European Manual of Medicine
Vascular Surgery C. D. Liapis Chief Editor K. Balzer, F. Benedetti-Valentini, J. Fernandes e Fernandes Editors
Editors
C. D. Liapis, K. Balzer, F. Benedetti-Valentini, J. Fernandes e Fernandes
Vascular Surgery With 385 Figures and 58 Tables
123
Series Editors
Volume Editors
Wolfgang Arnold, MD HNO und Poliklinik Klinikum rechts der Isar München Germany
Christos D. Liapis, MD, FACS, FRCS Department of Vascular Surgery Athens University Medical School Attikon University Hospital Athens Greece
Uwe Ganzer, MD HNO und Poliklinik Heinrich-Heine-Universität Düsseldorf Germany
Klaus Balzer, MD Division of Vascular Surgery Evangelisches Krankenhaus Mülheim Germany Fabrizio Benedetti-Valentini, MD Department of Vascular Surgery University of Rome „La Sapienza“ Rome Italy José Fernandes e Fernandes, MD, PhD Chief of Service Department of Vascular Surgery Hospital Santa Maria and Faculty of Medicine Director Instituto Cardiovascular de Lisboa Lisbon Portugal
ISBN-10 3-540-30955-1 Springer Berlin Heidelberg NewYork ISBN-13 978-3-540-30955-0 Springer Berlin Heidelberg NewYork Library of Congress Control Number: 2006928312 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag. Violations are liable for prosecution under the German Copyright Law. Springer is a part of Springer Science + Business Media springer.com © Springer-Verlag Berlin Heidelberg 2007
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V
Acknowledgements
When the invitation came from Springer-Verlag to produce this first European manual of vascular surgery, it was accepted enthusiastically by the editors, albeit with some trepidation concerning the demands of such a venture. This concern was due to the diverse nature of the vascular system, which covers every part of the human body; therefore, diseases of the vascular system affect all organs and all parts of the human anatomy and in order to provide a thorough perspective on the discipline of vascular surgery, the manual would have to cover the full spectrum of vascular diseases. However, the pressing need to produce a long-overdue European manual on vascular surgery was the driving force that brought together several of the finest minds in Europe, who so generously accepted the task of imparting their expert knowledge by contributing chapters in their own specific areas. The diversity of the discipline, coupled with the differences in management of vascular diseases by authors originating from different European countries, required the work to be carefully formatted to render it an effective reference book, based on recommended European standards for professionals and trainees with a common goal: optimum care of the vascular patient. The editors are deeply grateful to the distinguished authors and all their associates involved in this compilation. Apart from these tremendous contributions, this project would not have been possible without the enormous assistance of my associate Dr. Yannis Kakisis and the invaluable cooperation of Ms. Gabriele Schroeder and Ms. Waltraud Leuchtenberger of Springer-Verlag, Patrick Waltemate of LE-TeX and my administrative assistant Ms. Vivienne Rose. We hope the readership will benefit from this first European Manual of Medicine: Vascular Surgery.
The editors Christos D. Liapis Klaus Balzer Fabrizio Benedetti-Valentini José Fernandes e Fernandes
VII
Foreword Gregory D. Skalkeas Professor Emeritus, Academician, President of the Foundation of Biomedical Research of the Academy of Athens
Vascular surgery has acquired a well-established identity throughout the European Union, where vascular diseases are still the leading cause (40%) of death and disability. Proper management of vascular diseases is dependent on public awareness and appropriate training of specialists. This stands true for every medical discipline. For vascular surgery it has an additional aspect because, besides the required above-average standard of technical dexterity, the vascular surgeon should also be well versed in a variety of subjects such as molecular biology, in the use of ultrasound and – with the introduction of endovascular techniques – a skilful operator of guidewires and laparoscopic instruments. All the accumulated know-how and skills required for proper management of the vascular patient demand a rapid change in the training of vascular surgeons and an indepth knowledge of the various manifestations of vascular diseases. The information necessary for the above is disseminated through books, journals and the internet. Most of the time, however, articles in journals reflect the experience and enthusiasm of the authors on the subject but not the level of knowledge of the medical community as a whole. Electronic information is fast and reliable but always gives the reader the impression of being short-lived. Books, on the other hand, allow a reflection of what has been written and a true interactive role for the reader. Multi-author books have the inherited handicap of not conveying a specific message by virtue of the diversity of thought; however, when the authors happen to be experts in their field and to represent most of the countries within the European Continent that is striving to prove its successful function as a union, then such a collaboration can indeed convey a message: the level of knowledge and the modus vivendi of vascular surgery in Europe. The editor and authors of this compilation are to be congratulated for such an endeavour, worthy of the European spirit of unity and collaboration.
IX
Preface Sir Peter Bell Professor of Surgery, University of Leicester
European Manual of Medicine: Vascular Surgery Vascular surgery has evolved and expanded in a spectacular fashion during the last 50 years. During this time previously untreatable conditions have become treatable and dealt with on a regular basis by vascular surgeons. Many of the pioneers of vascular surgery were from Europe, starting with Cid Dos Santos who invented angiography and made the whole field of vascular surgery possible. Jean Kunlin in 1949 was the first surgeon to use a reversed vein by-pass graft successfully. In the field of aortic surgery, Lerich and Matas were pioneers in this area and Felix Eastcott started the long and successful treatment of carotid artery stenosis by surgery. Successive generations of Europeans have continued to be involved in the evolution of vascular surgery, taking it to a new phase of activity. European surgeons continue to be at the forefront of changes in vascular practice and have made it possible for the new era of laparoscopic and endovascular surgery to progress and flourish. One might ask why we need yet another textbook of vascular surgery. This is a perfectly reasonably question and the answer is because no book exists that offers comprehensive knowledge, both theoretical and practical, to every level of vascular surgeon. Buying books is expensive and it is therefore important that such books are of use to all of those who may wish to read them. The aim of this book is to be as useful to the vascular trainee as to the established vascular consultant. To this end the editors have enlisted and given a clear brief to leading practitioners in the field. All of the topics that one would normally expect to see in such a book are included and the text is sufficiently referenced to make it authoritative. Pictures and figures are also used but not extensively and are not a major selling point of this volume. The theoretical and practical aspects of open surgery, endovascular procedures and laparoscopic surgery are all covered in detail and venous disease and lymphatic problems are not ignored. One question that might be asked is: why are all the contributing surgeons from Europe and none from other countries or continents? This is intentional and not xenophobic, but an attempt to show that the necessary expertise to cover all aspects of the practice of vascular surgery exists in the expanded European community. It is also to acknowledge the fact that vascular procedures and practice are not necessarily the same the world over. The approach to some problems is different in Europe than it is in other continents and these differences are reflected in this book. I am sure that those who buy and read this book will not be disappointed in its content or style. It will be extremely useful to all readers and be a signpost to the future of vascular surgery.
XI
Introduction Christos D. Liapis, John D. Kakisis
Vascular diseases are the most frequent cause of death and disability of Europeans. The aim of the present book, European Manual of Medicine: Vascular Surgery, is to give an indication of European standards for the diagnosis and therapy of vascular diseases. It is designed with the same format as other books in the series European Manuals of Medicine and focuses on the description of each clinical entity (definition, epidemiology, aetiology, symptoms and complications) and on the recommended European standard diagnostic and therapeutic steps. In contrast to other textbooks, most of the information is presented in bulleted listings instead of lengthy paragraphs. This is done in the hope of enabling the reader to retrieve information easily and quickly. The first chapters of this book refer to the pathogenesis of vascular diseases, including the development of atherosclerosis and the effect of dyslipidaemia, clotting disorders and emerging biochemical risk factors. Subsequent chapters present the noninvasive and invasive means of diagnosis, including latest developments such as computer-guided diagnosis of vascular diseases. The preoperative evaluation and optimization as well as the peri-operative care of the vascular patient are also discussed. The book includes a review of the history of vascular surgery in Europe and a chapter on the training of vascular surgeons for endovascular procedures in order to highlight the continuity and the progress of vascular surgery over the past century and the future perspectives. The chapters of the book cover the entire range of arterial, venous and lymphatic disorders with an emphasis on all recent developments including endovascular and laparoscopic surgery. The text is comprehensive since the book is intended not only for vascular specialists but also for students, residents in vascular surgery and other interested physicians. The chapters have been written mainly by national representatives on the newly established Section of Vascular Surgery of the European Union of Medical Specialists (UEMS), thus drawing upon the collective experience of vascular surgeons/specialists from the various European countries. The authors are experts in their field, providing the reader with a professional opinion reflecting what is generally considered to be the state-of-the-art in each area. We hope that the readers, especially the hard working trainees in vascular surgery to whom this book is dedicated, will find it useful.
XIII
Contents
Vascular Surgery and the Vascular Patient 1.1 1.1.1 1.1.2 1.1.3 1.1.3.1
1.1.3.2
1.1.3.3
1.1.4
1.1.5
The History of Vascular Surgery in Europe . . . . . . . . . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . . . . The Origin and the Foundations of European Vascular Surgery . . . . . . . Europe, Cradle of the World’s Vascular Surgery . . . . . . . . . . . . . . . . . . . The Nursery of Vascular Surgery in Europe in the 1930s was the René Leriche School in Strasburg, France . . . . . . . . . . . . . . . . . . Reference to European Surgeons who Through their Pioneering Work Developed Vascular Surgery in their Continent with International Influence . . . . . . . . . . . . Medical and Interventional Vascular Contributions to the Development of Vascular Surgery in Europe and Worldwide . . European Vascular Surgical and Angiological Societies and Congresses . . . . . . . . . . . . . . . . . . . . . . . Epilogue . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . .
