):356-359. 457. Nicoloff AD, Taylor LM Jr, McLafferty RB, Moneta GL, Porter JM. Patient recovery after infrainguinal bypass grafting for limb salvage. J Vasc Surg. 1998;27(2):256-263; discussion 64-66. 458. Kessel DO, Berridge DC, Robertson I. Infusion techniques for peripheral arterial thrombolysis. Cochrane Database Syst Rev. 2004;(1):CD000985. 459. Nanjundappa A LJ. Critical limb ischemia. Endovascular Today. 2006:36-40. 460. Bernstein EF, Rhodes GA, Stuart SH, Coel MN, Fronek A. Toe pulse reappearance time in prediction of aortofemoral bypass success. Ann Surg. 1981;193(2):201-205. 461. Clagett GP, Sobel M, Jackson MR, Lip GY, Tangelder M, Verhaeghe R. Antithrombotic therapy in peripheral arterial occlusive disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3 suppl):609S-626S. 462. Ouriel K, Shortell CK, DeWeese JA, et al. A comparison of

thrombolytic therapy with operative revascularization in the initial treatment of acute peripheral arterial ischemia. J Vasc Surg. 1994;19(6):1021-1030. 463. Weaver FA, Comerota AJ, Youngblood M, Froehlich J, Hosking JD, Papanicolaou G. Surgical revascularization versus thrombolysis for nonembolic lower extremity native artery occlusions: results of a prospective randomized trial. The STILE Investigators. Surgery versus Thrombolysis for Ischemia of the Lower Extremity. J Vasc Surg. 1996;24(4):513521; discussion 21-23. 464. Results of a prospective randomized trial evaluating surgery versus thrombolysis for ischemia of the lower extremity. The STILE trial. Ann Surg. 1994;220(3):251-266; discussion 6668. 465. Ouriel K, Veith FJ, Sasahara AA. A comparison of recombinant urokinase with vascular surgery as initial treatment for acute arterial occlusion of the legs. Thrombolysis or Peripheral Arterial Surgery (TOPAS) Investigators. N Engl J Med. 1998;338(16):1105-1111. 466. Ouriel K, Veith FJ, Sasahara AA. Thrombolysis or peripheral arterial surgery: phase I results. TOPAS Investigators. J Vasc Surg. 1996;23(1):64-73; discussion 4-5. 467. Diffin DC, Kandarpa K. Assessment of peripheral intraarterial thrombolysis versus surgical revascularization in acute lower-limb ischemia: a review of limb-salvage and mortality statistics. J Vasc Interv Radiol. 1996;7(1):57-63.

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34

Medical Therapy of Intermittent Claudication Manu Rajachandran, MD / Robert M. Schainfeld, DO

The medical therapy of intermittent claudication is founded on two fundamental precepts (Table 34-1). The most compelling of these is that peripheral arterial disease is evidence for systemic atherosclerosis. Affected patients most likely have concomitant coronary artery and cerebrovascular diseases. As a result, they are at increased risk for adverse clinical outcomes including myocardial infarction, stroke, and death. These patients also frequently manifest symptoms of intermittent claudication, resulting in impaired functional status, or symptoms of critical limb ischemia—rest pain, ulcers, or gangrene, which ultimately threaten the viability of the limb. Therefore, management of these patients must employ therapeutic strategies that decrease their risk of cardiovascular events, reduce mortality, improve functional capacity and quality of life, and preserve limb integrity. In contrast to the relative intangibility of vascular risk reduction, symptomatic improvement in peripheral arterial disease after the institution of appropriate medical therapy can often become apparent to the patient within a matter of weeks or a few months and can significantly enhance a patient’s quality of life.

•

PENTOXIFYLLINE

Pentoxifylline was the first drug approved by the U.S. Food and Drug Administration (FDA) in 1984 for the treatment of claudication. It is a methylxanthine derivative that increases intracellular levels of cyclic adenosine monophosphate (cAMP). The drug improves red cell and white cell deformability, lowers plasma fibrogen concentrations, and possesses antiplatelet effects.1 The drug’s clinical effects have however been somewhat lackluster. Although pentoxifylline increased maximal treadmill walking distance by 12% as compared with placebo in one randomized clinical

US trial, there was no difference between the two groups in the increase in maximal treadmill walking distance when compared to baseline.2 Another study found only a 21% (nonsignificant) increase in maximal treadmill walking distance in patients treated with pentoxifylline as compared to placebo.3 Most recently, a trial that compared pentoxifylline, cilostazol, and placebo found that cilostazol was the sole agent that improved pain-free and maximal walking distances compared with placebo.4 Patients randomized to pentoxifylline in this study fared as well as those randomized to the placebo arm in terms of symptom relief. A meta-analysis found a net benefit of only an additional 44 m in the maximal distance walked on a treadmill (95% CI, 14–74 m) in patients treated with pentoxifylline.5 In addition to the marginal clinical benefit afforded by pentoxifylline in improving exercise capacity, use of the drug is hobbled by a paucity of information with regard to its impact on function status and quality of life. Importantly, with the recent and now routine inclusion of quality of life questionnaires into clinical drug trial designs for claudication, pentoxifylline failed to demonstrate improvement in daily functional status as assessed by the Walking Impairment Questionnaire (WIQ) or Medical Outcomes Scale Health Survey (MOS SF-36), when compared to cilostazol.4 It has been recently postulated that pentoxifylline may possess the potential to alter the natural history of peripheral arterial disease (PAD). The facts supporting this hypothesis, however, deserve close scrutiny. Although the use of pentoxifylline was associated with a reduction in hospital expenditures without a greater overall cost of PADrelated care, the drug did not alter the risk of PAD-related hospitalization.6 Compliance with taking pentoxifylline

704 • CHAPTER 34

TABLE 34-1. Pharmacological Treatment for Intermittent Claudication

Drug/study

No. of Subjects

Dosage

Duration (months)

Change in MWD (%)∗

p Value

ACC/AHA8 Guidelines (Class/Level of Evidence)

Pentoxifylline Porter et al.2 Lindgarde et al.3 Hood et al.5 Dawson et al.4

128 150 511 698

1.2 g 1.2 g Varied 1.2 g

6 6 Varied 6

12 21 30 0

0.19 0.09 10 mm Hg).69 Of the patients diagnosed with PAH, 9% have portal hypertension.70 Cirrhosis is not necessary for the development of PAH, as evidenced by cases of PPHTN in which portal hypertension was caused by nonhepatic causes.71 The prevalence of PAH in patients with portal hypertension is 2% to 5%.72,73 However, the risk of developing PAH increases with the duration of portal hypertension.73 On average, PPHTN is diagnosed in the fifth decade with an even male to female distribution.69,74,75 The mean survival after diagnosis is 15 months with a median survival of 6 months.74 The factors initiating endothelial injury and leading to the development of PAH are not known but appear to be more complicated than shear stress from increased pulmonary blood flow.76 Finally, in patients undergoing lung transplantation, the presence of moderate or severe PAH is known to increase mortality and morbidity.77,78 HIV Infection. HIV infection as a causative agent in the development of PAH is supported by a higher prevalence of PAH in HIV infected patients than in the general population (0.5% vs. 0.02%).79 Direct viral action on endothelial and smooth muscle cells has been dismissed as a possible mechanism as a result of the lack of viral material in lung tissue and lack of data showing that endothelial cells are capable of supporting growth of HIV.80,81 Furthermore, monkeys infected with the simian immunodeficiency virus developed PAH similar to that seen in humans, but viral material was not identified within the lung tissue.82 Alterations in pulmonary endothelial cell homeostasis or an autoimmune mechanism is now believed to be the most logical mechanism for PAH.83,84 The development of PAH is not related to the degree of immunosuppression or the CD4 cell count.85 PAH in patients infected with HIV portends a poor prognosis, with median survival of 6 months after diagnosis of PH.84 Controversy exists with regard to the impact of treatment of HIV on progression of PAH.84,86,87 and Toxins. Several appetite suppressants (anorexic drugs) are well known to increase risk for the development of PAH. Aminorex, fenfluramine, and dexfenfluramine have all been withdrawn from clinical use by the U.S. Food and Drug Administration (FDA) because of the increase risk of PAH is associated with consumption.88,89 Fenfluramine has been shown to increase the odd of developing PAH by a factor of 6.3. The risk increases to a factor of 23.1 when exposed for greater than 3 months. The mechanism by which anorexic drugs lead to PAH is thought to be related to inhibition of voltage gated potassium channels (vasoconstriction because of the increased intracellular calcium) and depressed basal nitric oxide production.90,91 Drugs

PAH Associated with Venous or Capillary Involvement PAH associated with venous or capillary involvement consists of two rare disorders: pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis. Histologi-

cally, these disease entities resemble other forms of PAH. However, the vasculopathy involves not only the precapillary vasculature but also the capillaries, venules, and veins. Clinically, these disease entities can be difficult to distinguish from IPAH. Development of pulmonary edema after initiation of medical therapy with calcium channel blocker and epoprostenol has been reported.92,93 Patients should be referred promptly to a lung transplant center for evaluation early in the course of the disease. Persistent Pulmonary Hypertension of the Newborn Persistent pulmonary hypertension of the newborn (PPHN) exist in three forms: hypertrophic, hypoplastic, and reactive. The hypertrophic form results in hypertrophied muscular tissue of the pulmonary arteries as a result of chronic fetal distress. Hypoplastic PPHN involves underdevelopment of the pulmonary arteries because of either congenital diaphragmatic hernia or amniotic fluid leakage. The reactive form has normal lung tissue but vasoconstriction because of an imbalance of vasoactive mediators. Prognosis The natural history and prognostic variables in patients with PAH is best studied in the IPAH population. The National Institute of Health (NIH) registry on the natural history of IPAH has demonstrated that the median survival is 2.8 years with a 1-, 3-, and 5-year survival rates of 68%, 48%, and 34%, respectively.94 Relative to IPAH, PAH in association with either HIV or collagen vascular disease has a worse prognosis, whereas patients with PAH in the setting of congenital heart disease fare better.95 Clinical factors that predict a favorable outcome in patients PAH have been elucidated.95 Functional class (Table 46-3), exercise tolerance (6-minute walk test [6MWT]), presence of a pericardial effusion, and hemodynamic variables have shown correlation with clinical outcome. Multiple studies have demonstrated that the NYHA Functional Class (NYHA-FC) is associated with improved survival and can be used as a predictor of mortality.95 For example, the median survival of IPAH patients with NYHA- FC I or II is 6 years versus 2.5 years for patients with NYHA-FC-III and 6 months for NYHA-FC-IV.94 Furthermore, IPAH patients with NYHA-FC IV have a significantly higher risk of death relative to patients with NYHA-FC I, II, or III when receiving similar medical therapy.96,97 Finally, IPAH patients who are in NYHA-FC III or IV and who fail to respond after 3 months of treatment have worse survival relative to those whose symptoms improve.98 The 6MWT is an easy, safe, and reproducible test for the assessment of exercise capacity in patients with PAH. Multiple studies have demonstrated that baseline distance during the 6MWT is predictive of survival.99−101 However, comparison of different distances and treatments modalities in each study limit the ability to assign a predicted survival to a distance walked. Echocardiography studies in patient with IPAH have found that the presence and severity of a pericardial effusion is an independent predictor of

NONEMBOLIC DISORDERS OF THE PULMONARY ARTERY • 909

TABLE 46-3. Functional Classification of Pulmonary Arterial Hypertension (PAH) Class

Description

I

PAH without a resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnoea or fatigue, chest pain or near-syncope. PAH resulting in a slight limitation of physical activity. The patient is comfortable at rest, but ordinary physical activity causes undue dyspnoea or fatigue, chest pain or near-syncope. PAH resulting in a marked limitation of physical activity. The patient is comfortable at rest, but less than ordinary activity causes undue dyspnoea or fatigue, chest pain or near-syncope. PAH resulting in an inability to carry out any physical activity without symptoms. The patient has signs of right heart failure. Dyspnoea, fatigue or both may be present even at rest, and discomfort is increased by any physical activity.

II

III

IV

Source: Reprinted with permission from Hoeper MM. Drug treatment of pulmonary arterial hypertension: current and future agents. Drugs. 2005;65;1337-1354.

can be divided into lifestyle alterations, conventional therapies, and vasodilator therapy. Finally, most available data is from studies of patients diagnosed with IPAH. Lifestyle Alterations Patients with PAH must be educated as to activities which are potentially hazardous to their well being. In general, any activity that has the potential to cause hypoxemia, pulmonary vasoconstriction, or syncope must be avoided.39 In patients with PAH who have cardiac arrest, resuscitation has demonstrated limited success (6% at 90 days).107 High altitude and air travel may not be well tolerated because of the potential for hypoxia, pulmonary vasoconstriction, and worsening of right-sided heart failure. Decongestants and appetite suppressants must also be avoided because of the risk of worsening PH. Also, heavy exertion increases the risk for syncope, cardiopulmonary arrest, and death. However, low-dose exercise may be beneficial to patients with PAH.108 Patient should be advised to receive immunization against influenza and pneumococcal pneumonia. Pregnancy should be discouraged as the hemodynamic changes during pregnancy impose a significant stress on women with PAH, with a resultant mortality rate of 30% to 50%.109 Finally, elective surgery should be approached with caution because of high risk for vasovagal events which can rapidly lead to syncope, cardiopulmonary arrest, and even death.36 Conventional Therapies

poor outcome in patients with IPAH.102,103 The negative effect of a pericardial effusion on exercise tolerance is as a result of impairment of right heart function. In individual studies, multiple different hemodynamic variables have been shown to predict outcome in IPAH patients.94,104−106 However, mean right atrial pressure (mRAP) and cardiac index have most consistently demonstrated predictive value, with mRAP being the most powerful hemodynamic predictor of survival.95 Treatment The leading cause of death in patients with PAH is progressive right heart failure. Thus, treatment of patients with PAH is aimed at improving or halting the progression of right heart failure, in order to improve symptoms and functional class as well as prolong life and delay the potential need for lung transplantation. A delay in the diagnosis of PAH of months to years is not uncommon as the nonspecific symptoms early in the course of the disease are often attributed to normal aging or weight gain. Unfortunately, 70% to 90% of patients have developed NYHA-FC III or IV symptoms by the time the correct diagnosis is made.36 As such, most clinical trials have focused on NYHA-FC III or IV patients with little data on the benefits and risks of treating patients who are less symptomatic or have only mildly elevated PA pressures.34,36 Patients should be referred to a specialized medical center experienced in the treatment of PAH to receive appropriate tailored therapy. Medical therapies for the treatment of patients with PAH

Anticoagulation with warfarin for patients with IPAH has demonstrated a survival benefit in two small trials.110,111 Based on these findings and the known role of in situ thrombosis in the pathogenesis of IPAH, warfarin therapy is generally recommended in the absence of contraindications, although the optimal INR is not known. As a result of the vasoconstrictor effects of hypoxia, oxygen supplementation is recommended to maintain oxygen saturation greater than 90%. Diuretics are indicated for the management of volume overload from right-sided heart failure. Digoxin has been used in the presence of right heart failure112 and for rate control in patients with atrial fibrillation or atrial flutter. However, limited data is available on the efficacy of digoxin in PAH. Vasodilator Therapy Several medications with pulmonary arterial vasodilatory effects have been approved by the FDA and are available for clinical use in patients with PAH. Figure 46-5 outlines the therapeutic approach to NYHA-FC III and IV patients with PAH. The therapeutic agent to be chosen depends upon the results of acute vasodilator testing and NYHA functional class. Acute reversibility to vasodilator therapy is defined as a drop in mean PAP by at least 10 mm Hg to less than 40 mm Hg with either an increase or no change in cardiac output. Inhaled nitric oxide, intravenous epoprostenol, and intravenous adenosine are all shortacting pulmonary vasodilators which are acceptable for use in testing for reversibility. Patients with NYHA-FC IV

910 • CHAPTER 46

Therapy for PAH functional class III/IV*

Anticoagulation and general care—expert referral

Vasoreactivity† Yes

No

Oral calcium channel antagonist

Sustained response‡

Functioal class III

Functional class IV§

Bosentan or PGI2-analogues

Epoprostenol, bosentan, treprostinil, IV iloprost

or Yes

No

Continue calcium channel antagonist

Epoprostenol

Sildenafil?¶

No improvement or deterioration (combination therapy?) Atrioseptostomy and/or lung trasplantation

• FIGURE 46-5.

Current treatment algorithm for PAH. PGI2 , prostaglandin I2 . ∗ The algorithm is restricted to patients in functional class III or IV because very few data are available for functional class I/II patients, and class III/IV patients represent the largest population among PAH patients. All treatments have been evaluated mainly in sporadic PAH and in PAH associated with scleroderma. Extrapolation of these recommendations to the other PAH subgroups should be made with caution. † A positive acute response to vasodilators is defined as a drop in mean PA pressure by at least 10 mm Hg to 3 mm in diameter.186 The largest series of embolization therapy (Baltimore-Yale series192,194,206−208 and Hammersmith series209−211 ) report no mortality related to the procedure. The most common complication is pleurisy, which can occur in 7% to 31% of patients. The cause of pleurisy has not been elucidated but does not appear related to pulmonary infarction. Paradoxical embolization can occur but does not appear to exceed 4% in the more recent series. Despite apparent successful therapy, a residual shunt may persist and recanalization may occur, in which case reembolization may be indicated. Screening for PAVMs should be done in all patients with HHT186 as well as family members of patients with HHT.212 Screening after embolization therapy should be performed at 1 month and 1 year to assess for residual shunt.186 Screening with 3-D helical CT is recommended every 3 to 5 years to assess for the development of new PAVMs.208 Antibiotic prophylaxis is recommended, even after treatment of a PAVM, for any procedure in which bacteremia is expected, that is, dental and surgical interventions.213 Female patients with PAVMs should be counseled as to the risk of PAVM growth and rupture during pregnancy.214

•

PULMONARY ARTERY STENOSIS

Pulmonary artery stenosis (PAS) is most often found in association with congenital heart disease or as a complication of congenital heart disease treatment. Historically, PAS has been treated primarily by pediatric specialists. However, because of the advances in the treatment of congenital heart disease, congenital heart disease patients now commonly live into adulthood and may be encountered by physicians who treat adults. The etiology of PAS is categorized as congenital, postsurgical, and acquired.215 PAS occurs in 2% to 3% of patients with congenital heart disease216 and has been associated with nearly every congenital heart disease, including pulmonary valve stenosis, aortic valve stenosis, atrial septal defect, ventricular septal defect, patent ductus arteriosus, transposition of the great vessels, and the tetralogy of Fallot.217 Congenital PAS occurs in isolation 40% of the time.218 It has also been associated with very rare congenital syndromes, including Williams Beuren syndrome,219,220 Alagille syndrome,221 and total generalized lipodystrophy.222 Postsurgical PAS can occur after either lung transplantation or correction of a congenital heart disease. Postlung transplant PAS is not common but carries a poor prognosis.223 Because of scarring at the site of anastomoses,215,224,225 PAS has been reported following the Blalock-Taussig, Waterston-Cooley, Potts, Glenn, and Fontan procedures. Indeed, any surgical manipulation of the PA may lead to scarring and stenosis.215 Acquired causes of PAS include Takayasu’s arteritis (TA) and rubella. Furthermore, external compression of the PA leading to

stenosis has been reported in intrathoracic malignancy, fibrosing mediastanitis, silicosis, and sarcoidosis.226,227 PAS occurs in four morphologic forms.218 Type I has a single constriction in the main right or left PA. Type II lesions are located at the bifurcation of the distal main PA and the origin of the right or left PA. Type III lesions are defined as stenosis at the ostium of multiple segmental pulmonary arteries with associated poststenotic dilatation and sparing of the main PA and proximal branch arteries. Type IV lesions are multiple stenoses involving both the segmental and central pulmonary arteries. Right-sided heart failure caused by pulmonary hypertension is the most serious potential complication of untreated PAS. Patients with hemodynamically significant PAS may present with dyspnea from pulmonary hypertension or signs and symptoms of right-sided heart failure. Pulmonary angiography remains the gold standard for diagnosis and preintervention evaluation of PAS. However, CT and MRI may be of benefit in some conditions. Patients with PAS and evidence of pulmonary hypertension may be misdiagnosed and treated for chronic pulmonary thromboembolic disease because of a similar appearance on ventilation perfusion imaging.228 Treatment of PAS is generally indicated when patients have significantly elevated right ventricular pressure, hypertension in the unaffected segments of the PA, marked decrease in flow in the affected segment of the lung, right ventricular dysfunction, or symptoms.216,229 Most data on the outcome of treatment modalities are limited to the pediatric population, since PAS is predominantly a pediatric disease. However, case reports do exist of successful treatment of PAS in the adult population. Stent implantation has become the preferred treatment modality, although surgery and balloon dilation are treatment options in some cases.230 Surgical repair of PAS is reserved for supravalvular pulmonary stenosis and stenosis at the bifurcation of branch pulmonary arteries.217 Proximal lesions of the PA should be addressed when a patient is undergoing surgical repair of a cardiac lesion.217 Surgical treatment of PAS in the peripheral PA is best avoided because of the high rates of restenosis (50%–60% at 5 years) and a higher rate of complications relative to other treatment options.230,231 Prior to the development of stents, balloon angioplasty was utilized as a less invasive alternative to surgery.232,233 Balloon angioplasty was found to be acutely successful in 50% to 60% of patients with a restenosis rate of 15% and a complication rate of 5% to 10%.234,235 The development of high pressure inflation (17–20 atmospheres) improved immediate success rates from 50% to 81% but with an increased rate of complications (13%).236 Complications from balloon angioplasty include transient pulmonary edema, PA dissection, aneurysm, rupture, and death. PA stenting has demonstrated both immediate (up to 96%) and sustained long-term success.237−241 Stent implantation has proven to improve significantly the pressure gradient across the lesion (from severe to mild), double the PA diameter at the site of the stenosis (5–6 mm prestent to 11 mm poststent), and increase ipsilateral lung

NONEMBOLIC DISORDERS OF THE PULMONARY ARTERY • 917

Large to Medium Vessel Vasculitis of the PA TA, BD, and its variant, Hughes-Stovin syndrome, are the predominant vasculitides affecting the large to medium sized arteries of the lung. Takayasu’s Arteritis. TA is a chronic, idiopathic, and in-

• FIGURE 46-11.

Successful stent implantation in patient with pulmonary atresia and ventricular septal defect.

Reproduced, with permission, from O’Laughlin MP. Catheterization treatment of stenosis and hypoplasia of pulmonary arteries. Pediatr Cardiol. 1998;19:48-56.

perfusion237−239 (Figure 46-11). The success of stent implantation compared to balloon angioplasty relates to the reduction in vessel recoil by providing a scaffold for the PA. Furthermore, the intimal tear that is required for successful balloon dilation is not needed with stent implantation.215 After stent implantation, all stents demonstrate some degree of tissue in growth.240 However, significant restenosis is rare and, when present, is nearly always treatable with redilation.215,238,240 Other complications of stent implantation include ventricular arrhythmias, thrombus formation, compromise of arterial side branches, intimal flaps with or without arterial rupture, and the misplacement and migration of stents.242,243 However, with increased clinical experience, morbidity, and mortality have improved.241 Although most series report data on interventions in patients with congenital lesions, multiple reports of successful stenting for external compression (i.e., malignancy) are available.226,227,244 Finally, stenting has proven to be a more cost-effective treatment for PAS than either surgery or balloon dilation.230

•

VASCULITIS

Vasculitis, inflammation of blood vessels, not only affects the systemic vasculature but also may involve the pulmonary vascular bed. Pulmonary vasculitis can be divided into those disease entities affecting the large to medium sized pulmonary arteries and those involving primarily the small vessels (i.e., arterioles, venules, and alveolar capillaries). Vasculitides affecting the large to medium sized pulmonary arteries usually manifest as either aneurysms or stenosis,245 whereas small vessel vasculitis leads to capillaritis and possibly diffuse alveolar hemorrhage (DAH).

flammatory disease affecting primarily large vessels, such as the aorta and its main branches.246 Although TA has been observed worldwide, most cases present in women of reproductive age, with the highest prevalence in individuals of Asian descent.247 The predominant clinical manifestations are from systemic arterial stenosis and occlusion, but aneurismal dilatation can occur. The clinical presentation relates to the systemic arteries involved: Subclavian (93%); aorta (65%); common carotid (58%); renal (38%); vertebral (35%); innominate (27%); axillary (20%); celiac (18%); superior mesenteric (18%); and common iliac (17%).246 Although originally thought to be rare, PA involvement occurs in 50% or more of cases when specifically investigated (Figure 46-12).248 It is often overlooked, however, as patients focus on systemic manifestations of TA and deny pulmonary symptoms even in the presence of moderate to severe pulmonary hypertension.249 No correlation exists between the extent of PA involvement and systemic arteritis.250 Rarely, the PA can be affected in the absence of systemic involvement,251−255 with patients reporting dyspnea, chest pain, or hemoptysis. In the absence of systemic arterial involvement, the diagnosis of TA may be difficult to establish and may be mistaken for chronic pulmonary embolism because of the similar appearance on ventilation perfusion scan and pulmonary angiography.254 An elevated erythrocyte sedimentation rate may not be present even in active disease,246 and reliance on clinical, angiographic, and pathologic data is required for diagnosis.254 The classification scheme for TA originally involved three varieties: Type I or Shimizu-Sano (aortic arch and branches), Type II or Kimoto (thoracic aorta and branches) and Type III or Inada (feature of Type I and II).255 However, the addition of Type IV or Oota has been advocated for those patients with PA involvement.249 The clinical impact of TA PA involvement on patient outcome is not known. Current treatment focuses predominantly on systemic involvement and consists of glucocorticoids with the addition of cytotoxic agents when glucocorticoids fail to arrest progression or patients relapse with glucocorticoid taper. Thus, the affect of treatment on pulmonary vasculature and pulmonary hypertension (when present) is not known. Behcet Disease. BD is a multisystem and chronic inflam-

matory disorder of unknown etiology. It is characterized by recurrent oral and genital ulcerations, ocular manifestations, and additional clinical manifestations in multiple organ systems.256 The diagnostic criteria proposed by the International Study Group of BD relies upon the presence of recurrent oral ulcerations, as well as any two of the following: Recurrent genital ulceration, eye lesions, skin

918 • CHAPTER 46

B

A

• FIGURE 46-12.

(A and B) Pulmonary angiogram demonstrating pulmonary arterial

stenosis.

Brugiere O, Mal H, Sleiman C, Groussard O, Mellot F, Fournier M. Isolated pulmonary arteries involvement in a patient with Takayasu’s arteritis. Eur Respir J. 1998;11:767-770.

lesions, and a positive pathergy test (the development of an aseptic erythematous nodule or pustule 24 to 48 hours after skin prick with a sterile needle).257 The onset of symptoms is usually in the third or fourth decade of life,258 with equal prevalence in both males and females.259 Although seen worldwide, the highest prevalence is in Turkey, with a clustering along the Silk Road, the ancient route of silk trade extending from eastern Asia to the Mediterranean basin.258 Male sex and onset of symptoms before 25 years of age are very strong prognostic indicators of disease severity.260 Pulmonary artery aneurysms (PAA), pulmonary arterial and venous thrombosis, and pulmonary infarction are noninfectious pulmonary manifestations of BD (Figure 46-13).259 Vasculitis in the pulmonary vasculature is the common mechanism responsible for PAA, thrombosis, and infarction in BD. Inflammation of the vasa vasorum leads to degeneration of the elastic lamina, in situ thrombus formation, and thickening and weakening of the vessel wall.256,261 The prevalence of thoracic involvement in BD is estimated to be 5% to 10%; however, studies are limited by small sample size and retrospective data in which patients came to attention secondary to symptoms.262−264 BD is thought to be the most common cause of PAAs.265 Patients who have BD and a PAA are mostly young males (89% male with a mean age of 30.1 years).266 Thrombophlebitis may also be associated with PAAs in patients with BD.263 On average, more than 5 years elapse between the diagnosis of BD and the manifestation of a PAA.266 Multiple PAAs are most commonly observed, but some patients present with a solitary aneurysm.261

The presence of PAAs in patients with BD is a very poor prognostic sign261,267 and may be the leading cause of death.264 Retrospective data has shown that the 1 year and 5 years survival after the recognition of a PAA is 57% and 39%, respectively.266 In one series, the mean length

• FIGURE 46-13.

Computed tomographic scan of the chest demonstrating bilateral PA aneurysms.

Reproduced, with permission, from Lohani S, Niven R. Images in clinical medicine. Bilateral pulmonary-artery aneurysms in Behcet’s syndrome. N Engl J Med. 2005;353:400.

NONEMBOLIC DISORDERS OF THE PULMONARY ARTERY • 919

of survival of patients who presented with hemoptysis was 10 months.263 Alarmingly, hemoptysis is the most common presenting symptom of PAAs.256 The mechanism of hemoptysis is thought to be due to the rupture of the aneurysm with erosion into a bronchus.259 This theory is supported by the observation of an air-filled cavity on CT after embolization of a ruptured PAA.268 Other mechanisms of hemoptysis in patients with BD include angiodysplastic bronchial arteries and pulmonary embolism with infarction.269 Because of the high mortality associated with PAAs, a screening chest X-ray with a follow-up spiral CT scan has been advocated for patients with BD.262 Spiral CT is preferred over magnetic resonance angiography because of the ability of the CT to assess lung parenchyma and vasculature.256 Furthermore, angiography should be used with caution, as an aneurysm may not be visualized because of the organized thrombus within the lumen of the vessel.261 Furthermore, in patients with BD, the risk for thrombosis at venous puncture sites and aneurysm formation at arterial puncture sites is increased.256 The management of PAAs in patients with BD includes medical therapy (steroids and immunosuppressive medications), percutaneous embolization, and surgical resection. Medical therapy with steroids and immunosuppressive medications is thought to be best if instituted when aneurysms are small and before irreversible arterial wall damage has occurred.270 Disappearance of PAAs has been reported with both steroids267,271 and immunosuppressive medications.272 Anticoagulation is not recommended, even in the presence of thrombi, because of the increased mortality most likely secondary to increased bleeding with PA rupture.258,266 Furthermore, in BD, thrombi form in situ in the pulmonary vasculature and are organized. In the presence of hemoptysis or an enlarging aneurysm, embolization is recommended.266,273 If embolization is not available, surgical intervention should be considered.273 However, caution should be used when considering surgical intervention, as rupture of a contralateral aneurysm has occurred after surgical resection, possibly related to increased flow through the contralateral lung.274

Hughes-Stovin Syndrome. Hughes-Stovin syndrome is

a very rare disorder in which patients develop deep venous thrombosis (usually caval veins) and single or multiple PA aneurysms.275 This syndrome predominately affects young males in the second to fourth decade of life and is thought to be a variant of BD, because of similar clinical, angiographic (Figure 46-14), and histologic features, that is, inflammation of the vasa vasorum.276 Hughs-Stovin syndrome is treated in a manner similar to BD, with steroids and immunosuppressants.277 However, the effectiveness of treatment is in doubt because of the high mortality associated with the syndrome, even when treated.276 Massive pulmonary hemorrhage caused by aneurysm rupture is a frequent terminal event.278

• FIGURE 46-14.

Angiogram of a pulmonary arterial

aneurysm.

Reproduced, with permission, Kindermann M, Wilkens H, Hartmann W, et al. Images in cardiovascular medicine: Hughes-Stovin syndrome. Circulation. 2003;108;e156.

Small Vessel Vasculitis of the PA Small vessel vasculitis of the pulmonary vasculature can involve the arterioles, venules, and/or alveolar capillaries. This disease is often termed capillaritis, a necrotizing inflammatory process that can lead to destruction of the interstitium and the alveolar capillary basement membrane. If destruction of the basement membrane allows red blood cells to enter the alveolar space, DAH may ensue. In capillaritis, the neutrophil plays a central role in the inflammatory and destructive process within the alveolar capillary. Histologically, capillaritis is characterized by an edematous interstitium infiltrated by neutrophils undergoing leukocytoclasis (fragmentation). The fragmented neutrophils lead to fibrinoid necrosis and loss of integrity of the alveolar capillary membrane, thereby allowing red blood cells to enter the alveolar space.279 While it is recognized that the infiltration and activation of neutrophils lead to release of proteolytic enzymes responsible for necrosis and the loss of integrity of the interstitium and alveolar capillary basement membrane, the stimuli which attract, prime, and activate the neutrophils are not known.280 Antineutrophil cytoplasmic autoantibodies (ANCA)281 and immune complex deposition282 may play a role in some diseases. Patients with capillaritis most often come to clinical attention as a result of the symptoms related to DAH. Hemoptysis is the most common clinical manifestation. However, even in the presence of significant alveolar bleeding, more than 30% of patients do not develop

920 • CHAPTER 46

A

B

• FIGURE 46-15.

Chest x-ray demonstrating DAH.

Reproduced, with permission, from Schwarz MM, Brown KK. Small vessel vasculitis of the lung. Thorax. 2000;55:502-510.

hemoptysis.280 Patients may also develop dyspnea, anemia, low-grade fever, and diffuse, bilateral alveolar infiltrate on chest radiograph (Figure 46-15). Approximately 50% of patients with DAH require assisted ventilation.280 Although capillaritis accounts for 80% of the cases of DAH, other etiologies including bland pulmonary hemorrhage and diffuse alveolar damage, which must be considered because of the differences in treatment and prognosis.283 Whereas the diagnosis of DAH is clinical, capillaritis requires a pathologic specimen for diagnosis. However, DAH can be assumed to be capillaritis in the presence of an associated disease condition. Capillaritis most commonly occurs in isolation, that is, isolated pauci-immune capillaritis. The ensuing discussion will divide capillaritis as follows (Table 46-5): (1) Isolated pauci-immune capillaritis; (2) Capillaritis in the setting of systemic vasculitis; (3) Capillaritis in the setting of collagen vascular disease; and (4) Miscellaneous conditions associated with autoantibody production.280 Pauci-Immune Capillaritis. Isolated pauciimmune capillaritis is small vessel vasculitis limited to the lung without systemic involvement.282 The disease can present with and without the presence of serum p-ANCA. Isolated pauci-immune capillaritis without p-ANCA is the most common form of pulmonary capillaritis and DAH in one series.282 When treated with corticosteroids Isolated

and cyclophosphamide, the prognosis was generally good. p-ANCA positive isolated pauci-immune capillaritis has been reported; however, long-term follow-up to determine if these patients developed a systemic disease is not available.284 Finally, concern has been raised that patients with isolated pauci-immune vasculiti s may have been misdiagnosed as having idiopathic pulmonary hemosiderosis in the past.280

Capillaritis in the Setting of Systemic Vasculitis. Wegener’s Granulomatosis. Wegener’s granulomatosis

(WG) is a syndrome consisting of a triad of necrotizing granulomatous inflammation of the upper and lower respiratory tract, necrotizing glomerulonephritis, and small vessel vasculitis. The presence of the full triad is not necessary for the WG diagnosis. In limited forms, c-ANCA is particularly helpful because of the strong association between cANCA and WG.285 Capillaritis is a common finding, occurring in up to 40% of patients.286,287 However, DAH occurs in less than 10% of patients with WG.287,288 Hemoptysis in patients with WG is usually caused by nodules and/or infiltrates than DAH.289 Patients who have WG and develop DAH usually have a more fulminant course in which DAH is the initial manifestation of their disease.289,290 Whereas patients with WG generally have a good prognosis, those with DAH have a very high mortality (up to 66%) even

NONEMBOLIC DISORDERS OF THE PULMONARY ARTERY • 921

TABLE 46-5. Aetiology of Small Vessel Vasculitis of the Lungs (Pulmonary Capillaritis) in Order of Relative Frequency Isolated pauci-immune pulmonary capillaritis Pulmonary allograft rejection SLE Wegener’s granulomatosis Microscopic polyangiitis Goodpasture’s syndrome Rheumatoid arthritis Polymyositis Primary antiphospholipid syndrome Scleroderma Idiopathic pauci-immune glomerulonephritis Henoch-Schoenlein purpura IgA nephropathy Behcet’s syndrome Hypersensitivity vasculitis PTU Diphenylhydantoin Churg-Strauss syndrome Essential cryoglobulinaemia Acquired immune deficiency syndrome Myasthenia gravis Ulcerative colitis Retinoic acid syndrome Autologous bone marrow transplantation Source: Reprinted, with permission, from Schwarz MM, Brown KK. Small vessel vasculitis of the lung. Thorax. 2000;55:502-510.

with aggressive medical treatment of corticosteroids and cyclophosphamide.283 Microscopic Polyangiitis. Microscopic polyangiitis is a

pauci-immune necrotizing vasculitis that affects small blood vessel (venules, arterioles and capillaries) of predominantly the kidneys and lungs with or without involvement of medium-sized vessels.291 Microscopic polyangiitis has a strong association with p-ANCA292 and is considered to be the small vessel variant of polyarteritis nodosa.280 These conditions are differentiated by the lack of small vessel, renal, and lung involvement in polyarteritis nodosa. Capillaritis and DAH can occur 10% to 30% of patients with microscopic polyangiitis.293,294 Capillaritis may be the only evidence of small vessel involvement that allows differentiation from other disease states.295 The mortality associated with the first episode of DAH is up to 25%, with recurrence expect in survivors.280 Goodpasture’s Syndrome. Goodpasture’s syndrome is a

disease associated with antibasement membrane antibodies (ABMA) direct against the noncollagenous carboxylterminal region of type IV basement membrane collagen molecule in the kidney and the lung.296 Rare cases of capillaritis associated with DAH have been reported; however,

DAH in Goodpasture’s syndrome is more frequently because of bland hemorrhage.297 Churge-Strauss Syndrome. Churge-Strauss syndrome (allergic granulomatosis and angiitis) is a systemic necrotizing vasculitis of small vessels in patients with asthma and eosinophilia. Asthma is the most common form of respiratory tract involvement preceding onset of vasculitis by 3 to 8 years. Fifty percent of patients have the presence of serum p-ANCA. Chest radiograph abnormalities are usually because of eosinophilic pneumonitis. However, alveolar hemorrhage has been reported, albeit rarely.298 Henoch-Schonlein Purpura. Henoch-Schonlein Purpura

(HSP) is a small vessel vasculitis characterized by palpable purpura, arthritis, abdominal pain, and renal involvement. HSP is predominantly a disease of children;299 however, adults can be affected.300 The deposition of IgA immune complexes in and around the walls of small vessels is the hallmark of HSP. Capillaritis and DAH, with histologic confirmation of IgA immune complex deposition, have been reported in HSP.301,302 However, the incidence of lung involvement is low, up to 6.5%, in HSP.303 IgA Nephropathy. IgA Nephropathy (Berger disease) is

a mesangial proliferative glomerulonephritis that is the most common nephropathy worldwide. Because of similar serologic abnormalities, IgA nephropathy is thought to be a spectrum of HSP. Capillaritis with fatal hemorrhage and IgA confirmation by biopsy has been reported in IgA nephropathy.304 Behcet Disease (BD). The details of BD have been dis-

cussed previously in the context of large to medium vessel vasculitis. While PA aneurysm is the predominant form of lung involvement in BD, small vessel involvement (capillaritis) can occur.305 Mixed Cryoglobulinemia. Mixed cryoglobulinemia is a small vessel vasculitis manifesting with palpable purpura, arthritis, glomerulonephritis, and hepatitis.306 A very strong association to infection with the hepatitis C virus has been observed. Interstitial lung disease is the most common form of pulmonary involvement, with only isolated case reports of capillaritis and DAH in mixed cryoglobulinemia.307,308 Capillaritis in the Setting of Collagen Vascular Disease Systemic Lupus Erythematosus. SLE is an autoimmune disorder of unknown etiology with diverse clinical manifestations characterized by the production of antibodies to components of the cell nucleus, that is, antinuclear antibodies (ANA). Lung manifestations include pneumonitis, pulmonary hypertension, pulmonary embolism with infarction, DAH with or without capillaritis, and pleural effusions.309,310 Capillaritis and DAH occur in approximately 4% of patients with SLE.311 Capillaritis is believed to be the most common cause of DAH in SLE, although

922 • CHAPTER 46

bland hemorrhage and diffuse alveolar damage are other etiologies.311,312 Acute lupus pneumonitis is the initial manifestation of SLE in 50% of cases,313 whereas DAH is rarely the initial manifestation and occurs later in the course in association with active glomerulonephritis.311,314 However, reports do exist of DAH as the initial manifestation of SLE.312 The mortality associated with DAH in SLE is 50%, which is the highest of any of the causes of DAH.280 On histologic examination, immune complex deposition in the walls of the small arteries and the alveolar interstitium is often but not always observed.315,316 Rheumatoid Arthritis. Rheumatoid arthritis is a systemic inflammatory disorder that predominantly manifests in the synovial membrane of diarthrodial joints. DAH in patients with rheumatoid arthritis can be due to bland pulmonary hemorrhage317 or capillaritis.318,319 Furthermore, vasculitis can be limited to the lung318 or part of systemic vasculitis, that is, glomerulonephritis.319 Mixed Connective Tissue Disease. MCTD is a variant of SLE. Several case reports of DAH in patients with MCTD exist.318,320,321 Most reports of DAH have associated glomerulonephritis.320,321 However, vasculitis may remain isolated to the lungs.318 Polymyositis. Polymyositis is an idiopathic inflammatory myopathy which affects the muscles of the shoulder and pelvic girdle most severely. Capillaritis with DAH has been reported to occur simultaneously with muscle involvement in patients with polymyositis.322 Scleroderma. Scleroderma is a multisystem disease char-

acterized by functional and structural abnormalities of small blood vessels, fibrosis of the skin and internal organs, immune system activation, and autoimmunity. Capillaritis and DAH have been reported to complicate scleroderma.323,324 Antiphospholipid Syndrome. Antiphospholipid syndrome is a syndrome in which patients develop arterial and venous thrombosis, thrombocytopenia, and placental insufficiency resulting in fetal loss. Two case reports exist in the literature describing DAH with capillaritis in patients with antiphospholipid syndrome.325 Miscellaneous Conditions Associated with Autoantibody Production. Capillaritis and DAH can also occur

in various conditions or treatments in which autoantibodies may be produced. Acute pulmonary allograft rejection presenting as capillaritis with DAH weeks to months after transplantation is a life threatening complication requiring immediate recognition and treatment.326 Myasthenia gravis, ulcerative colitis, Crohn disease, autoimmune hepatitis, acquired immune deficiency syndrome, and bone marrow transplantation are other conditions in which capillaritis and DAH have been reported.280,327

Several medications have also been reported to cause capillaritis and DAH. Propylthiouracil (PTU) has been demonstrated to be the etiologic factor for capillaritis with DAH through p-ANCA mediated vasculitis.328,329 Diphenylhydantoin is believed to have induced a hypersensitivity vasculitis leading to capillaritis in one patient.330 DAH has been reported in patients being treated with penicillamine for several medical conditions.331,332 Although immune complex deposition has never been demonstrated in the capillaries of the lungs, many believe that the presence of circulating immune complexes and concomitant glomerulonephritis is evidence enough for the diagnosis of capillaritis from penicillamine.280,331 Finally, retinoic acid used for the treatment of acute promyelocytic leukemia has been reported to cause capillaritis with DAH.333,334 Diagnosis of Capillaritis. Capillaritis with DAH can

present with or without hemoptysis. Patients may also present with dyspnea, anemia, low-grade fever, and diffuse, bilateral alveolar infiltrate on chest radiograph. For any patient presenting with DAH, it is crucial to aggressively exclude infection, often with bronchoscopy and bronchoalveolar lavage.280 Once the diagnosis of DAH is established, the clinician must determine if DAH is from capillaritis, bland hemorrhage, or diffuse alveolar damage. Strictly speaking, capillaritis is a histopathologic diagnosis in which biopsy is not always feasible because of mechanical ventilation or coagulopathy.280 In these cases, a thorough medical history and physical examination can often lead to clues of the underlying condition. Laboratory work-up should begin with a urinalysis looking for active urine sediment in order to diagnose active glomerulonephritis. Furthermore, ANCA, ANA, and ABMA are serologic tests which may direct the diagnostic work-up and treatment. The sensitivity and specificity of ANCA are best for Wegener’s granulomatosis.285 ANA is particularly helpful for the diagnosis of SLE, whereas ABMA is virtually diagnostic of Goodpasture’s syndrome.296 Table 46-6 outlines other tests which may be useful. Treatment of Capillaritis. Once the diagnosis of capillaritis is established, aggressive treatment should be initiated promptly owing to the potential for continued rapid deterioration. Because of the limited data on the efficacy of therapy, most experts agree that corticosteroids and cyclophosphamide are the mainstays of therapy.280,335,336 This regimen has proven to be effective for the treatment of Wegener’s granulomatosis,335 MPA,293 and Goodpasture’s syndrome.337 Because capillaritis in other conditions is mostly reported as individual cases, randomized data may never be available for direct comparison, and thus corticosteroids and cyclophosphamide should be given as first line therapy because of their efficacy in other conditions. Azathioprine, instead of cyclophosphamide, has proven efficacy in MPA338 and can also maintain remission in Wegener’s granulomatosis after induction of remission by cyclophosphamide.335 Plasmapheresis should be considered when corticosteroids and cyclophosphamide

NONEMBOLIC DISORDERS OF THE PULMONARY ARTERY • 923

TABLE 46-6. Ancillary Diagnostic Studies in Pulmonary Capillaritis Laboratory studies ANCA Cytoplasmic Perinuclear ANA Anti-dsDNA antibodies Complement levels Rheumatoid factor Antiglomerular basement membrane antibodies Cryoglobulins Erythrocyte sedimentation rate Other studies Assay for circulating immune complexes Urinalysis with microscopic examination for erythrocyte casts Radiologic examination of the sinuses Renal biopsy for necrotizing glomerulonephritis Skin biopsy for leukocytoclastic vasculitis Source: Reprinted from Green RJ, Ruoss SJ, Kraft SA, et al. Pulmonary capillaritis and alveolar hemorrhage: update on diagnosis and management. Chest. 1996;110:1305-1316.

fail.280,339 However, except for observed clinical benefit in Goodpasture’s syndrome, the efficacy of plasmapheresis in other conditions is not known.280 Prophylaxis against Pneumocystis carinii with Bactrim DS is recommended for all patients.280 Finally, broad spectrum antibiotic should also be considered upon presentation until infection is definitively excluded.283

•

PA NEOPLASM

PA neoplasms are extremely rare. In a Mayo Clinic review of patient records of more than a 30-year time period, only nine cases of PA neoplasm, all of which were sarcomas, were identified.340 Because of a paucity of literature on other forms of PA malignancy, only sarcomas are discussed further. Sarcomas in the PA arise most often from the dorsal area of the pulmonary trunk near the pulmonary valve.341 Rarely, PA sarcomas can be located at the bifurcation of the main PA or within the right or left PA. More distal locations are unusual. The sarcoma is believed to arise from the mesenchymal cells of the muscle anlage of the bulbus cordis.342 Histologically, PA sarcomas are classified as undifferentiated (34%), fibrosarcoma or fibromyxosarcoma (21%), leiomyosarcoma (20%), rhabdomyosarcoma (6%), mesenchymoma (6%), chondrosarcoma (4%), angiosarcoma (4%), osteosarcoma (3%), and malignant fibrous histiocytoma (2%).343 However, differentiation is not thought to be of clinical or prognostic utility.340 Patients with PA sarcoma come to clinical attention at a mean age of 52 years (range 13 to 86 years).344−346 A slight

• FIGURE 46-16.

Spiral CT scan—large filling defect in the

right main PA.

Reproduced, with permission, from Loredo JS, Fedullo PF, Piovella F, et al. Digital clubbing associated with pulmonary artery sarcoma. Chest. 1996;109:1651-1653.

female preponderance exists. Unfortunately, the disease is generally asymptomatic until the development of significant obstruction of right ventricular outflow, at which time patients may report symptoms of dyspnea, chest pain, syncope, or palpitations.347 Chest pain is thought to be secondary to emboli to the distal pulmonary circulation.348 Syncope and even sudden death are because of the progressive occlusion and obstruction of the PA by the tumor mass. Findings on chest radiograph include a hilar mass, an enlarged PA, pulmonary nodule, or pulmonary infiltrates.349,350 CT and MRI are noninvasive modalities which have demonstrated utility in the diagnosis of PA sarcoma (Figure 46-16).346,351,352 Because of similar symptoms and findings on ventilation perfusion scan, many patients with PA sarcoma have been initially misdiagnosed and treated for a pulmonary embolism, with the correct diagnosis being discovered postmortem.340,353−356 PA sarcoma should be considered in patients whose condition does not improve or worsens while receiving anticoagulation for a pulmonary embolism.340,353 The lack of risk factors for venous thrombosis, unilateral absence of blood flow on perfusion scan, elevated erythrocyte sedimentation rate, fevers, and weight loss are other features that should raise suspicion of PA sarcoma.340,353 Differentiation of a tumor

924 • CHAPTER 46

mass from a thrombus may be enhanced by use of GdDPTA on MRI.357 On CT, PA sarcoma should be suspected if the mass expands the artery or extends into the mediastinum or lungs.358 Patients with PA sarcoma often present with advanced disease because of a prolonged asymptomatic course. The mean survival after diagnosis without treatment is 1.5 months352 and only slightly better (several months) with

therapy.350,359 However, long-term survival has been reported in patients with a tumor confined to the PA.359 Thus, early diagnosis and management are paramount. Metastasis, most commonly within the lung but to other parts of the body as well, can occur.360 Surgical resection for cure and/or palliation is the mainstay of therapy. Because of the rarity of PA sarcoma, data on the efficacy of chemotherapy and radiation therapy is not available.

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314. Santos-Ocampo AS, Mandell BF, Fessler BJ. Alveolar hemorrhage in systemic lupus erythematosus: presentation and management. Chest. 2000;118:1083-1090. 315. Rodriguez-Iturbe B, Garcia R, Rubio L, Serrano H. Immunohistologic findings in the lung in systemic lupus erythematosus. Arch Pathol Lab Med. 1977;101:342-344. 316. Desnoyers MR, Bernstein S, Cooper AG, Kopelman RI. Pulmonary hemorrhage in lupus erythematosus without evidence of an immunologic cause. Arch Intern Med. 1984;144: 1398-1400. 317. Torralbo A, Herrero JA, Portoles J, Barrientos A. Alveolar hemorrhage associated with antineutrophil cytoplasmic antibodies in rheumatoid arthritis. Chest. 1994;105:1590-1592. 318. Schwarz MI, Zamora MR, Hodges TN, Chan ED, Bowler RP, Tuder RM. Isolated pulmonary capillaritis and diffuse alveolar hemorrhage in rheumatoid arthritis and mixed connective tissue disease. Chest. 1998;113:1609-1615. 319. Naschitz JE, Yeshurun D, Scharf Y, Sajrawi I, Lazarov NB, Boss JH. Recurrent massive alveolar hemorrhage, crescentic glomerulonephritis, and necrotizing vasculitis in a patient with rheumatoid arthritis. Arch Intern Med. 1989;149:406408.

331. Louie S, Gamble CN, Cross CE. Penicillamine associated pulmonary hemorrhage. J Rheumatol. 1986;13:963-966. 332. Sternlieb I, Bennett B, Scheinberg IH. D-penicillamine induced Goodpasture’s syndrome in wilson’s disease. Ann Intern Med. 1975;82:673-676. 333. Raanani P, Segal E, Levi I, et al. Diffuse alveolar hemorrhage in acute promyelocytic leukemia patients treated with ATRA—a manifestation of the basic disease or the treatment. Leuk Lymphoma. 2000;37:605-610. 334. Jung JI, Choi JE, Hahn ST, Min CK, Kim CC, Park SH. Radiologic features of all-trans-retinoic acid syndrome. AJR Am J Roentgenol. 2002;178:475-480. 335. Fauci AS, Haynes BF, Katz P, Wolff SM. Wegener’s granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med. 1983;98:76-85. 336. Lynch JP III, McCune WJ. Immunosuppressive and cytotoxic pharmacotherapy for pulmonary disorders. Am J Respir Crit Care Med. 1997;155:395-420. 337. Johnson JP, Moore J Jr, Austin HA III, Balow JE, Antonovych TT, Wilson CB. Therapy of anti-glomerular basement membrane antibody disease: analysis of prognostic significance of clinical, pathologic and treatment factors. Medicine (Baltimore). 1985;64:219-227.

934 • CHAPTER 46 338. Schwarz MI, Mortenson RL, Colby TV, et al. Pulmonary capillaritis: the association with progressive irreversible airflow limitation and hyperinflation. Am Rev Respir Dis. 1993; 148:507-511. 339. Lewis EJ, Hunsicker LG, Lan SP, Rohde RD, Lachin JM. A controlled trial of plasmapheresis therapy in severe lupus nephritis: the Lupus Nephritis Collaborative Study Group. N Engl J Med. 1992;326:1373-1379. 340. Parish JM, Rosenow EC III, Swensen SJ, Crotty TB. Pulmonary artery sarcoma: clinical features. Chest. 1996;110: 1480-1488. 341. Burke AP, Virmani R. Sarcomas of the great vessels. A clinicopathologic study. Cancer. 1993;71:1761-1773. 342. Baker PB, Goodwin RA. Pulmonary artery sarcomas. A review and report of a case. Arch Pathol Lab Med. 1985;109:3539. 343. McGlennen RC, Manivel JC, Stanley SJ, Slater DL, Wick MR, Dehner LP. Pulmonary artery trunk sarcoma: a clinicopathologic, ultrastructural, and immunohistochemical study of four cases. Mod Pathol. 1989;2:486-494. 344. Britton PD. Primary pulmonary artery sarcoma: a report of two cases, with special emphasis on the diagnostic problems. Clin Radiol. 1990;41:92-94. 345. Pagni S, Passik CS, Riordan C, D’Agostino RS. Sarcoma of the main pulmonary artery: an unusual etiology for recurrent pulmonary emboli. J Cardiovasc Surg (Torino). 1999;40:457461. 346. Smith WS, Lesar MS, Travis WD, et al. MR and CT findings in pulmonary artery sarcoma. J Comput Assist Tomogr. 1989;13:906-909. 347. Shmookler BM, Marsh HB, Roberts WC. Primary sarcoma of the pulmonary trunk and/or right or left main pulmonary artery—a rare cause of obstruction to right ventricular outflow: report on two patients and analysis of 35 previously described patients. Am J Med. 1977;63:263-272. 348. Berg GA, Hamid BN, Kenyon WE, Drakeley MJ. Primary pulmonary artery sarcoma: intra-operative similarity to pulmonary embolus. Postgrad Med J. 1987;63:389-391.

349. Moffat RE, Chang CH, Slaven JE. Roentgen considerations in primary pulmonary artery sarcoma. Radiology. 1972;104:283-288. 350. Rafal RB, Nichols JN, Markisz JA. Pulmonary artery sarcoma: diagnosis and postoperative follow-up with gadoliniumdiethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging. Mayo Clin Proc. 1995;70:173-176. 351. FitzGerald PM. Primary sarcoma of the pulmonary trunk: CT findings. J Comput Assist Tomogr. 1983;7:521-523. 352. Kotooka N, Nagaya N, Tanaka R. Pulmonary artery sarcoma. Heart. 2003;89:1388. 353. Loredo JS, Fedullo PF, Piovella F, Moser KM. Digital clubbing associated with pulmonary artery sarcoma. Chest. 1996;109:1651-1653. 354. Kauczor HU, Schwickert HC, Mayer E, Kersjes W, Moll R, Schweden F. Pulmonary artery sarcoma mimicking chronic thromboembolic disease: computed tomography and magnetic resonance imaging findings. Cardiovasc Intervent Radiol. 1994;17:185-189. 355. Varriale P, Chryssos B. Pulmonary artery sarcoma: another cause of sudden death. Clin Cardiol. 1991;14:160-164. 356. Delany SG, Doyle TC, Bunton RW, Hung NA, Joblin LU, Taylor DR. Pulmonary artery sarcoma mimicking pulmonary embolism. Chest. 1993;103:1631-1633. 357. Weinreb JC, Davis SD, Berkmen YM, Isom W, Naidich DP. Pulmonary artery sarcoma: evaluation using gd-DTPA. J Comput Assist Tomogr. 1990;14:647-649. 358. Yi CA, Lee KS, Choe YH, Han D, Kwon OJ, Kim S. Computed tomography in pulmonary artery sarcoma: distinguishing features from pulmonary embolic disease. J Comput Assist Tomogr. 2004;28:34-39. 359. Mattoo A, Fedullo PF, Kapelanski D, Ilowite JS. Pulmonary artery sarcoma: a case report of surgical cure and 5-year follow-up. Chest. 2002;122:745-747. 360. Bleisch VR, Kraus FT. Polypoid sarcoma of the pulmonary trunk: analysis of the literature and report of a case with leptomeric organelles and ultrastructural features of rhabdomyosarcoma. Cancer. 1980;46:314-324.

chapter

47

Steal Syndromes Raymond A. Dieter, Jr., MD, MS / George B. Kuzycz, MD

When one discusses vascular diseases, a number of problems or situations may develop and require the patient to seek medical assistance. Most such problems may be readily recognized and many may be treated conservatively and successfully with little effort or risk. Some situations, however, may produce vague or confusing symptoms and thus may be very difficult to sort out or to diagnose. These patients may then see numerous physicians and have extensive evaluation before the correct diagnosis or therapy is appropriately delineated. Such a diagnostic and therapeutic challenge for physicians may be a patient with a steal syndrome (SS). Patients present with the more classic, cerebral steal symptomatology in which the diagnosis was readily proven or established. We have also seen a number of individuals with vague, perplexing symptoms for evaluation and in whom eventually a steal syndrome was diagnosed. Those patients who have an established, symptomatic steal syndrome need to be provided the therapeutic options, including major invasive procedures or corrective surgery. Patients with asymptomatic incidentally encountered steal findings present a different situation. Many of these situations require little or no treatment and close periodic follow-up. Avoidance of major interventions and their potential complications may thus be minimized. The severely debilitating or acute life-threatening “steal” developments may require urgent or emergent intervention and the accompanying risk to preserve life or limb. Multiple considerations affect the ultimate therapy and prognosis for the patient (Table 47-1).

area as a result of a change in pressure gradient. This phenomenon can then occur in a number of situations. The classic example is where an artery is obstructed and the blood flow is then reversed in a vessel taking origin distal to the obstruction. The flow then travels around the obstruction and into the distal obstructed artery to serve the tissues distal to the obstruction. This may particularly occur when a greater need is recognized distally because of increased exercise or usage. When this occurs, the blood, which originally flows away from the vessel obstructed, now flows toward the obstructed vessel and reverses the flow of blood into the circuitous route. This then redirects blood away from the original end-organ and provides the blood and nutrients to the ischemic or needy tissues. Thus, the original end-organ may receive a smaller supply of blood or nutrients. If the patient has findings on vascular study of blood flow redirection, or reversal, and the patient is asymptomatic, the process is called a “steal phenomenon” (SP). If the patient becomes symptomatic as a result of their obstruction and flow reversal, the diagnosis of a steal syndrome (SS) is established. In essence, a steal occurs when blood is syphoned off from one area to another when a demand for blood or tissue nutrition presents at the second site. When this diversion occurs, the patient may develop symptoms relative to the area from which blood is diverted or stolen. The severity of the patient’s problem will then define how severe the steal and thus the steal syndrome. The organ or structure from which blood is stolen from may initiate symptoms such as dizziness, pain, syncope, or weakness.

•

•

DEFINITION

What is the definition of a steal syndrome? Different authors may ascribe different definitions or characteristics to this syndrome. A simple definition might be the taking of a blood supply from its usual direction and organ to another

ETIOLOGY AND CLASSIFICATION

There are a number of causes for the development of the “steal” in a patient (Table 47-2). The most commonly recognized and understood steal situation develops as a result of arteriosclerotic, occlusive disease. This usually develops in

936 • CHAPTER 47

TABLE 47-1. Steal Syndrome Considerations I. Etiology II. Anatomy and physiology III. Diagnosis A. Testing B. Symptoms C. Type of steal IV. Therapy A. Risks V. Prognosis

elderly patients who have a propensity to form arteriosclerotic (cholesterol) plaque build up within an artery, which may lead to occlusion of a major vessel. Most commonly, this will involve the cerebral central nervous system (CNS) vasculature-carotid and subclavian arteries. The classic example is the left subclavian artery occlusion with vertebral vessel flow redirection. However, the arteriosclerotic process may also cause obstruction of other vessels such as the iliac arteries, which may lead to the development of a steal. Such a phenomenon may become particularly evident during the correction of an obstructing lesion. Coronary symptoms may even develop as a result of an occlusive process postcoronary bypass using the internal mammary artery. Atherosclerotic occlusive disease is not the only etiology for a steal development. Iatrogenic causes include vascular surgery for congenital heart lesions, which may obstruct the normal subclavian routing and lead to CNS problems or symptoms. These patients may develop the SP but not the SS for years and their problems may thus be difficult to recognize. Arterial shunting of blood from a high-flow or high-pressure system to a low-resistance vessel may also lead to the steal occurring, e.g., the iliac steal postvascular repair of the iliac occlusion. Another iatrogenic cause is seen by the nephrologists who have noted a steal in a number of their fistula or shunt dialysis patients. When severe, these patients have required additional surgery to correct the problem and prevent tissue loss. Traumatic vascular le-

TABLE 47-2. Etiology of a Steal I. Arteriosclerotic occlusive disease A. Takayasu’s disease II. Traumatic III. Iatrogenic A. Dialysis access B. Congenital heart surgery 1. Blaloch-Taussig ligation subclavian artery C. Postoperative procedures D. Ligation anomalous origin subclavian artery IV. Spontaneous

TABLE 47-3. End-Organ Stolen From I. Brain A. Brain stem II. Heart A. Coronary artery III. Gastrointestinal tract IV. Extremity A. Lower B. Upper to hand

sions may also lead to steal through vascular occlusion or fistula formation. Such lesions may require extensive difficult surgical intervention. Further classification according to the end-organ stolen from is well illustrated (Table 47-3). The end-organ affected may be the brain/brain stem in the subclavian steal. However, the coronary artery and heart may develop ischemia when the subclavian artery occludes postcoronary bypass utilizing the left internal mammary artery. The distal organ “stolen from” may include the hand, gastrointestinal system, or lower extremity and thus the end-organ classification. Multiple vessels may be involved in the development of the SP. These vessels are usually larger vessels which carry a large volume of blood. Thus, when these vessels occlude, symptoms may be expected. Vessels that may be listed or involved in a “steal” include not only the larger readily recognized but also the smaller tributaries and capillaries (Table 47-4). Some of these steal situations may be

TABLE 47-4. Types of Steal and Vessels Involved (Usually Arteries) I. Cerebral A. Subclavian B. Vertebral II. Abdominal A. Mesenteric B. Aorta C. Vena cava D. Iliac III. Extremity A. Lower extremity 1. Femoral 2. Posterior tibial B. Upper extremity-dialysis access 1. Brachial 2. Radial 3. Accompanying veins IV. Coronary A. Subclavian

STEAL SYNDROMES • 937

recognized by their vessel names, e.g., subclavian or coronary steal. First described in 1960 by Contorni, a number of additions to our knowledge took place in a short time.1 The subclavian steal phenomenon (SSP) was shown to be a result of severe stenosis or occlusion of the subclavian artery. One year later, Ravitch demonstrated that the subclavian artery occlusion could be associated with neurologic symptoms.2 Fisher then called cerebrally symptomatic patients with subclavian flow reversal the subclavian steal syndrome (SSS).3 Brainstem ischemia could thus be considered a result of the SSS. It should be noted that the SSS occurs only when the subclavian artery occlusion is proximal to the vertebral artery origin and the vertebral artery is patent. The cerebral-subclavian steal is the most commonly recognized steal in which the subclavian artery becomes occluded and the flow is reversed in the left vertebral artery. This then changes the directional flow so that blood from the circle of Willis flows outward through the vertebral artery to the left upper extremity on demand. In the abdominal (mesenteric) steal, the blood is redirected from one organ to serve another during occlusion of the visceral vessels, or on aortic occlusion, into the iliac system. The dialysis access steal is seen particularly when the brachial artery or large radial artery fistulas are created and the arterial blood flows away from the hand. Another steal example is the coronary artery steal (CAS). This occurs when the proximal left subclavian artery occludes and the left internal mammary artery has been used to revascularize the coronary vessels. A possible iatrogenic cause may develop when the Blalock-Taussig operation is performed for congenital heart disease. During this surgery, division of the distal left subclavian artery, proximal to the origin of the left vertebral artery, may create a potential SP. With growth and aging, these individuals may develop symptoms, including headaches, as a result of an iatrogenic induced subclavian steal. Cerebral lesions and other anatomic lesions should be sought in order to be sure of the diagnosis, the anatomy, and the possible treatment. With time and growth, collateral circulation may then develop through multiple vessels to provide appropriate tissue nourishment.

•

ANATOMY AND PHYSIOLOGY

The anatomic location of the disease process and the number of lesions varies from patient to patient. When the subclavian artery acutely becomes severely stenotic, such that flow is reduced or totally occluded, the arm distally may become symptomatic caused by ischemia. When the stenosis occurs over a long period of time, collateral circulation may develop and maintain the viability of the distal extremity with or without symptoms. Netter’s textbook of anatomy delineates the cerebral arterial system simply and graphically.4 The developing collaterals will include the vertebral artery, arterial branches to the chest wall, the circle of Willis, the carotid artery, and other collateral vessels

A

[1]

[2]

B

[3] Normal flow

A [1]

[2] Reversed Flow B [3]

Obstruction inserted

A

[1]

[2]

B [3] Obstruction Rerouting after obstruction: A has supply diminished to preferve B.

• FIGURE 47-1.

Flow direction with resistance change: such a situation in which either (I) resistance increases (at A) or (II) resistance decreases (at B) will lead to less flow to organ (A) and more to organ (B). Technically, one might argue against this being a steal phenomenon, but we have considered this to be the practical case.

(Figure 47-1). The blood flow for the subclavian steal will usually take place through the right innominate into the right carotid and the circle of Willis [1]. The blood will then flow down the left vertebral [2] to the distal left subclavian artery [3] and then out to the brachial vessels and the arm and hand (B). Increased arm exercise will demand more circulation through the brachial vessels to the left upper extremity. During this period of time, vertebral basilar and other symptomatology may develop. Some individuals, however, have felt that such symptoms may not be because of a reduction in cerebral blood flow (A). This, however, is not the usual consideration. Of interest is the fact that many patients with the SP remain totally asymptomatic.

938 • CHAPTER 47

We have seen patients with multiple etiologies for what is felt to be a subclavian steal. This includes the individual with Takayasu’s disease, as well as the typical elderly arteriosclerotic obliterans process. However, traumatic occlusion of the subclavian artery as well as the iatrogenic causes for subclavian artery disease have been noted, including those patients who have had an anomalous right subclavian artery originating from the left descending thoracic aorta. Subsequent to ligation or division of the anomalous subclavian artery, patients may develop the SSS years later. After extensive arm usage they may pass out or develop syncope with no other anatomic abnormality except the ligated right subclavian artery. The steal syndrome may also develop when a blood flow circuit is modified or changed. Such may occur when an obstruction or new connection (bypass) reroutes the blood away from the usual distal end-organ and into a different pathway. When this occurs, the blood may literally take a shortcut and follow the path of least resistances as exemplified in Figure 47-1. At low flow or reduced need, both organs or areas normally perfused may not initiate any symptoms despite an obstruction, flow reversal, or change in distal resistance. Oxygen and nutrient supply are adequate at this point in time. But with increased demand by the end-organ (B) and decreased flow to organ (A), the blood may be shunted or “stolen” away from the usual recipient of the normally directed blood flow to organ (A). This decreased flow to (A) may then initiate hypoxic and hypovolemic symptoms referral to organ (A) in addition to decreased nutrient symptoms from organ (B). A parallel phenomenon occurs when a large vessel normally serves both a high-and low-resistance area. The blood will flow away from the higher-resistance area when no obstruction is present to the lower-resistance area or the obstruction has been removed.