3 3
1.2.2.2
1.2.2.3 1.2.3
3 7
1.2.3.1 1.2.3.2 1.2.4
8
1.2.5 1.2.6
10
1.2.7 1.2.8
12
1.3
14 17 19 20
1.3.1 1.3.2 1.3.2.1 1.3.2.2 1.3.2.3
1.2 1.2.1 1.2.2 1.2.2.1
Development of Atherosclerosis for the Vascular Surgeon . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . . Physiopathology of Atherosclerosis . . . . . . . . . . . . . . . . . . . Normal Blood Vessel Morphology . . . . . . . . . . . . . . . . . . . . . .
23 23
1.3.3
23
1.3.4
23 1.3.5
Initiation of Atherosclerosis and Role of Endothelial Dysfunction . . . . . . . . . . . . . . . . . . . . . . Evolution of the Atherosclerotic Plaque . . . . . . . . . . . . . . . . . . . . . . . . . . . Contributive Factors to Endothelial Dysfunction and Plaque Formation . . . . . . . . . . . . . Miscellaneous Factor . . . . . . . . . . . . . . The Oxidized LDL Hypothesis . . . . . . Plaque Instability and Complicated Plaques . . . . . . . . . . Classification of Atherosclerotic Plaques . . . . . . . . . . . . . . . . . . . . . . . . . . . Assessment and Evaluation of the Risk of an Atherosclerotic Plaque . . . . . . . . . . . . . . . . . . . . . . . . . . . General Therapeutic Measures . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . Lipids and Peripheral Arterial Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . . . Effect of Lipid Lowering on PAD . . . Prevention of PAD . . . . . . . . . . . . . . . . Improvement of Symptoms Associated with PAD . . . . . . . . . . . . . Reduction of the Risk of Vascular Events Associated with PAD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Peripheral Vascular Surgery and Statins . . . . . . . . . . . . . . . . . . . . . . . . . . . Additional Potential Actions of Lipid-lowering Drugs that may Benefit PAD Patients . . . . . Are all Statins the Same? . . . . . . . . . . .
23 26
28 28 28 30 30
31 31 32 32
35 35 35 35 35
36 36
37 37
XIV
Contents
1.3.6
1.4
1.4.1 1.4.2 1.4.2.1 1.4.3 1.4.3.1 1.4.3.2 1.4.3.3 1.4.3.4
1.4.3.5
1.4.4
1.5 1.5.1 1.5.1.1 1.5.1.2 1.5.1.3 1.5.1.4 1.5.1.5 1.5.1.6 1.5.2 1.5.2.1 1.5.2.2 1.5.2.3 1.5.3 1.5.3.1 1.5.3.2 1.5.3.3 1.5.3.4
Concluding Comments . . . . . . . . . . . . 37 References . . . . . . . . . . . . . . . . . . . . . . . . 38 Clotting Disorders: What Should the Vascular Surgeon Know About Hypercoagulation States in Venous Diseases? . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . . . Venous Thrombosis . . . . . . . . . . . . . . . Risk Factors . . . . . . . . . . . . . . . . . . . . . . What Should a Surgeon do when Faced with Hypercoagulation? . . . . . Should a Search for Thrombophilia be Undertaken? . . . . How Should the Search be Done? . . . . . . . . . . . . . . . . . . . . . . . . . Diagnosing Thrombotic Disease in Patients with Thrombophilia . . . . . Treating Thromboembolic Disease in Patients with Thrombophilia . . . . . . . . . . . . . . Specific Considerations in Treating Thromboembolic Disease Related to Thrombophilia . . Summary . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . Noninvasive Diagnosis of Vascular Diseases . . . . . . . . . . . . . . . Peripheral Arterial Disease . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . . . Physical Examination . . . . . . . . . . . . . . Basic Haematological and Biochemical Tests . . . . . . . . . . . . . Special Investigations, Other Than Imaging . . . . . . . . . . . . . . . . . . . . . Imaging Techniques . . . . . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . . . Disease of Arteries Supplying the Brain . . . . . . . . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . . . Imaging Techniques . . . . . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . . . Diseases of the Venous Circulation . . . . . . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . . . Chronic Venous Insufficiency . . . . . . Deep Vein Thrombosis . . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . .
41 41 41 41 45 45
1.6 1.6.1 1.6.2 1.6.3 1.6.3.1 1.6.3.2 1.6.3.3 1.6.3.4 1.6.3.5 1.6.3.6 1.6.4 1.6.4.1 1.6.4.2
45 46
1.7
46
1.7.1 1.7.2
46 47 47
51 51 51 51
1.7.2.1 1.7.2.2 1.7.2.3 1.7.2.4 1.7.2.5
1.7.3
Invasive Diagnosis of Vascular Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . . . History . . . . . . . . . . . . . . . . . . . . . . . . . . . Arteriography . . . . . . . . . . . . . . . . . . . . . Techniques . . . . . . . . . . . . . . . . . . . . . . . Pre-procedure Evaluation and Preparation . . . . . . . . . . . . . . . . . . . Technique . . . . . . . . . . . . . . . . . . . . . . . . Post-procedure Care . . . . . . . . . . . . . . . Complications . . . . . . . . . . . . . . . . . . . . Direct Toxicity . . . . . . . . . . . . . . . . . . . Phlebography . . . . . . . . . . . . . . . . . . . . . Indications . . . . . . . . . . . . . . . . . . . . . . . Techniques . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . Computer-Aided Diagnosis of Vascular Disease . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . . Computer-Aided Diagnosis in Vascular Imaging . . . . . . . . . . . . . . . Image Pre-processing . . . . . . . . . . . . . . Definition of Regions of Interest – Automatic Segmentation . . . . . . . . . Extraction and Selection of Characteristic Features . . . . . . . . . Classification . . . . . . . . . . . . . . . . . . . . . ANALYSIS: a Modular Software System to Support Diagnosis of Vascular Disease . . . . . . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . .
65 65 65 68 68 69 69 70 70 71 72 72 72 74
77 77 77 78 78 78 80
81 82 82
51 1.8 51 54 55 56 56 56 59
1.8.1 1.8.2 1.8.2.1 1.8.2.2 1.8.2.3 1.8.3 1.8.3.1
59 59 59 61 61 62
1.8.3.3 1.8.3.4 1.8.3.5
Preoperative Evaluation of a Vascular Patient . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . . . Systemic Evaluation . . . . . . . . . . . . . . . Cardiovascular System . . . . . . . . . . . . . Respiratory System . . . . . . . . . . . . . . . . Renal System . . . . . . . . . . . . . . . . . . . . . Evaluation of Specific Vascular Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . Aneurysmal Disease: Abdominal Aortic Aneurysm . . . . . . Peripheral Vascular Disease: Chronic Lower Limb Ischaemia . . . . Peripheral Vascular Disease: Acute Limb Ischaemia . . . . . . . . . . . . . Carotid Disease . . . . . . . . . . . . . . . . . . .