•

DIAGNOSIS

Many of the patients found to have a SP are asymptomatic and the steal is found only during diagnostic studies for other reasons. Such asymptomatic findings are unexpected in most patients and are usually not treated. When symptoms do develop, the type and severity depends on the organ or structures involved. The SSS patients may have both arm and cerebral symptoms, but the arteriovenous (A-V) access patients usually will not have cerebral symptoms. Suspicion and awareness in the symptomatic patient will lead to a more concentrated physical examination and subsequent appropriate diagnostic testing. Weakened or absent pulses, an auscultatory bruit, and blood pressure variance from extremity to extremity may all be clues to the problem. Diagnosis of this syndrome relies primarily on the awareness and then the performance of the appropriate diagnostic studies. These studies include a good physical examination. When considering a SSS, the physical examination should include comments regarding the presence or ab-

sence of the radial and carotid pulses, the blood pressure in both upper extremities, and if a bruit is present. Diagnostic studies may include a number of imaging techniques, including the colored Doppler studies, angiography, and magnetic resonance angiography.5 Standard xray examinations usually will yield no benefit. More recently, CT scan angiography is being utilized to diagnose and delineate vascular problems. False-positive and falsenegative studies must be guarded against and further delineated. Angiography, utilizing the standard injection of contrast dye, has been the mainstay in diagnosing extracranial and intracranial, vascular disease. Initially, direct needle vascular puncture and injection of iodine based contrast material was utilized. Carotid and brachial artery puncture with appropriate timing produced good quality radiographs. These studies required multiple access sites and retrograde injection when utilizing the brachial artery. With the development of the catheter angiographic techniques, especially through the groin, multiple injections and multiple vessels could be studied with single vessel access. Smaller catheters, flexible guidewires, power injectors, and introducer sheaths, all added to the increased angiographic techniques aided by safer contrast materials. Thus, stenotic as well as forward and reverse flow studies were readily accepted and performed. Currently, when intraarterial angiography is necessary, a retrograde transfemoral catheter approach is preferred unless the groin presents a contraindication such as occlusive disease, infection, or previous graft concerns. In addition, the noninvasive studies may include the vascular ultrasound, magnetic resonance imaging (MRI) and angiography (MRA), and positron emission tomography (PET) scanning techniques. Duplex ultrasonography of carotid, vertebral, and subclavian arteries may be very revealing in screening for stenosis, occlusion, and flow. Flow direction in the subclavian and vertebral artery may be evaluated at the same time. Provactive maneuvers and the “bunny” waveform evaluation may further define the steal process. Invasive studies including arch angiography and selective carotid and subclavian studies will all assist in the diagnosis. If the patient is asymptomatic, most of the time the steal phenomena will be diagnosed only coincidentally. In the past, digital subtraction angiography has been utilized to a great extent, but has a lesser value with the advent of the more modern studies. The question of evaluating these patients and their cerebral blood flow utilizing the PET (exercise thallium-201 stress imaging) scan has been raised by Mase et. al.6 They found a dramatic decrease of cerebral blood flow on PET study in the steal syndrome. Their patient had complained of headache and dizziness. Extensive evaluation included cranial MRI, oxygen-labeled gases, oxygen extraction fraction, and regional metabolic rate for oxygen. They suggested that PET scanning could possibly be a study to assist in the evaluation of an individual and whether or not the steal syndrome was significant. In response to this, Steve Powel questions the value of performing a PET scan in these

STEAL SYNDROMES • 939

individuals.7 He stated that vascular surgeons have known for years that a history of upper extremity claudication, a subclavian bruit, and a diminished blood pressure in the affected arm are diagnostic in most patients. Watson et. al, however, felt that this technique could become a valuable study in the future.8

•

SPECIFIC STEAL PATIENTS

Subclavian Steal Subclavian steal occurs on an infrequent basis but represents the most frequent of the steal diagnoses. The patients may be totally asymptomatic and the problem found incidentally during other studies. However, when the symptoms do develop, the patients are now felt to have the steal syndrome as compared to the SP. The symptoms vary from patient to patient but, in general, are related to the central nervous system and to the upper extremity. The most common symptoms are dizziness, syncope, headache, and weakness—all manifestations of vertebral basilar insufficiency.9 Other such central nervous system problems may include blurred vision, nausea, vomiting, and drop attacks as well as auditory phenomenon. On occasion chest pain may develop and produce symptoms suggesting angina. The upper extremity may present with ulceration of the fingertips, paresthesias, and painful symptomatology both at rest or with exercise. Stroke or hemiparesis as well as hemisensory dysfunction are less common and might suggest carotid disease as compared to subclavian difficulties. Less commonly, lower extremity claudication and gastrointestinal complaints such as distention, pain, and shock may be seen. These patients when examined may be totally normal on examination or there may be obvious physical findings such as differential blood pressure in the right and left upper extremity, carotid bruits, absence of left radial pulsation, as well as digital ulceration and discoloration of the upper extremity. Most of our patients have not had major symptoms or have been asymptomatic. It should be noted that some individuals feel that the reversal of flow in the vertebral system and the flow away from the circle of Willis may actually cause no symptomatology. In the younger individual in whom subclavian artery stenosis or occlusion is present, headaches seem to be one of the main presenting difficulties. The examination of these patients utilizing noninvasive techniques such as duplex ultrasound, CT scan angiography, and magnetic resonance angiography all may further delineate and confirm the diagnosis. The patient’s collateral circulation may be extensive and through multiple routes including the internal or external carotid, the vertebral artery, the thyrocervical and costocervical trunk, as well as transcervical anastomosis between the inferior thyroid vessels and indirect communications (Table 47-5). Arch angiography will delineate the major vessels coming off of the arch with a single injection and hopefully avoid selective angiography and the potential complications of such.

TABLE 47-5. Subclavian Artery Occlusion Collaterals I. Vertebral communication via circle of Willis from the internal carotid artery II. Anastomoses between the inferior thyroid arteries and transcervical vessels III. Indirect vertebral to vertebral-spinal branch anastomosis IV. Vertebral collateralization from the external carotid and the thyrocervical and the costocervical trunks V. Internal thoracic or aorta internal thoracic artery communication through the intercostals

We have seen a number of patients with congenital aortic arch and anomalous subclavian artery abnormalities. Years ago patients with the anomalous subclavian origin difficulty were treated primarily with ligation and division of the anomalous vessel and no reattachment to the aorta anterior to the esophagus. When we first saw these patients, diagnostic angiography and symptomatology led us to total operative correction and avoidance of potential future subclavian steal symptoms.10,11 The same consideration has been given to the patient with congenital cardiac abnormalities requiring transfer of the subclavian artery and distal ligation. The question then becomes relevant as to whether a bypass to the distal subclavian artery should be considered with the appearance of symptoms or whether the vertebral artery could have been ligated at the initial surgery. The three major SSSs include the subclavian, the innominate, and the carotid steal (Table 47-6). The subclavian steal is the most frequent and the other two are very uncommon and questioned as to their diagnoses. In the subclavian steal, vertebral basilar insufficiency, vertigo, transient blindness, and syncopal episodes are the most common patient complaints (Table 47-7). Blood pressure changes greater than 20 mm Hg between the right and left arm may be very suggestive. Further, the differential diagnosis must be considered in those who have normal blood pressure in both arms with symptomatology suggestive of the steal. Bilateral subclavian steal would be very uncommon, and care with placement of diagnostic catheters to avoid erroneous data is required. Patients who have concomitant carotid disease

TABLE 47-6. Types of Subclavian Steal Syndromes (SSS) or Phenomenon (SSP) I. II. III. IV. V.

Subclavian steal Innominate steal (right side only) Carotid basilar steal External carotid to vertebral steal Coronary subclavian steal (CSS) via mammary artery graft

940 • CHAPTER 47

TABLE 47-7. Subclavian Steal Syndrome (SSS) Symptomatology I. Upper extremity A. Pain: rest or claudication B. Paresthesias C. Ulceration or gangrene II. Central nervous system A. Headache B. Dizziness/vertigo C. Syncopal or drop attacks D. Nausea and vomiting E. Ataxia III. Vision A. Blurred B. Diplopic IV. Auditory V. Cardiac A. Angina or chest pain VI. Hemiparesis: uncommon VII. Gastrointestinal: uncommon

at the same time as a steal syndrome will usually require carotid surgery prior to correction of the steal. Morbidity from this syndrome is usually low, but severely debilitated patients may be seen with episodes of arm and intracranial ischemic symptoms. The finding of extracranial arterial occlusion during angiographic studies has been reported as high as 15% to 17% in studied patients. Many of these will have concomitant obstructive findings in the carotid system and, as many as 5% of the patients may have an asymptomatic subclavian SP. However, this usually is around 1% or less. SSS does occur more commonly in males and particularly in the older Caucasian population. The Takayasu arteritis symptoms, however, may occur in the younger female individual. Treatment of the SSP is usually not required as these patients are asymptomatic and the lesion is an incidental finding. When the SSP patient progresses to the SSS, therapy must then be considered. When possible, correcting the blood pressure, diabetes, and activity (especially arm usage) level may all reduce the need for intervention. However, when intervention requires surgery, the patient’s surgical approach should restore antegrade vertebral artery flow, increase the cerebral arterial flow, and hopefully relieve the cerebral symptomatology (Table 47-8). We have preferred avoiding a major thoracotomy if possible, particularly when the SSS is found in the older individuals. Most patients with the finding of a subclavian steal have not required surgery. Many of the patients will have a carotid stenosis along with the steal. In these individuals, a carotid endarterectomy may be the best approach. On occasion, however, this surgery may either exacerbate or not relieve the steal syndrome and the patient may then require a second surgery. The consideration for surgery should take into account the phrenic

TABLE 47-8. Therapeutic Options for Treatment of the Subclavian Steal Syndrome I. Observation II. Correction A. Lipid abnormality B. Blood pressure C. Diabetes mellitus D. Smoking cessation III. Percutaneous approach A. Angioplasty +/− stent placement. B. Endovascular atherectomy. IV. Intrathoracic A. Endarterectomy with patch graft of subclavian or vertebral artery B. Complete correction of congenital aortic arch abnormalities C. Ligation of vertebral artery and its branches D. Aortosubclavian bypass E. Aortoinnominate bypass V. Extrathoracic A. Endarterectomy of stenotic or occluded vessels (subclavian, brachiocephalic, vertebral, or thyrocervical). B. Grafting (vein or synthetic material) 1. Carotid—axillary 2. Carotid—subclavian 3. Subclavian—subclavian 4. Femoral—axillary 5. Carotid—vertebral 6. Axillary—axillary C. Direct anastomoses 1. Vertebral to carotid 2. Subclavian to carotid

nerve, the scalenus anticus muscle, and the recurrent laryngeal nerve. We have performed both extrathoracic as well as the intrathoracic procedures with success in the appropriate clinical situation. One should be aware, however, that the subclavian artery may be very friable and difficult to suture. Various bypass procedures include the subclavian-subclavian bypass via the supraclavicular approach, an axillo-axillary bypass (may be a safer approach), and a femoral axillary bypass with a tunneled graft. We prefer to avoid the latter. Patients must be cautioned to notify physicians of the graft, especially when a midsternotomy is to be performed. In our experience, midsternotomy has not been required for the treatment of most of these patients. However, some authors have reported utilization of this approach, particularly in Takayasu’s syndrome, where additional vessels may require bypass. The transfemoral catheter angioplasty approach may be utilized in a number of these patients, particularly the ones with a stenosis as compared to a complete obstruction. Restenosis, a consideration in the transformal patients, requires periodic prospective patient monitoring.

STEAL SYNDROMES • 941

In patients with congenital vascular abnormalities, we have attempted to perform total correction, with respect to the aberrant retroesophageal right subclavian artery. Combining various techniques in some patients may be more appropriate than a single, more complicated, and potentially higher-risk procedure. Complications of these procedures certainly do occur. One must be aware of the potential for thrombosis and rethrombosis of the graft or anastomosis.12 When this does occur, the risk to the patient includes a stroke and hemiplegia. Thoracic duct injury may lead to a lymph fistula. Laryngeal or phrenic nerve injuries may occur while performing subclavian or innominate surgical procedures. Adequacy of the graft without injury to the other structures will avoid postoperative symptoms such as dyspnea caused by diaphragmatic palsy and Horner’s syndrome. The correction of these patients’ problems without morbidity and mortality may be a challenge to the most adept. Other considerations, including the medicolegal pitfalls, may also be a concern. Therapy for these patients is varied and requires considerable evaluation prior to a definitive approach.13 Certainly, one needs to know whether the patient is symptomatic, and whether the symptoms are felt to be a result of the steal, or whether the symptoms could be because of another etiology. Multiple causes of arm claudication may be present. If there is an indication for another diagnosis, evaluation for such should be taken into consideration prior to any surgery. Symptoms thought to be caused by the steal syndrome may mimic those caused by a thoracic outlet syndrome, a carpal tunnel compression, or other processes that create pain in the arm, especially with usage of that extremity. There may be multiple types of steal present, and this therefore requires the appropriate diagnosis. With multiple types of steal, it is pertinent to define the correct anatomic and functional flow abnormality. Flow abnormalities in the vertebral artery may be divided into three categories: stage 1, reduced antegrade flow; stage 2, exercise-induced reversal of flow; stage 3, permanent reversal of flow. Knowing the characteristics of the obstruction and symptomatology, the correct diagnosis and the patient’s limitations one can then develop the best approach for treatment, whether medical or surgical.

•

CORONARY SUBCLAVIAN STEAL

A separate subclavian steal occurance has been described in patients having coronary artery surgery. This syndrome has been variously classified as a SSS, an internal thoracic artery steal syndrome, and a coronary subclavian steal (CSS). It has occurred in individuals who have had occlusive coronary disease requiring coronary bypass procedures. As experience has progressed, the internal mammary bypass has been utilized to a greater degree as a donor vessel. When the left internal mammary artery is anastomosed to a coronary artery, the patients have a situation where occlusion of the subclavian artery may create symptomatology suggestive of both recurrent coronary disease as well as the

CNS symptoms of subclavian artery occlusion. The development of angina in these individuals should be studied with both noninvasive and invasive considerations to evaluate the potential for an occluded subclavian artery with coronary circulation hypoperfusion because of a steal into the upper extremity, especially with exercise. If the subclavian artery is stenotic but not totally occluded, angioplastic procedures with or without stent placement has relieved a number of these patients. Transfemoral, percutaneous, and directional atherectomy has also been utilized for the treatment of the occlusion and relief of the coronary anginal symptomatology. If this is not feasible, subclavian, or axillary bypass grafting (Gore-Tex) has been utilized for treatment of these individuals. Pocar and Ferges et al. have discussed the incidence of perioperative internal thoracic artery steal syndrome following coronary bypass surgery.14,15 The flow reversal in the LIMA graft has been demonstrated to be the explanation for the repeat chest pain and symptoms in these individuals. When possible, a noncardiac extrathoracic approach should be considered for the treatment of these individuals.16 There have been reports stating that as long as coronary perfusion is maintained, isoflurane does not cause coronary steal or ischemia. Teo and Koe, however, have reported where this was not the case and where isoflurane did not have myocardial protective properties in their patients.17 The patient requiring coronary surgery should thus be considered for arch angiography, particularly when there is a discrepancy in the blood pressure between the two upper extremities. Elian et al. had seven patients who presented with recurrent angina because of subclavian artery stenosis.18 In each of these, the internal mammary graft was open and, in their studies, they did not see a true steal mechanism. However, stent angioplasty and stenting of the subclavian artery resulted in immediate disappearance of the angina.

•

HEMOACCESS STEAL

Patients with chronic renal failure and elevated blood urea nitrogen (BUN) and creatinine are a frequent medical problem in the community. Because of this, renal dialysis and renal dialysis centers have continued to develop throughout North America and the world. With the finding of these nephrotic or prenephrotic patients who require dialysis, a decision must be made whether they will have peritoneal dialysis or hemodialysis. If the patients are to have hemodialysis, appropriate hemoaccess procedures are required. Acutely ill patients may be treated with temporary hemodialysis procedures through the subclavian, internal jugular, or femoral veins. Those patients requiring longterm dialysis may be then converted to other more convenient chronic long-term access modalities. The most common such procedures include A-V anastomatic access using the radial artery or loop grafting (gortex, vein, bovine) at the elbow using the brachial artery and vein. The creation of the hemodialysis fistula at or just above the wrist may proceed well with a good flow and little symptomatology once

942 • CHAPTER 47

the patient’s wound has healed and matured. However, a number of these patients may have a high flow through the fistula and develop symptoms distal to the anastomosis of swelling, painful edema, loss of function, and discoloration of the extremity and hand. Ulceration of the fingers and numbness have been seen. In these individuals additional surgery may be required to ligate the distal end of the fistula to hopefully avoid and reduce the steal symptomatology. However, the most common difficulties noted in the creation of brachial/radial A-V access is not the steal but the small vein, low flow, and thrombotic considerations. Studies have been carried out to evaluate the patient as to the potential for developing the steal concern and the risk factors such as hypertension, race, diabetes, smoking, and coronary disease.19 Diabetic patients, people of aboriginal race, and women may develop more steal symptoms compared to men. If complications or infection develop, repeated surgery as well as a risk to the extremity viability may be seen, possibly requiring further surgery. Patients having more proximal procedures such as a brachial artery to vein anastomosis, a proximal radial artery to vein anastomosis or a prosthetic graft procedure, may have an increased risk of developing the SP. Patients with the more proximal procedure are more apt to develop a steal than the ones with the distal procedure according to Davidson et al.19 They demonstrated an approximate 6% overall rate of steal in these proximal renal dialysis access patients. The best patient access procedure is performed when good distal vessels, both arterial and venous, exist and when the patient otherwise has a good palpable distal pulse. If they require a more central shunt, then the risks would certainly be enhanced. The arterial steal syndrome in the brachial artery-based procedure has, on occasion, led to loss of distal function, but with close observation this should be minimized. The brachiocephalic as well as the A-V grafts may all develop the steal syndrome. Femoralfemoral grafting and potential steal is very uncommon. Various techniques have been proposed as to the best approach to resolve the patient’s difficulty when a steal syndrome is considered (Table 47-9). Angiography may assist in the decision as to whether surgical intervention is required to alleviate the symptoms or the findings and whether there are other accompanying abnormalities leading to or enhancing the problem.20 Individual techniques to

TABLE 47-9. Treatment Modalities for Upper Extremity Hemoaccess Steal Syndrome I. II. III. IV. V. VI.

Arteriography Distal ligation Lengthening of graft Circular constriction Take down access— move to new site Correction of proximal stenosis

reduce the incidence of steal or the symptomatology as a result have been utilized. These have included the ligation of distal vessels, the graft lengthening procedures to increase the resistance in a graft, the placement of a stricture, or band on a graft subsequent to noninvasive as well as invasive studies. This banding technique has also been used for distal venous aneurysm formation post-A-V access. The individuals with a cold hand that is painful at rest and during dialysis more commonly will require further consideration and surgical intervention to avoid destructive arthropathy and reflex sympathetic dystrophy. An additional finding of angiography in some individuals may be a significant arterial stenosis. Thus, angiography is warranted to select the proper course of treatment for these individuals. Preferably, modification of the fistula or graft will resolve the problem rather than complete removal of the fistula or graft.

•

AORTOILIAC (MESENTERIC ARTERIAL) STEAL

Trippel et al. discussed the incidence of this syndrome 35 years ago and mentioned that it was originally described several years prior to their presentation by Dr. DeBakey.21 Occasionally, patients are seen with total obstruction of the subrenal aorta and absence or diminished femoral, popliteal, or pedal pulses because of occlusive disease of the aorta and iliac vessels. These individuals will have large, collateral, circulatory changes through connecting vessels. The collateral vessels may include the celiac, the inferior mesenteric, the superior mesenteric artery, and the distal iliac or femoral vessels. In these circumstances when aortofemoral bypass grafting is accomplished, the patient may develop severe abdominal pain with an intraabdominal crisis. Symptomatic individuals may progress rapidly to gangrene of the bowel and massive sepsis. Exploratory laparotomy will usually demonstrate no inappropriately placed ligatures or twists. The patient may, however, have a mesenteric vessel stenosis and a meandering mesenteric artery. Reconstruction with perfusion of the distal extremities relieves the pressure and high flow to the mesenteric vessels and may lead to decreased flow in the mesenteric system, increased leg flow, and death of the bowel.22 It has been our experience that when this occurs, no other revascularization technique has assisted these individuals. However, the enlarged, central, anastomotic artery on angiography may demonstrate and suggest a potential compromise of the mesenteric circulation as well as a stenosis or stricture of two or three of the mesenteric vessels.

•

SPLANCHNIC STEAL

A separate, splanchnic steal syndrome has also been described. Keswani et al reported a patient that they felt had a splanchnic steal syndrome.23 Their patient developed light-headedness, right-sided numbness, and weakness after eating along, with slurred speech. Following evaluation, the patient was found to have internal carotid stenosis and

STEAL SYNDROMES • 943

poor collateral flow to the left hemisphere. Subsequent to correction of her internal carotid stenosis, her postprandial weakness disappeared and she no longer had difficulty after large meals. They discussed the incidence of postprandial hypotension in wheelchair-bound elderly individuals and hypothesized that this postprandial drop in blood pressure may be caused by inadequate sympathetic response in the elderly. They further demonstrated how their patient was relieved of symptomatology because of diminished gastrointestinal flow and cerebral hypoxia. They reduced the “splanchnic steal” by having the patient eat smaller and more frequent meals and by correcting the carotid stenosis, thus relieving the patients symptoms.

•

OTHER

Other potential steal syndromes may be present or considered in patients but to a much lesser degree and lesser understanding of the process. We have seen patients with posterior tibial artery to vein fistulae who had audible bruits and palpable thrills. These individuals complained of pain and coldness in the extremity distal to this area. With cor-

rection of the fistula or with spontaneous healing of the traumatic lesion, the patient’s symptoms improved and disappeared. It has been our feeling that this represented a localized, traumatic, posterior, tibial artery steal syndrome. This process has also been noted following balloon angioplasty. Another group of patients that have been considered to have a potential for a steal syndrome have been the patients with an aortocaval fistula. In these individuals, the aortic blood flow may be diverted from a higher blood pressure into a lower pressure system (the vena cava) and when this occurs, diminished blood flow to the lower extremities and to the pelvic organs may occur. Most of these patients will be seen prior to complaining of severe distal pain because of other more central symptomatology. However, the flow from the high to the low pressure system and the diversion of blood seems to be aperfect setup for the creation of a SP or syndrome. Correction of the lesion should reduce both the distal and central symptoms if there is no distal obstruction. If there is an obstruction distally, correction of the fistula along with distal bypass should relieve the symptomatology.

REFERENCES 1. Contorni L. Il circola collateral vertebraovertebrale nell obliterazionne iell’ arterio subclavia all sua origine. Minerva Chir. 1960;15:268-271. 2. Reivich M, Holling HE, Roberts B, et al. Reversal of blood flow through the vertebral artery and it’s effect on cerebral circulation. N Eng J Med. 1961;265:878-885. 3. Fisher CM. Editorial comment: a new vascular syndrome— the subclavian steal. N Engl J Med. 1961;265:912-913. 4. Netter FH. Atlas of Human Anatomy. 3rd ed. Univ of Rochester School of Medicine and Dentistry. Rochester NY, Teterboro, NJ: Icon Learning Systems; 2003. 5. Kalaria VG, Jacob S, Irwin W, Schainfeld RM. Duplex ultrasonography of vertebral and subclavian arteries. J Amer Soc Echocardiogr. 2005;18(10):1107-1111. 6. Mase M, Yamada K, Matsumoto T, Fujimoto S, Lida A. Cerebral blood flow and metabolism of steal syndrome evaluated by PET. Neurology. 1999;52(7):1515-1516. 7. Powell S. Response to determine functional significance of subclavian artery stenosis using exercise thallium 201 stress imaging. [Letters to the Editor]. South Med J. 2005;98(12): 1223. 8. Watson S, Bedi S, Singh S. Determining functional significance of subclavian artery stenosis using exercise thallium-201 stress imaging. South Med J. 2005;98:559-560. 9. Dieter RA Jr, Maganini RO, Dieter R. Subclavian steal syndrome. In: John C, ed. Text Book of Angiology. New York, NY: Springer; 2000:629-634. 10. Piffare R, Dieter RA Jr, Niedballa RG. Definitive surgical treatment of the aberrant retroesophageal right subclavian artery in the adult. Thorac Cardiovasc Surg. 1971;61:154-159.

11. Dieter RA Jr, Kuzycz G. The steal syndrome: iatrogenic causes. Internat Surg. 1998;83:355-357. 12. Thrombosis of the subclavian arteries in the steal syndrome, complications of extracranial cerebrovascular procedures. In: Baum S, ed. Abrams Angiography. Vascular and Interventional Radiology. Vol 1. 4th ed. Boston, MA: Little, Brown & Co; 164-165, 287-291. 13. Brophy DP. Subclavian Steal Syndrome, e Medicine Journal [serial online]. Knowledge Resource Library. http://www. emedicine.com/radio/topic 663.htm. February 15, 2006: 1-9. 14. Pocar M, Moneta A, Passolunjhi D, Mattioli R, Clerissi J, Donatelli F. Perioperative internal thoracic artery steal syndrome after coronary bypass surgery. J Thor Cardiovasc Surg. 2005;130:562-563. 15. Fergus T, Pacanowski JP Jr, Fasseas P, Nanjundappa A, Ahmed MH, Dieter RS. Coronary subclavian steal: presentation and management: two case reports. Angiol. 2006;57:T1T4. 16. Kern KB, Warner NE, Sulek CA, Osaki K, Lobato EB. Angina as an indication for noncardiac surgery: the case of the coronary subclavian steal syndrome. Anesthesiol. 2000;92(2):610612. 17. Teo A, Koh KF. Isoflurane in coronary steal. Anesthes. 2003;58:95-96. 18. Elian D, Gerniak A, Guetta V, et al. Subclavian coronary steal syndrome, and obligatory common fate between subclavian artery, internal mammory graft and coronary circulation. Cardiol. 2002;97:175-179. 19. Davidson D, Louridas G, Guzman R, et al. Steal syndrome

944 • CHAPTER 47 complicating upper extremity hemoaccess procedures, incidence and risks factors. Canad Surg. 2003;46(6):408412. 20. Asif A, Leon C, Merrill D, et al. Arterial steal syndrome secondary to dialysis: a modest proposal for an old paradigm. Amer J Kidney Dis. 2006;48(1):88-97. 21. Trippel OH, Juraj MN, Midell AI. The aortoiliac steal, a

review of this syndrome and a report of one additional case. Ann Surg. 1972;175(3):454-457. 22. Connolly JE, Stemmer EA. Intestinal gangrene as the result of mesenteric anterial steal. Am J Surg. 1973;12:197204. 23. Keswini SC, Wityk R. A case of steal syndrome. Lancet Neurol. 2003;2:379.

48

chapter

Hemodialysis Access John B. Chang, MD / Robert W. Chang, MD / Lorena De Marco Garcia, MD

•

INTRODUCTION

Patients with acute and chronic renal failure require dependable access for dialysis. Dialysis access failure has been reported to be one of the most frequent causes of hospitalization among patients with end-stage renal disease (ESRD).1 With our ability to treat ESRD, improving the longevity of our patient population has been steadily increasing. The Kidney Dialysis Outcomes Quality Initiative (DOQI),2 as published by the National Kidney Foundation, sets forth recommendations as part of a national consensus that parishioners avoid percutaneous-catheter based arteriovenous (AV) hemodialysis access in favor of autogenous access (AA), followed by prosthetic access (PA), as a second preference. With vascular access (VA) complications accounting for 15% of hospital admissions among hemodialysis patients,3,4 and Medicare costs approximating $182 million in 2003,4 the population of patients requiring hemodialysis access is expected to increase by 10% per year from a group which exceeded 345 000 patients in 2000.5 The current DOQI recommendations for practice patterns are the insertion of an AA in 50% of long-term access patients. However, some centers have had trouble achieving this goal as a result of vein mapping results or availability of forearm basilic vein.6 The DOQI guidelines-recommended surgical referral pattern should begin when a patient exhibits a creatinine clearance of less than 25 mL/min or a serum creatinine greater than 4 mg/dL or when AV access is anticipated within 1 year.2 The introduction of hemodialysis as routine treatment of ESRD made it necessary to find a simple form of repeated access to the vascular system. It was only after the introduction of external silastic cannulae by Quinton and Scribner7 in 1960 that extracorporeal treatment could be established. Several years later, Brescia and Cimino8 devised the AV fistula, which overcame the limitations of frequent

infections and thrombosis. In the 1970s the implantation of grafts was introduced,9−11 which permitted renal replacement therapy in patients devoid of venous vessels. Currently, complications of VA (i.e., dysfunction, thrombosis, or infection) are a major cause of hospital admission. They affect the quality of life. For this there are objective reasons (they make it difficult to administer sufficient dose of dialysis) and subjective ones (anxiety because of uncertainty about correct functioning).12 Furthermore, they give rise to frustration in health care personnel.13−15 Recently, repeated VA failure has been identified as a risk factor for mortality.16 Finally, VA failure causes high economic costs, accounting for up to one-third of ESRD expenditure.17 The radiocephalic AV fistula is the preferred VA because of its low complication rates, its long survival, and its ease of puncture once it has matured.18−20 Nevertheless, its establishment on the wrist or in the anatomical snuffbox of the nondominant arm is potentially inconvenient for two reasons: (1) Four to eight weeks are necessary until the venous wall has arterialized and (2) a high rate, 8% to 30% of initial failure or insufficient development is observed, necessitating the use of other modalities of VA.21 Recently, AV fistulae higher up in the forearm and on the upper arm have been put forward as acceptable alternatives. Some studies have documented primary patency rate >80% in the first 2 years of observation,22 but there is no information on the long-term outcome for this type of AV fistula. The second mode of permanent VA are grafts, the use of which has increased in recent years, and in numerous centers it is today the most frequently used type of VA.23 This tendency has been related to recent demographic changes in the hemodialysis population, the scarcity of transplants with the consecutive increased time on hemodialysis treatment, and increase comorbidity of patients beginning renal replacement therapy. In fact the median age of incident patients is actually around 60 years, more than half of the

946 • CHAPTER 48

patients have at least two comorbid conditions, and 20% to 40% are diabetic patient—all factors that could affect the success of the VA.17,24 On top of this, patients are not infrequently referred to the nephrologists in the terminal stages of renal failure or during an episode of acute deterioration of pre-existing renal failure. In these circumstances, it is frequently impossible to create a VA in time.25

•

ACUTE ACCESS

For patients who require immediate dialysis access, that is, those requiring hemodialysis of less than 3-week duration, a double-lumen cuffed or noncuffed catheter should be inserted into the femoral, internal jugular, or subclavian vein.26 The most common catheter for this purpose is the Quinton catheter, which can be placed at the bedside and must be able to support a flow rate of 250 mL/min.27 In case of femoral vein catheter insertion, the catheter should not remain longer than 5 days, because of the high propensity for infection or dislodgment with ambulation.28 Most importantly, the subclavian position should be avoided if the patient is to be considered for an ipsilateral arm access procedure because the incidence of subclavian vein stenosis or thrombosis or both increases steadily with the presence of a catheter in this position, rendering the extremity useless for insertion of a permanent access.29,30

•

SUBACUTE ACCESS

For the patient who requires hemodialysis for more than 3-week duration, insertion of a cuffed, tunneled, doublelumen catheter should be considered. The preference of location would be the internal jugular vein. The right internal jugular vein is preferred because of its proximity to the atrial-caval junction (allowing for better flow), but with the added emphasis of placing the catheter in the right internal jugular. Aside from complications associated with insertion, (hemothorax and pneumothorax), the tunneled cuffed catheter can be relied on to function for an average of 6 months, after which infection, fibrin sheath formation, or thrombosis may curtail usage.31 Using endoluminal therapy or percutaneous mechanical techniques, prolonged usage can be obtained up to 12.7 months as reported in a study.32 Local infection and sepsis,31 and infection elsewhere33 are typical reasons for removal of the catheter.

•

CHRONIC ACCESS AUTOGENOUS

Snuffbox Fistula These consist of end-to-side anastomosis between the distal cephalic vein and the thenar branch of the radial artery, the pulse of which is usually palpable through the floor of the anatomic snuffbox, created through the one incision. In one European study over a 12-year period, 11% thrombosed within 24 hours of creation, and 80% had matured for hemodialysis within 6 weeks. The 1- and 5-year patency rates were 65% and 45%. Of the fistulae

that thrombosed, ipsilateral wrist angio access was successfully constructed in 45%.34 Similar results were obtained in another study,35 which reported on 139 patients who underwent snuffbox fistula creation with and without diabetic nephropathy. After 57 months, 87% of patients without diabetic nephropathy had patent access, whereas 72% were patent among patients with diabetic nephropathy, and they concluded that patients with diabetic nephropathy may not arterialize their accesses as well as patients without diabetic nephropathy (Figure 48-1). Radial-Cephalic Direct autogenous radial artery-cephalic vein fistula was first described in 1966.36 This access has also been called the Cimino fistula or the wrist fistula. Different configurations of anastomosis have been employed with varying results as far as development of a steal phenomenon or speed of maturation,37 although the cephalic vein end-toside configuration seems to be the most popular. Cephalic veins of less than 1.6 mm in diameter have been associated with early failure38 (Figures 48-2 and 48-3). Results of the Cimino fistula have been generally good, with 6-, 12-, and 36-month patency rate of 80%, 71%, and 64%, respectively.39 In a series, reported factors suspected to have influence on AV fistula included age, BUN, blood pressure at the time of operation, serum cholesterol, and creatinine levels. The 1-year patency rate was 59.8% and 40.8% at 5 years.40 Other reports suggest that early failure is considered one of the major determinants affecting the long-term patency, because, after 1 year, the rate of access failure was slow, steady, and near the same regardless of the type of surgery of the fistula.41 Our routine practice of creating a fistula technique is as follows: 1. One incision at the wrist between the distal radial artery and cephalic vein under local anesthesia. 2. Between the distal radial artery and the cephalic vein. 3. Divide the distal end of the cephalic vein, after the patient is heparinized. 4. Bring the end of the cephalic vein to the site of the radial artery in an end-to-side fashion with an arteriotomy of 5 to 8 mm in length. 5. With the radial artery cross-clamped proximally after the arteriotomy is made, release the distal clamp of the radial artery. If pulsatile backflow is observed, we then ligate the radial artery distal to the end-to-side anastomosis. This pulsatile flow indicates complete palmar arcade. By doing these techniques, we are able to improve on the following important points: 1. Maturation is fast. 2. Minimize early thrombosis because of flow-related problems.

HEMODIALYSIS ACCESS • 947

Ligated distal cephalic vein

Snuff box

Anastomosis

Left cephalic vein

Ligation at distal radial artery Left radial artery

• FIGURE 48-1.

A snuffbox AV fistula. A small vertical incision is made on the snuffbox at the area of the pulsating distal radial artery. The distal cephalic vein is dissected and ligated. The distal end of the cephalic vein is brought to the side of the radial artery. An end-to-side anastomosis is made using 7.0 Prolene sutures. If the patient has a good pulsatile back flow from the distal radial artery, with the proximal being cross-clamped, indicating complete palmar arcade, the distal radial artery, distal to the anastomosis can be ligated in order to convert from anatomic end-to-side anastomosis to functional end-to-end anastomosis.

3. Minimize distal venous hypertension if you want to construct side-to-side anastomosis. 4. Minimize distal ischemic change because of reversal of the flow from the distal radial artery into the vein at the later stage when the venous system becomes enlarged.

•

BRACHIAL–CEPHALIC ACCESS

Anastomosis of the antecubital veins with the brachial artery can be accomplished with good results. Despite favorable results, the fistula has a higher incidence of steal, especially with long donor arteriotomies. In one study, the antecubital vein fistula had a primary patency rate of 80% at a medium follow-up of 36 months, compared with 66% of brachial–cephalic fistulae at 24 months.42 This study suggests that the brachial–cephalic fistula was a favorable alternative in elderly patients, women, and diabetic patients. In another study, 74% 1-year patency rate was accomplished.43

•

BASILIC VEIN TRANSPOSITION

Brachial–Radial at Forearm Hakaim et al.44 showed superior patency and maturation rates of primary brachial–basilic vein with transposition, compared with 78% and 79% for brachial–basilic and transposed brachial–basilic access.

Brachial–Basilic at Upper Arm This procedure was first described in 1976.45 The procedure involved mobilization, distal division, and superficial tunneling and transposition of the basilic vein with distal end-to-side anastomosis with the brachial artery. The technical alternatives and modification include elevating the basilic vein rather than rerouting it46 or superficializing the basilic vein as part of a staged procedure.47 Others employed endoscopic techniques as a means of reducing the incision length.48 In a large study, the long-term follow-up for patients having undergone the procedure were, 1-year patency of 84%, 73% at 3 and 5 years, and 52% at 10 years.49 Also, less favorable results were reported in other studies.50

•

LOWER EXTREMITY AA

In a rare incidence, lower extremity AA can be done. This technique involved dissection and mobilization of the entire superficial femoral vein, with transposition into a superficial position in the thigh, and end-to-side anastomosis.51 In a retrospective analysis of 25 patients for more than 2 years, cumulative patency was 78% and 73% for 6 and 12 months follow-up. Steal syndrome necessitated further intervention in 40%, and of those, 80% required another procedure to treat steal. Major wound complications affected 28%, and one patient required above-knee amputation after developing a compartment syndrome. Therefore,

948 • CHAPTER 48

Left radial artery

Left cephalic vein Incision

Left ulnar artery Anastomosis Ligated distal cephalic vein Palmar arcade

• FIGURE 48-2.