85 85 85 85 86 88 89 89 89 90 91
Contents
1.8.3.6
Venous Disease . . . . . . . . . . . . . . . . . . . 92 References . . . . . . . . . . . . . . . . . . . . . . . . 93
1.9
Peri-operative Care of the Vascular Patient . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . . . Preoperative Planning . . . . . . . . . . . . . Effects of Anaesthesia . . . . . . . . . . . . . . Peri-operative Monitoring . . . . . . . . . Monitoring for Cardiac Ischaemia . . . . . . . . . . . . . . . . . . . . . . . . Peri-operative Temperature Control . . . . . . . . . . . . . . . . . . . . . . . . . . Level of Hypnotic Depth . . . . . . . . . . . Prevention of Cardiac Ischaemia . . . Preoperative Revascularization . . . . . Good Peri-operative Haemodynamic Control . . . . . . . . . . . Anaemia . . . . . . . . . . . . . . . . . . . . . . . . . Adrenergic Tone . . . . . . . . . . . . . . . . . . Postoperative Ischaemia Prevention . . . . . . . . . . . . . . . . . . . . . . . Aneurysm Surgery . . . . . . . . . . . . . . . . Effects of Clamping and Declamping . . . . . . . . . . . . . . . . . . . . . . Prevention of Spinal Cord Ischaemia in Thoracic Aortic Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . Autotransfusion During Surgery . . . . Heparin . . . . . . . . . . . . . . . . . . . . . . . . . . Peri-operative Heparin . . . . . . . . . . . . Prophylaxis of Deep Leg Vein Thrombosis . . . . . . . . . . . . . . . . . . . . . Peri-operative Monitoring after Arterial Reconstructions . . . . Prophylactic Antibiotic Administration . . . . . . . . . . . . . . . . . Postoperative Pain Treatment . . . . Pulmonary Complications, Prophylaxis and Treatment . . . . . . . Peri-operative Care and Endovascular Surgery . . . . . . . Intensive Care Ward is Needed Only for Selected Patients . . . . . . . . Pre- and Postoperative Gut Function and Nutrition . . . . . . . . . . Discharge Planning . . . . . . . . . . . . . . Summary . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
1.9.1 1.9.2 1.9.3 1.9.4 1.9.4.1 1.9.4.2 1.9.4.3 1.9.5 1.9.5.1 1.9.5.2 1.9.5.3 1.9.5.4 1.9.5.5 1.9.6 1.9.6.1 1.9.6.2
1.9.6.3 1.9.7 1.9.7.1 1.9.7.2 1.9.8 1.9.9 1.9.10 1.9.11 1.9.12 1.9.13 1.9.14 1.9.15 1.9.16
95 95 95 95 96 96 96 97 97 97 97 97 97 98 98 98
99 99 99 99 100 100 100 100 100 101 101 101 102 103 103
1.10
1.11
1.11.1 1.11.2 1.11.3 1.11.4 1.11.5 1.11.6 1.11.7 1.11.7.1 1.11.7.2 1.11.7.3 1.11.7.4 1.11.7.5 1.11.7.6 1.11.8
1.12 1.12.1 1.12.1.1 1.12.1.2 1.12.1.3 1.12.1.4 1.12.1.5 1.12.1.6 1.12.1.7 1.12.2 1.12.2.1 1.12.2.2 1.12.2.3 1.12.3 1.12.3.1 1.12.3.2 1.12.3.3 1.12.3.4 1.12.3.5
Training of the Vascular Surgeonfor Endovascular Procedures . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . Peripheral Arterial Disease and Emerging Biochemical Vascular Risk Factors . . . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . Homocysteine (Hcy) . . . . . . . . . . . . C-reactive Protein (CRP) . . . . . . . . Lipoprotein (a) [Lp(a)] . . . . . . . . . . Fibrinogen . . . . . . . . . . . . . . . . . . . . . . Endothelium . . . . . . . . . . . . . . . . . . . . PAD and Other Potentially Relevant Emerging Risk Factors . . Creatinine . . . . . . . . . . . . . . . . . . . . . . Urate . . . . . . . . . . . . . . . . . . . . . . . . . . Microalbuminuria . . . . . . . . . . . . . . Insulin Resistance and Metabolic Syndrome . . . . . . . . . . . . . . . . . . . . . . Platelets, Fibrinolysis and D-Dimers . . . . . . . . . . . . . . . . . . Other Markers of Inflammation . . Conclusions . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . Quality Control in Vascular Surgery . . . . . . . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . Physical Examination . . . . . . . . . . . . Angiography . . . . . . . . . . . . . . . . . . . . Continuous Wave (CW) Doppler . . . . . . . . . . . . . . . . . . . . . . . . Duplex and Colour Duplex Scan . . Intravascular Ultrasonography (IVUS) . . . . . . . . . . . . . . . . . . . . . . . . . Angioscopy . . . . . . . . . . . . . . . . . . . . . Flowmetry . . . . . . . . . . . . . . . . . . . . . . Arteries of the Abdomen . . . . . . . . Abdominal Aorta . . . . . . . . . . . . . . . Visceral Arteries . . . . . . . . . . . . . . . . Renal Arteries . . . . . . . . . . . . . . . . . . Lower Extremity By-pass . . . . . . . . Angiography . . . . . . . . . . . . . . . . . . . . Ultrasound (CW Doppler, PW Doppler, Duplex, Colour Duplex) Angioscopy . . . . . . . . . . . . . . . . . . . . . Flowmetry . . . . . . . . . . . . . . . . . . . . . . Conclusions . . . . . . . . . . . . . . . . . . . .
107 110
111 111 111 111 112 112 113 113 113 113 114 114 114 114 114 115
117 117 117 117 117 118 118 118 119 119 119 119 120 120 121 122 123 124 124
XV
XVI
Contents
1.12.4
Carotid Arteries . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
124 127
2.2.5.3 2.2.6 2.2.6.1
Cerebrovascular Arteries 2.1
2.1.1 2.1.2 2.1.3 2.1.4 2.1.5 2.1.6
2.2 2.2.1 2.2.2 2.2.3 2.2.3.1 2.2.3.2 2.2.3.3 2.2.3.4 2.2.3.5 2.2.3.6 2.2.4 2.2.4.1 2.2.4.2 2.2.4.3 2.2.4.4 2.2.4.5 2.2.4.6 2.2.4.7 2.2.4.8 2.2.4.9 2.2.5 2.2.5.1 2.2.5.2
Haemodynamic Changes and Other Risk Factors for Complications During Carotid Procedures . . . . . . . . . . . . . . Cerebral Blood Flow . . . . . . . . . . . . . General Complications . . . . . . . . . . Cerebral Monitoring and Protection During CEA . . . . . . Cerebral Embolization during CEA and CAS . . . . . . . . . . . . . . . . . . Adjuvant Medical Therapy . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . Extracranial Carotid Artery Disease . . . . . . . . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . Pathogenesis of Brain Ischaemia . . Clinical Manifestations . . . . . . . . . . Amaurosis fugax . . . . . . . . . . . . . . . . Transient/Reversible Cerebral Ischaemia . . . . . . . . . . . . . . . . . . . . . . Established Stroke . . . . . . . . . . . . . . . Stroke in Evolution (“Waving and Waning”) . . . . . . . . . . . . . . . . . . . Global Cerebral Ischaemia . . . . . . . Asymptomatic Carotid Disease . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Arteriography . . . . . . . . . . . . . . . . . . . Colour Flow Duplex Scan . . . . . . . High-resolution Ultrasonography . . . . . . . . . . . . . . . . Measuring the Degree of Stenosis . Transcranial Doppler Examination . . . . . . . . . . . . . . . . . . . Other Flow-imaging Techniques . . Indications for Arteriography . . . . Computerized Tomography and Magnetic Resonance Imaging Examination of the Retina . . . . . . . Selection, Treatment and Results . . Medical Treatment . . . . . . . . . . . . . . Surgical Treatment . . . . . . . . . . . . . .
131 131 131 132 133 133 134 134
137 137 138 140 140 140 140 140 140 141 141 141 141 143 143 144 144 144
2.3 2.3.1 2.3.2 2.3.3 2.3.4 2.3.5
2.4 2.4.1 2.4.1.1 2.4.1.2 2.4.1.3 2.4.1.4 2.4.1.5 2.4.1.6 2.4.2 2.4.2.1 2.4.2.2 2.4.2.3 2.4.2.4 2.4.2.5 2.4.2.6 2.4.2.7 2.4.2.8 2.4.2.9 2.4.2.10 2.4.2.11
2.5 2.5.1
144 144 145 145 145
2.5.2 2.5.2.1 2.5.2.2
Technique of Carotid Endarterectomy . . . . . . . . . . . . . . . . . Endovascular Treatment . . . . . . . . . What are the Established Indications for Endovascular Procedures in Extracranial Carotid Disease? . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
149 150
Eversion Carotid Endarterectomy Technique . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . Technique . . . . . . . . . . . . . . . . . . . . . . Advantages . . . . . . . . . . . . . . . . . . . . . Disadvantages . . . . . . . . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
155 155 155 159 159 159 159
Fibromuscular Dysplasia . . . . . . . . . Basics . . . . . . . . . . . . . . . . . . . . . . . . . . Anatomy . . . . . . . . . . . . . . . . . . . . . . . Physiology, Pathophysiology . . . . . Organ-related Questions . . . . . . . . . Principles of Clinical Examination . . . . . . . . . . . . . . . . . . . . Technical Diagnostic Procedures . . Organ-specific Radiology . . . . . . . . Organ-related Diseases . . . . . . . . . . Synonyms . . . . . . . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Complications . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Differential Diagnosis . . . . . . . . . . . Prognosis . . . . . . . . . . . . . . . . . . . . . . . Exemplary Surgical Procedures . . . Special Remarks . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . Aneurysms of the Extracranial Carotid Arteries . . . . . . . . . . . . . . . . Definition and Historical Background . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Atherosclerosis Aneurysms . . . . . . Previous Surgery/POS Endarterectomy . . . . . . . . . . . . . . . . .
146 149
161 161 161 161 165 165 165 166 166 166 166 166 167 168 168 168 169 169 169 170 170
173 173 173 173 174
Contents
2.5.2.3 2.5.2.4 2.5.2.5 2.5.2.6 2.5.3 2.5.4 2.5.5 2.5.5.1
2.5.6 2.5.6.1 2.5.6.2
2.6 2.6.1 2.6.2 2.6.3 2.6.4 2.6.4.1
2.6.4.2 2.6.4.3 2.6.5 2.6.5.1 2.6.5.2 2.6.5.3 2.6.5.4 2.6.5.5 2.6.5.6 2.6.6 2.6.6.1
2.6.6.2
2.6.6.3 2.6.6.4 2.6.7 2.6.8
Trauma . . . . . . . . . . . . . . . . . . . . . . . . . Infection . . . . . . . . . . . . . . . . . . . . . . . Dissections . . . . . . . . . . . . . . . . . . . . . Other Possible Causes . . . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Complications . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Recommended European Standard Diagnostic Steps of Investigation . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Conservative Treatment . . . . . . . . . Surgery . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . Endovascular Treatment of Carotid Stenosis . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . Indications for Surgery – Indications for Angioplasty . . . . . Types of Stents . . . . . . . . . . . . . . . . . . Brain Protection Devices . . . . . . . . . Distal Occlusion Balloon (Theron’s System, PercuSurge GuardWire® Medtronic) (Fig. 2.6.5) . . . . . . . . . . . . . . . . . . . . . . Filters . . . . . . . . . . . . . . . . . . . . . . . . . . Proximal Occlusion System . . . . . . Preoperative Evaluation . . . . . . . . . . Neurological Examination . . . . . . . Special Imaging Examination . . . . Duplex Ultrasound . . . . . . . . . . . . . . Digital Subtraction Angiography (DSA) . . . . . . . . . . . . . . . . . . . . . . . . . . Magnetic Resonance Angiography (MRA) (Fig. 2.6.10) . . Brain Computed Tomography (CT) . . . . . . . . . . . . . . . . . . . . . . . . . . . Technique . . . . . . . . . . . . . . . . . . . . . . Step 1: Approach to the Common Carotid Artery Access Site . . . . . . . . . . . . . . . . . . . . . . . . . . . . Step 2: Cannulation of the Common Carotid Artery (Fig. 2.6.12) . . . . . . . . . . . . . . . . . . . . . Step 3: Angioplasty and Stenting . . Step 4: Control Angiography . . . . . Peri-operative Monitoring . . . . . . . Complications . . . . . . . . . . . . . . . . . .