Primary AVF. A small vertical incision is made on the radial aspect of the wrist on the nondominant hand if at all possible. Preoperative cephalic vein map of the area with a duplex scan may help in evaluation of the quality of the cephalic vein. After dissection of the distal cephalic vein, distal end is ligated. The distal end of the proximal cephalic vein is brought to the radial artery, which can be dissected out through the same incision. End-to-side anastomosis is made between the distal ends of the cephalic vein to the side of the radial artery using 7.0 prolene sutures. At the time of arterial anastomosis, the palmar arcade can be checked by confirming pulsatile back flow from the distal radial artery with proximal radial artery being cross-clamped. If the patient has complete palmar arcade with pulsatile back flow the radial artery distal to the anastomosis can be ligated. In this way, the patient has an anatomical end-to-side anastomosis with a functional end-to-end anastomosis.

it has been suggested not to undertake this technique without serious evaluation, such as good-risk patients who have no other possible sites for fistula creation.

•

PROSTHETIC ACCESS

There are currently 2 major manufacturers of expanded polytetrafluoroethylene (PTFE) for use in hemodialysis access; Gore-Tex (W. L. Gore & Associates, Flagstaff, AZ) and Impra (Impra, Inc., Tempe, AZ). Although manufacturer claim that each of these are having distinct patency and cost advantages over the other, this has not been borne out comparative investigations of either product.52,53 Stenosis of the venous outflow, generally as a result of neointimal hyperplasia, remains the sentinel cause of graft failure, accounting for approximately 80% of graft failure.54 Measurement of the outflow tract have been correlated

• FIGURE 48-3.

Primary AVF at the left wrist. An anastomic end vein, topside arterial anastomosis. This can then be converted to a function end-do-side anastomosis by ligating the clipping with wet clips of the radial artery, distal to the anastomosis. This can be done if the patient has pulsatile back flow at the radiotomy with proximal cross-clamp indicating an intact palmar arcade. A distal cephalic vein indicated by one arrow; distal radial artery, distal to the anastomosis is indicated by two arrows; and the proximal radial artery, proximal to the anastomosis is indicated by three arrows.

with graft patency: lesions that account for less than 30% stenosis were associated with a less than 30% thrombosis rate at 6 months, whereas lesions that accounted for greater than 50% of the outflow were associated with an almost 100% failure rate at 6 months.55 As a result of the association of turbulent flow at the anastomosis with the formation of neointimal hyperplasia,56,57 investigators designed expanded PTFE grafts that incorporated a cuffed geometry of the venous anastomosis site, a design that had shown bench utility in minimizing shear stress.58 This configuration was studied prospectively in 48 patients, although overall primary patency was not affected, secondary patency was increased from 32% to 64% at 12 months.59 There are many varieties of prosthetic angio access graft procedures. Forearm, Loop (U-Shaped) Technique. A small transverse incision is made on the up-

per portion of the forearm, approximately 2 fingerbreadths distal to the antecubital vein. The superficial vein and antecubital vein are isolated. Depending upon the condition of the antecubital vein, sometimes one has to use the basilic portion or a separate portion proximally, or at the antecubital vein. Using the same incision, the brachial artery is isolated. Then a subcutaneous tunnel is made distally to the distal forearm near the wrist curving back to the antecubital incision in a U-shape. Small counted incisions at the distal forearm are made to facilitate the tunnelling procedure with the ease of bringing the graft into the tunnel. After appropriate heparinization, we normally make an end-to-side

HEMODIALYSIS ACCESS • 949

Left shoulder

Left brachial artery Left basilic vein

Transverse incision at antecubital fossa Left cephalic vein Left brachial vein Ringed PTFE graft

Left brachial artery

Anastomosis

Anastomosis Incision Ringed PTFE graft Anastomosis

Small counter incision to make tunnel

• FIGURE 48-4.

Forearm loop AVG. A transverse incision is made on the proximal portion of the forearm, slightly distal to the elbow joint. The brachial artery and antecubital vein is freed. If the quality of the antecubital vein at the same incision is good, then the vein can be used. The brachial artery is freed through the same incision. An end-to-side anastomosis is made between the ends of a 6-mm PTFE graft and to the side of the antecubital vein using 6.0 or 7.0 PTFE sutures. Then a subcutaneous tunnel is made in a U-shape, making a 2-count incision distally to facilitate the curvature of the tunnel. The graft is passed through the tunnel back to the antecubital incision. The other end of the PTFE graft is then anastomosed to the side of the brachial artery using 6.0 or 7.0 PTFE sutures.

anastomosis on the venous side first, using either 6.0 or 7.0 PTFE sutures. The graft is then passed through the tunnel into the antecubital incision. At this point, an arterial anastomosis is made in an end-to-side fashion. Following the completion of the procedure, we either neutralize the heparin or leave the heparin on board with careful hemostasis (Figure 48-4). Forearm, Straight Graft Using the brachial artery or the radial artery and the antecubital vein or distal cephalic vein, the graft is placed in the subcutaneous tunnel. Upper Arm, Loop (C-Shaped) In patients who had failed or nonaccessible forearm angio access with a graft, we use the upper arm. A longitudinal small incision is made on the inner aspect of the upper arm

• FIGURE 48-5.

AVG, left upper arm, C-shape. A vertical incision is made on the medial aspect of the upper thigh at the area of the brachial artery. Through the same incision, the brachial artery and vena comitantes (brachial vein) is freed. An end-to-side anastomosis is made between the side of the vein and the end of the PTFE graft using 6.0 or 7.0 PTFE sutures. The graft is passed through a tunnel which is made in a C-shape, using a small count incision. After the graft is passed through the tunnel, the other end of the graft is anastomosed with the brachial artery in an end-to-side fashion using PTFE sutures.

to expose the brachial artery and vein. From that incision, a tunnel is made curving down distally, laterally then upwardly on the lateral aspect of the upper arm, then curving medially and downward into the incision. Following heparinization, end-to-side anastomosis is made between the PTFE graft and the vein. The graft is then passed through the tunnel distally, laterally, upwardly, and then medially into the incision. The other end of the PTFE graft is anastomosed to the arterial side in an end-to-side fashion. The reason for this type of anastomosis is to make thrombectomy

950 • CHAPTER 48

• FIGURE 48-6.

A loop AVG using axillary artery and ipsilateral axillary vein. An anastomosis is made through a single transverse incision in the left anterior chest wall below the clavicle. Through the same incision, the axillary vein can be freed. Following venous anastomosis, the graft is tunneled subcutaneously down the distal end of the upper arm, then curving back to the shoulder in a loop-shape. The other end of the PTFE is anastomosed to the axillary artery.

Neck

Left axial vein Left axial artery

Ringed PTFE graft Incision

Anastomosis

easy at a later date. Following the completion of the procedure, the heparin is either neutralized or left on board without neutralization (Figure 48-5).

saphenous vein is freed. Using a subcutaneous tunnel created distally in a U-shape, an anastomosis can be made on the vein side then to the other side (Figure 48-8).

Axillary Artery-Ipsilateral Axillary Vein, U-Shaped (or C-Shaped)

Femoral Artery-Femoral Vein (U-Shaped)

This technique is utilized on the patient who has exhausted the site at the ipsilateral forearm and upper arm, by making a small transposition on the ipsilateral anterior chest wall, approximately 2 fingerbreadths below the clavicle and parallel to the clavicle. The pectoris major muscle is split along the direction of the muscle fiber. The pectoris minor muscle is retracted laterally. The axillary artery and vein are freed and isolated. Using either a U-shape or C-shape, a tunnel is made on the ipsilateral shoulder and chest wall, to create an arterial-venous graft (Figure 48-6). Axillary Artery-Contralateral Axillary Vein Access (U- or C-Shaped) This is an alternative choice when the ipsilateral vein or artery is not suitable for the same side, the artery and veins were isolated from two separate incisions in the chest wall (Figure 48-7). Femoral Artery-Greater Saphenous Vein Graft (U-Shaped) The superficial femoral artery is exposed through a vertical incision. Through the same incision, the proximal greater

Incisions made in a vertical fashion on the upper portion of the body, the superficial artery and vein are isolated, using a subcutaneous tunnel in U-shape. There is much other variety of choices, which can be made (Figure 48-9).

•

COMPLICATION AND MANAGEMENT

Acute Thrombosis The patency of hemodialysis access grafts is compromised primarily by areas of intimal fibromuscular hyperplasia in perivenous fibrosis that develops in response to turbulence and shear stress. The events affect the venous outflow, primarily at the graft-to-vein anastomosis.60−62 Numerous studies have demonstrated the effectiveness of balloon angioplasty, but this procedure is associated with a high rate of recurrent loss of patency. As a result of this, acute thrombosis occurs. The three main principles in the management of acutely thrombosed grafts are complete thrombus removal, total graft imaging, and identification and correction of all significant stenoses. We prefer open or percutaneous thrombectomy. In the case of open thrombectomy, in order to achieve complete thrombectomy, we make a transverse incision over the suitable site

HEMODIALYSIS ACCESS • 951

Right axial vein

Left axial vein Left axial artery

Right axial artery

Anastomosis

Ringed PTFE graft

Incision

• FIGURE 48-7.

AVG, using axillary artery and contralateral axillary vein. In a situation where the ipsilateral vein or artery is not sufficient because of the prior surgery or other problems, then the artery and vein can be used in either side. In this drawing, a transverse incision is made on the right anterior chest wall, 2 fingerbreadths below the clavicle and parallel to the clavicle. The axillary vein is then freed. With a similar technique, an incision is made on the left anterior chest wall, and the contralateral axillary artery is freed. An end-to-side anastomosis is first made to the vein, then a gentle U-shape subcutaneous tunnel is made over the sternum, and graft is then passed through the tunnel to the contralateral axillary artery for anastomosis.

of the graft and make a transverse incision at the graft using No. 3 and No. 4 Fogarty catheters. Following complete thrombectomy, an on-table angiogram should be performed to identify any underlying stenoses. If this is identified, this is corrected either by balloon angioplasty or stent, or open revision. If the venous anastomosis site is not salvageable with this technique, then we extend the graft further to the proximal suitable vein site. After angioplasty, the 6-month primary patency rate is only 31% to 64%.62−65 The outcomes are further adversely affected by preexisting graft thrombosis,66,67 and repeated treatments.62 Angioplasty is also jeopardized by elastic recoil and venous rupture. In view of these restrictions, investigators have primarily studied the Wallstent, as first reported more than 15 years ago.68 Various indications for stent use have been studied; including elastic recoil/dissection after angioplasty,69−74 rapid recurrences after PTA,75,76 venous rupture after PTA,77,78 and prophylaxis against recurrent stenosis.79−81 Nitinol stents are gaining greater acceptance in their application in other anatomic regions, especially the carotid and superficial femoral arteries. A retrospective study showed 6-month primary access patency rates of 51% in patients treated with the nitinol SMART (shape memory

alloy recoverable technology) stent (Cordis, Miami Lakes, FL).82 Further application of this SMART stent have been reported better patency rates than PTA alone.83 Aneurysms (Pseudoaneurysms) 1. At the graft 2. At the vein 3. At the artery (Figures 48-10 to 48-14). Pseudoaneurysms are associated with an increase risk of graft thrombosis, pain, cosmetic problems, infection, bleeding, and difficulty accessing the graft.84 Pseudoaneurysms formation in PTFE AV grafts is relatively uncommon, but well documented, occurring in 2% to 10% of grafts.85 Management of pseudoaneurysms of the graft is by segmental resection and bypassing the graft with a newer graft. Several series have been reported repairing pseudoaneurysms by using covered stents.84,86 The pseudoaneurysm at the arterial anastomosis can be repaired surgically. A pseudoaneurysm at the venous anastomosis or venous system can be repaired surgically, and in some instances with a covered stent.

952 • CHAPTER 48

Left common femoral artery Left femoral vein Left superficial femoral artery Left greater saphenous vein

Anastomosis Ringed PTFE graft

• FIGURE 48-8.

Loop AVG at the thigh using SFA and proximal greater saphenous vein or SFV. A small vertical incision is made on the medial aspect of the upper thigh. Either the proximal greater saphenous vein or SFV can be freed although the same incision as the SFA. A loop-type of tunnel is made distally back to the groin incision. An end-to-side anastomosis is made between the vein and graft. The graft is then placed through the tunnel back to the groin incision. The other end of the graft is anastomosed to the SFA.

Stenosis Stenosis at the venous anastomosis can be treated surgically or with PTA and stent procedure as described above in the management of acute thrombosis. Stenosis at the arterial anastomosis can be treated by angioplasty, if not feasible with angioplasty, it may require surgical repair. Infection Infection is common in prosthetic hemodialysis access but is also seen in autogenous venous access.87 Infection is the second leading cause for access loss and can cause significant morbidity or even mortality. Infectious complications of all types are the second leading cause of death in dialysis patients, accounting for 15% to 36%.88−91 Impaired humoral

and cellular immunity, nutritional deficiencies, and type of VA are thought to be among the major determinants.92 The severity of infection can be graded as follows93 : Grade 0: None Grade 1: Resolved with antibiotic treatment Grade 2: Loss of AV access because of ligation, removal of bypass Grade 3: Loss of limb The bacteriology of hemodialysis-related infections shows a predominance of gram-positive organisms, with Staphylococcus aureus being he most common isolate. Gram-negative organisms account for roughly another 25%, and a smaller percentage are polymicrobial.94,95 Two reports exist of infection with Clostridium perfringens.96,97

HEMODIALYSIS ACCESS • 953

Left basilic vein Left radial artery Incision for basilic vein harvest

Incision for left radial artery exposure and anastomosis

Ligated distal end of basilic vein

• FIGURE 48-9.

Basilic vein transposition. A longitudinal incision is made over the course of the basilic vein, which can be started and mapped preoperatively using a duplex scan. The basilic vein is then transposed subcutaneously to the side of the radial artery, which can be exposed through a small vertical incision on the radial aspect of the wrist. An end-to-side anastomosis is made between the distal end of the basilic vein and the side of the radial artery using 7.0 Prolene sutures. If the patient has a good pulsatile back flow with the proximal radial artery being cross-clamped, indicating intact palmar arcade, the radial artery distal to the anastomosis can be ligated to convert from anatomic end-to-side anastomosis to functional end-to-end anastomosis.

• FIGURE 48-11.

Angiogram of aneurysmal dilatation of the cephalic vein. An angiogram showing an aneurysmal dilatation of the cephalic vein (arrow), and dilatation of the brachial artery (two arrows), with no distal flow beyond the anastomosis (triangle), indicating steal.

Steal Steal after an AV access was first described in 1969 following Bescia-Cimino hemodialysis access.98 It has been documented in 73% of autogenous AV access and 91% PA had a form of steal. Despite the frequency of demonstrable alterations in flow, a symptomatic steal syndrome is much less common. After proper diagnostic evaluation on symptomatic steal, treatment options are as follows99 : 1. Banding or reducing the flow. 2. Ligation. 3. Extending the graft further to increase overall resistance. Banding with suture plication of a proximal portion of the access and monitoring the first option.100 Others obtained similar results using a band around the access and tightening it until the desired result is achieved.101 The banding procedure involves narrowing the lumen of the conduit more than 1 cm or more rather than simple suture stenosis. Making the band wider is the thought to allow more accurate adjustments in flow with possibly less turbulent flow, and minimize acute thrombosis.

• FIGURE 48-10.

Aneurysmal degradation of left cephalic vein system. A huge aneurysmal degradation of the left cephalic vein system after primary AVS.

Venous Hypertension Venous hypertension manifested by minimal arm swelling is quite common in hemodialysis patients with upper

954 • CHAPTER 48

A

B

• FIGURE

C

extremity access. The reporting standard document recommends the severity from Grade 0 to 3, as follows: Grade 0: None Grade 1: Mild (minimal symptoms, discoloration, minimal extremity swelling)—no treatment needed

• FIGURE 48-13.

Multiple large graft aneurysms. This figure shows a patient with multiple large graft aneurysms (one and two arrows), which was resected and replaced with a new graft (triangle).

48-12. (A) Large aneurysm. This is an operative picture showing a large aneurysm at the vein distal to the anastomosis (one arrow); and the proximal brachial artery proximal to the anastomosis (two arrows). (B) Large-sized aneurysm. This figure is a gross specimen, showing the large size of the aneurysm of Figure 12A. (C) Skin following aneurysm repair. This figure is following the aneurysm repair with the skin incision closed (arrow).

Grade 2: Moderate (intermittent discomfort, severe swelling)—intervention usually needed Grade 3: Severe (persistent discomfort with hyperpigmentation, persistent swelling, severe or massive, venous ulceration)—intervention mandatory

• FIGURE 48-14.

Repair of multiple large graft aneurysms. This figure shows the patient after completion of aneurysm repair and skin closure at the right upper arm (arrow).

HEMODIALYSIS ACCESS • 955

A variety of surgical techniques have been described to alleviate the symptoms from the central venous obstruction. The first venous reconstruction described for central venous obstruction came in 1976 by Doty and Baker, who described a reconstruction of the inferior vena cava using a spiraled saphenous vein graft.102 Others have described using a prosthetic graft from subclavian vein to the right atrium. One report even cited the use of the femoral vein as an outflow vessel.103 Fortunately most patients can be managed by procedures that do not require entering the thoracic cavity or lengthy extra-anatomic bypasses. For lesions of the subclavian medial to the internal jugular vein an autologous internal jugular to internal jugular vein crossover technique has been described.104 For the more common stenosis seen lateral to the internal jugular, an ipsilateral internal jugular turn-down technique can be used,105 or we find a technically easier procedure that preserves the internal jugular to be a subclavian-to-ipsilateral internal jugular bypass using 6 mm PTFE. This can be done under local anesthesia and, with a functioning AV access, has had a very satisfactory long-term patency.106 Neuropathy Neuropathy is a common finding among hemodialysis patients. The Reporting Standard document107 sets out four gradations of severity to describe neuropathy related to hemodialysis access as follows: Grade 0: No symptoms Grade 1: Mild, intermittent sensory changes (pain/ paresthesia/numbness with sensory deficit) Grade 2: Moderate, persistent sensory changes

Grade 3: Severe, sensory changes and progressive loss of motor function (movement/strength/muscle wasting) The major causes of neuropathy in the hemodialysis patient include uremic neuropathy, diabetic neuropathy, mononeuropathies from anatomic compression such as occurs in carpal tunnel syndrome, and the uncommon but important ischemic monomanic neuropathy (IMN) that can occur acutely after access creation. Hand pain and numbness are not uncommon with long-standing dialysis fistulae or shunts.108 It is seen in 50% to 70% of patients on long-term hemodialysis.109,110 Several studies have demonstrated that initiation of dialysis tends to improve but not necessarily eliminate the symptoms over time. The nerve conduction velocities tend to stabilize but not improve.109−113 Worsening of the symptoms over time is an indication of inadequate dialysis. Carpal tunnel syndrome occurs with greater frequency in dialysis patients than in the general population. IMN is a distinctive syndrome of nerve injury resulting from acute vascular compromise in an extremity.114 The pathogenesis of IMN is likely related to preexisting marginal distal tissue perfusion in some diabetic patients. The additional flow requirements imposed by a proximal shunt cannot be compensated, leading to ischemia of the nerves. The ischemia is transient or insufficient to cause muscle or skin necrosis but results in severe ischemic nerve injury. Because IMN represents a form of steal, treatment of the syndrome must include either ligation of the access or correction of the steal physiology. Even with early access closure, paralysis and pain may be permanent or only partially reversible.115−118

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92. Jaar BG, Hermann JA, Furth SL, et al. Septicemia in diabetic hemodialysis patients: comparison on incidence, risk factors, and mortality with non-diabetic hemodialysis patients. Am J Kidney Dis. 2000;35:282-292.

109. Pirzada NA, Morgenlander JC. Peripheral neuropathy in patients with chronic renal failure: a treatable source of discomfort and disability. Postgrad Med. 1997;102:249261.

93. Adams ED, Sidaway AN. Non thrombotic complications of arteriovenous access for hemodialysis. In: Rutherford RB, ed. Vascular Surgery. Vol 2. 6th ed. Philadelphia, PA: ElsevierSaunders; 2005:1692-1606.

110. Burn DJ, Bates D. Neurology and the kidney. J Neurol Neurosurg Psychiatry. 1998;65:810-821.

94. Marr KA, Sexton DJ, Conlon PJ, et al. Catheter-related bacteremia and outcome of attempted catheter salvage in patients undergoing hemodialysis. Ann Intern Med. 1997;127: 275-280. 95. Saad TF. Bacteremia associated with tunneled, cuff hemodialysis catheters. Am J Kidney Dis. 1999;34:1114-1124. 96. Claeys LGY, Matamoros R. Anaerobic cellulitis as the result of Clostridium perfringens: a rare cause of vascular access graft infection. J Vasc Surg. 2002;35:1287-1288. 97. Oliveras A, Orfila A, Inigo V. Clostridium perfringens: an unusual pathogen infecting arteriovenous shunts for dialysis. Nephron. 1998;80:479. 98. Storey BG, George CR, Stewart JH, et al. Embolic and ischemic complications after anastomosis of radial artery to cephalic vein. Surgery. 1969;66:325-327. 99. West JC, Evans RD, Kelley SE, et al. Arterial insufficiency in hemodialysis access procedures: reconstruction by an interposition PTFE conduit. Am J Surg. 1987;153:300-301.

111. Ogura T, Makinodan A, Kubo T, et al. Electrophysiological course of uremic neuropathy in hemodialysis patients. Postgrad Med J . 2001;77:451-454. 112. Nielson VK. The peripheral nerve function in chronic renal failure: VIII. Longitudinal course during terminal renal failure and regular hemodialysis. Acta Med Scand. 1974;195: 155-162. 113. Bolton CF, Lindsay RM, Linton AL. The course of uremic neuropathy during chronic hemodialysis. Can J Neurol Sci. 1975;2:332-333. 114. Kaku DA, Malamut RI, Frey DJ, et al. Conduction block as an early sign of reversible injury in ischemic monomelic neuropathy. Neurology. 1993;43:1126-1130. 115. Hye RJ, Wolf YG. Ischemic monomelic neuropathy: an unrecognized complication of hemodialysis access. Ann Vasc Surg. 1994;8:578-582. 116. Wytrzes L, Markley HG, Fisher M, et al. Brachial neuropathy after brachial artery-antecubital vein shunts for chronic hemodialysis. Neurology. 1987;37:1398-1400.

100. Rivers SP, Scher LA, Veith FJ. Correction of steal syndrome secondary to hemodialysis access fistulas: a simplified quantitative technique. Surgery. 1992;112:593-597.

117. Miles AM. Vascular steal syndrome and ischemic monomelic neuropathy: two variants of upper limb ischemia after hemodialysis vascular access surgery. Nephrol Dial Transplant. 1999;14:297-300.

101. Mattson WJ. Recognition and treatment of vascular steal secondary to hemodialysis prostheses. Am J Surg. 1987;154: 198-201.

118. Redfern AB, Zimmerman NB. Neurologic and ischemic complications of upper extremity vascular access for dialysis. J Hand Surg. 1995;20A:199-204.

chapter

49

Vascular Trauma Brian J. Daley, MD / J. Fernando Aycinena, MD / Ali F. Mallat, MD / Dana A. Taylor, MD

The world of surgery is constantly changing as new and novel technologies are applied to diagnosis and treatment modalities. Over just the last few years, vascular surgery has seen a major paradigm shift following the endovascular explosion and the minimally invasive trends established in general surgery and gynecology. The reductions in surgical stress, shortened lengths of stay and of convalescence, and equivalent or improved outcomes have made endovascular operations and minimally invasive surgery a standard of care. Minimally invasive vascular surgery, however, poses even a new set of anatomic and physiologic hurdles beyond even the technical challenges of endovascular surgery. Dealing with not only the injury or disease itself, minimally invasive vascular techniques must be technically sound as to avoid loss of vascular control, sufficiently brief so as to avoid interruption of tissue oxygenation and immediately safe from the devastating vascular complications possible such as embolism or thrombosis. It is likely that endovascular techniques will replace open surgical techniques (if they have not already replaced) because of the benefits of the minimally invasive approach. Over the next few years, the practice of vascular trauma will likely bear this out and not the scientific outcome parameters. The problem is that the therapeutic interventions are changing at a rapid pace, the surgeons are becoming more facile with the techniques, and the endovascular equipment arena is constantly changing. The final chapter is unlikely to be written for some time, and in trauma, as always, will never be validated by strict evidence-based medicine. Also looming on the horizon for vascular disease is the possibility of avoiding surgery altogether with gene manipulation. Unfortunately, this modality is unlikely to be temporally adequate to deal with the topic of this chapter, and there will always be a need for immediate vascular intervention in trauma, yet the reconstructions may be manipulated postrepair to assure patency.

•

HISTORY

Experience with vascular injuries predates any recorded history as our species developed from not only the gatherers but also the hunters. Understanding vascular anatomy for a quick and successful kill is still passed on orally in nonWestern and nonliterate cultures. Understanding vascular anatomy is essentially for appropriate dressing of the carcass and understanding vascular anatomy for the harvesting of blood as a renewable food resource in some cultures is necessary. Lastly, the reality of war has driven the knowledge of vascular anatomy not only for killing one’s opponent but also for the salvage of the injured combatant. The first medical discussions of vascular injury are found in the Edwin Smith Papyrus from approximately 3000 BC. Galen may be the best resource for his descriptions of arterial and venous injuries in the wounds seen by the gladiators. He advises ligature for arterial injuries and styptic for venous wounds. Galen and his remaining theories remained in practice through the Dark Ages, when surgical care was left to the barbers and other tradesman. Through the Napoleonic Age and into the 19th century, vascular surgery was comprised solely of amputation as no other therapy existed. Suffice it to say, any large vessel vascular injury was fatal, and only peripheral extremity injuries would be the vascular trauma that survived to the surgeon’s table. One needs to bear in mind this was the same therapy for open fractures or large soft tissue injury as well. Arteriovenous fistulas (AVFs), which were the sequelae of survivable injuries, were frequent and surgical treatment constituted the literature of this age. Despite the case reports of Carrel and Hunter, the application of vascular reconstruction for injuries would wait until late in the 20th century. During the Civil War, The Practice of Surgery by Samuel Cooper1 (the text of choice for the South) and Samuel D. Gross’s A Manual of Military Surgery2 (North) both elaborate immediate amputation

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of any extremity injury with ligation of the artery and often the vein to avoid hemorrhage, gangrene and/or sepsis, and death. The exhaustive reports during World War I by Makins3 and World War II by DeBakey and Simeone4 are unfortunate testimonials of logistics and the lack of standard techniques resulting in virtually the same outcomes. Control of life-threatening bleeding and avoiding gangrene and sepsis took preference over limb salvage, exactly the same as the last 2000 years. Despite the capability of arterial suturing for direct injury, the key problem in trauma during this time period remained finding a suitable vascular replacement. During the Korean War and through today’s latest conflicts, vascular grafts from autogenous vein have been used with documented limb salvage.5−7 Unfortunately, the scourge of interpersonal violence in American cities has had probably more to do with shaping current techniques and therapies for vascular trauma than mankind’s long military experience.8 The are no subtle differences in the comparisons of military versus civilian vascular trauma—types of weapons, projectile velocity, transport times, and availability of diagnostic and therapeutic resources are but a few. While the civilian trauma systems may have had their basis in the military, modern vascular treatments are primarily based on that urban experience. Whereas, the majority of survivable war related injuries involve extremity injuries or wounds with devastating soft-tissue trauma as well, the modern “knife and gun club” presents with far more isolated injuries, with injuries that would not be survivable with prolonged transport or delayed resuscitation and in settings where resources are virtually unlimited. Lastly, a new classification of vascular injuries must be named. With the burgeoning growth of interventional and endovascular techniques, iatrogenic injuries are increasing in frequency. This is not new,9,10 but now only we see more with the rapidly expanding volume in the diagnostic and therapeutic setting. Also, we see the subsequent need for secondary interventions as medical care improves and allows patients to live longer and with severe disease.11 While many of these injuries are related to the treatment for vascular disease, others are for diagnosis, monitoring, or nonvascular disease therapies and performed by practioners without vascular surgical skills.

•

CURRENT ISSUES

Three key issues in the management of the trauma patient suffering vascular injury have come to light recently. We seem to be capable of learning from our past and the laboratory and carrying this to the bedside with improved outcomes. The first is the concept of directed resuscitation— fashioned and now carried down to basic physiologic principles. The second is the concept of the damage control procedure. Short abbreviated interventions reduce the second hit of surgical intervention, and allow restoration of normal physiology between stresses. Lastly, there is a rebirth of delayed repair—temporizing often with “damage

control” until definitive intervention is possible—a concept that most often seen with blunt aortic injury (BAI), but applicable to virtually any injury or anatomic region. The standard resuscitation model was challenged by many researchers seeking to reduce the purely iatrogenic problems of Adult Respiratory Distress Syndrome seen after aggressive resuscitation. Shock is inadequate end-organ perfusion. In today’s molecular nomenclature, however, this amounts to cellular or even subcellular hypoxia. Resuscitation is the restoration of organ perfusion and the restoration of molecular level oxygenation. Aggressive fluid administration was borne out of the wartime experiences, where the renal failure from hypovolemia in World War II and Korea was traded for ARDS or the Da Nang Lung of Vietnam. The choice of crystalloid, colloids, and/or hypertonic solutions remains the constant and current battlefield for the surgical researchers seeking the Holy Grail of resuscitation. Bickell et al.12 challenged resuscitation dogma on a different level and demonstrated that preoperative resuscitation of the trauma patient was not to be guided by rigid protocols, but rather by common sense and simple standard markers. Their study marked a “delay” in resuscitation to avoid overzealous fluid until the bleeding could be surgically stopped with improved outcome. Until the arterial injury/venous injury/bleeding is stopped, it makes little sense to pour fluid and resources to the patient until operation can be performed simply to reach an arbitrary physiologic parameter. Such misdirected resuscitation leads to further bleeding and a loss of endogenous clotting factors. As documented now, most accepted clinical parameters such as blood pressure and pulse are not good indicators of occult hypoperfusion. Many authors have sought the single marker of adequate resuscitation. In the Eastern Association for the Surgery of Trauma’s (EAST) Practice Guideline on the Endpoints of Resuscitation,13 it is scientifically supported to monitor lactate and/or base deficit and to gauge adequate resuscitation by the correction of this molecular/ cellular level acidosis. Once the vascular injury is fixed, salvage depends more on correcting this physiology rather than technical aplomb.14 Stemming from both these concepts has been the rebirth of what has been termed “damage control.”15 In order to again reduce overzealous and futile resuscitative efforts, abbreviated procedures are performed in fitting with the patient’s physiology. Rather than carrying on in the face of the fatal triad of coagulopathy, hypothermia, and acidosis, the arterial bleeding is stopped, often by ligation, the venous bleeding is controlled by packing and enteric soilage is limited. The operative wound is not formally closed, but temporized for reduction of heat and fluid losses, to allow tissue edema without creating a compartment syndrome, and as a window to the area of concern. Many employ some technique, which is homemade or commercially available, that creates a water-tight, compressive temporary closure with great success. The patient is then returned for resuscitation to restore normal physiology—correct hypothermia,16

VASCULAR TRAUMA • 961

restore clotting capacity and reverse the acidosis. This process can be applied anywhere—the chest, the abdomen, and even the extremities.17 Once the patient’s physiology has been corrected, the patient is returned for definitive procedures—arterial reconstruction, restoration of bowel continuity, osteosynthesis, or whatever. It should be noted that there is a substantial set of these patients in whom the physiologic derangements will not be corrected and the patient will expire. From our experience, this number is approximately 50%. Traumatic injury is unlike elective surgery in that the patient has already suffered a major systemic stress, and is now faced with secondary stress from surgery. With the realization that there are such risks to emergent operative repair—i.e., the cure is worse than the disease, delayed repair has not only been applied in extremis, but for the stable patient. The best example of this has been BAI.18−21 The diagnosis of BAI is derived mostly from the high index of suspicion of the causative mechanism as well as incidental findings on screening radiographs. The diagnosis is confirmed by aortography, today either direct intra-aortic contrast injection, or from rapid acquisition computed tomography (CT),22,23 which allows evaluation of other key thoracic anatomy as well.24−26 BAI is the result of a rapid acceleration or deceleration, and therefore not exclusive to any particular mechanism or any particular direction of force. The aorta is disrupted usually just distal to the left subclavian artery.27 The incidence of BAI is greater than seen by the clinician as most victims exsanguinate and die at the scene. The fortunate few in whom the adventitia remains intact enter the emergency department with near normal blood pressures. Findings that are worrisome on the initial chest radiograph during the initial evaluation are widened mediastinum, the loss of the aortic knob, left apical cap, nasogastric tube deviation, or even large left hemothorax.28 These nondiagnostic findings should be followed by diagnostic testing, from obtaining an erect chest radiograph to aortography. With the new generation of CT scanners available, contrasted CT of the chest is a rapid, sensitive and specific test to ascertain if BAI or some other injury is present.29 For many centers, this has replaced aortogram as the diagnostic test of choice and carries with it a sensitivity of 97% to 100%, negative predictive value of 100%, and specificity of 83% to 99%.23,25 The second interesting facet of BAI is the timing of repair. The natural history of this injury is rapid exsanguinations once the adventia is disrupted. Formerly, this mandated immediate repair, before this nonsurvivable event occurred. Several anecdotal reports of survivors without repair, of increased mortality in the elderly with trauma and thoracotomy, as well as the blossoming concept of maximizing resuscitation altered the immediate repair plan of care. More recently, with the multiply injured patient, in whom a thoracotomy represents a taxing metabolic and physiologic stress, BAI therapy has been delayed. Resuscitation is guided by correcting the immediate life-threatening in-

juries, restoring perfusion and avoiding hypertension.23,30 The repair of the stable BAI is turned into an elective procedure and can even be accomplished by endovascular technique to further reduce the surgical insult.31−35 For open procedures, the debate continues over the use of bypass36,37 ; it remains as an operator-dependent surgical decision based on associated injuries.38,39 This concept of reducing or delaying additional surgical stresses after acute injury can be applied not only to lifethreatening abdominal or thoracic injury, but to other devastating injuries, such as extremity vascular and/or skeletal injuries, or massive soft tissue injuries. The goal remains to restore normal physiology, and use operation as a means to and not an end of resuscitation.