174 174 174 174 175 175 175
2.6.8.1 2.6.8.2 2.6.8.3 2.6.8.4
175 176 176 177 179
2.6.9 2.6.10
181 181 181 183 184
2.6.8.5 2.6.8.6 2.6.8.7
2.7 2.7.1 2.7.2 2.7.3 2.7.4 2.7.5 2.7.6 2.7.6.1
2.7.6.2 184 184 186 187 188 188 188
2.7.7 2.7.7.1 2.7.7.2 2.7.8
2.8 188 189 189 190
190
2.8.1 2.8.2 2.8.2.1 2.8.2.2 2.8.3 2.8.4
191 192 193 193 193
2.8.4.1 2.8.4.2
Technical Failure . . . . . . . . . . . . . . . . Contrast Encephalopathy . . . . . . . . Access Site Complications . . . . . . . . Hyperperfusion Syndrome (Fig. 2.6.16) . . . . . . . . . . . . . . . . . . . . . Hypotension and Bradycardia . . . Embolic Complication . . . . . . . . . . . Complications Involving Brain Protection Devices . . . . . . . . . . . . . . Follow-up . . . . . . . . . . . . . . . . . . . . . . Carotid Angioplasty and Stenting (CAS): Present and Future References . . . . . . . . . . . . . . . . . . . . . . Carotid body tumour . . . . . . . . . . . . Synonyms . . . . . . . . . . . . . . . . . . . . . . Definition of the Disease . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Complications . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Recommended European Standard Diagnostic Steps of Investigation . . . . . . . . . . . . . . . . . Additional Useful Diagnostic Procedures . . . . . . . . . . . . . . . . . . . . . Therapy . . . . . . . . . . . . . . . . . . . . . . . . Conservative therapy . . . . . . . . . . . . Surgery . . . . . . . . . . . . . . . . . . . . . . . . . Differential Diagnosis . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . Combined Treatment of Coronary Plus Other Arterial Pathologies: the Magnitude of the Polyatherosclerotic Patient . . . Introduction . . . . . . . . . . . . . . . . . . . . The Magnitude of Multifocal Arterial Disease . . . . . . . . . . . . . . . . . Material and Methods . . . . . . . . . . . Results . . . . . . . . . . . . . . . . . . . . . . . . . Multifocal Occlusive and Aneurysmal Arterial Disease . Multifocal Carotid and Coronary Occlusive Disease . . . . . Material and Methods . . . . . . . . . . . Results . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
193 193 193 193 194 194 195 195 196 197 201 201 201 201 202 202 203
203 205 206 206 206 208 208
209 209 209 209 209 211 212 213 214 214 214
XVII
XVIII
Contents
Upper Extremity Arteries 3.1 3.1.1 3.1.2 3.1.2.1 3.1.2.2 3.1.2.3 3.1.2.4 3.1.3 3.1.3.1 3.1.3.2 3.1.3.3 3.1.3.4 3.1.3.5 3.1.4 3.1.4.1 3.1.4.2 3.1.4.3 3.1.5 3.1.5.1 3.1.5.2 3.1.5.3 3.1.6 3.1.6.1 3.1.6.2 3.1.6.3 3.1.6.4 3.1.7 3.1.7.1 3.1.7.2 3.1.7.3 3.1.8 3.1.9
3.2 3.2.1 3.2.1.1 3.2.1.2 3.2.1.3 3.2.1.4 3.2.1.5 3.2.2 3.2.2.1
Upper Extremity Occlusive Disease . . . . . . . . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . Types of Upper Extremity Occlusive Disease . . . . . . . . . . . . . . . Acute and Chronic Ischaemia . . . . Raynaud’s Phenomenon . . . . . . . . . Trophic Lesions . . . . . . . . . . . . . . . . . Differential Diagnosis of Upper Extremity Occlusive Disease . . . . . Embolism . . . . . . . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . Therapy . . . . . . . . . . . . . . . . . . . . . . . . Occlusive Arterial Disease . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Proximal Arterial Disease . . . . . . . . Distal Arterial Disease . . . . . . . . . . . Aneurysms . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Therapy . . . . . . . . . . . . . . . . . . . . . . . . Arteriovenous Fistulae . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Investigations . . . . . . . . . . . . . . . . . . . Therapy . . . . . . . . . . . . . . . . . . . . . . . . Vascular Trauma . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Therapy . . . . . . . . . . . . . . . . . . . . . . . . Iatrogenic Aetiologies . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . Vasospastic Disorders of the Upper Extremities . . . . . . . . . Raynaud’s Syndrome . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Therapy . . . . . . . . . . . . . . . . . . . . . . . . Hyperhidrosis . . . . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . .
219 219 219 219 219 220 220 220 220 220 220 221 221 222 222 222 226 232 232 232 232 232 232 233 233 233 233 233 233 233 233 234 234
237 237 237 237 237 237 239 240 240
3.2.2.2 3.2.2.3 3.2.2.4 3.2.3 3.2.3.1 3.2.3.2 3.2.3.3 3.2.3.4 3.2.4 3.2.4.1 3.2.4.2 3.2.4.3 3.2.4.4 3.2.5 3.2.5.1 3.2.5.2 3.2.5.3 3.2.6 3.2.6.1 3.2.6.2 3.2.6.3 3.2.6.4 3.2.6.5
3.3 3.3.1 3.3.2 3.3.2.1 3.3.2.2 3.3.2.3 3.3.2.4 3.3.2.5 3.3.3
3.3.3.1 3.3.3.2 3.3.3.3 3.3.3.4 3.3.4
3.3.4.1 3.3.4.2 3.3.5
Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Acrocyanosis . . . . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Therapy . . . . . . . . . . . . . . . . . . . . . . . . Livedo Reticularis . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Therapy . . . . . . . . . . . . . . . . . . . . . . . . Cold Hypersensitivity . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Therapy . . . . . . . . . . . . . . . . . . . . . . . . Complex Regional Pain Syndrome . . . . . . . . . . . . . . . . . . . . . . Synonyms . . . . . . . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Aetiology . . . . . . . . . . . . . . . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Therapy . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
240 240 241 242 242 242 242 243 243 243 243 243 243 243 243 244 244
Thoracic Outlet Syndrome . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Neurogenic Thoracic Outlet Compression Syndrome (N-TOCS) Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Clinical Examination . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Arterial Thoracic Outlet Compression Syndrome (A-TOCS) . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Investigations/Examination . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . A Case Apart: Primary Subclavian–Axillary Vein Thrombosis . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Primary SVT . . . . . . . . . . . . . . . . . . . Summary . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
247 247
245 245 245 245 245 245 246
247 247 247 247 248 248
251 251 251 251 251
254 254 254 256 256
Contents
3.4 3.4.1 3.4.2 3.4.2.1 3.4.2.2 3.4.3 3.4.3.1
3.4.4 3.4.4.1 3.4.4.2 3.4.4.3 3.4.5
Traumatic Injury of Upper Extremity Arteries . . . . . . . . . . . . . . Epidemiology . . . . . . . . . . . . . . . . . . . Aetiology . . . . . . . . . . . . . . . . . . . . . . . Penetrating Trauma . . . . . . . . . . . . . Blunt Trauma . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Recommended European Standard Diagnostic Steps of Investigation . . . . . . . . . . . . . . . . . Therapy . . . . . . . . . . . . . . . . . . . . . . . . Conservative Therapy . . . . . . . . . . . Endovascular Therapy . . . . . . . . . . . Surgery . . . . . . . . . . . . . . . . . . . . . . . . . Prognosis . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
257 257 257 257 257 257
257 258 258 258 258 259 260
4.2.3.5 4.2.3.6 4.2.3.7 4.2.4 4.2.4.1 4.2.4.2 4.2.5 4.2.5.1 4.2.5.2 4.2.6 4.2.6.1
4.2.6.2 4.2.6.3 4.2.7
Thoracic Aorta 4.1 4.1.1 4.1.2 4.1.3 4.1.3.1 4.1.3.2 4.1.4 4.1.4.1 4.1.4.2 4.1.4.3 4.1.5 4.1.5.1 4.1.6 4.1.7
4.2 4.2.1 4.2.2 4.2.3 4.2.3.1 4.2.3.2
4.2.3.3 4.2.3.4
Thoracoabdominal Aneurysms . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Investigations . . . . . . . . . . . . . . . . . . . Imaging . . . . . . . . . . . . . . . . . . . . . . . . Additional Investigations . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Operative Repair . . . . . . . . . . . . . . . . Open Surgery: Operative Technique . . . . . . . . . . . . . . . . . . . . . . Open Surgery: Adjuvant Techniques . . . . . . . . . . . . . . . . . . . . . Endovascular Intervention . . . . . . . Visceral Hybrid Procedure . . . . . . . Outcome . . . . . . . . . . . . . . . . . . . . . . . Summary and Conclusions . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
265 265 265 266 266 266 267 267
Aortic Dissection . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology . . . . . . . . . . . . . . . . . . . Aetiology . . . . . . . . . . . . . . . . . . . . . . . Association with Atherosclerotic Disease . . . . . . . . . . . . . . . . . . . . . . . . . Association with Genetic Disease/Congenital Malformations . . . . . . . . . . . . . . . . . . Association with Trauma . . . . . . . . Other Associations . . . . . . . . . . . . . .
277 277 277 277
267 267 269 269 271 272 273
277
277 277 277
4.2.8 4.2.8.1 4.2.8.2
4.3 4.3.1 4.3.2 4.3.2.1 4.3.2.2 4.3.2.3 4.3.3 4.3.3.1 4.3.3.2 4.3.4 4.3.5 4.3.5.1
4.3.6 4.3.6.1 4.3.6.2
Localization . . . . . . . . . . . . . . . . . . . . Classification . . . . . . . . . . . . . . . . . . . Factors Determining Extension of Dissection . . . . . . . . . . . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Stanford Type A . . . . . . . . . . . . . . . . Stanford Type B . . . . . . . . . . . . . . . . Complications . . . . . . . . . . . . . . . . . . Type A . . . . . . . . . . . . . . . . . . . . . . . . . Type B . . . . . . . . . . . . . . . . . . . . . . . . . Diagnosis/Investigation . . . . . . . . . . Recommended European Standard Diagnostic Steps of Investigation . . . . . . . . . . . . . . . . . Additional Useful Diagnostic Procedures . . . . . . . . . . . . . . . . . . . . . Clinical Judgement . . . . . . . . . . . . . . Prognosis of Acute or Subacute Aortic Dissection Without Treatment . . . . . . . . . . . . . . . . . . . . . . Therapy . . . . . . . . . . . . . . . . . . . . . . . . Treatment of Type A Aortic Dissection . . . . . . . . . . . . . . . . . . . . . . Treatment of Type B Aortic Dissection . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . Trauma of the Thoracic Aorta . . . . Introduction . . . . . . . . . . . . . . . . . . . . Epidemiology . . . . . . . . . . . . . . . . . . . Automobile-related Incidences . . . Blunt Thoracic Trauma . . . . . . . . . . Outcome . . . . . . . . . . . . . . . . . . . . . . . Aetiology . . . . . . . . . . . . . . . . . . . . . . . Anatomy . . . . . . . . . . . . . . . . . . . . . . . Mechanism of Pathology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Recommended European Standard Diagnostic Steps of Investigation . . . . . . . . . . . . . . . . . Therapy . . . . . . . . . . . . . . . . . . . . . . . . Surgery . . . . . . . . . . . . . . . . . . . . . . . . . Endovascular Approach . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
278 278 279 282 282 282 283 283 283 285
285 285 285
289 289 289 290 296 299 299 299 299 299 300 300 300 301 301 302
302 306 306 309 312
XIX
XX
Contents
Abdominal Aorta and Iliac Arteries 5.1 5.1.1 5.1.2 5.1.3 5.1.3.1 5.1.3.2 5.1.3.3 5.1.3.4 5.1.3.5 5.1.4 5.1.4.1 5.1.4.2 5.1.4.3 5.1.5 5.1.5.1
5.1.5.2 5.1.6 5.1.6.1 5.1.6.2 5.1.6.3 5.1.6.4 5.1.7 5.1.8
5.2
5.2.1 5.2.2 5.2.2.1 5.2.3 5.2.3.1
5.3 5.3.1 5.3.2 5.3.3 5.3.4 5.3.4.1
Abdominal Aortic Aneurysm (AAA) . . . . . . . . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Risk Factors . . . . . . . . . . . . . . . . . . . . Prevalence . . . . . . . . . . . . . . . . . . . . . . Incidence of AAA Rupture . . . . . . . Disease Progression . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Expanding Aneurysm . . . . . . . . . . . Inflammatory AAA . . . . . . . . . . . . . . Rupture . . . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Recommended European Standard Diagnostic Steps of Investigation . . . . . . . . . . . . . . . . . Aspects on Screening . . . . . . . . . . . . Therapy . . . . . . . . . . . . . . . . . . . . . . . . Open Surgery . . . . . . . . . . . . . . . . . . . Endovascular Aortic Repair (EVAR) . . . . . . . . . . . . . . . . . . . . . . . . Rupture and Reconstruction . . . . . Outcome . . . . . . . . . . . . . . . . . . . . . . . Possible Complications of Surgery . . . . . . . . . . . . . . . . . . . . . . Practical Recommendations . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
317 317 317 317 318 318 319 319 320 320 320 320 320 321
5.3.4.2 5.3.4.3 5.3.5 5.3.5.1 5.3.5.2 5.3.6 5.3.6.1
5.3.7 5.3.7.1 5.3.7.2
5.4
5.4.1 5.4.2 321 321 322 322 322 322 323 323 323 323
Treatment Options for Abdominal Aortic Aneurysm (AAA) . . . . . . . . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . Open Repair . . . . . . . . . . . . . . . . . . . . Complications . . . . . . . . . . . . . . . . . . Endovascular Repair . . . . . . . . . . . . Complications . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
325 325 325 327 327 328 329
Inflammatory Aneurysms of the Abdominal Aorta . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology . . . . . . . . . . . . . . . . . . . Aetiology . . . . . . . . . . . . . . . . . . . . . . . Extension of Inflammation . . . . . . .
331 331 331 332 333 333
5.4.2.1 5.4.2.2 5.4.3 5.4.3.1 5.4.3.2 5.4.3.3 5.4.3.4 5.4.4
5.5 5.5.1 5.5.2 5.5.3 5.5.3.1 5.5.4 5.5.5 5.5.6 5.5.6.1 5.5.6.2 5.5.7 5.5.7.1 5.5.7.2
Infection . . . . . . . . . . . . . . . . . . . . . . . Autoimmune Disease . . . . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Literature . . . . . . . . . . . . . . . . . . . . . . . Rupture . . . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Recommended European Standard Diagnostic Steps of Investigation . . . . . . . . . . . . . . . . . Therapy . . . . . . . . . . . . . . . . . . . . . . . . Surgery . . . . . . . . . . . . . . . . . . . . . . . . . Endovascular Treatment . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . Technically Challenging Cases for Endovascular Repair of Aortic Aneurysms . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . Universally Challenging Situations . . . . . . . . . . . . . . . . . . . . . . Vascular Access Morphology . . . . . Aortic Aneurysm Configuration . . Special Challenging Situations . . . . The Case of Aortic Arch Aneurysm . . . . . . . . . . . . . . . . . . . . . . The Case of Aortic Dissection . . . . The Case of Aortic Bronchial and Enteric Fistula . . . . . . . . . . . . . . Other Challenging Cases for EVAR . . . . . . . . . . . . . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . Aortoiliac Occlusive Disease . . . . . Basics . . . . . . . . . . . . . . . . . . . . . . . . . . Synonyms . . . . . . . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Morphological Features in the Chronic Forms . . . . . . . . . . . . Epidemiology . . . . . . . . . . . . . . . . . . . Aetiology . . . . . . . . . . . . . . . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Chronic AIOD . . . . . . . . . . . . . . . . . . Acute AIOD . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Recommended European Standard . . . . . . . . . . . . . . . . . . . . . . . Additional/Useful Diagnostic Procedures . . . . . . . . . . . . . . . . . . . . .
333 333 333 334 334 334
335 336 336 338 341
343 343 343 343 343 347 347 347 349 350 350 351 355 355 355 355 356 357 357 358 358 359 359 359 360
Contents
5.5.8 5.5.8.1 5.5.8.2 5.5.9 5.5.9.1 5.5.9.2 5.5.10 5.5.11 5.5.11.1 5.5.11.1 5.5.11.2 5.5.11.3
5.5.11.4 5.5.11.5 5.5.11.6 5.5.11.7 5.5.11.8 5.5.11.9 5.5.11.10 5.5.11.11 5.5.11.12
5.6
5.6.1 5.6.2 5.6.2.1
Treatment . . . . . . . . . . . . . . . . . . . . . . Conservative Treatment . . . . . . . . . Endovascular and Surgical Treatment . . . . . . . . . . . . . . . . . . . . . . Differential Diagnosis . . . . . . . . . . . In the Case of Chronic AIOD . . . . In the Case of Acute AIOD . . . . . . . Prognosis . . . . . . . . . . . . . . . . . . . . . . . Surgical and Endovascular Principle . . . . . . . . . . . . . . . . . . . . . . . Aortoiliac Angioplasty and Stenting . . . . . . . . . . . . . . . . . . . . . . . . Unilateral and Bilateral Aortofemoral By-pass . . . . . . . . . . . Unilateral or Bilateral Aortoiliac By-pass . . . . . . . . . . . . . . . . . . . . . . . . . Aortic Exclusion and Bilateral Aortoiliac or Bilateral Aortofemoral Prosthetic Reconstruction . . . . . . . . . . . . . . . . . Unilateral or Bilateral Thoracoiliofemoral By-pass . . . . . . Aortoiliac Endarterectomy . . . . . . . Iliofemoral By-pass . . . . . . . . . . . . . . Femoro-femoral Cross-over By-pass . . . . . . . . . . . . . . . . . . . . . . . . . Unilateral or Bilateral Axillofemoral By-pass . . . . . . . . . . . Retrograde Femoral Embolectomy . . . . . . . . . . . . . . . . . . . New Surgical Trends . . . . . . . . . . . . . Aortobifemoral Video-assisted By-pass with Hand-Port System . . Aortobifemoral Totally Laparoscopic By-pass with Coggia’s Technique . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . Aortobifemoral By-pass: Laparoscopy-Assisted and Totally Laparoscopic Operative Procedures . . . . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . Operative Procedures . . . . . . . . . . . . Laparoscopy-Assisted Operative Procedures with Vascular Suturing by the Minimally Invasive Route . . . . . . . . . . . . . . . . . .