•

DIAGNOSIS

The diagnosis of vascular trauma is generally quite simple— it is based on the clinical manifestations on the physical examination: After the initial assessment, a thorough palpation of all major pulses (radial/ulnar, brachial, dorsalis pedis/posterior tibial, popliteal, femoral, and carotid) is performed as part of the secondary survey. Palpable pulses are sufficient to determine if further testing is needed.39 A thorough history taking is of paramount importance especially in the aging population as vascular disease may have already altered pulses or present reconstructed anatomy. The expectation should be palpable pulses in all sites. Any alteration in pulses is concern for an injury and should be investigated further, with operation and/or confirmatory testing. The decision making for operative exploration depends mostly on the physiologic state of the patient. If they are hypotensive, and the pathway to resuscitation involves stopping the bleeding from the vascular injury, further diagnostic and therapeutic intervention should occur in the operating room (OR). If the patient is physiologically stable, other modes of diagnosis may be employed. Louis Pasteur is quoted “in the field of observation, chance favors the prepared mind.” The diagnosis of vascular injury also depends on the clinician’s index of suspicion. The clinical manifestations are usually dependent on the mechanism, the location, the time since the injury and the overall severity of the injury, yet there are injuries that have no such manifestations, or the manifestations of such injuries are delayed but devastating. A vascular injury may exist with palpable pulses, so the physician must be acutely aware of such circumstances to reliably diagnose occult injury. Not surprisingly, the outcome of these injuries is often excellent.40 Blunt trauma patients are more prone to intimal injury and dissection then full thickness transection injury from penetrating trauma. This type of injury usually involves large vessels like thoracic aorta in a deceleration injury or carotid injury from a direct blow where the elasticity of each layer of the vessel reacts differently.41 Extremity vessels are more commonly involved in penetrating trauma but may also be injured because of the blunt mechanisms such as fractures and/or dislocations. A knee dislocation is

962 • CHAPTER 49

especially worrisome for popliteal injury, which may present as the spectrum of vascular injury, from total occlusion to AVFs.32,42 Penetrating trauma can present with other clinical manifestations beside pulse alterations, such as external or internal bleeding, pulsatile hematoma, or distal ischemia. The injury may present only as end-organ malperfusion such as altered neurologic states from carotid injury or limb ischemia from superficial femoral artery injuries. On the other hand, other injuries may not cause any clinical signs because of the collaterals such as with the profunda femoris artery. The time of occurrence of the injury should be documented since it directly impacts both the diagnosis and management. The duration of time since injury can dictate the amount of blood loss as well as ischemia time to prevent permanent injury.44 The correctable defect in the trauma patient is hypoperfusion and stems either from hypovolemia or impairment of cardiac function. All trauma patients should be treated as having a vascular injury until the physical examination or further testing rules this out. For vascular injuries, further tailoring of the examination can be done to the location of injury and specific clinical signs. We describe the main points of diagnosis and management based on the location of injury for convenience. Both arterial and/or venous injuries are detailed.

•

DIAGNOSTIC ADJUNCTS

Other than the physical examinations, diagnostic adjuncts such as ultrasound and angiography are used to help diagnose vascular injury. Again, the unstable patient with suspected vascular injury needs to be in the operating room. These modalities should be employed only in the stable patient within time constraints for ischemia or potential ischemia. The role of both modalities is changing rapidly as technologic advances are made and now that these same approaches can now offer therapeutic roles as well.

•

ULTRASOUND

The use of sound energy to detect and describe blood flow and blood vessels is a fundamental part of vascular diagnosis outside of trauma.45 It only makes sense that this modality, which is easy, mobile, painless, interpretable by the surgeon and repeatable, would be applied to the trauma victim. The two forms of ultrasound, Doppler flow and B-mode imaging now have been combined within a graphic format of color imaging which makes interpretation intuitive. The details of this modality are covered in depth elsewhere, but the use of ultrasound is playing a larger role in vascular diagnosis. It, however, is limited and has not yet reached “gold standard” applicability for any disease process.46

•

ANGIOGRAPHY

Angiography has advanced technologically to be an excellent diagnostic tool to a means of therapy with reduced complications.47 Again the in-depth review of the

principle and techniques is described elsewhere. Delineation of the vascular system was formerly accomplished by filling the vessel in question with radio-opaque contrast material and obtaining at the least biplanar radiographs to assess continuity, intimal integrity and anatomy. Today, with advances in technology, contrast angiography can be direct, i.e., with contrast media directly in the vessel, or indirect, i.e., using intrinsic properties of the imaging modality and blood vessels to differentiate the above goals.48 Today, digital subtraction angiography offers clear images with lower contrast doses to provide this information with minimal risks of radiation and contrast.49 Rapid spiral CT with increasing numbers of detectors now offers a similar digital image that is amenable to computer manipulations to give high quality imaging in three dimensions. Today, these multidetector images are encroaching on the gold standards of contrast angiography. Magnetic resonance angiograms may also be performed with a noniodinated contrast, gadolinium, and without ionizing radiation. Currently, however, these MRAs are not as accurate for lesions, although if the past development of CT is a comparator, MRA imaging quality will also be improved to produce reliable diagnostic images.50

•

TREATMENT OVERVIEW AND OUTCOME

Vascular injuries are managed by four primary techniques: 1. Observation: Best for nonocclusive injuries found on diagnostic evaluation. 2. Direct repair (arteriorrhaphy/venorrhaphy): Amenable in only roughly 10% of cases. 3. Patch or interposition grafts: The majority of modern repairs. 4. Ligation. This applies to open, endovascular, and minimally invasive techniques as well, in which only the technical approach is different. The choice of management technique is fluid and depends on the clinical status of the patient, the extremity, and the resources available. Time is perhaps the greatest factor and must be accounted for in every therapeutic plan. Just as our history reminds us, the goal is survival—life over limb. Restoring blood volume, reducing further blood loss and reestablishing flow are the priorities. Today’s outcomes from vascular trauma are marvelous. An overall survival of 93% and limb salvage rate of 98% are quoted.51 These figures are the product of time, frequency, and location of injury. While even a common but relatively minor injury can be fatal, there are virtually fatal injuries that are fortunately infrequent. The surgeon facing any vascular injury, however, must be ready for even the most devastating of injuries, prolonged presentation, and abnormal physiology and rapidly fashion a plan of care that is based upon these goals.

VASCULAR TRAUMA • 963

•

HEAD TRAUMA

Blunt Trauma to the scalp comes from unnamed vessels but with significant blood flow that failure to stop bleeding can cause significant hemorrhage, shock, hypothermia, and disseminated intravascular coagulation (DIC) or even death. Temporal artery injury is usually manifested by active bleeding or expanding hematoma on the side of the head. Nonexpanding hematomas and smaller size hematomas although may occur with temporal artery injury are more frequently associated with venous injury. Bleeding from the scalp may be exacerbated when patient is coagulopathic as a result of the significant blood loss or hypothermia. Control of bleeding is the main treatment and is generally effected by suturing the wound closed and direct pressure. The single named vessel which may bleed is the superficial temporal artery and is treated uniformly with ligation. Evacuation of the hematoma prior to intervention reduces infection and deformity as well as exposes bleeding vessels needing direct ligation or clipping. Since the scalp is heavily vascularized, one should not be concerned about ischemic changes form ligation of these vessels, but one must be sure to debride any nonviable tissue prior to definitive closure. Vascular injuries to the face are usually ligated with the rich collateral flow available from the branches of the external carotid and jugular system. Basilar skull fracture can be associated with carotid injury. Basilar skull fracture is a clinical diagnosis and suspected when a patient presents with raccoon eyes, hemotympanum and/or Battle’s sign (mastoid contusion). Carotid injury must also be expected after significant force that results in mandibular or Le Fort type fractures.52 Blunt carotid injury (BCI) can be from a partial occlusion because of a hematoma in the arterial wall, an intimal flap or a local thrombus as well as wall disruption. Because of the specific course of the internal carotid artery inside a bony compartment, a fixed point is created and again a difference in elasticity or stretch of the arterial walls is possible. Occlusion from external compression or thrombosis after intimal injury is the rule and presents as significant neurologic deficits unexplained by other anatomic injuries.54,55 Therefore, internal carotid injury at the skull base level is suspected when focal neurologic impairment is identified. After blunt trauma significant carotid disruption is rare and therefore local hemorrhage or expanding hematomas are very rare or rapidly fatal before definitive diagnosis or repair are made. Controversy exists in the screening regimen for blunt carotid injury. Although quite rare by some accounts (0.5%–0.004% of trauma victims),54 BCI can have devastatingly poor outcomes.55 Quite logically, these poor outcomes are reduced by aggressive screening, but the utility of such widespread screening for large populations with such a low incidence of injury remains problematic. Furthermore, generally the treatment for BCI is anticoagulation, which may be difficult or precluded by neurologic bleeding or

other associated injuries present in the multisystem trauma victim, and currently experimental methods may be employed based on atherosclerotic therapies.56 Penetrating scalp injuries are treated similarly. Large lacerations require expeditious control and injuries from gunshot wounds are generally sufficiently small so as not to require any therapy other than debridement and local wound care. Intracranial vascular injuries are the purview of the neurosurgeon, although embolization may be a useful adjunct for lifesaving control.

•

NECK INJURIES

Blunt Blunt vascular injury in the neck although rare can be fatal or even worse, result in a devastating neurologic insult and result from even minimal trauma.57−59 Unfortunately, physical examination may miss many cases because of lack of physical signs or the clinical result is neurologically irreversible. Inspection may show ecchymosis, abrasions, or a seat belt sign at the base of the neck. A large hematoma may cause tracheal compression and deviation, as well as facial swelling caused by impaired venous return. Even a small size hematoma when deep and paratracheal can cause laryngospasm and become a major airway threat. It is always prudent to intubate a patient with a neck hematoma before tracheal compression occurs. Auscultation may reveal a carotid murmur when there is a partial occlusion of the carotid artery because of an intimal flap or dissection, but as in atherosclerotic disease, a near complete occlusion of the carotid artery may not manifest a murmur on auscultation. A thorough neurologic examination is mandatory for any trauma patient. This is important for isolated neck injuries as well. Finding altered function secondary to an embolic or an occlusive event, i.e., fitting a stroke like pattern initiates the evaluation and treatment for BCI. Vertebral artery injury is associated with cervical vertebral fractures and would be very hard to diagnose on physical examination if one omits the neurologic examination. When arterial injury is suspected, even based on mechanisms alone, physical examination should always be supplemented by Doppler ultrasound or CT angiogram of the neck. Presently, arteriogram is the gold standard to rule out vascular injury,60,61 but CT technology is likely to eclipse this in the near future.62,63 One must also be wary of carotid injury from iatrogenic mechanisms as well. Diagnostic angiography, endovascular therapies for virtually any problem at/or above the arch vessels, or cardiac catheterization with or without coronary manipulation places the carotid system at risk. Similarly, the diagnosis my not be evident until neurologic changes have occurred.64−66 BCI can occur more proximally than the base of the skull. Using CT angiography or 4 vessel angiography are the gold standards for diagnosis. Injuries to the carotid around the bifurcation and in the common carotid are also generally managed with anticoagulation unless an easily repairable

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intimal flap is seen.67,68 Vertebral injuries are also managed with anticoagulation or embolization.69 It is important to note that vascular injuries to the neck in blunt trauma have a very low incidence and the frequency of such diagnosis has been on the rise probably because of the aggressive screening in the recent years.55,69−71 While a constellation of associated injuries are noted in BCI (Seatbelt mark, cervical spine fractures, mandible fracture) routine screening for patients with these injuries is hotly debated.72−75 New endovascular alternatives are described frequently.76,77 Despite this, the outcome is often devastating.78,79 Vertebral artery injuries are very amenable to angiographic or endovascular treatment with good outcomes.80 Injury to the jugular vein can cause an expanding hematoma and may not be controlled by simple compression because of the amount of swelling and bleeding. The development of a hematoma in the neck is worrisome more for potential airway compromise than exsanguination, and early airway control is advisable. Although a constant; jugular vein injury is not differentiated from arterial neck injury by color of the blood, lack of arterial pulsations by palpating a pulsatile mass in the later. If the patient is stable and the hematoma is not expanding or impinging on the airway, nonoperative therapy is possible, otherwise operative ligation is needed. AVFs are a consequence of injury of both vessels or of failed surgical repair. AVFs were probably more frequent before aggressive surgical repair, and the historical reports spend a great deal of discussion over the only available therapy then of ligation. Classically, the diagnosis is made by a thrill or bruit in the area of injury. High flow vessels may lead to venous congestion, either manifest as edema or even near congestive heart failure. Physical examination reveals a pulsatile mass and confirms the thrill. Today, AVFs either recognized at the time of injury and repaired or unrecognized until presenting late are managed with both arterial and venous reconstruction. Current management options are dependent on location, as endovascular procedures avoid some very morbid surgical approaches. Beside open repair or ligation, endovascular stenting (both arterial and venous), or embolization are feasible and readily performed.52,81 Penetrating Penetrating injury to the neck may present a major threat to life because of the hemorrhage or airway compromise. As with any trauma patient the airway should be secured, breathing maintained and shock treated. Airway control is paramount—it is easier to extubate the uninjured patient than to delay and be faced with a very difficult airway and a potentially impossible surgical airway. Bleeding control is obtained by simple pressure until further definitive treatment can be accomplished in the operating room. The dynamics of injury is an integral part of the history— a high-velocity missile will cause different injuries than a penknife. On inspection, one should assess the location, the depth, and extent of the injury. Long lacerations made with a knife in a suicide attempt tend to be superficial to the

platysma and would cause only superficial bleeding which is easy to control, whereas injuries penetrating the platysma require operative exploration and proximal and distal vascular control. High-velocity projectiles may not only create vascular injuries but result in airway, esophageal, nervous, or bony injuries as well and can be managed in damage control fashion, including the use of shunts.82 Operative exploration for trauma is conducted in a similar technical fashion to elective carotid surgery to avoid those iatrogenic injuries intrinsic to the surgical approach such as cranial nerve injuries. The standard approach to the carotid sheath is the common incision along the anterior border of the sternocleidomastoid muscle. The muscle is retracted laterally and the carotid sheath is visible beneath. Opening the sheath exposed the internal jugular vein medially and the vagus nerve posteriorly as well. There are clinical manifestations that are an immediate indication for surgical exploration. Such signs and symptoms are active arterial bleeding, expanding hematomas, thrill, or bruit and diminished or absent distal carotid sounds or pulse. Neurologic impairment with a focal deficit is also an indication for exploration. Other signs that constitute an indication for exploration are related to airway injury such as subcutaneous air, stridor, hoarseness, dysphagia, and hemoptysis. Palpation is useful to assess the extent and size of the hematoma as well as to identify the location of the trachea if swelling occurs. If the wound is not actively bleeding, it is prudent not to probe or expose the wound until definitive control can be established in the operating room. The location of the injury determined during the physical examination directs the subsequent management. Anatomically the neck can be initially divided into two simple triangles: anterior and posterior triangles divided by the sternocleidomastoid muscle. All major vessels are contained in the anterior triangle. The platysma constitutes the superficial border of the anterior triangle and if not violated a major vessel injury is far less likely. The neck is also divided into three zones from inferior to superior. Zone I, or the thoracic inlet, extends from the sternal notch to the cricoid cartilage. The proximal location of this zone signifies that the great vessels in the chest or at the base of the neck are injured and prudent planning for the operative approach to assure proximal control is very important. When patient is stable, an arteriogram or high resolution CT angiogram is indicated to identify the extent of the injury.83 When unstable, patient should be explored to control bleeding and a combined median sternotomy and anterior neck approach is best. Most surgeons would begin with the neck incision and extend inferiorly as needed for control. If the arch vessels are involved a thoracic extension into the second rib interspace (i.e., the trap-door incision) is performed. Zone II, or the midzone, extends from the cricoid cartilage to the angle of the mandible. An injury at this zone is fairly easy to identify by physical examination and the management is dependent on the symptoms. If any of the above

VASCULAR TRAUMA • 965

signs, the so-called hard signs, is present then exploration is indicated. When no hard signs are present and patient is stable an arteriogram or CT angiogram may be done. This may obviate operation84 and the ensuing complications. Additional testing is performed for other structures in the neck such as bronchoscopy and esophagoscopy, to rule out as associated injury. Zone III is between the angle of the mandible and the skull base. Symptoms and physical examination findings can be very subtle at this location.68 An onsite Doppler ultrasound may not rule out injury at this location because of bony structures. Carotid arteriogram or a high resolution CT angiogram employed to determine injury. Because distal control is often impossible, ligation, embolization, or packing of the foramen lacerum with sternocleidomastoid muscle may be the only recourse. The unfortunate outcome is often survival but with a dense neurologic insult for the younger patient without collateralization. Exposure at this location may require a mandibular disarticulation, although endovascular techniques offer both diagnostic accuracy and interventional therapy. Injury to the neck may not be limited to one zone and may involve two or three zones at the same time especially in gunshot wounds or high-velocity missile injury. When arterial injury is suspected by proximity or mechanism, exploration or arteriogram is indicated to rule out or define the extent of the injury. Recently, CT angiography of the neck defines vascular as well as other system injuries quickly and assists in therapeutic planning. With the newly found interventional skills, adopted from embolization as well as endovascular treatment for carotid occlusive disease, the use of the angiography/endovascular suite is particularly appealing.85 For injuries to the vertebral system an area in which the surgical options for approach are virtually impossible and even the open therapy involves ligation, the endovascular route is ideal.86

•

CHEST VASCULAR INJURIES

Blunt History taking again should focus on the mechanism of injury. Blunt injury should be classified between a deceleration injury and a direct impact to heighten the surgeon’s index of suspicion for BAI. Unfortunately, physical examination can be very limited in these types of injuries and not be helpful to identify the location or the extent of the injured vessel. After securing the airway and ventilation, a vascular injury is suspected when a patient is hypotensive or shows signs of shock. Major vascular injuries must always be considered, but usually solid organ injuries are the cause and identified at the time of abdominal exploration. The evaluation for the hypotensive patient undergoing active resuscitation includes a chest radiograph to show if hemothorax, BAI, or pneumothorax is present and Focused Assessment with Sonography for Trauma (FAST) examination of the abdomen to evaluate for free fluid. Each pertinent issue is addressed immediately as it is identified

to restore normal physiologic parameters. When stable, patients are evaluated with CT scanning. On inspection, abrasion, ecchymoses, and “seat belt signs” should be noted. Palpation may reveal crepitus, chest wall instability, or subcutaneous emphysema. Distended jugular veins may indicate a tension hemothorax or pericardial tamponade. Decreased or muffled breath sounds on auscultation may lead to a diagnosis of hemothorax. Unequal blood pressures or pulses in the extremities may indicate an innominate artery injury. Palpable fracture of the sternum is another signs that should raise the suspicion of an innominate artery injury. Some commonly noted signs in patients with BAI are pseudocoarctation and intrascapular murmur.87−89 Unfortunately, physical examination can be very limited as to identify the location or the extent of the injured vessel but represent sufficient energy transfer to create such an injury. A negative finding on physical examination should not rule out aortic injury if suspected by the history.90,91 Similarly, there may be no external signs of injury and yet an injury may exist. A thoracic vascular injury may not be detected until a chest tube is placed; a CT scan is performed or worse until a hemorrhagic shock has occurred. The presence or absence of restraints does not appear to affect the incidence of BAI.92 In the chest, the vessels more prone to injury after a blunt trauma include the thoracic aorta most commonly, followed by innominate artery, pulmonary veins and vena cava. Aortic injuries constitute up to 15% of immediate deaths after a motor vehicle crash with the proximal descending aorta disruption in up to 65% of the cases.93,94 An initial rush of blood of more than 1500 mL on insertion of chest tube or ongoing hemorrhage of more than 200 mL/h is an indication for exploratory thoracotomy since major vessel injury is clinically suspected and bleeding control is lifesaving. Serial monitoring of chest tube output is also necessary, as continued outputs in excess of 200 mL/h also warrant exploration. As with any trauma patient there must be a concerted effort to maintain endorgan perfusion, maintain euthermia and avoid coagulopathy. When stable, patients can be diagnosed with major thoraco–abdominal vascular injuries by routine contrasted trauma CT scan.95−98 Other than BAI, virtually any thoracic vessel can be injured by a blunt mechanism.99−101 Similar to BAI, any free rupture likely leads to rapid death, and only the victims who have contained hematoma or intact adventia survive to hospital. Because of this particular fact, they are amenable again to evaluation with rapid sequence helical acquisition CT with contrast and endovascular repair; venous injuries are diagnosed and treated similarly.99,100,102,103 Because these injuries are infrequent, there are no prospective management series, and endovascular or open techniques become interchangeable regardless of mechanism. Thoracic vena cava injury is very rare but carries a mortality rate greater than 60%. Such injury may be suspected after hemopericardium and cardiac tamponade. Pulmonary vein injury when associated with bronchus disruption

966 • CHAPTER 49

may lead to a systemic air embolism when intrabronchial pressure increases to above 60 Torr.104 As above this usually manifest as mental status changes, seizures, and cardiac arrest. On the other hand, penetrating injury can have different outcomes depending on the mechanism and location of the injury. Again the type of weapon used, the trajectory of the projectile and the time since injury are all pertinent to the evaluation and therapeutic plans.105 Approximately 85% of gunshot wounds to the chest on reaching the hospital will require only tube thoracostomy for evacuation of blood and air, and restoration of normal physiologic parameters from bleeding and disruption of lung tissue integrity. For those patients who do not resuscitate or have the same signs of massive ongoing bleeding, major vascular injury is suspected and those patients mandate exploration. Simply “connecting the dots” between wounds or tracing the presumed trajectory of the missile; either by visual inspection or chest radiography diagnoses the presumed anatomic injury. This is crucial for surgical planning, primarily choosing the incision that is most expedient for control and definitive repair. The standard thoracotomy must be a mastered skill for any general and vascular surgeon. The transverse incision is made over the inframammary crease starting at the lateral sternal border of the concerned side and extending to the anterior axillary line. The pectoralis and intercostals muscles are divided and the fifth intercostals space is entered. The internal mammary artery and vein are near the lateral border of the sternum so care must be taken to not injure them. The lung is collapsed and a rib spreader is inserted. The lung is retracted upward and the inferior pulmonary ligament is divided. On the left, the descending thoracic aorta is visualized in the posterior mediastinum. The mediastinal pleura is incised. Vascular control is obtained with blunt dissection of the aorta being careful not to injure the esophagus which is anterior to the aorta. The vascular clamp is placed around the aorta to occlude it just above the diaphragm. On the right, access to the superior vena cava, azygos system, inferior vena cava (IVC), and esophagus are subpleural in the posterior mediastinum. The “cardiac box” is the topographic anatomy that predicts cardiac and major vascular injury. Any penetrating wound within the parallelogram defined by connecting the midclavicular lines at the clavicles and the costal margins is worrisome. Ultrasonography (echocardiography) is a rapid and repeatable noninvasive method to diagnose pericardial fluid. If the patient is hemodynamically unstable, pericardial fluid is present or both are present, median sternotomy is the best approach for control of cardiac and most major vascular injuries. This box applies post trauma as well. Median sternotomy is the rapid and best approach for most major vascular injuries of the arch and distal vessels— heart, ascending and aortic arch, innominate, carotids and proximal subclavian vessels, vena cava, and jugular veins as well. Sternotomy is performed by incising the skin from the sternal notch to just below the xiphoid process. Blunt

finger dissection develops the pretracheal space superiorly and the subxiphiod space inferiorly to allow the power saw or Lebschke knife to cut the sternum vertically. Both halves are retracted laterally and the pericardial sac and great vessels are in plain view. The sternotomy may be extended into the neck for more distal injuries to the carotids or subclavian vessels. A suspected injury to the more distal left subclavian vessels should be approached by thoracotomy and sternotomy extended up the neck for the right side. If the injury suspected is distal to the arch, a left thoracotomy is the best approach for descending aortic injury. Pulmonary hilar injuries are best controlled through a thoracotomy on the side of suspected injury. Repair of the injury can be accomplished with continuous size appropriate monofilament suture or interposition grafts. The decision point is extent of the vascular injury and the ability to mobilize uninjured segments together for a tensionless anastomosis. This requires that there be a ready supply of vascular graft material available. The technique of clamp and sew is employed most frequently as the additional time for initiating cardiopulmonary bypass is prohibitive; anticoagulation is inappropriate because of additional injuries or both. Autogenous graft material is also infrequently used because of availability, size mismatch, and time constraints. The operating team, especially the anesthesiology team, must be ready for the potential massive blood loss encountered when opening and exposing the injury and the changes in physiology resulting from control before repair is effected. Over resuscitation can result in cardiac strain and the anesthesiologist must be ready to rapidly shift from massive transfusion to vasodilating therapy virtually in a heartbeat. Concomitantly, other concerns must be shared. If the left subclavian artery is clamped, blood pressure monitoring is inaccurate on the left side, if the pulmonary hilum is to be clamped, ventilatory adjustments must be made, but most of all, someone must be watching the clock. Hypothermia, coagulopathy, and even likely neurologic injury are time dependent, and with the success of damage control procedures and the aggressive intensive are unit resuscitative capabilities, the initial procedure must be limited. For our patients in extremis, undergoing massive resuscitation, we limit operating room time to 60 minutes—door to door. Emergency Department Thoracotomy Emergency department thoracotomy (EDT) is a dramatic surgical display that factually rarely results in salvage.106 The procedure can consume vast resources and is not without substantial healthcare provider risk,107 nevertheless, its results can truly be awesome, and it does have role within very strict guidelines. Clear indications for which patient and which practioner performs EDT are facility dependent. First and foremost, there must be the immediately available resources to care for the patient with their chest open and cross clamps in place, and there must be clear decision points for terminating interventions if normal

VASCULAR TRAUMA • 967

physiology is not reestablished. Well-defined algorithms have been published.108 For our Trauma Center, even where an operating room, surgeons, anesthesiologists, and laboratory resources are immediately available, we strictly limit EDT based upon our Center’s outcome data. For penetrating chest injury only, we perform EDT only if ECG monitor electrical activity is present, FAST examination shows cardiac motion of any kind and no abdominal fluid, and there have been signs of life within 10 minutes of arrival. The goal of EDT is to restore sufficient circulation for immediate operation. This is accomplished by relieving cardiac tamponade, cross clamping the descending aorta to restore circulating volume quickly to maintain perfusion, and rapidly controlling active thoracic bleeding until the patient is rapidly transported to the operating room. EDT is simply a left anterolateral thoracotomy. It is performed by making an incision from the midsternum across the chest horizontally just below the nipple to the table. The chest is rapidly entered at the fourth interspace and the surgeon’s hand enters the chest to evacuate hematoma, gain access to the pericardium and find the aorta. The pericardium is opened on the anterior surface and care is taken to preserve the phrenic nerve which runs for superior to inferior along the lateral border of the pericardial sac. The pericardium is tough and difficult to grasp so often it is easier to incise a centimeter size hole with the knife, and then use the scissors to fully open the pericardium and evacuate any clots. Bleeding from the heart or great vessels is controlled by a finger, simple sutures, clamps, temporary ligation, or any other method that allows resuscitation to progress. Open cardiac massage to revive the heart is done, and to try to preserve blood flow to the brain. Clamping the descending aorta will decrease the volume needed to restore perfusion to the brain and is accomplished by the surgeon hand sliding along the posterior thoracic wall, up onto the vertebral column. The aorta is generally flaccid and feels like a penrose drain; passing a nasogastric tube makes aortic identification easier as the tube can be felt to the right of the aorta. The cross clamp is applied by breaking through the pleura and applying the clamp across all the structures on top of the vertebral column. An injury to the left lung hilum is controlled by simply cross clamping the entire hilum. If no blood is found in the left thorax, the thoracotomy can be extended across the sternum to open the right chest in similar fashion for immediate control of bleeding.

•

TRANSMEDIASTINAL GUNSHOT WOUNDS

Transmediastinal gunshot wounds are particularly worrisome for major vascular injury. They are also worrisome for aerodigestive tract injury and/or neurologic injury as well. As discussed frequently, the unstable patient needs operation. Current management of the stable patient includes helical CT.92,109−112 Despite normal or easily corrected vital signs, significant major vascular injury may still exist with transmediastinal gunshots.113

•

SUBCLAVIAN INJURIES

The subclavian vessels broach the neck, the thorax, and the extremity. The surgeon must be prepared to deal with any region and be expected to gain control rapidly and without delay. For the stable patient, arteriography is crucial for operative strategy.114,115 Endovascular techniques are superior to open procedures which risk multiple incisions, complex approaches and dangerous dissections. Nervous structures at risk for injury include vagus, phrenic, and the brachial plexus. Because of the proximity of these structures to the vessels, preoperative examination is imperative to document the deficits from the injury. Exposure for the subclavian vessels is different for the right and the left side. On the right, median sternotomy with a cervical extension offers the best approach. On the left, however, a left thoracotomy and potential supra clavicular incision offer the exposure for control. The incisions may be combined through the sternum in the so called trap-door approach. Because of the bony structures and fixed position of the arch, there is insufficient mobility to fashion a tension-free anastomosis and interposition grafts are employed; because of the caliber of the vessel, polytetraflouroethylene (PTFE) grafts are most commonly used.116

•

SUMMARY

In summary, major vascular injuries that reach the hospital; either blunt or penetrating are managed with similar schema—hypotensive patients go to the operating room and stable patients are evaluated with helical CT. Thoracic injuries are particularly amenable to endovascular techniques because of the current technology and surgeon increasing experience. It is beneficial to the patient to avoid thoracotomy as the second insult, temporizing with damage control and definitive repair when the patient is warm, fluid replete, and not coagulopathic.

•

ABDOMINAL VASCULAR INJURIES

The data from civilian trauma centers reveal that the incidence of abdominal vascular trauma is significantly higher than that in military injuries, because of the logistics of devastating injuries making it alive to medical care. The Ben Taub General Hospital in Houston published a 30-year review in 1989 that documented civilian inner city abdominal vascular injuries at 33.8%.117 The military, abdominal vascular injury experience demonstrates only an incidence of 2% in the paper by DeBakey and Simeone in 1946,4 of 2.3% in Korean conflict6 and Rich et al.7 reported an incidence of 2.9% in Vietnam due primarily to logistics, and ballistics. The high-velocity, repeating weapons (projectile velocity greater than 2000 feet/s) and other weapons designed to fragment as compared to the single shot lowvelocity weapons being used by the civilian population transfer greater injury. The projectiles are designed for stopping power, a military objective, rather than accuracy.

968 • CHAPTER 49

Despite remarkable improvements in prehospital care in theater, the simple fact remains that the individual is injured in a “hostile” environment. Intercity violence has forced prehospital system improvements that have resulted in shorter transport times and earlier surgical intervention. The incidence of abdominal vascular injury sustained after blunt trauma is 5% to 10% while penetrating stab wounds to the abdomen similarly have a low incidence of vascular injury.117,118 The most commonly injured abdominal vessels were the IVC (25%), the aorta (21%), the iliac arteries (20%), the iliac veins (17%), the superior mesenteric vein (SMV) (11%), and the SMA (10%).119 Iatrogenic injuries to abdominal vessels are caused by laparoscopy (primarily trocar injuries), angiography, cardiac catheterization, abdominal procedures (pelvic and retroperitoneal dissections), and spinal procedures.120−124 Injuries created are similar to stab wounds and the only caveat for the operating surgeon is that a major vascular injury has been described even during the most mundane cases.125 Early diagnosis and a high index of suspicion must always be maintained when sharp objects are manipulated in proximity to vascular structures. Repair is dependent on the clinical status of the patient and endovascular and minimally invasive techniques are acceptable in the stable patient.126,127 Patients in extremis require immediate control by whatever means are most expedient.128 Diagnosis Physical examination is relatively inconclusive; decision for operation is made largely depending on the amount of hemorrhage and associated shock, or the presence of peritoneal signs. The usefulness of the physical examination is limited in the trauma patients who are intubated, have altered consciousness or who have other distracting injuries. The physical findings also depend on the location of the injury— contained within the retroperitoneum or intraperitoneal injury/hemorrhage. Contained hematomas may present with a hypotension which responds to a fluid bolus. Active free hemorrhage presents with shock that transiently responds or is refractory to resuscitation. Although there is considerable hemorrhage within the peritoneum there may not be either a distended abdomen or peritoneal signs. Inspection of the bluntly injured patient may identify a seat belt sign, abrasion or ecchymosis. The EAST practice management guidelines for the evaluation of blunt abdominal trauma recommended that patients with seatbelt sign should be admitted for observation and serial physical examination.129 Auscultation is rarely useful, and palpation can elicit peritonitis. When hemorrhage is contained retroperitoneally or in the lesser sac, the patient may show signs of transient hypotension that is usually corrected with fluid resuscitation. In this case hypotension may be delayed, or not seen until the time of exploration. Patients with abdominal vascular injuries, a systolic blood pressure in the emergency department of more than 100 mm Hg

and a base deficit of more than −7.2 have been shown to have favorable survival rate of 96.2%.130 Equivocal physical examination findings or altered mental status constitute an indication for objective diagnostic measures like CT scan, FAST, etc. FAST offers immediate information that is repeatable and simple. It requires no ionizing radiation and many of the ultrasound machines are portable and lightweight. Because of its high accuracy when used to evaluate hypotensive patients who present with blunt abdominal trauma, every abdominal physical examination should be complemented with FAST when possible. Detection of intraperitoneal fluid is best made by this surgeon performed examination.131−133 In the hemodynamically stable blunt trauma patient, FAST is performed and may be complemented with CT scan. CT offers several additional data to detect injury (retroperitoneum, contrast studies, osseous anatomy) and plan therapeutic maneuvers. Hemodynamically unstable patients may be evaluated initially with FAST to ascertain if the hemorrhage is indeed within the abdomen. The hemodynamically unstable patient with abdominal hemorrhage needs to be taken to the operating room as quickly as possible. In the emergency department the ATLS regimen is initiated as quickly as is possible—high flow intravenous access, crystalloid and O-negative blood infusion and an active attempt to prevent hypothermia.134 Although the only important decision is if and when take the patient to the operating room, being prepared for other contingencies is necessary—assuring the availability of blood and blood products for massive hemorrhage, quickly administering antibiotic/tetanus prophylaxis, and preparing the operating room and associated personnel for impending arrival are crucial system issues. The precise diagnosis is made at operation with the most likely source coming from a solid organ injury, but full exploration is needed to fully evaluate all organs and vessels. Nonoperative therapy for solid organ injury is now standard. There are cases in which angiographic or endovascular techniques are employed to stop bleeding in the liver and spleen135,136 identified on CT. These interventions avoid laparotomy and its associated morbidity but are not wholly innocuous.137 If the FAST or a CT scan detects free fluid, and there is no evidence of a solid organ injury (spleen or liver) in a patient mandates either deep peritoneal lavage to determine the nature of the fluid or exploratory laparotomy. Laparoscopy in experienced hand may also be an alternative in selected stable patients. The concern here is for hollow viscus injury, but mesenteric injury that devitalizes an intestinal segment, or creates a potential defect for bowel herniation. Hematuria, although is nonspecific, it may be a sign of retroperitoneal injury especially when associated with the pelvic fractures. An unstable pelvic fracture can be associated with pelvic vascular disruption. The control of pelvic hemorrhage associated with pelvic fractures is embolization. There have been reports of packing of the pelvic fractures most recently,138 a challenge to the strict policy of

VASCULAR TRAUMA • 969

never opening a contained retroperitoneal or preperitoneal hemorrhage from a pelvic fracture. Currently, this practice is best left to the experienced surgeons who routinely employ this technique. Penetrating abdominal vascular injuries are evaluated with physical examination looking for entrance and exit wounds from the nipples to the upper thighs. Other findings on physical findings worrisome for intra-abdominal injury are hematuria and loss of femoral pulses. The trajectory of the missile or stab wound predicts the organ or vessel injured. As in the blunt vascular trauma the physical examination depends on whether the hematoma is contained or active hemorrhage is present. A FAST may be performed to evaluate for cardiac tamponade from cardiac injury. A chest X-ray and an abdominal X-ray are of diagnostic value in revealing a hemothorax and the trajectory of the missile. In penetrating injury, the location and the number of lacerations or entry points are noted. For most gunshot wounds, intra-abdominal injury occurs frequently, and exploration is generally the next step.139 There are some injuries that miss the peritoneum, and for the stable patient evaluation with CT to track the course of the projectile is acceptable and avoids nontherapeutic laparotomy and its consequences.140 There is a subset of patients with gunshot wounds to the abdomen who can be evaluated with CT and observed despite intra-abdominal injuries.141,142 For knife wounds, violation of the abdominal wall fascia is a key in decision making. Unlike the cavitary distribution of energy from guns that creates a conical blast injury in the tissue of adjacent organs; only fascial penetration creates the potential for penetrating abdominal injury with sharp objects. If this is not obvious from peritonitis or evisceration, a local wound exploration in a stable patient using local anesthesia may determine the depth of the laceration. Again, selective exploration is performed to avoid unneeded laparotomy. Laparoscopy is often used at our center, not only for diagnosis, but therapy as well. Repair of intra-abdominal injuries requires advanced laparoscopic skills.143,144 Management Virtually, an EDT is never indicated to cross clamp the aorta in cases of imminent or cardiac arrest for abdominal injuries. A large series by Feliciano et al.145 revealed only one of 59 patients with isolated penetrating wounds to the abdomen survived after an EDT. Determining the patients and situations for which this dramatic intervention is undertaken is paramount to performing it. The management of both penetrating and blunt abdominal vascular trauma depends on the location of the injury. Hematoma when identified by CT scan or at operative exploration are explored for penetrating injury and observed intraoperatively for blunt mechanisms. If the hematoma is expanding, it too is explored to control the bleeding point. The abdomen has been divided into 3 zones to classify the vessel or vessels injured and to help the surgeon in operative

1

2

2

3

3

• FIGURE 49-1.

Retroperitoneal zones. Zone 1: Midline retroperitoneum; Zone 2: Upper lateral retroperitoneum; Zone 3: Pelvic retroperitoneum.

Reproduced, with permission, from Valentine RJ. Abdominal aorta. In: Thal ER, Weigelt JA, Carrico CJ, eds. Operative Trauma Management: An Atlas. 2nd ed. New York, NY: McGraw-Hill; 2002:302-315.

decision making: (1) Zone I include the midline retroperitoneum, (2) Zone II include the upper retroperitoneum with renal artery and vein, and (3) Zone III or pelvic retroperitoneum (Figure 49-1 and Table 49-1).

TABLE 49-1. Anatomic Location of Intra-Abdominal and Retroperitoneal Vasculature Zone 1: Midline retroperitoneum subdivided into supramesocolic and inframesocolic areas Supramesocolic area—Suprarenal abdominal aorta, celiac axis, proximal SMA, proximal renal artery, and superior mesenteric vein (either supramesocolic or retromesocolic) Inframesocolic area—Infrarenal abdominal aorta and infrahepatic IVC Zone 2: Upper lateral retroperitoneum Renal artery and renal vein Zone 3: Pelvic retroperitoneum Iliac artery and iliac vein Portal–retrohepatic area Portal vein, hepatic artery, and retrohepatic vena cava

970 • CHAPTER 49

Pathophysiology Vascular injuries from blunt trauma are associated with rapid deceleration in motor vehicle crashes and falls. The forces can avulse branches from major vessels at their fixation points, such as the major visceral arteries. Blunt forces may create intimal injuries with thrombosis which has been seen in the renal arteries, or crush injury from a direct blow. A direct blow may completely disrupt the layers of the vessel and cause local hematoma or even massive hemorrhage if there is loss of containing tissue planes. Lastly, blunt injury can create penetrating injury by lacerating vessels from bone fragments, probably seen commonly with high-energy pelvic fractures. Penetrating injuries produce blast injuries, intimal flaps and thrombosis, disrupt the wall, or completely transect the vessel. An AVF may be produced. Understanding that the large amount of energy transferred from guns is dissipated in the soft tissue means that penetrating injuries than can also create vascular injury from blunt forces as well. Formerly, a gunshot in proximity to any vessel required angiography. This policy is now refined by evidencebased study and discussed in the peripheral vascular injury section. The question of reducing the hypercoaguable state following traumatic injury and repair is always at question. Very often, there is a contraindication to anticoagulant therapy because of associated injuries. Others conjecture there has been the intervening development of a coagulopathy that “effectively” offers early protection. Whereas anticoagulation has been demonstrated to be of benefit in BCI, nontrauma vascular stents,146 and peripheral arterial venous repairs,147 there is no conclusive evidence that anticoagulation after thoracic or abdominal vascular repair improves patency, limb salvage, or survival.148 Operating Room Once in the operating room the patient is prepped and draped from the chin to the lower thighs. This is performed to gain distal vascular control, for vein harvests, and immediate access to the chest cavity if needed for a thoracic injury and proximal aortic control. A midline abdominal incision is made and the peritoneal cavity is entered. Clotted and nonclotted blood is evacuated. If needed, an aortic compression device may be used to compress the aorta at the aortic hiatus.149 This quick measure allows the surgeon to better localize the source and to plan the next steps in the conduct of the operation. All four quadrants of the abdomen are packed with laparotomy pads. This allows anesthesia to catch up with blood products and fluid resuscitation. The bleeding must be controlled by direct pressure or packing during these initial steps so that an adequate exploration may performed. The exploration is best done in an orderly fashion. We prefer to start at the aorta at the diaphragm and work clockwise to be sure to evaluate all areas. The packs are removed and a rapid inspection is done for active bleeding, expanding hematomas, and contamination. When bleeding

is encountered, it is stopped. Active bleeding from solid organs maybe packed. A splenectomy maybe performed if this is expeditious, or simply clamping the hilum may suffice to stop active hemorrhage. Arterial injuries maybe controlled with direct pressure with fingers, laparotomy pads, or sponge sticks. Proximal and distal control is the goal but immediate control is performed with the former. Major venous control is obtained with finger pressure, laparotomy pads, sponge sticks, or vascular clamps. If exsanguinating hemorrhage persists, aortic control is obtained at the nearest easily accessible level—the diaphragmatic hiatus is easily performed, especially if one has used direct pressure with fingers or T-bar (aortic compression device) at the beginning of the operation. An atraumatic vascular clamp must be used for prolonged control. Once the hemorrhage is under control the contamination is controlled with applying Babcock clamps, noncrushing intestinal clamps, or stapling devices. Small injuries to the intestines with soilage may be controlled with a simple running suture. Each quadrant of the abdomen is palpated and visually inspected. Solid organs are mobilized if needed, the bowel is evaluated from diaphragmatic hiatus to rectum, and the lesser sac and upper retroperitoneum are investigated. When the entire abdominal cavity and the retro peritoneum have been evaluated, the injuries identified, a surgical plan is developed based greatly on the physiologic state of the patient. Modern surgical planning for major vascular injuries now includes aggressive resuscitation, temporizing measures before definitive repair, and the use of noninvasive or less invasive modalities such as angiography, embolization, and endovascular repair. The surgeon must anticipate the ongoing physiologic processes in the patient with a major vascular injury, including the development of abdominal compartment syndrome (ACS). Simply, the interstitial fluid that accumulates from both injury and resuscitation creates swelling. If this swelling occurs in a closed space, intracompartmental hypertension is created. This is true in the brain, in the extremities, and in the intraperitoneal spaces as well. The syndrome of increased abdominal hypertension which leads to organ dysfunction has been named ACS.150 ACS involves abdominal pressures greater than 25 cm of water and is generally measured by intravesicular pressures. For ACS to be present there must be an impact on ventilation (increased peak pressures, low tidal volumes, etc.), decreased venous return (hypotension, ongoing volume needs, elevated central venous pressures, etc.) and/or decreased urine output. The treatment of ACS is release of the compartment, as is performed with other elevated compartment pressures in other locations. There may be initial success with intragastric decompression or neuromuscular blockade, however, ACS generally involves opening (or re opening) the abdominal fascia. Temporary closure is obtained with watertight vacuum dressings. After the initial resuscitation is completed, and the physiologic response to injury abates, the abdominal fascia is reapproximated (see subsection on Damage Control below).

VASCULAR TRAUMA • 971

Hemorrhage and hematomas from abdominal vascular injuries are localized by their anatomic zones. Zone 1, midline retroperitoneum; Zone 2, upper lateral retroperitoneum; Zone 3, pelvic retroperitoneum; and the portal– retrohepatic area. These zones have been described earlier. Zone 1—Midline Supramesocolic Injuries A hematoma or active bleeding in Zone 1 mandates an exploration for both penetrating and blunt injuries. The supramesocolic area is superior to the transverse mesocolon. A hematoma or bleeding in this region may indicate an injury to the suprarenal aorta, celiac axis, proximal superior mesenteric artery (SMA), or proximal renal artery. Proximal aortic control should be obtained prior to opening the supramesocolic hematoma as a result of the difficulty in exposure of the vessels in this area. There are several techniques for obtaining proximal control of the aorta. If the injury is supraceliac, intrathoracic control may be needed at the descending thoracic aorta via a left anterior thoracotomy. Another technique to gain access to the aorta is by left medial visceral rotation. The left colon is mobilized by incising the left lateral peritoneal attachments from the splenic flexure to the distal sigmoid. The splenophrenic and splenorenal ligaments are divided and the spleen, fundus of the stomach, tail of the pancreas, and kidney are mobilized by blunt dissection (Figure 49-2). This will expose the entire abdominal aorta, left iliac system, suprarenal aorta, celiac axis, proximal SMA, and left renal arteries. The kidney does not need to be included in the rotation to expose the celiac axis but if it performed, it allows access to the posterior wall of the aorta. An alternate approach is to leave the kidney and rotate the spleen, pancreas, and left colon (Figure 49-3). Another approach that is quicker than the medial visceral rotation is to incise the left triangular ligament and retract the left lobe of the liver. The hepatogastric ligament is incised just to the right of the esophagus and extended along the lesser curvature of the stomach. The stomach and esophagus are retracted to the left. The posterior peritoneum is excised and the right crus of the diaphragm is exposed (Figure 49-4A). The aorta is posterior to the right crus and exposed by blunt dissection. The surgeon’s index and middle fingers are placed on either side of the aorta and used to guide the clamp into position (Figure 49-4B).151 Most injuries to the suprarenal aorta may be repaired with a lateral arteriorrhaphy with a 3-0 or 4-0 polypropylene suture after adequate debridement of the edges. The surgeon must be sure the closure is tension free. Generally an end-to-end anastomosis can be performed if the defect is less than 2 cm in length. If tension is present, or the defect is larger, a patch angioplasty or an interposition graft of Dacron or PTFE is used. Patch angioplasty is also indicated when there is a large defect that will cause luminal compromise if the wound is repaired in a simple running fashion. The graft is oversewn with 3–0 or 4–0 polyproplene, the repair flushed by briefly opening the proximal clamp,

and the distal clamp is removed. Prior to removal of the proximal clamp, the surgeon must notify anesthesia to prepare to infuse fluid. The proximal clamp is then removed slowly. Long clamp times produce profound acidosis from the ischemic lower extremities and warrant prophylactic administration of intravenous bicarbonate.152 When there is gross contamination it is preferred to use saphenous vein or hypogastric artery interposition grafts over prosthetic material.153 Enteric spillage is not a contraindication for prosthetic graft.154,155 The abdominal cavity should be irrigated well and the enteric spillage controlled prior to the repair. Injuries to the celiac artery and branches are also difficult to expose because of the dense neural plexus and lymphatic tissue which cover this region of the aorta. Exposure here requires time consuming dissection which the patient in extremis may not have. Fortunately if the injury is distal the celiac axis, i.e., the left gastric and splenic arteries, they may be ligated because of the extensive collateral circulation that exists between the celiac and superior mesenteric systems. The common hepatic artery may also be ligated proximal to the gastroduodenal artery based on similar redundant blood supply. The liver will receive adequate blood supply from the portal vein and gastroduodenal artery. It may be feasible to repair the hepatic artery if the patient is stable. The repair may be done by whichever method offers the best technical repair—lateral arteriorrhaphy, end-to-end anastomosis, or saphenous vein interposition graft. If the patient is unstable with other injuries one must not hesitate to ligate the common hepatic artery. Although the same approach can be applied to injuries of the celiac axis, the larger size of the common hepatic artery generally makes this technically easier. If the patient is unstable, ligation is performed and the consequences are dealt with when the patient is resuscitated; rewarmed; and not coagulopathic. In stable patients with minimal injuries repair may be performed with an interposition saphenous vein graft. Proceeding just inferiorly along the aorta, the SMA is the next anterior structure the surgeon encounters. The SMA gives off the inferior pancreaticoduodenal artery, the middle colic artery, the jejunal arterial arcade with multiple intestinal branches, the right colic artery, and the ileocolic artery in sequence. SMA injuries are divided into four zones: r Zone 1: Between the origin and the inferior pancre-

aticoduodenal artery r Zone 2: Between the inferior pancreaticoduodenal

artery and the middle colic artery r Zone 3: Distal to the middle colic artery r Zone 4: The segmental intestinal branches

Ligation of Zone 1 or 2 of the SMA in a patient that has been in hemorrhagic shock will result in small bowel and right colon ischemia caused by vasoconstriction of the collateral vessels.156 Ligation of Zone 3 and 4 may result in localized segments of ischemia of the small bowel.

972 • CHAPTER 49 L. adrenal L. kidney

Pancreas L. ureter

Inferior mesenteric v.

Spleen

Inferior mesenteric a.

• FIGURE 49-2.

Left medial visceral rotation.

Reproduced, with permission, from Valentine RJ. Abdominal aorta. In: Thal ER, Weigelt JA, Carrico CJ, eds. Operative Trauma Management: An Atlas. 2nd ed. New York, NY: McGraw-Hill; 2002: 302-315.

SMA injuries may also be divided into two zones: the short retropancreatic segment and the segment that emerges from under the body of the pancreas, over the uncinate process and the third portion of the duodenum.157−159 Exposure of the SMA is performed with a left medial rotation as previously described. The kidney does not need to be rotated medially. If an injury to the posterior wall of the aorta is suspected, then medial rotation of the kidney is necessary to fully expose the posterior wall. Alternatively, the surgeon may expose this area by opening the lesser sac and approaching the aorta directly. The SMA resides at the

inferior border of the pancreas and falls inferiorly over the third portion of the retroperitoneal duodenum. To expose Zone 1 of the SMA, the pancreas may be transected through its neck if there is extensive bleeding and rapid control is needed. This is done easily and quickly with a linear stapler. If there is extensive damage to this area and potential injury to the pancreas, the SMA should be ligated, and if the patient is stable a jump graft of saphenous vein or PTFE from the distal infrarenal aorta is safest, as it is away from injured pancreas. The choice of anastomosis in this repair is inconsequential and depends on how best the vessel

VASCULAR TRAUMA • 973

Spleen

Pancreas

Renal v., a.

Inferior mesenteric v.

Superior mesenteric v., Superior mesenteric a.

Transverse mesocolon

Duodenum

Lateral colon attachment incised

• FIGURE 49-3.

Left medial visceral rotation with kidney left in situ.

Reproduced, with permission, from Valentine RJ. Abdominal aorta. In: Thal ER, Weigelt JA, Carrico CJ, eds. Operative Trauma Management: An Atlas. 2nd ed. New York, NY: McGraw-Hill; 2002:302-315.

974 • CHAPTER 49 R. crus incised

Celiac trunk L. adrenal gland

Hepatogastric ligament divided Inferior vena cava

Hematoma Pancreas retracted

Pancreas

A

B

• FIGURE 49-4.

Superior mesenteric artery exposure. (A) Lesser sac approach. (B) Transected pancreas approach.

Reproduced, with permission, from Valentine RJ. Abdominal aorta. In: Thal ER, Weigelt JA, Carrico CJ, eds. Operative Trauma Management: An Atlas. 2nd ed. New York, NY: McGraw-Hill; 2002: 302-315.

and graft lay in apposition. It may be an end to end to the distal transected portion of the SMA or an end to side, the anterior, or lateral side to the SMA. The repair must be a tension-free and the aortic suture line needs to be covered with soft tissue to prevent the formation of an aortoenteric fistula postoperatively. If the patient is unstable a temporary intraluminal shunt may even be placed and definitive repair deferred to until after the patient is resuscitated in the critical care unit for 24 to 48 hours.160 Nevertheless, SMA injury is lethal in 40% of cases and this is increased in proximal injuries. Zone 2 injuries may be exposed by dividing the ligament of Treitz and mobilizing the duodenum laterally (Figure 49-5). The middle colic artery is identified and traced to its origin, the SMA. For more exposure, the inferior border of the pancreas can be retracted cephalad. Zone 2 injuries are repaired similarly to Zone 1 injuries.

Zone 3 and 4 injuries are approached directly through the mesentery of the small intestine. Attempts should be made to restore continuity of the vessels involved in these injuries if the patient is stable. Ligation in these segments will result in ischemic bowel and need for resection, whereas ligation of more proximal vessels are fed by collateral flow from either the celiac or inferior mesenteric arteries. Injuries to the SMV are difficult to manage because of the location posterior to the pancreas and to the right of the SMA. As with the injuries to the SMA, the pancreas may need to be transected to gain control. If the injury is visible below the inferior border the pancreas, digital pressure should be applied and a repair is accomplished with a running 5-0 polypropylene suture. An end-to-end tension-free anastomosis may be performed for a transected SMV.

VASCULAR TRAUMA • 975

Transverse colon elevated

Ligament of Treitz divided

Inferior mesenteric v.

Inferior mesenteric a.

Aorta Inferior vena cava

• FIGURE 49-5.

Zone 2 exposure.

Reproduced, with permission, from Valentine RJ. Abdominal aorta. In: Thal ER, Weigelt JA, Carrico CJ, eds. Operative Trauma Management: An Atlas. 2nd ed. New York, NY: McGraw-Hill; 2002: 302-315.

Penetrating posterior injuries may be difficult to expose because of the numerous collaterals. Care must be taken to ligate these collaterals for proper exposure to be achieved and to avoid further bleeding. When extensive vascular and abdominal injuries are present the SMV may be ligated. There are reports in young patients with survival rates of 85% after ligation of the SMV. Stone and associates emphasized aggressive fluid resuscitation after ligation of the SMV because of splanchnic hypervolemia that leads to peripheral hypovolemia. This hypovolemia may last for several days. Because of the venous congestion and swelling of the intestines the abdomen should not be closed and a temporary closure be performed and the patient monitored closely for ACS. A second look should be performed in 24 to 48 hours to evaluate the bowel for ischemia.160 Injuries to the inferior mesenteric artery are routinely ligated, as there is collateral flow to supply the colon.

•

RENOVASCULAR INJURIES

The proximal renal arteries may be exposed by retracting the transverse colon superiorly and the small bowel to the right. The retroperitoneum is incised directly over the aorta. The left renal vein is identified and retracted superiorly to expose the renal arteries. The vena cava may need to be retracted to the right. Proximal control is best obtained with vessel loops. Additionally, the entire right renal artery

can be exposed by a right medial rotation of the colon and an extensive Kocher maneuver. This will mobilize the duodenum and head of the pancreas to the midline so as to identify the vena cava and the right renal vein. To fully expose the entire renal artery the vena cava and the right renal vein are retracted. Similarly, medial visceral rotation on the left gives access to the left kidney and its hilum. Repair should be attempted if the patient is stable, bilateral injuries, or if a single kidney is present. Time limits the return of functional renal tissue. It is recommended revascularization be attempted in a stable patient within 4 to 6 hours of the injury; revascularization up to 20 hours is possible for patients with bilateral injuries or a single kidney.162,163 A nephrectomy should be performed if the patient is unstable, there is prolonged ischemia, or has extensive injuries. Nonoperative treatment is an option if the diagnosis is delayed, and the patient is not actively bleeding from the kidney. These patients need to be monitored for the development of hypertension in the future. Repairs may be done by simple closure, patch angioplasty, resection and anastomosis, or interposition graft. Iatrogenic injuries, especially from transplantation must be dealt with quickly, but the physiologic state of these patients and isolated vascular injuries is more amenable to endovascular techniques.164 Renal vein injuries may be repaired by lateral venorrhaphy or by ligation in extensive injuries. A nephrectomy should be concomitantly performed after ligation of the

976 • CHAPTER 49

right renal vein. The left renal vein may be ligated and the kidney survives as a result of the collateral drainage through the left gonadal vein, the left adrenal vein, and the lumbar veins. Blunt injury to the renal artery resulting in thrombosis may not present early enough to consider auto transplantation although some have reported success.165 Most surgeons would opt for operation only if both kidneys are totally involved. Endovascular stents are more commonly employed today.166 Zone 1: Midline Inframesocolic Injuries The inframesocolic area is described as the space inferior to the transverse mesocolon. Hemorrhage or bleeding in this region may indicate an injury to the infrarenal abdominal aorta or infrahepatic IVC. To expose the infrarenal aorta, the transverse colon is elevated cephalad and the small bowel is packed to the right. The posterior peritoneum is incised superiorly and the structures exposed from the left renal vein and inferiorly to the aortic bifurcation. The superior incision includes the ligament of Treitz and the third and fourth portions of the duodenum are then retracted to the right. Care must be taken not to injure the inferior mesenteric vessels just left to the aorta. Direct pressure with a digit or sponge stick allows proximal and distal control of the aorta. All surfaces of the aorta must be visualized including the posterior wall, to locate all injuries and their extent for determining proper definitive care. The edges of the wound are debrided and approximated with a running polypropylene 3-0 or 4-0 suture. Most wounds may be approximated with a simple lateral arteriorrhaphy. A patch angioplasty is indicated when there is a large defect that will cause luminal compromise. End-toend anastomosis may be performed if the aorta is mobilized to create a tension-free anastomosis. If greater than 2 cm of the aorta is damaged then an interposition graft of PTFE or Dacron should be placed to create a tension-free repair. One must be wary of long clamp times which can produce profound acidosis from the ischemic lower extremities and warrant prophylactic bicarbonate. When there is gross contamination it is preferred but not mandatory to use saphenous vein or hypogastric artery over prosthetic material. If there is gross contamination from colon injuries extra-anatomic bypass may be an additional option to reestablish perfusion to the lower extremities. The ends of the aorta are oversewn and an extra-anatomic bypass is performed. Bypass techniques depend on the location and complexity of the injury present—axillofemoral inflow, either bilaterally or unilaterally with femorofemoral bypass are possible. It may be preferable to perform a unilateral axillofemoral bypass graft with an end-to-end iliac artery anastomosis.167,168 If a vena cava injury is suspected a right medial visceral rotation will expose the vena cava and the aorta. The lateral peritoneal attachments from the cecum to the hepatic flexure are incised. The right colon is reflected to the right by blunt dissection in a plane anterior to Gerota’s fascia. The

duodenum and head of pancreas are mobilized by incising the hepatoduodenal ligament and the retroperitoneum. This allows visualization to the vena cava and access to the vasculature of the right kidney. The aortic bifurcation and iliac arteries are exposed by extending the incision inferiorly along the root of the small bowel mesentery.169 The cava wall is tenuous and great care must be taken or further injury can result. Proximal and distal control are best obtained with gentle digital pressure or sponge sticks. Again, full evaluation of the cava must be performed, and it may be easier to assess the integrity of the vessel by further opening the traumatic venotomy to visualize the posterior of lateral walls. Venorrhaphy of these injuries may be accomplished by 3-0 or 4-0 polypropylene suture intravascularly, and then the anterior venotomy closed similarly. Ligation is again an option of last resort, but there have been reports of salvage.170,171 For those facile with total hepatic isolation from transplant experience, this also provides an option for repair of caval injuries.172 Aortic and cava injuries are devastating and survival hovers approximately 50%.173 While a subtle exsanguinations intraoperatively the majority die from multisystem failure. Caval flow after repair can be demonstrated by ultrasound.174 Zone 2: Upper Lateral Retroperitoneum Hematoma or hemorrhage in Zone 2 may indicate injury to the renal artery, the renal vein, or the kidney. Penetrating trauma mandates exploration. Blunt trauma with a nonexpanding hematoma does not mandate exploration. Exposure and repair options are described in renovascular injuries in zone 1. Late complications such as AVF are successfully dealt with endovascularly.175 Zone 3: Pelvic Retroperitoneum Hematoma or hemorrhage in Zone 3 may indicate injury to the iliac artery, iliac vein, or both. Hematomas from blunt trauma need to be exposed only if there is hemorrhage intraperitoneally, or a rapidly expanding hematoma, or absent or diminished femoral pulses. Prior teaching was absolute about not opening pelvic hematomas, as the large area, venous plexus and open bone marrow was felt to be uncontrollable. There are reports of packing and damage control procedures, but this is not commonplace. All hematomas should be explored in penetrating injuries. While obtaining proximal and distal control, digital pressure against the bone is very effective until definitive vascular clamps can be applied. The common iliac arteries are exposed by retracting the small bowel superiorly and to the right. The retroperitoneum over the aorta is incised exposing the aorta and the common iliac arteries. Care must be taken when dissecting distally not to injure the ureter that crosses over the bifurcation of the common iliac artery. For injuries in this region it is best to fully demonstrate the ureter to assure its safety and determine if there is concomitant injury.

VASCULAR TRAUMA • 977

When obtaining arterial control, one must be cautious not to injure the veins lying posterior to the arteries. Once proximal control is obtained, distal control of the external iliac artery is obtained at the pelvic brim. If there is difficulty obtaining control of the external iliac artery a transverse lower abdominal incision or a longitudinal incision over the groin with division of the inguinal ligament may be needed. Control of the internal iliac artery is essential to control back bleeding. Vessel loops are ideal for control in this location, as clamps may be hard to apply or cumbersome during repair efforts. Common and external iliac arteries injuries need to be repaired. The common and the external iliac arteries should not be ligated. Ligation will lead to ischemia of the lower extremity. The internal iliac artery, however, may be ligated.176 As with other major vessels, small injuries are debrided and repaired with a lateral arteriorrhaphy. Again care must be taken not to narrow the lumen—a venous or PTFE patch may be necessary. Similarly, more extensive injuries are debrided and repaired by an end-to-end anastomosis, saphenous vein or PTFE graft. If resuscitation efforts are ongoing, or other time issues present themselves, temporary shunting can be utilized. Implanting the common iliac to the opposite common iliac artery, or using the internal iliac as an interposition graft are autologous repairs that may helpful in the stable patient to avoid prosthetic material.173 Extensive injuries with enteric contamination are a vexing problem. Options discussed previously dividing the artery proximal to the injury, oversewing with a double row of sutures, and covering with peritoneum. If the extremity appears to be ischemic, an extra-anatomic femoral– femoral crossover graft is performed. Other options are controlling the enteric contamination, washing the cavity extensively and proceeding with the repair, even using PTFE.177 Iliac vein injuries are difficult to expose. The vein may be compressed with fingers or sponge sticks for immediate control and injury assessment. Some authors recommend temporary division of the iliac artery to gain access to the vein; every attempt should be made to carefully dissect and retract the artery before adding an additional anastomosis and increasing ischemia. One should recall that to better mobilize the common iliac artery, the internal iliac artery may be divided and not repaired. Repairs are done by lateral venorrhaphy with a technique to avoid narrowing the vein. Ligation may be performed and we have had some personal success with this without devastating ipsilateral venous insufficiency. Survival from iliac injuries also ranges at 60%.176,179 Portal–Retrohepatic Area Hematoma or hemorrhage in the portal area may indicate injury to the portal vein, hepatic artery, or common bile duct. If a hematoma is present with no active hemorrhage, proximal and distal control of the porta hepatis is obtained with vascular clamps. If there is active hemorrhage fin-

ger compression (Pringle maneuver) is applied until the anatomy is clear enough for vascular clamps to be applied. Once control is obtained, the structures are carefully dissected and inspected. Hepatic artery injuries may be repaired with lateral arteriorrhaphy or may be ligated if beyond the origin of the gastroduodenal artery. If the right hepatic artery is ligated, a cholecystectomy must be performed as this represents interruption of the end artery to the gall bladder. Reconstruction is usually not performed because of the severity of associated injuries to the liver and surrounding organs. Intrahepatic arterial bleeding is likewise controlled with hepatic artery ligation or embolization. There remains sufficient oxygen in the portal system to prevent hepatic ischemia.180,181 Portal vein injuries in the hepatoduodenal ligament are approached in the same fashion as the hepatic artery injuries. The structures of the porta hepatis are dissected carefully and isolated. An extensive Kocher maneuver with mobilization of the common bile duct to the left and the cystic duct superior allows visualization of the suprapancreatic and posterior portal vein. Retropancreatic portal vein injuries are difficult to isolate. An extensive Kocher maneuver is performed. The same avascular plane that determines resectability in malignancy is exploited for control. This space is developed between the pancreatic head and the portal vein gingerly with a clamp and then the pancreas is divided between two clamps or with a stapler device. Small injuries may be repaired primary with lateral venorrhaphy after applying a partially occluding vascular clamp. The repair is performed with a 4-0 or 5-0 polypropylene suture. More extensive injuries must be repaired by tension-free end-to-end anastomosis, and prostheses have been employed.182 Many of the newer techniques are borrowed from transplantation and include interposition venous grafting or PTFE.183−185 If the patient is unstable with an extensive injury to the portal vein ligation should be an option. The ends of the portal vein are oversewn with a nonabsorbable suture. Hypovolemia as seen with SMV ligation mandates aggressive resuscitation because of the splanchnic fluid sequestration. The abdomen needs to be vacuum packed as a result of the intestinal edema and for a second-look in 24 to 48 hours to evaluate the viability of the bowel. Ligation to the portal vein and the hepatic artery is not compatible with life. This is a situation where reconstruction of the portal vein should be performed. The reconstruction may be done with a saphenous vein graft. Injury to lobar branches of the portal vein and hepatic artery will create an ischemic lobe which can be resected “electively” at second look. Hematoma or hemorrhage in the retrohepatic area may indicate injury to the retrohepatic vena cava, a hepatic vein or renal vessel. Injuries to the IVC in this area challenge the surgeon and have a high mortality rate. The challenge is to avoid opening a stable and self-tamponaded injury, even from a penetrating injury. Such “nonoperative” treatment may prevent likely loss of control and

978 • CHAPTER 49

exsanguniation in exchange for the potential of delayed complications. Damage control dogma strongly supports this train of thought. Nonexpanding and contained retrohepatic hematomas should be packed with laparotomy pads and a second look performed in 24 to 48 hours. If the hematoma is expanding or ruptured with massive venous bleeding, a temporizing procedure is to compress the liver posteriorly and the Pringle maneuver is applied. The surgical team, anesthesiologist, and the blood bank are notified for a massive transfusion. Gaining access to and controlling these retrohepatic caval injuries is intense. The surgeon must bring to bear every potential resource to stop the bleeding. If available, endovascular or interventional techniques using occlusive balloon catheters within the cava, aorta, or both, can isolate the injury and avoid further blood loss,136 a second incision/thoracotomy and ensuing coagulopathies.186 Similarly, there is no dishonor in asking for the surgical expertise of hepatic and/or transplant surgeons who may be available for this infrequent injury. Unfortunately, both of these call for resources which may not be readily available. To visualize and repair retro hepatic injuries, the liver is mobilized by incising the triangular and anterior coronary ligaments and rotating the liver anteriorly and medially. Once rotated, if the wound is visible, it can quickly be controlled by grasping with forceps or an Allis clamp. It may be possible then for a Satinsky clamp to be applied for definitive control. If one is unable to visualize the wound because of massive hemorrhage, it is unlikely to be better on multiple attempts and another technique must be tried. The atriocaval shunt was described by Schrock in 1968. The shunt traverses the hepatic veins and is positioned after sternotomy, right atriotomy, and passage of the shunt (either an endotracheal tube or chest thoracosotmy tube) is positioned across the injury. Further control is established with Rommel ties at the diaphragm and suprarenally on the cava to force blood through the shunt. This is is technically challenging, two teams are needed and basically mentioned only for historical interest. Today, hepatic vascular isolation with a Pringle maneuver and infrahepatic and suprahepatic caval clamping is borrowed from elective hepatic surgery and is more likely to be known to the surgeon. The last approach is direct transhepatic approach by transecting the liver to expose the injury. Damage control and packing the liver may be an option for limited injuries. Repairs of the vena cava are done with continuous 4-0 polypropylene sutures. Roughly one-third of retrohepatic caval injuries survive operation. Damage Control The “damage control” laparotomy is part of every trauma surgeon’s armamentarium. Although a historical tenet that was buried beneath surgical hubris as bigger and longer operations were technically possible, it was concisely modernized and codified by Rotondo.15 The focus is no longer on definitive repair at any cost and/or in one sitting, but

on the physiologic status of the patient. Rotondo15 defined “damage control” as: 1. Initial control of hemorrhage and contamination. 2. Intraperitoneal packing and rapid closure, allowing for aggressive resuscitation in the intensive care unit. 3. Subsequent definitive reexploration. In “damage control,” intestinal reanastomosis may be delayed until reexploration. Arterial injuries may be shunted and extensive venous injuries packed or ligated. Any diffuse retroperitoneal or pelvic bleeding may be tightly packed. The patient is resuscitated in the intensive care unit and returns to the operating room after acidosis, hypothermia, and coagulopathy are returned to normal (24–48 hours). During this resuscitation, adjusts such as embolization if solid organs or end arteries may be employed to help vascular control.187 Angiography and embolization is also an adjunct to nonoperative therapy for solid organ injuries- primarily liver and spleen. Avoiding the additional physiologic stress of laparotomy is beneficial not only in the isolated injury but the multiply injured patient. There is a unique set of complications that may arise hepatic or splenic necrosis are the most obvious and can lead to bile leaks, infections, persistent fevers, and pelvic effusions which must factor into the decision in utilizing these modalities.188 Angiography is also used for pelvic bleeding. With the aggressive and ubiquitous use of CT scanning, arterial pelvic bleeding is readily diagnosed. Pelvic stabilization is accomplished by a simple pelvic binder or tying a sheet around the pelvis between the anterior superior iliac crests and greater trochanters. Arterial bleeding is very amenable to embolization.189

•

PERIPHERAL VASCULAR INJURIES

Vascular trauma in the extremities results from both penetrating and blunt injuries, although in today’s violent society, young men with penetrating trauma constitute the vast majority of injuries. The most common clinical presentation is acute limb ischemia and the most common injuries are complete transections and partial lacerations from penetrating wounds. Although peripheral vascular injuries are more common in upper extremities in civilian trauma patients, the same are seen more frequently in the lower extremities among the military patients. The historical context of peripheral vascular trauma is notable for the fact that only recently has there been the surgical environment to allow primary repair. The classic history until the late 20th century was of nonoperative therapy for injuries that did not require immediate ligation and allow the natural history of such wounds to progress to aneurysm, AVF, or gangrene. Complete transections usually allow the vessel to retract and the normal hemostatic events to occur with vasoconstriction and initial thrombus formation. The hallmark is loss of distal pulses. Partial lacerations may be insidious and present as an ischemic limb because of an occlusion by