360 360
5.6.3 5.6.3.1
361 363 363 363 363
5.6.3.2 5.6.3.3 5.6.3.4
364 364
5.6.4 5.6.4.1
365
5.6.4.2
366 5.6.5 5.6.5.1 5.6.5.2 367 367 368 368
5.6.6 5.6.7
5.7 368 369 369 370 371
372 373
5.7.1 5.7.2 5.7.3 5.7.4 5.7.5 5.7.6 5.7.7 5.7.8 5.7.9 5.7.10
375 375 375
Aortouniiliac Endoprosthesis and Femoro-femoral Crossover for AAA Repair . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Indications . . . . . . . . . . . . . . . . . . . . . Contraindications . . . . . . . . . . . . . . . Preoperative Management . . . . . . . Procedure . . . . . . . . . . . . . . . . . . . . . . Results and Complications . . . . . . . Patency of the Femoro-femoral Crossover By-pass . . . . . . . . . . . . . . Local Wound Complications, Graft Infection and Morbidity . . . Conclusion . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
377
377 379 380 380 381 381
381 382 382 382 383 384 384
387 387 387 387 388 388 388 389 390 391 395 395
Visceral Arteries 6.1
375
Totally Laparoscopic Operative Procedures . . . . . . . . . . . . . . . . . . . . . Retrocolic or Prerenal Transperitoneal Procedure as Described by Coggia [8, 11] . . . . . . Combined Transperitoneal and Retroperitoneal Procedures . . Retroperitoneal Operation . . . . . . . Direct Transperitoneal Procedure [7] . . . . . . . . . . . . . . . . . . . Instrumentation . . . . . . . . . . . . . . . . . Standard Laparoscopic Instruments . . . . . . . . . . . . . . . . . . . . Specific Laparoscopic Instruments for Vascular Laparoscopy . . . . . . . . . . . . . . . . . . . . Complications . . . . . . . . . . . . . . . . . . Intraoperative Complications . . . . Early Postoperative Complications . . . . . . . . . . . . . . . . . . Current Indications and Results . . Conclusions . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
6.1.1 6.1.2 6.1.3
Occlusive Disease of the Coeliac and Superior Mesenteric Arteries . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology . . . . . . . . . . . . . . . . . . . Aetiology . . . . . . . . . . . . . . . . . . . . . . .
401 401 401 401
XXI
XXII
Contents
6.1.4 6.1.5 6.1.5.1
Symptoms . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Recommended European Standard Diagnostic Steps of Investigation . . . . . . . . . . . . . . . . . Additional Useful Diagnostic Procedures . . . . . . . . . . . . . . . . . . . . . Therapy . . . . . . . . . . . . . . . . . . . . . . . . Surgery . . . . . . . . . . . . . . . . . . . . . . . . . Angioplasty . . . . . . . . . . . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
402 402
6.2 6.2.1 6.2.2 6.2.3 6.2.4 6.2.5 6.2.6 6.2.7 6.2.7.1 6.2.7.2 6.2.8
Visceral Artery Aneurysms . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . Epidemiology . . . . . . . . . . . . . . . . . . . Aetiology . . . . . . . . . . . . . . . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Complications . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Therapy . . . . . . . . . . . . . . . . . . . . . . . . Surgery . . . . . . . . . . . . . . . . . . . . . . . . . Endovascular Therapy . . . . . . . . . . . Prognosis . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
411 411 411 411 412 412 413 413 413 414 414 415
6.3
Acute Ischaemia of the Visceral Arteries . . . . . . . . . . . . . . . . . . . . . . . . Acute Intestinal Ischaemia . . . . . . . Basics . . . . . . . . . . . . . . . . . . . . . . . . . . Acute Thrombotic or Embolic Arterial Occlusion . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Complications . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Mesenteric Venous Thrombosis . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Therapy . . . . . . . . . . . . . . . . . . . . . . . . Intestinal Ischaemia after Aortoiliac Surgery . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Acute Renal Ischaemia . . . . . . . . . . .
6.1.5.2 6.1.6 6.1.6.1 6.1.6.2 6.1.7
6.3.1 6.3.1.1 6.3.2 6.3.2.1 6.3.2.2 6.3.2.3 6.3.2.4 6.3.2.5 6.3.3 6.3.3.1 6.3.3.2 6.3.3.3 6.3.3.4 6.3.4 6.3.4.1 6.3.4.2 6.3.4.3 6.3.4.4 6.3.5
6.3.5.1 6.3.5.2
Thrombosis . . . . . . . . . . . . . . . . . . . . . Embolism . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
422 422 423
402
Lower Extremity Arteries 403 403 404 406 408 408
417 417 417 417 417 417 418 418 419 419 419 420 420 420 420 420 421 421 421 422
7.1 7.1.1 7.1.2 7.1.2.1 7.1.2.2 7.1.2.3 7.1.2.4 7.1.3
7.2 7.2.1 7.2.2 7.2.3 7.2.4 7.2.4.1 7.2.4.2 7.2.4.3 7.2.5 7.2.6 7.2.7 7.2.7.1 7.2.7.2 7.2.7.3
7.3 7.3.1 7.3.2 7.3.3 7.3.4 7.3.4.1 7.3.4.2 7.3.4.3 7.3.5 7.3.5.1 7.3.5.2 7.3.5.3 7.3.5.4
Lower Limb Arterial Recanalization . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . Problems and Questions . . . . . . . . . Solved Problems . . . . . . . . . . . . . . . . Unsolved Problems . . . . . . . . . . . . . . Permanent Problems . . . . . . . . . . . . Arising Questions . . . . . . . . . . . . . . . Conclusions . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . .
427 427 427 428 428 430 430 432 433
Femorodistal By-pass Surgery . . . . Introduction . . . . . . . . . . . . . . . . . . . . General Considerations . . . . . . . . . . Operative Indications . . . . . . . . . . . . Technical Considerations . . . . . . . . Proximal Anastomotic Site . . . . . . . Graft Material . . . . . . . . . . . . . . . . . . . Distal Anastomotic Site (Fig. 7.2.3) . . . . . . . . . . . . . . . . . . . . . . Special Considerations . . . . . . . . . . . Graft Surveillance . . . . . . . . . . . . . . . Results . . . . . . . . . . . . . . . . . . . . . . . . . Survival . . . . . . . . . . . . . . . . . . . . . . . . Graft Patency and Limb Salvage . . Quality of Life . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
437 437 437 438 438 438 439 441 442 443 443 443 443 445 445
Acute Ischaemia of the Lower Extremities . . . . . . . . . . . . . . . . . . . . . Synonyms . . . . . . . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology . . . . . . . . . . . . . . . . . . . Aetiology . . . . . . . . . . . . . . . . . . . . . . . Embolism . . . . . . . . . . . . . . . . . . . . . . Thrombosis . . . . . . . . . . . . . . . . . . . . . Trauma . . . . . . . . . . . . . . . . . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . Paraesthesia . . . . . . . . . . . . . . . . . . . . Paralysis . . . . . . . . . . . . . . . . . . . . . . . . Pallor . . . . . . . . . . . . . . . . . . . . . . . . . .
449 449 449 449 449 449 450 451 451 451 451 451 452
Contents
7.3.5.5 7.3.6 7.3.7 7.3.7.1
7.3.7.2 7.3.8 7.3.8.1 7.3.8.2 7.3.8.3 7.3.9 7.3.10
7.4 7.4.1 7.4.2 7.4.2.1 7.4.2.2 7.4.2.3 7.4.2.4 7.4.2.5 7.4.2.6 7.4.2.7 7.4.3 7.4.3.1 7.4.3.2 7.4.3.3 7.4.3.4 7.4.3.5 7.4.3.6 7.4.4 7.4.4.1 7.4.4.2 7.4.4.3 7.4.4.4 7.4.4.5 7.4.4.6 7.4.5 7.4.5.1 7.4.5.2 7.4.5.3 7.4.5.4
Pulselessness . . . . . . . . . . . . . . . . . . . . Complications . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Recommended European Standard Diagnostic Steps of Investigation . . . . . . . . . . . . . . . . . Additional Useful Diagnostic Procedures . . . . . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Conservative Treatment . . . . . . . . . Surgery . . . . . . . . . . . . . . . . . . . . . . . . . Thrombolytic Therapy . . . . . . . . . . . Differential Diagnosis . . . . . . . . . . . Prognosis . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . Lower Extremity Aneurysms . . . . . Basic Concepts . . . . . . . . . . . . . . . . . . Popliteal Aneurysms (PA) . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Complications . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Prognosis . . . . . . . . . . . . . . . . . . . . . . Aneurysms of the Common Femoral Artery . . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Prognosis . . . . . . . . . . . . . . . . . . . . . . Aneurysms of the Superficial Femoral Artery . . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Prognosis . . . . . . . . . . . . . . . . . . . . . . Aneurysms of the Distal Branches . . . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Clinical Symptoms . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . Therapy . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . .
452 452 452
452 453 453 453 453 455 457 457 457 459 459 459 460 460 460 460 460 461 462 462 462 462 463 464 464 466
7.5 7.5.1 7.5.2 7.5.3 7.5.4 7.5.5 7.5.6 7.5.6.1
7.5.7 7.5.7.1 7.5.7.2 7.5.7.3 7.5.7.4
7.6
7.6.1 7.6.2 7.6.3 7.6.4 7.6.4.1
7.6.5 7.6.5.1 7.6.6
7.7 466 466 467 467 467 467 467 468 468 468 468 468 468
7.7.1 7.7.1.1 7.7.1.2
7.7.2 7.7.2.1 7.7.2.2 7.7.2.3 7.7.3 7.7.3.1
Buerger’s Disease of the Lower Extremities . . . . . . . . . . . . . . . . . . . . . Synonym . . . . . . . . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology . . . . . . . . . . . . . . . . . . . Aetiology . . . . . . . . . . . . . . . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Recommended European Standard Diagnostic Steps of Investigation . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Conservative Treatment . . . . . . . . . Surgery . . . . . . . . . . . . . . . . . . . . . . . . . Differential Diagnosis . . . . . . . . . . . Prognosis . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . Popliteal Artery Entrapment and Popliteal Adventitial Cystic Disease . . . . . . . . . . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Recommended European Standard Diagnostic Steps of Investigation . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Recommended European Standard Surgical Procedures . . . . Special Remarks . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . Vascular Trauma of the Lower Limb . . . . . . . . . . . . . . . . . . . . . . . . . . . The Problem . . . . . . . . . . . . . . . . . . . . Encountering Vascular Injury . . . . How Can Ischaemia of the Lower Limb be Detected or Ruled Out Reliably? . . . . . . . . . . . Mechanisms of Injury . . . . . . . . . . . Sharp Injury . . . . . . . . . . . . . . . . . . . . Blunt injury . . . . . . . . . . . . . . . . . . . . . Iatrogenic . . . . . . . . . . . . . . . . . . . . . . Consequences of Arterial Injury of the Lower Limb . . . . . . . . . . . . . . Compartment Syndrome . . . . . . . .
471 471 471 471 471 472 473
473 476 476 476 477 477 477
479 479 479 479 480
480 481 481 483 484
485 485 486
486 488 488 488 490 493 493
XXIII
XXIV
Contents
7.7.3.2 7.7.4
7.7.5
False Aneurysms and ArterioVenous Fistulas . . . . . . . . . . . . . . . . . The Management of Vascular Trauma (With Special Reference to the Knee Joint) . . . . . . . . . . . . . . . Bulleted Summary . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
494
494 497 497
Diabetic Foot 8.1 8.1.1 8.1.2 8.1.2.1 8.1.2.2 8.1.2.3 8.1.3 8.1.3.1 8.1.3.2 8.1.4 8.1.4.1 8.1.4.2 8.1.4.3 8.1.4.4 8.1.5 8.1.5.1 8.1.5.2 8.1.5.3 8.1.5.4 8.1.6 8.1.7 8.1.7.1 8.1.7.2 8.1.7.3 8.1.7.4 8.1.7.5 8.1.7.6 8.1.7.7 8.1.8
Diabetic Foot . . . . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology . . . . . . . . . . . . . . . . . . . Foot Ulcers . . . . . . . . . . . . . . . . . . . . . Amputation . . . . . . . . . . . . . . . . . . . . . Social and Economic Costs . . . . . . . Aetiology . . . . . . . . . . . . . . . . . . . . . . . Pathogenesis of the Neuropathic Ulcer . . . . . . . . . . . . . . . . . . . . . . . . . . . Pathogenesis of the Ischaemic Ulcer . . . . . . . . . . . . . . . . . . . . . . . . . . . Complications: NeuroOsteoarthropathy . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology . . . . . . . . . . . . . . . . . . . Aetiology . . . . . . . . . . . . . . . . . . . . . . . Symptoms/Investigations/ Diagnosis/Treatment . . . . . . . . . . . . Diagnosis/Investigations . . . . . . . . . Clinical Examination . . . . . . . . . . . . Circulation . . . . . . . . . . . . . . . . . . . . . Paraclinical Evaluation . . . . . . . . . . Classification Systems . . . . . . . . . . . Differential Diagnosis . . . . . . . . . . . Infections . . . . . . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . Pathophysiology . . . . . . . . . . . . . . . . Microbiology . . . . . . . . . . . . . . . . . . . Clinical Presentation . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Severity Classification . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Treatment of the Diabetic Ulcer . . References . . . . . . . . . . . . . . . . . . . . . .
9.1.1 9.1.1.1 9.1.2 9.1.3 9.1.3.1 9.1.3.2 9.1.4 9.1.4.1
501 501 501 501 501 502 503
9.1.4.2 9.1.5 9.1.6 9.1.6.1 9.1.6.2 9.1.6.3 9.1.6.4
503 505 506 506 506 507 507 507 507 508 509 509 509 510 510 511 512 512 513 514 515 517 518
9.1.6.5 9.1.6.6 9.1.6.7 9.1.7 9.1.8
Introduction . . . . . . . . . . . . . . . . . . . . Scope of the Problem . . . . . . . . . . . . Incidence and Morbidity of Amputation . . . . . . . . . . . . . . . . . . Classification and Indications . . . . Emergency Amputation . . . . . . . . . Elective Amputations . . . . . . . . . . . . Determination of Amputation Level . . . . . . . . . . . . . . . . . . . . . . . . . . . Transcutaneous Oxygen Tension (PtCO2) Measurement . . . . . . . . . . . Clearance of [133Xe] . . . . . . . . . . . . . Preoperative Management . . . . . . . Surgical Techniques of Amputation . . . . . . . . . . . . . . . . . . . . Toe Amputation . . . . . . . . . . . . . . . . . Ray Amputation . . . . . . . . . . . . . . . . Transmetatarsal Amputation . . . . . Syme’s Amputation (Ankle Disarticulation) . . . . . . . . . . Below-knee Amputation . . . . . . . . . Above-knee Amputation . . . . . . . . . Amputation of the Upper Extremity . . . . . . . . . . . . . . . . . . . . . . Postoperative Considerations and Rehabilitation . . . . . . . . . . . . . . . Complications . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
525 525 525 526 526 526 527 528 528 528 528 528 529 530 531 532 533 534 534 535 535
Venous Diseases 10.1 10.1.1 10.1.2 10.1.2.1 10.1.2.2 10.1.2.3 10.1.3 10.1.3.1 10.1.3.2 10.1.3.3 10.1.3.4 10.1.3.5 10.1.3.6
Chronic Venous Insufficiency . . . . Introduction . . . . . . . . . . . . . . . . . . . . Functional Anatomy and Physiology of the Venous System . . Superficial Veins . . . . . . . . . . . . . . . . Deep Veins . . . . . . . . . . . . . . . . . . . . . Perforating Veins . . . . . . . . . . . . . . . . Chronic Venous Insufficiency . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
539 539 539 539 539 539 539 539 540 541 543 545 549 549
Deep Venous Thrombosis . . . . . . . . Epidemiology/Aetiology . . . . . . . . .
551 551
Amputations 9.1
Amputation of Extremities . . . . . . .
525
10.2 10.2.1
Contents
10.2.2 10.2.3 10.2.3.1 10.2.3.2 10.2.3.3 10.2.4 10.2.4.1 10.2.4.2 10.2.4.3 10.2.5 10.2.6
Symptoms . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Clinical Signs . . . . . . . . . . . . . . . . . . . Laboratory Tests and Imaging . . . . Recommended European Standard . . . . . . . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Conservative Treatment of DVT . . Invasive Treatment of DVT . . . . . . Prevention of DVT . . . . . . . . . . . . . . Differential Diagnosis . . . . . . . . . . . Prognosis . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
551 551 551 552 552 552 552 553 556 556 557 557
12.1.6 12.1.6.1 12.1.6.2 12.1.7 12.1.7.1 12.1.7.2 12.1.7.3 12.1.8
Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Examination . . . . . . . . . . . . . . . . . . . Laboratory Investigations and Imaging . . . . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Treatment According to the Type of the Malformation . . . . . . . . . . . . . Conservative Treatment . . . . . . . . . Surgery . . . . . . . . . . . . . . . . . . . . . . . . . Prognosis . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
580 580 580 581 581 582 583 583 583
Angioaccess Surgery Lymphatics 11.1 11.1.1 11.1.1.1 11.1.1.2 11.1.2 11.1.3 11.1.3.1 11.1.3.2 11.1.4 11.1.5 11.1.5.1 11.1.5.2 11.1.5.3 11.1.6 11.1.6.1 11.1.6.2
Lymphoedema . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . Capillary Microcirculation . . . . . . . Capillary Circulation and Limb Oedema . . . . . . . . . . . . . . . . . . . . . . . . Definition of Lymphoedema . . . . . Aetiology/Epidemiology . . . . . . . . . Primary Lymphoedema . . . . . . . . . . Secondary Lymphoedema . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . History and Examination . . . . . . . . Laboratory Tests . . . . . . . . . . . . . . . . Imaging . . . . . . . . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Conservative Treatment . . . . . . . . . Surgery . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
13.1 561 561 561 562 563 563 563 565 566 566 566 567 567 568 568 568 570
Arteriovenous Malformations 12.1 12.1.1 12.1.2 12.1.2.1 12.1.3 12.1.3.1 12.1.4 12.1.4.1 12.1.5 12.1.5.1 12.1.5.2
Arteriovenous Malformations . . . . Synonyms . . . . . . . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Terminology . . . . . . . . . . . . . . . . . . . . Epidemiology . . . . . . . . . . . . . . . . . . . Classification . . . . . . . . . . . . . . . . . . . Aetiology . . . . . . . . . . . . . . . . . . . . . . . Embryology and Anatomy . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Vascular Bone Syndrome . . . . . . . . Specific Vascular Malformations . .