VASCULAR TRAUMA • 979

dissection or distal thrombus. Blunt trauma as well as low velocity gunshot wounds and stab wounds are associated with acute ischemia; on the other hand, high-velocity missiles or crushing mechanisms cause massive soft tissue loss around the injured vessel and eliminate the tamponade effect of these investing structures, thus increase the chance of extensive, but obvious external bleeding. There have always been vascular injuries associated with blunt mechanisms. Today, with the array of diagnostic and therapeutic options available, there is an ever-improving limb salvage rate—again the limiting factor is always duration of ischemia. With the concomitant increase in invasive diagnostic and therapeutic procedures, there has been an expected rise in vascular complications from interventional coronary procedures, elective endovascular, and angiographic approaches and long tern venous access. Such events rarely present with the same threatening manner as acute trauma, although there are cases in which limb survival and even patient survival are at risk. Diagnosis Prehospital information is a very important in extremity vascular trauma. When a complete vessel transection occurs, the initial bleeding is brisk and pulsatile until vascular contraction and initial thrombus occur. Thrombus formation is also enhanced by the ensuing lower blood pressure. After resuscitation with adequate volume expansion and restoration of a normal blood pressure, rebleeding may occur if this key clue to a major extremity vascular injury was overlooked. During history taking, details from emergency medical personnel or bystanders about on-scene active arterial bleeding, the amount quality, and color should be elicited. Secondly, the timing of injury is paramount, especially when the limb shows signs of ischemia. Presence or absence of pulse at the injury scene and information about associated injury to muscles, tendons, bones, and nerves can help differentiate a primary injury to these structures versus a progression of the ischemic process. Although muscle is moderately tolerant of ischemia, delays greater than 6 hours portend limb loss. Any delay increases the risks of ischemia, its sequelae, as well as reperfusion injury and the devastating effects of compartment syndrome. After the primary survey is completed, bleeding is stopped and resuscitation is ongoing, the secondary physical examination focuses on the injured extremity. Bleeding which was identified early and controlled with direct pressure or clamping, is examined to determine where best to restore blood flow and how to get this accomplished as quickly as possible. Again, the best place for an actively bleeding vascular injury is the operating room. Fortunately, today’s modern operative suites are amenable to radiological or endovascular procedures and the administrative personnel must be made aware of the need for those specialized services at any time.190 The clinical manifestations of ischemia are remembered by rote as the 5 P’s: Pain, Paralysis, Paresthesia, Pallor, and

Pulselessness. The pain of ischemia is excruciating, especially for the na¨ıve extremity. Therefore, pain out of proportion to physical findings is the indicator of a vascular injury until proven wrong. In the unconscious or neuromuscularly blocked patients, these signs cannot be elicited and the surgeon must default to demonstrating that there is not an injury. The demonstration by the physical examination is sufficient to rule out a significant vascular injury. Conversely, any deviation from the normal examination must be investigated. Of note pallor is a very nonspecific signs that is present when patient is hypothermic or the extremity is exposed during transport. Comparison to the contralateral side helps isolate specific findings from global events. Physical examination is not only important in the diagnosis but also in the management. A comprehensive examination also helps to carry out the decision about the futility of the arterial repair in an extremity that has no neurologic function or is unusable because of significant soft tissue or bone loss. Specific scoring systems have been developed to assist in determining when an ablative procedure is the best choice—Mangled extremity score (MESS) and the Gustillo classification are a few of the better known and validated systems.191−193 Although scoring systems are present, each case must be individualized, especially if amputation is considered primarily.194 Another simple example of employing physical examination for deciding on repair is the identification of a good palmar flow using Allen test in a setting of ulnar or radial artery injury. If there is a sufficient collateral flow, further revascularization offers no gain but risks surgical complications. In such cases of combined trauma, vascular repair should be accomplished quickly, even if temporized by shunting, before skeletal repair. Avoiding ischemia and preventing further reperfusion injury allows the limb to survive immediately, and before the full effects of the injury are known on nervous injury and functional outcome. If revasculatization cannot be accomplished, then no further intervention other than amputation is needed.195,196 There are associated injuries that should raise the likelihood of a specific arterial injury: Fracture–dislocation of the posterior portion of the first rib and subclavian artery injury, brachial plexus and subclavian artery or vein injury with neck hyperextension, brachial artery injuries and supracondylar fractures of the humerus, and knee dislocation and popliteal artery injury. Since knee dislocation has been associated to popliteal artery injury, arteriogram of the involved extremity had been a common practice. A recent study has shown that the mere presence of a palpable pulse distal to the extremity can obviate arteriography, an examination though very useful has its own set of complications and may delay further treatment of other injuries in a setting where time is a critical matter.197 Classically, any extremity vascular injury has been described to have either hard signs, meaning a finding that demands immediate exploration or soft signs, a finding that requires investigation. Hard signs include external bleeding, a pulseless limb distal to the injury, distal ischemia

980 • CHAPTER 49

and a pulsatile hematoma. Soft signs are location of the injury and its proximity to a large vessel, the presence of a decreased or diminished distal pulses as well as associated hypotension. In the extremities and in contrast to vascular injury of the chest and abdomen, the history and physical examination can locate the injured vessel and the level of the injury in the majority of the cases. Inspection alone offers a good assessment of the location of the injury, sites of the injury, presence of active bleeding, expanding hematoma and distal pallor. When possible, the patient should move the involved extremity voluntarily to rule out paralysis. Palpation also assesses the patient for paresthesias and numbness. Numbness portends early ischemic complications, a “hard” sign that should urge an immediate restoration of blood flow before paralysis occurs; a sign that usually indicate irreversible ischemia. Auscultation helps the examiner identify the presence of a pseudoaneurysm or AVF by hearing a bruit or feeling a thrill. Auscultation via ultrasound is usually sufficient to identify the acute signs of ischemia through the ankle– brachial index (ABI). Briefly, the distal systolic Doppler pressure of the extremity is measured and divided by the brachial systolic pressure of the uninjured extremity. An ABI less than 1.0 (0.9) is indicative of arterial injury and should prompt further diagnostic investigation. Again, comparison to the opposite extremity can help distinguish preexisting vascular insufficiency as its prevalence becomes greater in our aging population. The ABI is also important to monitor the status of the distal circulation over time in patients with life-threatening injuries in other body areas that require operative intervention (craniotomy, thoracotomy, or laparotomy) or in patients who are too unstable to undergo exploration of the arterial system. As in blunt traumatic knee dislocation, physical examination alone has been considered as a replacement for arteriography in penetrating extremity injury to rule out vascular injury. Frykberg et al.39 found it to be a very reliable way to exclude vascular injury with a diagnostic accuracy of 99.5% and a false negative rate of only 0.8%. Gonzalez and Falimirski198 reported an equivalent result with a diagnostic accuracy of 98.7% in 460 patients. Using only the presence or absence of hard signs should be used as a reliable method to avoid delays in treatment and reduce the cost of any further diagnostic testing especially in a critically injured trauma patient. Noninvasive methods have been reportedly employed in the evaluation of trauma using the standard arterial pressure ratio between normal pressure and extremity pressure the ratio can help determine if a arterial injury is present or absent. Unfortunately the use of Doppler offers no therapeutic benefit and only helps to determine if further testing is necessary. The use of duplex ultrasonography that is real time mode scanning with pulse Doppler flow indication can determine the velocity spectra in that vessel. These color flow images of an area of injury can also be used as a screen for trauma; however, the same caveats apply and require a highly sophisticated technician and machine.

Therapy As the era of endovascular surgery blossoms the use of angiography with both diagnostic and therapeutic effects is present. It is likely that this will replace virtually every other mode both of confirming diagnosis and therapeutic intervention. Addressing extremity vascular injuries is similar to any other injury. The area of injury is localized; control of inflow and outflow is obtained. The injury may be repaired, patched, bridged with an interposition graft, or ligated. Unique to extremity injuries is the addition of thrombectomy to assure outflow, and the instillation of heparin into the distal vessels to prevent further thrombosis while the repair is affected. Completion Angiography/Ultrasonography After completion of an extremity vascular repair it is paramount to document flow by either a completion angiogram, or demonstration of adequate flow by ultrasound. The large conducting vessels in the chest and abdomen rarely clot, but the supply vessels of the extremities are prone to spasm, embolism, and thrombosis. Embolectomy is a crucial part of restoring peripheral flow, and completion arteriography documents patent vessels or directs further therapy to reestablish flow.199

•

VENOUS INJURY

Venous injuries usually present as dark nonpulsitatile bleeding if the wound is open or more commonly as hematoma or contusion. Venous injury is usually contained by the surrounding tissue because of the low pressure in the venous system. There may be associated arterial injuries and then the venous injury is diagnosed at the time of exploration. The superficial femoral vein is the most commonly injured major vein and the popliteal vein is the second most common.200 In the thigh when blunt injury has created venous bleeding, hypotension might occur even before a large size hematoma becomes clinically apparent. Ecchymosis, abrasions, and thigh deformity may be the only clue for the diagnosis.

•

COMPARTMENT SYNDROME

Compartment syndrome can occur with any traumatic injury to the extremity. The compartment syndrome may arise from the initial injury from ischemia from a vascular injury from thrombosis form a venous injury or from reperfusion injury after flow is reestablished. A high index of suspicion must be maintained at all times for the development of this syndrome,201 but uniform fasciotomy for any arterial injury is not indicated.202 The pathophysiology has been well established but in simplistic terms a vicious cycle of injury leading to edema leading to increase compartment pressure is leading to further ischemia and further injury and edema eventually leads to the cessation of oxygenated blood getting in tissues.203 This can occur in the face of all of the above mentioned injuries; it often occurs when there are palpable pulses

VASCULAR TRAUMA • 981

present as the injury occurs primarily from obstruction of venous capillary flow. Treatment involves releasing the containing structures of the particular compartment. Compartment injury should be assumed in all injuries and fasciotomy should be preformed virtually when ever the diagnosis is entertained on physical findings, or when the patient is unable to describe symptoms. The use of compartment pressure monitors confirms the clinical suspicion. An elevated pressure with 20 mm Hg of the diastolic pressure or 20 mm Hg below mean arterial pressure is the lower limit for threatened limb ischemia and should provoke fasciotomy.204 Fasciotomy is performed most commonly through two incisions—one medially and one laterally to open all four compartments—the lateral incision made parallel to the fibula and a fingerbreadth anteriorly opens the anterior and lateral compartments. The medial incision made parallel to the tibia and a fingerbreadth posteriorly to the bony edge is used to open the deep and superficial posterior compartments. The lateral incision and fasciotomy must avoid the peroneal nerve as it passes the fibular neck. Liberal and expedient fasciotomy is limb saving.201,205

•

FEMORAL INJURIES

The femoral artery is the most frequently injured extremity artery.206,207 Roughly one-third of the time there is an associated venous injury and a quarter of the time an associated nervous injury. The frequency of the femoral site likely is increased by its frequency for an access site for diagnostic and endovascular and cardiovascular procedures. For most of history a femoral arterial wound was fatal, or lead to the development of AVF. The older literature is replete with the diagnosis and care of AVF (i.e., ligation), today’s leading cause is iatrogenic and the repair involves both artery and vein.11,208,209 As with other vascular injuries, an unstable patient is best evaluated, resuscitated and repaired in the operating room. Germane to extremity trauma, is the complete exposure of the entire limb, not only for evaluation of distal pulses, but the harvest of potential endogenous conduits, and thrombectomy and fasciotomy. Prepping another source of autogenous vein is always helpful—usually the uninjured contralateral limb. Direct pressure is the best method for control until proximal and distal exposure and vascular clamping can be effected. The most common incision is the longitudinal groin and thigh incision directly over the course of the femoral artery. Once control is gained, and in the groin this may require exposure above the inguinal ligament, which can be divided for just such a need. Distally the profunda femoris as well as the superficial femoral artery require control. If more proximal control is needed, a retroperitoneal approach to the external iliac artery can be made through a separate oblique incision in the flank. After gaining proximal and distal control, repair is affected. Because of the mobility available form proximal and distal dissection, sufficient length can be gained for

primary end-to-end anastomosis frequently. About as frequently, interposition grafting is performed to avoid tension, using saphenous vein harvested distally from the same extremity, or from the uninjured limb.210 Iatrogenic hematomas are frequent with the number of femoral lines and with its prominence as an access for most invasive radiologic and cardiac procedures. A hematoma or leak may spread out of sight into the retroperitoneum. Similarly, AVF may be created and require repair. A good repair without impinging on the caliber of the lumen of the artery and vein is necessary, and may require a patch to avoid narrowing the lumen(s). Interposing tissue between the vessels protects the fistula from reoccurring. AVF in this region are amenable to endovascular intervention.211−213

•

POPLITEAL INJURIES

The popliteal artery is the only vessel to the shank and must be preserved if the calf and foot are to be salvaged. Severe blunt injuries or wartime injuries may mangle the limb, destroy bone and nerves which lead to amputation. Most penetrating injuries are reconstructable and the limb salvageable.214 Anticoagulation after repair of popliteal injuries is beneficial.215 Popliteal injuries arise from both mechanisms, but concern arises with posterior knee dislocations, which may relocate spontaneously or be relocated without continued vigilance of the popliteal artery. While angiography is not universally indicated, aggressive monitoring of the physical examination is needed. Missed injuries may result in AVF.216 Currently, repair is performed via endovascular techniques if at all possible.217 Exploration of the popliteal fossa is begun by a sigmoid incision with a transverse arm across the back of the knee to avoid a debilitating contracture. Virtually repair is always by interposition grafting and vein is the conduit of choice in this location.218 When there are combined venous and arterial injuries, outcomes are improved if both vessels are repaired.219 Vascular inflow should be established first in combined orthopedic and vascular injuries, even if it is temporary.220

•

DISTAL LOWER EXTREMITY INJURIES

Injuries to the distal lower extremity vessels are controversial as there is little new literature to guide decision making.221,222 Liberal use of angiography is paramount. Whereas the anatomy is often variable, the operative decision making has been as well. The demonstration of sufficient collateral flow is important is deciding which distal vessel to target. Simply, the peroneal is insufficient to assure limb salvage. If there is an isolated injury to one of the three vessels ligation is acceptable. If there is injury to the anterior tibial or posterior tibial, or both, reconstruction should be performed. If all three vessels are injured, reconstruction to either the anterior or posterior tibial artery is needed. Most reconstructions will be extra-anatomic, and vein, harvested from the uninjured limb is used. Again, any mechanism, including surgical misadventures can cause injury.223

982 • CHAPTER 49

•

SUMMARY

An evidence based summary of lower extremity arterial and venous injuries has been completed by the EAST in the practice guideline format.224,225 While a lot of that literature has been referred to in the above paragraphs, the assessment of the data following rigorous review is best summarized in that there is no overwhelming scientific support (i.e., a Level 1 recommendation) for the diagnosis and management of such injuries.

•

AXILLARY AND BRACHIAL INJURIES

Axillary artery injuries are infrequent, but complex because of associated injuries of the brachial plexus. Repair follows the same principles and salvage rates are high.226 Brachial injuries are the most common site of injury in the upper extremity, accounting for approximately half of all injuries seen in penetrating wounds, and the majority of iatrogenic injuries requiring intervention. Although there are collaterals, the majority of brachial artery injuries are easy to diagnose by ischemia and pulselessness. Repair is necessary and end-to-end anastomosis or vein interpositions are preferred. The median nerve is intimately associated with the artery and must be inspected for injury. Care must be taken to avoid the nerve during operative exposure. Ligation results in an unacceptable high rate of amputation.4 Endovascular repair is well known and very successful.227,228

•

DISTAL UPPER EXTREMITY INJURIES

Radial and ulna artery injury rates are poorly known, probably because of the ability to ligate either the radial or ulnar artery after demonstrating adequate collateral flow from the other vessel. Repair is indicated if there is insufficient flow or both vessels are injured vide infra shank injuries and the military history of amputation with combined injuries.4 Radial arteries are cannulated almost with impunity and complications are infrequent. Radial artery thrombosis likely fails to manifest symptoms unless there is inadequate flow through the ulnar connection to the palmar arch. Ischemia after arterial line placement is generally cured by removal of the line. If this is unsuccessful, anticoagulation and arteriography are performed. AVF aneurysms form commonly and can be treated by ligation.

•

VENOUS INJURY

Venous injury in the extremities is most often associated with arterial injury, and often of small clinical consequence as history has supported ligation as an acceptable clinical course, and complications are infrequent, however, in the stable patients there is benefit to repair.224 Hemodynamically compromised patients should under ligation as the expedient procedure. Several locations should mandate attempt at venous repair—especially femoral and politeal to avoid not only limb loss but long tern venous insufficiency. Even a repair with thromboses days later is not met

when the same concerns. Overall patience for venous repair is 60%.229 Patients with venous repair have less edema, and most repairs remain patent after a modest initial failure rate.230,231 Concerns over thromboembolism are unfounded.

•

ENDOVASCULAR CONSIDERATIONS

Therapeutic Interventions The first description about the use of intraluminal prosthesis in humans by Parodi et al.232 was for degenerative aortic disease. The first stents used in these situations were made out of Dacron and since then a number of alternatives are available for the current management of vascular pathology.232 Marked improvements in technique and equipment have allowed the introduction of such interventions to the care of the trauma patient. There are a number of case reports on the treatment of iatrogenic or traumatic vascular lesions, namely pseudoaneurysms, AVFs, arterial ruptures, perforations, and occlusions.233−238 Vascular trauma has increased over the past decade, either in the form of arterial or venous and generally results from complications of interventional procedures and civilian or military blunt or penetrating injuries. Trauma is now the third leading cause of death and the No. 1 killer of people younger than 45 years. Vascular injuries compromise 3% of all civilian traumas239 and penetrating trauma accounts for approximately 90% of arterial injuries.233 Reuben et al.240 identified an overall utilization of endovascular procedures in over 12,000 vascular injuries in a 9-year interval nationwide retrospective study of 2.2%. Newer diagnostic and therapeutic modalities improve patient outcome, but arteriography remains the diagnostic study of choice and operative intervention is still considered the gold standard for vascular trauma until more data is obtained from endovascular approaches. Trauma patients frequently have multiple injuries which may compromise routine vascular repairs. Endovascular stent–graft placement offers a new and less invasive technique for the treatment of acute traumatic vascular injuries.233 It has the advantages that it can be performed under local anesthesia, is well tolerated by the patient, and is associated with a shorter hospitalization time than that of surgery.234 This less invasive method seems to be associated with less blood loss and requirement for anesthesia. If successfully applied, the endovascular approach offers the advantage of simplicity and decreased operative time238,241 which in the severely traumatized patient with risks of coagulopathy, acidosis, and hypothermia or in the patient with multiple comorbidities seems to be a reasonable option. The endovascular approach allows arteriography at the same intervention, adding diagnostic advantages over an open procedure. It allows embolization of active bleeding vessels (i.e., pelvic fractures) and to obtain proximal.239 As any other intervention, the endovascular procedures carry their own risks and complications such as stent

VASCULAR TRAUMA • 983

TABLE 49-2. Indications for Endovascular Technique Inaccesibility of the vascular lesion (central vessel involvement) Contaminated field (access site remote from injured area) Anatomic distortion creating venous hypertension with excessive bleeding Severe medical comorbidities

deformation and kinking, difficult access, thrombosis, loss of vessel branches after placement, and the formation of intimal hyperplasia at the junction of the artery and the stent– graft. The Palmaz stent has been associated with only minimal inflammatory reaction and hyperplasia.235,237,239,244 A serious and often lethal complication associated with endovascular procedures is the potential microembolization of aneurysmal contents239 but seldom reported in trauma patients. It has been approximately 30 years since an endovascular technique to control traumatic hemorrhage was first described and such should be an essential part of vascular trauma management, but yet is rarely considered as part of frontline management for vascular trauma.242 Endoluminal approaches may be beneficial in those circumstances in which operative therapy may be limited (Table 49-2). Patients with vascular trauma who present with hemodynamic instability, signs of active bleeding or ischemia (hard signs of vascular injury) should have operative intervention. Patients who have endovascular repairs tend to have higher revised trauma scores implying better hemodynamic stability.240 At present, surgery is considered the gold standard approach and is not until enough level one data has been published about the safety and efficacy of endovascular techniques to recommend it as initial management for vascular injuries. Several endovascular device options are available for the treatment of an injured vessel.239,244,245 The most common used device is a self expandable stent rendered nonporous with an outer covering which can be Dacron, PTFE, vein (saphenous or jugular), or other material. The composition of the covering does not appear to make a difference in outcome.246 The most widely used stents for vascular injury are the Palmaz stent, Corvita stent–graft, Wallgraft, and the Hemobahn graft. Heparin is used during insertion but the use of long term anticoagulation is not needed239 although some advocate the use of clopidogrel for a short period of time postoperatively and acetylsalicylic acid for life.234 The efficacy of endovascular therapies for cerebrovascular injuries remains unclear. While there is a clear role of endovascular coiling for intracranial aneurysms242 its role in trauma is still experimental.248 Case reports had been published in the setting of closed head injury.249,250 One of the areas in which endovascular interventions have been widely applied is in penetrating or blunt cervi-

cal trauma. Internal carotid injuries may complicate percutaneous procedures as central line or hemodyalisis access placement. Even asymptomatic lesions pose a significant risk of stroke or hemorrhage warranting their treatment251 and stent or graft placement is gaining acceptance for this purpose. Dissections, intimal hyperplasias and specially AVFs of the carotid or vertebral arteries and jugular veins have been successfully treated with this approach and its use is of great significance when the lesions are near the skull base allowing the surgeon to avoid mandible disarticulation.81,239,252−257 Thoracic outlet injuries may be associated with subclavian and axillary vessels, innominate artery and brachiocephalic injuries all of which have been successfully controlled with coiling and stents.102,233,239,258−260 Mechanism of injury may include penetrating trauma, compression with contusion, avulsion and traction form rotational stress. The incisions used to approach and repair such vessels require clavicular resection, sternotomy or thoracotomy and each one of them may be associated with increased morbidity239,241 which may be avoided with a percutaneous approach. The technical success reported for endovascular stent–graft repair of axillary or subclavian artery injury is 94%.261 Cardiac catheterization may be complicated with coronary artery injury such as dissections and perforations. The placement of covered stents has been described and allows treatment of those iatrogenic injuries during the same procedure decreasing the need for additional anesthesia or additional operative interventions.262,263 Aortic stent–grafts are frequently used for aneurysms, ulcers and fistulas but may be indicated in the posttraumatic aortic rupture or descending dissections following trauma.264,265 The initial management of the latter is medical control of the blood pressure with nitrates or beta blockers, but the option of endovascular repair must be entertained specially in patients who are poor surgical candidates. Description of the use of aortic extender cuffs emergently or electively for the treatment of blunt (stenosis, pseudoaneuysms)266 and penetrating abdominal aortic trauma (aortocaval fistulas) have been described.267 Injuries to other intraabdominal vessles (renal, portal vein, IVC) or active bleeding from solid organs (spleen, liver) using this technique is reported elsewhere.268−271 The use of endovascular techniques for peripheral trauma has increased as consequence of the rising percutaneous diagnostic and therapeutic invasive procedures. Vascular access for cardiac catheterization accounts for the vast majority of the case reports in the literature. The relative occurrence and severity of iatrogenic arterial injury compared with those of penetrating and blunt vascular trauma is unknown.11 Covered stents are preferred for major peripheral vascular injuries but the use of Dacron plugs and embolization has been use with successful outcomes.211 The most common site for iatrogenic vascular injury seen is in the femoral artery (58%)43 but iliac vessels272 and popliteal

984 • CHAPTER 49

A

B

• FIGURE 49-6.

Arteriograms of a traumatic lower extremity AVF after a gunshot wound to the thigh. (A) The guidewire is seen in the superficial femoral artery and contrast filling the femoral vein. (B) In the same patient a covered Viabahn stent is placed to exclude femoral vessel traumatic AVF.

Images courtesy of Dr. Scott Stevens from University of Tennessee Medical Center, Knoxville.

lesions217,273 are also seen and they can be repaired with endoprocedures in appropriately selected patients (Figure 49-6). The most common application for endovascular therapy in the trauma patient is in the setting of pelvic fractures

with active extravasation. Frequently used for coiling of hypogastric artery branches in polytraumatized patients who are not candidates for operative intervention providing a minimally invasive therapeutic option to control potential life-threatening hemorrhage.274−276

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arteriovenous fistulas: repair with percutaneous implantation of endovascular covered stents. Radiology. 2000;214(1): 127-131. 237. Nyman U, Uher P, Lindh M, Lindblad B, Brunkwall J, Ivancev K. Stent–graft treatment of iatrogenic iliac artery perforations: report of three cases. Eur J Vasc Endovasc Surg. 1999; 17(3):259-263. 238. Aytekin C, Boyvat F, Yildirim E, Coskun M. Endovascular stent–graft placement as emergency treatment for ruptured iliac pseudoaneurysm. Cardiovasc Intervent Radiol. 2002; 25(4):320-322. 239. McArthur CS, Marin ML. Endovascular therapy for the treatment of arterial trauma. Mt Sinai J Med. 2004;71(1): 4-11. 240. Reuben BR, Whitten MG, Sarfatu MR, Kraiss LW. Increasing utilization of endovascular therapy in trauma: analysis of the National Trauma Bank. University of Utah, Salt Lake City. Abstract presented at: Annual Vascular Meeting 2006, Baltimore, Maryland. 2006. 241. Xenos ES, Freeman M, Stevens S, Cassada D, Pacanowski J, Goldman M. Covered stents for injuries of subclavian and axillary arteries. J Vasc Surg. 2003;38(3):451-454. 242. Beregi JP, Prat A, Willoteaux S, Vasseur MA, Boularand V, Desmoucelle F. Covered stents in the treatment of peripheral arterial aneurysms: procedural results and midterm followup. Cardiovasc Intervent Radiol. 1999;22(1):13-19. 243. Nicholson AA. Vascular radiology in trauma. Cardiovasc Intervent Radiol. 2004;27(2):105-120. 244. Marin ML, Veith FJ. Clinical application of endovascular grafts in aortoiliac occlusive disease and vascular trauma. Cardiovasc Surg. 1995;3(2):115-120. 245. Marin ML, Veith FJ, Panetta TF, et al. Transluminally placed endovascular stented graft repair for arterial trauma. J Vasc Surg. 1994;20(3):466-472. 246. Marin ML, Veith FJ. Endovascular stents and stented grafts for the treatment of aneurysms and other arterial lesions. Adv Surg. 1996;29:93-109. 247. Sluzewski M. Procedural morbidity and mortality of elective coil treatment of unruptured intracranial aneurysms. AJNR Am J Neuroradiol. 2006;27(8):1678-1680. 248. Biffl WL, Moore EE, Elliott JP, Brega KE, Burch JM. Blunt cerebrovascular injuries. Curr Probl Surg. 1999;36(7):505599. 249. Kuether TA, O’Neill O, Nesbit GM, Barnwell SL. Endovascular treatment of traumatic dural sinus thrombosis: case report. Neurosurgery. 1998;42(5):1163-1166. 250. Suzuki S, Endo M, Kurata A, et al. Efficacy of endovascular surgery for the treatment of acute epidural hematomas. AJNR Am J Neuroradiol. 2004;25(7):1177-1180. 251. Hurst RW, Haskal ZJ, Zager E, Bagley LJ, Flamm ES. Endovascular stent treatment of cervical internal carotid artery aneurysms with parent vessel preservation. Surg Neurol. 1998;50(4):313-317. 252. Naesens R, Mestdagh C, Breemersch M, Defreyne L. Direct carotid-cavernous fistula: a case report and review of the literature. Bull Soc Belge Ophtalmol. 2006;299:43-54. 253. Inamasu J, Guiot BH. Iatrogenic carotid artery injury in neurosurgery. Neurosurg Rev. 2005;28(4):239-247.

254. Chang EF, Claus CP, Vreman HJ, Wong RJ, NobleHaeusslein LJ. Heme regulation in traumatic brain injury: relevance to the adult and developing brain. J Cereb Blood Flow Metab. 2005;25(11):1401-1417. 255. Hung CL, Wu YJ, Lin CS, Hou CJ. Sequential endovascular coil embolization for a traumatic cervical vertebral AV fistula. Catheter Cardiovasc Interv. 2003;60(2):267269. 256. Duncan IC, Fourie PA. Percutaneous management of concomitant post-traumatic high vertebrovertebral and caroticojugular fistulas using balloons, coils, and a covered stent. J Endovasc Ther. 2003;10(5):882-886. 257. Sanabria A, Jimenez CM. Endovascular management of an exsanguinating wound of the right internal jugular vein in zone III of the neck: case report. J Trauma. 2003;55(1):158161. 258. Jeroukhimov I, Altshuler A, Peer A, Bass A, Halevy A. Endovascular stent–graft is a good alternative to traditional management of subclavian vein injury. J Trauma. 2004; 57(6):1329-1330. 259. Kumar V. Endovascular treatment of penetrating injury of axillary vein with Viabahn endoprosthesis. J Vasc Surg. 2004; 40(6):1243-1244. 260. Zanchetta M, Rigatelli G, Dimopoulos K, Pedon L, Zennaro M, Maiolino P. Endoluminal repair of axillary artery and vein rupture after reduction of shoulder dislocation. A case report. Minerva Cardioangiol. 2002;50(1): 69-73. 261. Rich NM, Hobson RW, Jarstfer BS, Geer TM. Subclavian artery trauma. J Trauma. 1973;13(6):485-496. 262. Rogers JH, Lasala JM. Coronary artery dissection and perforation complicating percutaneous coronary intervention. J Invasive Cardiol. 2004;16(9):493-499. 263. Tortoledo F, Izaguirre L, Trujillo MH, Tortoledo MA. Endovascular repair of accidental ligation of the right coronary artery during cardiorrhaphy for penetrating heart wound. Cardiol Rev. 2003;11(6):303-305. 264. Thomson I, Muduioa G, Gray A. Vascular trauma in New Zealand: an 11-year review of NZVASC, the New Zealand Society of Vascular Surgeons’ audit database. N Z Med J. 2004;117(1201):U1048. 265. Teruya TH, Bianchi C, Abou-Zamzam AM, Ballard JL. Endovascular treatment of a blunt traumatic abdominal aortic injury with a commercially available stent graft. Ann Vasc Surg. 2005;19(4):474-478. 266. Sigler L, Gutierrez-Carreno R, Martinez-Lopez C, Lizola RI, Sanchez-Fabela C. Aortocava fistula: experience with five patients. Vasc Surg. 2001;35(3):207-212. 267. Mejia JC, Myers JG, Stewart RM, Dent DL, Connaughton JC. A right renal vein pseudoaneurysm secondary to blunt abdominal trauma: a case report and review of the literature. J Trauma. 2006;60(5):1124-1128. 268. Benson DA, Stockinger ZT, McSwain NE Jr. Embolization of an acute renal arteriovenous fistula following a stab wound: case report and review of the literature. Am Surg. 2005;71 (1):62-65. 269. Owen RJ, Rose JD. Endovascular treatment of a portal vein tear during TIPSS. Cardiovasc Intervent Radiol. 2000;23(3): 230-232.

992 • CHAPTER 49 270. Castelli P, Caronno R, Piffaretti G, Tozzi M. Emergency endovascular repair for traumatic injury of the inferior vena cava. Eur J Cardiothorac Surg. 2005;28(6):906-908.

274. Starnes BW, Arthurs ZM. Endovascular management of vascular trauma. Perspect Vasc Surg Endovasc Ther. 2006;18(2): 114-129.

271. Buckman RF, Pathak AS, Badellino MM, Bradley KM. Injuries of the inferior vena cava. Surg Clin North Am. 2001; 81(6):1431-1447. 272. Lee JT, Bongard FS. Iliac vessel injuries. Surg Clin North Am. 2002;82(1):21-48.

275. Zhou W, Bush RL, Terramani TT, Lin PH, Lumsden AB. Treatment options of iatrogenic pelvic vein injuries: conventional operative versus endovascular approach— case reports. Vasc Endovascular Surg. 2004;38(6):569573.

273. Verhoeven EL, Prins TR, van Det M, van den Dungen JJ. Stent–graft repair of a recurrent popliteal arteriovenous fistula. J Endovasc Ther. 2002;9(3):375-378.

276. Howells GA, Janczyk RJ. Principles of Vascular Trauma. Mastery of Vascular and Endovascular Surgery. Lippincott Williams & Wilkins; 2006.

chapter

50

Primary Vascular Tumors Samuel L. Johnston, MD / Terrence C. Demos, MD / Edward J. Keuer, MD / Mamdouh Bakhos, MD / Robert S. Dieter, MD, RVT

•

INTRODUCTION

Peripheral vascular tumors are rare, yet some physicians encounter patients with these tumors regularly and most physicians encounter them at least several times in the course of their practice. The clinical significance of vascular tumors ranges from trivial to cosmetically and psychosocially burdensome to life threatening. Some have characteristic clinical manifestations while many are found incidentally but have characteristic imaging findings. However, rare lesions and variable clinical presentations can result in delayed or misdiagnosis. This chapter will provide an overview of primary vascular tumors, emphasizing those affecting arteries and capillaries.

•

tinguishing hemangiomas from VM and is the official classification schema of the International Society for the Study of Vascular Anomalies. Despite the current acceptance of this standard, imprecise terminology remains widespread in the scientific literature.3 Furthermore, pathologists, who are often unaware of a patient’s clinical presentation, still use histopathologic diagnoses and classify vascular lesions by the type of vessel that predominates (arterial, venous, or lymphatic). In contrast, clinicians often make the diagnosis without relying on biopsy or histopathology.

•

BENIGN NEOPLASMS

Hemangioma CLASSIFICATIONS

Primary vascular neoplasms are defined as those arising from vascular elements, such as endothelial cells and pericytes. Most involve the microvasculature and manifest in the skin, but others affect deep structures and occasionally manifest in large vessels. Historically, clinicians and pathologists have used conflicting descriptions and schemes in classifying vascular tumors and vascular malformations (VM). In some cases, different labels have been used to describe the same disease while in other cases the same label has been applied to vastly different diseases. In 1982, Mulliken and Glowacki1 published a classification system based on endothelial characteristics and biologic behavior, in part to address this confusion (Table 50-1). A subsequent revision of their classification system broadened the category of vascular tumors of infancy to include pyogenic granuloma, tufted angioma, kaposiform hemangioendothelioma (KH), and hemangiopericytoma.2 This revised classification has become the standard for dis-

Hemangiomas are benign tumors of vascular endothelium and, by far, the most common form of primary vascular tumor. They most commonly affect the skin, but can occur in nearly any organ (Table 50-2). Hemangiomas are often without clinical significance, but they can cause complications such as disfigurement, ulceration, bleeding, organ failure, and death. Most hemangiomas present early in life. In some cases, hemangiomas are inherited as part of rare syndromes. Newly diagnosed superficial hemangiomas are uncommon after 30 years of age, but deep hemangiomas are often discovered incidentally in adults during imaging studies. Hemangiomas have often been confused with VM.1 The clinical distinction between hemangiomas and VM is not always initially apparent, but the diagnosis usually becomes clear with time. There are several features that distinguish hemangiomas from VM. Hemangiomas are more common in Caucasians than other races, more common in females than males, have early growth that is disproportionate to that of the patient, are composed of immature hyperplastic

994 • CHAPTER 50

TABLE 50-1. Classification of Primary Vascular Tumors

TABLE 50-3. Differentiating Vascular Anomalies

Benign neoplasms Hemangioma Capillary Cavernous Pyogenic granuloma (lobular capillary hemangioma) Glomus tumor Tufted angioma (Angioblastoma of Nakagawa) Intermediate-grade neoplasms Kaposiform hemangioendothelioma Kaposi sarcoma Malignant neoplasms Angio sarcoma Hemangiopericytoma

Hemangiomas

Vascular Malformation

Endothelial cell hyperplasia

Dysplastic vessels with normal endothelial turnover Present at birth Growth proportional to child No regression

Adapted from Mulliken JB, Glowacki J. Hemangiomas and vascular malformations in infants and children: a classification based on endothelial characteristics. Plast Reconstr Surg. 1982;69(3):412-422 and Cotran RS, et al. Robbins Pathologic Basis of Disease. 6th ed. Philadelphia: PA: Saunders; 1999.

endothelial cells, have increased numbers of mast cells, and have upregulated expression of proliferative cell markers (see Pathophysiology below) (Table 50-3). In contrast to hemangiomas: VM have equal sex distribution, are often present and fully formed at birth, grow proportionately with the child, are composed of mature and often combined arterial, venous, or lymphatic vascular elements, have normal numbers of mast cells, have no

TABLE 50-2. Distribution of 570 Hemangiomas Location Cutaneous or mucosal Oral cavity Face Arm Leg Scalp Vulva or scrotum Other Liver Central nervous system Heart Bone GI tract, kidney, mesentery Muscle Total

No. of Cases 370 80 75 60 50 46 5 54 109 43 16 12 10 10 570

Adapted from Geshickter CF, Keasbey LE. Tumors of blood vessels. Am J Cancer. 1935;23:568.

Small or absent at birth Rapid growth during infancy Involution phase during childhood

Adapted from Mulliken JB, Glowacki J. Hemangiomas and vascular malformations in infants and children: a classification based on endothelial characteristics. Plast Reconstr Surg. 1982;69(3):412-422.

increase in proliferative cell markers, and unlike hemangiomas, endothelial cells from VM do not grow in tissue culture. Pathophysiology. Although theories abound, the etiology of hemangiomas and the mechanisms that control their proliferation and involution are not well understood. At least four general theories predominate, as discussed below. Chorionic Villi. There is strong evidence of a relationship between hemangiomas and placental chorionic villi. The gene expression profiles of hemangiomas and placentae are similar and they share a tissue-specific marker called GLUT1.4 It has been hypothesized that hemangiomas represent the embolization of placental tissue to the fetus.5 However, contrary to popular belief, it has recently been shown that chorionic villous sampling is probably not a contributing factor to the development of hemangiomas.6 Angiogenesis. Hemangiomas have long been thought to

represent a localized derangement of angiogenesis (the growth of new vessels from existing vessels). As evidence for this theory, proliferating hemangiomas have upregulated expression of angiogenic factors, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (BFGF), fibroblast growth factor (FGF), and type-IV collagenase.7−9 Furthermore, therapy directed at inhibiting angiogenesis, such as corticosteroids and interferons, is often effective in causing involution of hemangiomas. Vasculogenesis. More recently, however, some have argued that hemangiomas are mediated not by angiogenesis, but instead, by an error in vasculogenesis (the formation of blood vessels from angioblasts). This theory postulates that hemangiomas represent an incomplete maturation of the endothelial component of the fetal vasculature. The supporters of this theory point to the clonality of proliferating hemangioma endothelial cells.10,11

PRIMARY VASCULAR TUMORS • 995

Immune-Mediated. Immunohistochemical staining sug-

gests a causal role for hematopoietic cells of myeloid origin.12 Expression of specific clusters of differentiation (CD83, CD32, CD14, CD15), possibly triggered by local tissue hypoxia, have been demonstrated in hemangioma endothelial cells. The evidence for these differing putative mechanisms suggests either a multifactorial process or the presence of different disease entities under the umbrella diagnosis of “hemangioma.” Pathologic Classifications. Hemangiomas are classified by pathologists as being capillary, cavernous, or pyogenic

granuloma (lobular capillary hemangioma).13 However, the American Academy of Dermatology refers to capillary hemangiomas as “superficial hemangiomas” and cavernous hemangiomas as “deep hemangiomas.”14 Hemangiomas that involve both superficial and deep tissue are called combined (or compound) lesions. Capillary Hemangioma. Capillary (“strawberry”) heman-

giomas represent the major common form of hemangioma. Most often, they are located in the skin or subcutaneous tissue. Grossly, these lesions appear red to purple in color (Figure 50-1). Histologically, one sees a proliferation of capillary-sized vessels surrounding a feeder vessel

B

A

• FIGURE C

50-1. Capillary (superficial) Hemangioma. (A) Periorbital. (B) Nasal (late state of resolution). (C) Hip (early stage of resolution).

996 • CHAPTER 50

• FIGURE 50-3.

Combined hemangioma with resolution of superficial component, revealing deep (cavernous) component. Pyogenic Granuloma. See next section.

Pediatric Hemangiomas. Hemangioma of infancy (HOI)

• FIGURE 50-2.

Capillary hemangioma (hematoxylin and

eosin [stain]).

Courtesy of Madhu Dahiya, M.D., Department of Pathology, Loyola University Medical Center and Stritch School of Medicine, Maywood, IL.

(Figure 50-2). This architecture has been referred to as “lobular” and has also been used to describe pyogenic granuloma and epithelioid hemangioma. The sine qua non of capillary hemangiomas is the presence a proliferating phase and an involuting phase.

is the most common soft tissue tumor in the pediatric population, occurring in nearly 10% of Caucasian infants. Although the etiology and pathophysiology of hemangiomas remains unclear (see above), a number of risk factors have been identified (Table 50-4). Of those affected, 20% have multiple lesions.16 The vast majority of HOI occur sporadically, although familial autosomal dominant cases have been reported.17 Most HOI are superficial (capillary type). Many are not evident at birth, in contrast to VM, but become noticeable within the first few days or months of life. HOI can involve nearly any organ, but most are cutaneous on the head and

Cavernous Hemangioma. Cavernous (deep) heman-

giomas are less common than capillary (superficial) hemangiomas. They are generally larger, less well circumscribed, and more likely to involve deep structures, such as solid organs (e.g., liver). Grossly, they appear as indistinct purplish-blue nodules or masses in the skin (Figure 50-3). Histologically, they appear as massively engorged capillary hemangiomas (Figure 50-4), but unlike capillary hemangiomas, cavernous hemangiomas tend not to involute or do so more slowly and incompletely. They are also more likely to cause local tissue destruction. Many cavernous hemangiomas are discovered incidentally on imaging studies. Both computed tomography (CT) and magnetic resonance (MR) imaging show an enhancing heterogeneous mass resulting from fibrous, vascular and fat components. There may be erosion of adjacent bones. The most characteristic imaging findings, however, are phleboliths, which are small rounded calcifications or ring calcifications of venous walls or thrombi. Phleboliths are found in up to one-third of cavernous hemangiomas (Figures 50-5 and 50-6).15 Complex hemangiomas with thrombus, hemosiderin, and hyalinization may resemble neoplasms.

• FIGURE 50-4.

Cavernous hemangioma (hematoxylin

and eosin [stain]).

Courtesy Madhu of Dahiya, M.D., Department of Pathology, Loyola University Medical Center and Stritch School of Medicine, Maywood, IL.

PRIMARY VASCULAR TUMORS • 997

B

A

• FIGURE 50-5.

Retroperitoneal hemangioma or KH with phleboliths. (A) Abdominal radiograph shows cluster of calcified phleboliths (arrow). (B) CT shows heterogeneous lesion containing phleboliths (arrow). Retroperitoneal hemangiomas are rare, but round and circular calcifications in masses anywhere in the body suggest vascular lesions.

neck (Figure 50-1A and 50-1B) (Table 50-2). Superficial hemangiomas appear as red papules, nodules, or plaques. Deep tissue hemangiomas often have a bluish hue (Figure 50-3).

Hemangiomas are characterized by a phase of proliferation followed by phase of involution and regression. They typically grow to maximal size by age 6 to 18 months and their growth is disproportionate to that of the infant. With

A

B

• FIGURE 50-6.

Adrenal hemangioma. (A) Radiograph shows left shows left kidney (K) displaced caudally by suprarenal mass (arrow) with small irregular calcifications. (B) CT shows the large heterogeneous adrenal hemangioma containing multiple phleboliths. These multiple small well-defined phleboliths shown by CT are typical findings in hemangiomas and other vascular tumors.

998 • CHAPTER 50

TABLE 50-4. Risk Factors: Infantile Hemangiomas Caucasian race Female gender (5:1 female to male) Advanced maternal age (>35 y) Preterm infants Low birth weight Multiple gestations Placenta previa Preeclampsia

(US) is a useful imaging modality for screening infants with more than five cutaneous hemangiomas for visceral lesions. Tumors in patients with hemangiomatosis recur in 90% of cases, so treatment should be as conservative as possible.22 Syndromes. Aside from hemangiomatosis, there are sev-

few exceptions, they range in size from a few millimeters to several centimeters in diameter. Most will spontaneously involute. As a general rule, approximately 10% involute per year after 1 year of age. By 7 years of age, 75% to 90% will have involuted. However, even when a lesion fully involutes and regresses, a residual hypopigmented scar with redundant skin is evident in 50% of cases. The risk of scarring increases with larger combined lesions, and with lesions of the nose, ear, lip, or breast.

eral other rare clinical syndromes associated with hemangiomas (Table 50-5).13 Gorham disease (vanishing bone disease) is a syndrome of massive osteolysis that can occur with hemangiomatosis. Maffucci syndrome is a nonhereditary mesodermal dysplasia that manifests with multiple cavernous hemangiomas and enchondromas, most of which affect the phalanges and long bones (Figure 50-8). Patients with blue rubber bleb nevus syndrome (Bean syndrome), Peutz-Jeghers syndrome, and Klippel-Trenaunay-Weber syndrome may have multiple bowel hemangiomas that bleed and cause iron-deficient anemia. PHACE syndrome affects multiple organ systems and is discussed separately (see below). The Kasabach-Merritt syndrome (KMS) is a consumptive coagulopathy associated with specific hemangiomas, especially KH and tufted angioma (see below). Contrary to reports in older literature, KMS is rarely, if ever, associated with infantile hemangioma.

Congenital Hemangiomas. Congenital hemangiomas

Complications and Regionally Important Lesions.

are rare and of two types: Rapidly involuting congenital hemangioma (RICH) and noninvoluting congenital hemangioma (NICH).18 RICH is similar to HOI but is fully developed at birth, lacks female preponderance, and pursues a course of rapid involution. Imaging studies can aid in making a diagnosis and differentiating this tumor from other entities, but occasionally biopsy is necessary. Accurate diagnosis of RICH is important in order to avoid unnecessary interventional therapy for this rapidly regressing lesion. NICH is so called because it is fully formed at birth and never involutes. Enjolras et al.19 published a series of 53 patients and found that all NICH lesions were single, averaged 5 cm in size, and more than 40% were on the head and neck.

Most hemangiomas are asymptomatic. However, lesions affecting the face often cause psychosocial distress (Figure 50-1A and 50-1B). An additional 10% of pediatric hemangiomas will result in structural, coagulopathic, or metabolic complications (Table 50-6).

Hemangiomatosis. Most hemangiomas are single and cu-

taneous, but 20% of patients will have more than one lesion.16 Hemangiomatosis is a syndrome that mostly affects neonates and is defined by the presence of multiple small hemangiomas (≥5 lesions).13,20 Most cases are confined to the skin. Sometimes, hundreds of lesions are present and envelop an entire extremity (Figure 50-7). A more severe variant can result in significant morbidity and rarely mortality because of systemic involvement.21,22 In order of decreasing frequency, the liver, GI tract, brain, and lung may be affected. Hepatomegaly, congestive heart failure (CHF) and anemia appear early in severely affected infants, and death may result from heart failure. Despite its potentially aggressive nature, there are no reports of hemangiomatosis progressing to malignancy, and it remains a benign lesion that is often histologically identical to other common manifestations of hemangioma. Ultrasound

Psychosocial distress, both for the patient and the family, is the most common complication of pediatric hemangiomas. Much has been published on this topic.14,16,23,24 These issues are best dealt with by educating the parents and patient as to the natural course of the disease, explaining the treatment plans, and discussing reasonable expectations. Frequent and regular office follow-up is often necessary. Contact with other families through support groups and via the Internet may also be helpful.

PSYCHOLOGIC ISSUES.

Ulceration and bleeding are common complications of rapidly proliferating cutaneous hemangiomas and those located in areas of friction and pressure, such as the intertriginous areas.25 These lesions are generally painful, susceptible to secondary infection and often result in larger residual scaring and discoloration.

ULCERATION AND BLEEDING.

Soft tissue hemangiomas may present as a mass, with pain and discomfort, or as an incidental finding on an imaging study. Functional impairment may arise when a hemangioma interferes with a vital structure. Physical examination findings are often subtle. Generally, there is no discoloration of the overlying skin. The size of the lesion cannot be reliably assessed by palpation. Thrills and bruits are rarely present. Therefore, imaging studies (e.g.,

SOFT TISSUE LESIONS.

PRIMARY VASCULAR TUMORS • 999

B

A

C

• FIGURE 50-7.

Hemangiomatosis. (A) Angiogram shows a large angiomatous lesion of the left ankle. (B) CT shows markedly enlarged left thigh with subcutaneous angiomatous tissue. (C) Pelvic CT shows angiomatous subcutaneous tissue of left body wall and within pelvis displacing B: bladder. All organs can be involved in addition to soft tissue and bones. The prognosis is largely determined by the presence and extent of visceral involvement.

plain films, CT, MR, US, angiography) are especially useful in establishing the diagnosis (Figures 50-9 to 50-12). Biopsy should be performed if there is uncertainty regarding the diagnosis, particularly if there is a question of malignancy. SKELETAL LESIONS. Hemangiomas are the most common benign vascular tumor of bone in children and adults, but constitute only 1% of bone tumors.26,27 Most skeletal hemangiomas occur in the vertebrae (Figure 50-13) and skull (Figure 50-14) and are asymptomatic. Most of these tumors are discovered incidentally on routine imaging tests where they have a characteristic appearance. Appendicular skeletal lesions (Figure 50-15) are much less common, difficult to diagnose on imaging studies, and more likely to present with pain, swelling, or pathologic fracture.28

Periorbital hemangiomas are among the most complicated lesions, as the visible portion often represents only the tip of the iceberg (Figure 50-1A). Periorbital hemangiomas can compromise visual axis maturation, resulting in a range of functional disabilities.29,30 Patients may present with exophthalmos, proptosis, astigmatism,

PERIORBITAL LESIONS.

ptosis, strabismus, or visual impairment. MR is useful to assess the extent of the lesion and potential compromise to vital structures. Vision may be compromised by even small lesions so early pediatric ophthalmologic consultation is crucial. Hoarseness or stridor in an infant patient of 6 to 12 weeks of age may herald a subglottic hemangioma.31 Patients at highest risk for this complication have hemangiomas affecting the “beard” region of the face, which corresponds to the cranial nerve V3 trigeminal distribution (preauricular, anterior neck, chin, and lower lip). Early consultation with ENT is advisable. Bronchoscopy may be necessary to establish the diagnosis and/or treat the lesion.

UPPER AIRWAY LESIONS.

PHACE SYNDROME. The PHACE syndrome (Online Mendelian Inheritance in Man [OMIM] No. 606519) describes patients with: (1) Posterior fossa malformation; (2) Hemangioma; (3) Arterial abnormalities (including coarctation of the Aorta); (4) Cardiac defects; and (5) Eye abnormalities (Figure 50-16).32−34 It is thought to be caused

1000 • CHAPTER 50

TABLE 50-5. Clinical Syndromes Associated with Vascular Tumors Description Hemangiomatosis Gorham disease (vanishing bone disease) Maffucci syndrome Blue rubber bleb nevus syndrome (Bean syndrome) Peutz-Jeghers syndrome

Klippel-trenaunay-weber syndrome

PHACE syndrome

Kasabach-Merritt syndrome Stewart-Treves syndrome Kettle’s syndrome

Benign, but potentially aggressive syndrome of multiple cutaneous hemangiomas; sometimes involving other organs (liver, GI tract, brain, lung) Extremely rare syndrome of massive osteolysis that can occur with hemangiomatosis Dyschondroplasia with multiple cavernous hemangiomas. Twenty-percent develop malignant tumors, especially chondrosarcoma; rarely AS Autosomal dominant. Cavernous hemangiomas of the skin, GI tract, and other viscera Autosomal dominant. Multiple GI hemangiomas and hamartomatous polyps. Melanotic mucosal and cutaneous pigmentation around the lips, oral mucosa, face, genitalia and palms; increased risk of various carcinomas Nonhereditary, sporadic disorder characterized by soft tissue and bony hypertrophy, varicose veins, and cutaneous portwine stain of the lower extremities; occasional GI involvement (1) Posterior fossa malformation; (2) Hemangiomas; (3) Arterial abnormalities and coarctation of the Aorta; (4) Cardiac defects; and (5) Eye abnormalities Consumptive coagulopathy (thrombocytopenia and DIC) associated with KH, tufted angioma and (rarely) AS AS of the breast following radical mastectomy. Associated with chronic lymphedema AS of the lower extremities in patients with melanoma following inguinal lymphadenectomy. Associated with chronic lymphedema

by an unknown embryonic insult that occurs during the first trimester of gestation. However, a strong female predominance exists, suggesting X-linked inheritance, but no familial cases have been reported. Infants with PHACE syndrome present a spectrum of anomalies and disease severity. The diagnosis should be considered in any infant presenting with a large plaque-like lesion on the face. The vascular lesion, which is a true hemangioma, can be confused with the port wine stain (a VM) associated with the Sturge-Weber syndrome. Affected patients require an extensive work-up and consultation with a dermatologist, ophthalmologist, neurologist, cardiologist, and radiologist familiar with the syndrome. MR of the head and neck should be considered to evaluate for posterior fossa abnormalities (e.g., the DandyWalker complex, cerebellar hypoplasia, and abnormalities of the vermis). Cerebral vascular compromise and stroke can result from compression of the carotid arteries or circle of Willis by hemangioma.35−37 Carotid and vertebral anomalies are best evaluated by MR angiography or traditional (invasive) angiography with digital subtraction. The aortic arch can be evaluated by CT angiography, MR angiography, or more invasively by angiography. Transthoracic echocardiography should be performed to evaluate for congenital heart disease, such as atrial septal defect, or ventricular septal defect. In the general population, most visceral hemangiomas occur in the absence of cutaneous hemangiomas. However, in the pediatric population, the presence

VISCERAL LESIONS.

of large or multiple (≥5) cutaneous hemangiomas is a significant risk factor for the presence of visceral (especially hepatic) and brain hemangiomas. US is an effective noninvasive and relatively inexpensive method for screening the abdomen. In patients younger than 5 months of age, US may also be used to screen for the presence of brain hemangiomas. The liver is the most common site of visceral hemangiomas (affecting 5% of the general population), and hemangioma is the most common benign hepatic tumor. Most liver hemangiomas are without clinical significance and are discovered incidentally during abdominal imaging studies (Figures 50-17 and 50-18). Most liver hemangiomas have characteristic imaging findings on CT, MR, and US (Figure 50-19A to 50-19D). Angiography is rarely used to establish the diagnosis, but classically shows highly vascular lesions with parallel arterial feeders and late venous stain. Technetium-99 m-labeled red blood cell (RBC) nuclear imaging can also be helpful when the diagnosis is in doubt based on other imaging studies (Figure 50-19E and 50-19F).38 When significant arterial–venous shunting occurs within a liver hemangioma, high-output CHF may result. Massive liver hemangiomas sometimes compress adjacent structures, such as renal veins and the inferior vena cava (IVC), causing abdominal compartment syndrome. In very rare instances, liver hemangiomas can cause a consumptive hypothyroidism as a result of high expression of the thyroid hormone inactivating enzyme type-3 iodothyronine deiodinase (D3).39

PRIMARY VASCULAR TUMORS • 1001

A

B

• FIGURE 50-8.

Maffucci syndrome (enchondromatosis with hemangiomas). (A) Hand radiograph shows extensive bone and soft tissue deformities caused by enchondromas. (B) Arteriogram shows numerous soft tissue hemangiomas. Lesions are unilateral in one-half of patients. The hands are the most common site of involvement. Malignant transformation as high as 20% has been reported, usually after 40 years of age and most often chondrosarcoma, but many other neoplasms, including AS, also occur.

The presence of iron-deficient anemia or bowel obstruction in the pediatric population should prompt the consideration of gastrointestinal (GI) hemangioma. GI hemangiomas may present focally within the bowel wall, diffusely as intestinal hemangiomatosis, or as an extrinsic abdominal or pelvic cavernous hemangioma with direct invasion of the GI tract.40 In these cases, a gastroenterol-

TABLE 50-6. Complications of Hemangiomas Cosmetic Psychosocial Ulceration and bleeding Persistent soft tissue deformity Skeletal deformity and/or pain Ophthalmologic complications Upper airway obstruction Cerebral vasculopathy and stroke (PHACE syndrome) Spinal dysraphism Genitourinary abnormalities High-output CHF Consumptive coagulopathy (KMS)

ogy consult is warranted. The diagnosis may be established with endoscopy, tomographic imaging of the abdomen and pelvis (e.g., CT, MR), or angiography. GI hemangiomas are often associated with clinical syndromes (Table 50-5) and, when encountered, should raise the possibility of blue rubber bleb nevus syndrome (Bean syndrome), KlippelTrenaunay-Weber syndrome, or Peutz-Jeghers syndrome.41 Congestive Heart Failure. High-output CHF as a result of arteriovenous (AV) shunting is an occasional complication of hemangiomas. In these cases, the offending lesion(s) is most often hepatic (see above). These patients should be evaluated by a cardiologist. An initial evaluation should include an electrocardiogram (ECG), an echocardiogram, a chest X-ray and basic laboratory work. Cardiac catheterization is often unnecessary in patients younger than 30 years of age, but may be useful in establishing the severity of the shunt. The liver, and potentially other viscera, should be evaluated for hemangioma by imaging studies (US, CT, MR, nuclear). LUMBOSACRAL SPINE LESIONS. Hemangiomas affecting the lumbosacral region are of special significance (Figure 50-20). Their presence is associated with occult spinal

1002 • CHAPTER 50

• FIGURE 50-9.

Hemangioma of forearm. Round and circular (arrows) calcifications of this soft tissue mass are highly suggestive of vascular lesion.

dysraphism. Lesions that are macular and telangiectatic are of greatest concern. Deviation of the supragluteal cleft is another diagnostic clue to the presence of this complication. Genital or renal anomalies may accompany these lesions. The lumbosacral spine can often be sufficiently imaged by US in infants younger than 4 months. MR of the lumbar spine and pelvis should be performed in older patients.42−44 Consider obtaining consultations with a neurologist, neurosurgeon, and urologist. Adult Presentations and Considerations. Most hemangiomas present during infancy. However, diagnosis in adults is not uncommon. Whereas HOI tend to be superficial

A

and visible, hemangiomas diagnosed in adulthood tend to be deep and subclinical. With the exception of pyogenic granulomas, de novo cutaneous hemangiomas are vanishingly rare in adults. Indeed, most hemangiomas diagnosed in adults are found incidentally during imaging studies. It is unusual for an adult to complain of functional impairment as a result of a hemangioma. Adults with symptomatic hemangiomas tend to have vague or nonspecific symptoms, such as pain or discomfort with an insidious onset and chronic duration. Pregnancy and hormonal therapy can increase the size of an already existing hemangioma and make it more likely to become symptomatic.

B

• FIGURE 50-10.

Hemangioma of thumb. (A) Radiograph shows soft tissue mass adjacent to thumb. (B) Angiogram shows hypervascularity and stain of mass.

PRIMARY VASCULAR TUMORS • 1003

B

A

• FIGURE

C

50-11. Hemangioma of hand. (A) Radiograph shows metacarpals and phalanges displaced by soft tissue mass with phleboliths (arrows). (B) Arteriogram early image shows large abnormal vessels. (C) Arteriogram late image shows persistent faint vascular opacification. Phleboliths suggest a primary vascular lesion, and lack of early venous fillings favors a hemangioma rather than an AV malformation.

1004 • CHAPTER 50

• FIGURE 50-12.

Soft tissue hemangioma of the neck (arrow) shown by sagittal T2-weighted MR image.

Isolated liver hemangiomas are the most prevalent, with 5% of the population being affected. Women, especially with a history of multiparity, are affected more often than men (5:1), and tend to present at a younger age and with larger tumors. Hemangiomas affecting the digestive tract are less prevalent, but should be considered in the differential diagnosis of young adult patients presenting with iron-deficient anemia. GI hemangiomas affect women and men equally and tend to present in the third decade of life.45 They may be focal or present as intestinal hemangiomatosis40 The skeleton is the second most prevalent anatomic location for hemangiomas in adults. Yet, skeletal hemangiomas are relatively rare, constituting approximately 1% bone tumors.13,26,27 As in children, most occur in the vertebrae (Figure 50-13) and calvaria (Figure 50-14) and rarely in the appendicular skeleton (Figure 50-15). Histologically, they can be capillary or cavernous. They are diagnosed in all age groups, including the elderly, and affect men and women equally.28 Intramuscular and other soft tissue hemangiomas are occasionally seen in adults (Figures 50-9 to 50-11). They can easily be confused with malignant tumors, and differentiation from angiosarcoma (AS) is vital. Intramuscular cavernous hemangiomas are more easily distinguished as benign, but are sometimes misdiagnosed as lipomas. Work-Up. Patients with hemangiomas most often present

with an obvious cutaneous lesion seen early during infancy.

Other presentations are less straightforward. Many specific aspects of the work-up have been described in the preceding section: “Complications and Regionally Important Lesions.” Here we describe a general approach to the work-up of a patient with suspected hemangioma. Establishing the correct diagnosis and determining the extent of disease is predicated on taking a careful history and performing a thorough physical examination. When evaluating a patient with a known or suspected hemangioma, it is important to establish the course of the lesions (i.e., proliferation and involution). Further, any complications should be documented along with what prior work-up has already been performed (e.g., imaging studies, biopsy), as well as prior treatments and the response to those treatments. An understanding of the patient’s other past medical history, birth history, maternal pregnancy history, and a review of systems (including psychologic concerns) are imperative. The physical examination should be comprehensive in addition to a thorough examination of the skin. Skin findings should document lesion location, size, morphology, and presence of ulceration, bleeding, or secondary infection. Petechiae, purpura, and ecchymoses are indicative of a bleeding diasthesis such as KMS. It may be helpful to obtain serial photographs to monitor the patient’s clinical course. Other major organs and organ systems should also be evaluated for involvement such as evidence of airway obstruction, CHF, visceral complications, neurologic deficits, or skeletal abnormalities. A high index of suspicion for deep tissue involvement may warrant evaluation, such as imaging studies. Laboratory tests are unnecessary in the work-up of the vast majority of patients with hemangiomas, but should be obtained if there is evidence of a bleeding diathesis or metabolic derangement. If there is any suspicion of malignancy, biopsy is necessary. Hemangiomas are small and uncomplicated in 90% of patients. However, physicians who encounter these patients should have a low threshold for consulting a dermatologist. Further work-up with imaging tests, other specialty consultations and, occasionally, biopsy may be warranted if the diagnosis is in question, the patient has complications, or therapeutic interventions are being considered. Management. Most hemangiomas are small, cutaneous, and asymptomatic and require no treatment. In these cases, close follow-up is advisable in order to ensure that the patient remains asymptomatic and free of complications. Medical therapy and, occasionally, surgical resection or embolic therapy, are required to treat complicated hemangiomas. A multidisciplinary approach is often necessary. The goals of treatment are not only the prevention of potential complications, such as loss of function, disfigurement, bleeding, infection and pain, but also to address the inherent psychosocial distress that often affects patients and their families. Although it is a potentially difficult conversation, patients and families should be made aware of the potential for unpredictability and the extremely

PRIMARY VASCULAR TUMORS • 1005

A

B

C

• FIGURE 50-13.

Hemangioma of lumbar vertebra. (A) Bone scan shows nonspecific uptake in lumbar vertebra (arrow). (B) Lateral radiograph shows characteristic vertical bony striations. (C) CT shows vertical striations in cross section as characteristic dots within the low attenuation lesion (arrow) in right side of vertebral body. While the bone scan is nonspecific, the characteristic radiographic and CT findings are easily recognized.

1006 • CHAPTER 50

A

• FIGURE 50-14.

Hemangioma of calvaria. (A) Lateral skull radiograph shows characteristic stellate trabecular pattern (arrows). (B) CT shows expansile lesion (arrow) with intact inner and outer table and abnormal diploic space trabeculae. Calvarial hemangiomas have a stellate “sunburst” appearance as a result of periosteal spicules that radiate from their center.

heterogeneous clinical characteristics of hemangiomas. Patient and family education, as well as a frank discussion of realistic expectations, is usually helpful. Generalized guidelines for the management of hemangiomas of infancy have been published by the American Academy of Dermatology.14 In practice, treatment of hemangiomas must be individualized according to various factors, such as the age of the patient, rate of proliferation/involution, location of the lesion, size of the lesion, and the potential for complications. Most lesions are primarily cutaneous and therefore best managed by dermatologists. Hemangiomas that are most likely to require intervention include periorbital lesions, lesions affecting the upper airway, ulcerated lesions, very large or rapidly expanding lesions, large hepatic lesions, and lesions that cause significant disfigurement.46 The appropriate consulting specialties should be involved early in the management of these patients in order to establish questionable diagnoses, institute therapy and prevent complications. Chemotherapy. The first-line chemotherapy for complicated hemangiomas is high-dose systemic corticosteroid (2–3 mg/kg/d for 3–12 months during the proliferative phase). The physician should be aware of the significant potential for side effects, which are especially considerable in the pediatric population. Intralesional corticosteroids (e.g., triamcinolone acetonide) and topical corticosteroids have been used effectively for small superficial lesions

B

with less risk of adrenal suppression and other major side effects.47 Following its successful use in the treatment of HIV patients with Kaposi’s sarcoma (KS), the recombinant cytokine interferon alpha 2b (IFN-␣ 2b) was found to be useful in the treatment of pediatric hemangiomas. IFN-␣ 2b has subsequently become an established second-line therapy for corticosteroid-refractory hemangiomas. The mechanism of IFN-␣ 2b is antiangiogenesis. Despite its efficacy, the use of IFN-␣ 2b is limited by its transient, but often poorly-tolerated side effects including fever, malaise, neutropenia, and transaminitis. Severe neurotoxicity including spastic diplegia and demyelination, has also been reported.48 Vincristine has also been used successfully in the treatment of corticosteroid-refractory hemangiomas, particularly in the setting of KMS.49,50 The mechanism of action is apoptosis of hemangioma tumor cells. Its use is limited by its long list of significant side effects, including peripheral neuropathy, constipation, jaw pain, leukopenia, and anemia. Furthermore, it must be must be administered under the supervision of a hematologist/oncologist and via a central line. Ulceration and Bleeding. Ulceration and bleeding caused by hemangiomas should be treated with direct pressure and local wound care with topical antibiotics (e.g., metronidazole gel plus mupirocin), barrier creams, nonstick

PRIMARY VASCULAR TUMORS • 1007

dressings, and topical corticosteroids.25,51 Becaplermin, a recombinant platelet-derived growth factor, has been successfully used in difficult cases (which is counterintuitive because it promotes angiogenesis).52 Analgesia with oral acetaminophen and topical analgesics (e.g., lidocaine hydrochloride ointment) may also be useful. In refractory cases, surgical resection may be necessary. But since the resultant scar from the surgical resection of a hemangioma is often worse than the result of its spontaneous involution, surgery is best avoided for purely cosmetic reasons. Intramuscular Lesions. The treatment of intramuscular hemangiomas is surgical excision. In large or complex lesions, presurgical transcatheter arterial embolization has been successfully used.53 Intramuscular hemangiomas have never been reported to metastasize, but local recurrence rates are high (18%–50%), so one must be judicious when deciding which lesions should be resected.13,54 Skeletal Lesions. Treatment of skeletal hemangiomas is

necessary only when there is severe functional compromise, such as vertebral hemangioma causing spinal cord compression or long bone hemangioma causing pathologic fracture. Consultation with an orthopedic surgeon is recommended. Treatment is either surgery or radiotherapy and the prognosis is favorable following either therapy. A

B

• FIGURE 50-15.

Hemangioma of tibia. (A) Bone scan shows nonspecific focal tibial uptake (arrow). (B) Radiographs show focal tibial abnormality (arrows). Hemangiomas of the calvaria and vertebra have characteristic appearances but long bone lesions are rare and have varied, nonspecific bone manifestations.

Periorbital Lesions. Periorbital hemangiomas should be

managed by an ophthalmologist experienced with these lesions. Potential therapies include patching the unaffected eye (to ensure use of the affected eye), medical therapy (e.g., corticosteroids), and surgical resection of the hemangioma.29 Upper Airway Lesions. Upper airway obstruction as a

result of hemangioma should be treated promptly with systemic corticosteroids. Early evaluation by an otolaryngologist is reasonable, as tracheostomy and/or surgical resection of the hemangioma are occasionally necessary.31 Laser ablation of upper airway hemangiomas has also been successful.55 Visceral Lesions. Large symptomatic visceral (e.g., hep-

atic) hemangiomas are usually responsive to chemotherapy. Refractory cases are traditionally surgically resected. More recently, selective arterial embolization has been successfully used, sometimes as a combined approach with surgery, to treat medically refractory and surgically difficult lesions.56,57 However, results from embolization may be temporary and complications, such as abcess formation, have been reported.58

• FIGURE 50-16.

A large segmental facial hemangioma, as seen in the PHACE syndrome.

Congestive Heart Failure. High-output CHF caused by AV shunting in patients with large visceral (especially hepatic) hemangiomas is treated by correcting the shunt as soon as possible. Chemotherapy-induced tumor involution using corticosteroids is often the best initial approach.

1008 • CHAPTER 50

• FIGURE 50-17.

Liver hemangioma; Single level CT before and after intravenous contrast material. Hemangioma (arrow) on 1st image prior to intravenous contrast material is low attenuation. Next five images after IV contrast injection show peripheral hypervascular foci that increase and then the hemangioma becomes isodense and finally hyperdense compared to the liver. Liver hemangiomas, incidental findings in 5% of the general population, must be distinguished from significant lesions. Well-defined focal collections of intravenous contrast material in peripheral slow flow sites of a hemangioma on CT, MR, nuclear medicine RBC study, and angiography are diagnostic. Uniform circumferential enhancement and delayed centripetal uniform enhancement are not.

A

B

• FIGURE 50-18.

Liver hemangioma; MR. (A) T1-weighted image shows focal low signal lesion (arrow). (B) T1-weighted image after IV contrast shows characteristic peripheral, discrete foci of intense enhancement (arrows).

PRIMARY VASCULAR TUMORS • 1009

B

A

C

D

E

F

• FIGURE 50-19.

Large liver hemangioma—CT, MR, US, liver spleen scan, and RBC spleen scan. (A) CT shows only a single site of dense enhancement (white arrow) in this large lobulated lesion (black arrow). (B) T1-weighted MR shows large lobulated low signal lesion. (C) T2-weighted MR shows characteristic uniform high signal of lesion. (D) US shows suggestive but nonspecific echogenicity of lesion (arrows). (E) Liver spleen scan shows large defect at site of lesion (arrow ). (F) RBC scan shows diagnostic delayed uptake of lesion (arrow) Large liver hemangiomas may not show diagnostic imaging features because large vascular spaces do not accumulate enough contrast to show characteristic discrete focal peripheral enhancement. Small (