573 573 573 573 573 573 575 575 576 576 577
13.1.1 13.1.2 13.1.2.1 13.1.2.2 13.1.2.3 13.1.2.4 13.1.3 13.1.3.1 13.1.3.2
Vascular Access to Patients in Haemodialysis . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . Urgent (Acute) Haemodialysis . . . . External A–V Shunt . . . . . . . . . . . . . Subclavian Catheters . . . . . . . . . . . . Jugular Catheters . . . . . . . . . . . . . . . . Femoral Catheters . . . . . . . . . . . . . . . Chronic Haemodialysis . . . . . . . . . . Internal A–V Shunt (A–V Fistula) . . . . . . . . . . . . . . . . . . . . . . . . . Arteriovenous Grafts . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
587 587 587 587 588 588 589 589 589 591 594
Multidisciplinary Vascular Issues 14.1 14.1.1 14.1.2 14.1.2.1 14.1.2.2 14.1.2.3 14.1.3 14.1.4 14.1.5 14.1.6 14.1.6.1 14.1.6.2 14.1.6.3 14.1.6.4 14.1.7 14.1.7.1
Infections in Vascular Surgery . . . . Introduction . . . . . . . . . . . . . . . . . . . . Pathogenesis of Infection . . . . . . . . Pathogen Virulence . . . . . . . . . . . . . Host Response . . . . . . . . . . . . . . . . . . Device Factors . . . . . . . . . . . . . . . . . . Microbiology and Diagnosis . . . . . Imaging . . . . . . . . . . . . . . . . . . . . . . . . Antimicrobial Therapy . . . . . . . . . . . Prevention . . . . . . . . . . . . . . . . . . . . . . Primary Prophylaxis . . . . . . . . . . . . . Local Antibiotic Prophylaxis . . . . . Secondary Prophylaxis . . . . . . . . . . . Other Measures of Prevention . . . . Infections in Specific Vascular Implants . . . . . . . . . . . . . . . . . . . . . . . Prosthetic Graft Infections (PGI) . .
597 597 597 597 598 598 598 599 599 600 600 602 602 602 602 602
XXV
XXVI
Contents
14.1.7.2 14.1.7.3 14.1.7.4 14.1.7.5 14.1.7.6
14.2 14.2.1 14.2.2 14.2.2.1 14.2.2.2 14.2.3 14.2.3.1 14.2.3.2 14.2.4
14.3 14.3.1 14.3.2 14.3.2.1 14.3.3 14.3.3.1 14.3.3.2 14.3.3.3 14.3.4
14.4
Peripheral Vascular Stent Infections (PVSIs) . . . . . . . . . . . . . . . Prosthetic Carotid Patches Infections (PCPIs) . . . . . . . . . . . . . . Arterial Closure Devices Infections . . . . . . . . . . . . . . . . . . . . . . Venal Caval Filter Infections . . . . . Infections of Haemodialysis Prosthetic Grafts and Autologous Arteriovenous Fistulas (HPGFIs) . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . Vascular Problems in Urological Surgery . . . . . . . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . Vascular Lesions on Preoperative Evaluation . . . . . . Abdominal Aortic Aneurysm (AAA) . . . . . . . . . . . . . . . . . . . . . . . . . Renal Tumours Involving the Vena Cava . . . . . . . . . . . . . . . . . . Unexpected – Iatrogenic Vascular Injuries . . . . . . . . . . . . . . . . Venous Injuries . . . . . . . . . . . . . . . . . Arterial Injuries . . . . . . . . . . . . . . . . . Bulleted Summary . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . Vascular Trauma in Orthopaedic Surgery . . . . . . . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . Basic Principles in Microvascular Surgery . . . . . . . . Basic Microvascular Techniques . . Application of Microvascular Surgery to Trauma Orthopaedics . . Replantation . . . . . . . . . . . . . . . . . . . . Major Limb Revascularization and Replantation . . . . . . . . . . . . . . . . Open Fractures – Type IIIb and IIIc . . . . . . . . . . . . . . . . . . . . . . . . Vascular Complication in Orthopaedic Patients . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . Treatment of Aortic Arch Diseases . . . . . . . . . . . . . . . . . . . . . . . .
14.4.1 604 607 608 609
609 611
615 615 615 615 616 618 618 619 620 620
623 623 623 624 626 626 630 634 635 635
639
14.4.1.1 14.4.1.2 14.4.2 14.4.2.1 14.4.2.2 14.4.2.3 14.4.2.4 14.4.2.5 14.4.2.6 14.4.2.7 14.4.2.8 14.4.3 14.4.3.1 14.4.3.2 14.4.3.3 14.4.3.4 14.4.3.5 14.4.4 14.4.5 14.4.5.1 14.4.5.2 14.4.5.3 14.4.5.4 14.4.5.5 14.5.5.6 14.5.5.7 14.4.6 14.4.6.1 14.4.6.2 14.4.6.3 14.4.6.4 14.4.6.5 14.4.7
14.4.7.1 14.4.7.2 14.4.7.3 14.4.7.4 14.4.8 14.4.8.1 14.4.8.2 14.4.8.3 14.4.8.4 14.4.9
Aortic Arch Aneurysms in Coarctation of the Aorta . . . . . . Epidemiology/Aetiology . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Intramural Haematoma . . . . . . . . . . Synonyms . . . . . . . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Differential Diagnosis . . . . . . . . . . . Prognosis . . . . . . . . . . . . . . . . . . . . . . . Obstructed Aortic Arch . . . . . . . . . . Synonyms . . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Recurrent Obstruction of the Aortic Arch . . . . . . . . . . . . . . . . . . . . Takayasu’s Arteritis . . . . . . . . . . . . . . Synonyms . . . . . . . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Prognosis . . . . . . . . . . . . . . . . . . . . . . . Aortic Arch Atherosclerotic Aneurysm . . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Prognosis . . . . . . . . . . . . . . . . . . . . . . . Atheromas and Penetrating Atherosclerotic Ulcerations of the Aortic Arch . . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Aortic Arch Thrombosis . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Aortic Arch Trauma . . . . . . . . . . . . .
639 639 640 640 640 640 640 640 640 640 641 641 641 641 641 641 641 642 642 643 643 643 643 644 644 644 645 645 645 645 646 646 647
648 648 648 648 648 649 649 649 649 649 650
Contents
14.4.9.1 14.4.9.2 14.4.9.3 14.4.9.4 14.4.9.5 14.4.9.6 14.4.9.7 14.4.9.8 14.4.9.9 14.4.10 14.4.10.1 14.4.10.2 14.4.10.3 14.4.10.4 14.4.10.5 14.4.10.6 14.4.11 14.4.11.1 14.4.11.2 14.4.11.3 14.4.11.4 14.4.11.5 14.4.11.6
Synonyms . . . . . . . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Complications . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Differential Diagnosis . . . . . . . . . . . Prognosis . . . . . . . . . . . . . . . . . . . . . . . Ascending Aortic Dissection . . . . . Synonyms . . . . . . . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Differential Diagnosis . . . . . . . . . . . Marfan’s Syndrome . . . . . . . . . . . . . . Synonyms . . . . . . . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Complications . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . .
650 650 650 650 651 651 651 651 652 652 652 652 652 653 653 654 654 654 654 654 654 654 655
14.4.11.7 14.4.11.8 14.4.11.9 14.4.12 14.4.12.1 14.4.12.2 14.4.12.3 14.4.12.4 14.4.12.5 14.4.12.6 14.4.12.7 14.4.12.8 14.4.12.9 14.4.13 14.4.13.1 14.4.13.2 14.4.13.3 14.4.13.4 14.4.13.5 14.4.13.6 14.4.13.7 14.4.13.8
Treatment . . . . . . . . . . . . . . . . . . . . . . Differential Diagnosis . . . . . . . . . . . Prognosis . . . . . . . . . . . . . . . . . . . . . . . Ehlers–Danlos Syndrome . . . . . . . . Synonyms . . . . . . . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Complications . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Differential Diagnosis . . . . . . . . . . . Prognosis . . . . . . . . . . . . . . . . . . . . . . . Noonan Syndrome . . . . . . . . . . . . . . Synonyms . . . . . . . . . . . . . . . . . . . . . . Definition . . . . . . . . . . . . . . . . . . . . . . Epidemiology/Aetiology . . . . . . . . . Symptoms . . . . . . . . . . . . . . . . . . . . . . Complications . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . Treatment . . . . . . . . . . . . . . . . . . . . . . Differential Diagnosis . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . .
655 655 655 655 655 656 656 656 656 656 656 656 656 656 656 656 656 656 657 657 657 657 657
XXVII
XXIX
List of Contributors
Acosta, Stefan, MD, PhD Department of Vascular Surgery Malmö General Hospital Malmö, Sweden (E-mail:
[email protected])
Barbas, Maria José, MD Hospital Garcia de Orta Servico de Angiologia e Cirurgia Vascular Almada, Portugal (E-mail:
[email protected])
Angelides, Nicos S., MD Cardiovascular and Thoracic Unit Nicosia General Hospital Nicosia, Cyprus (E-mail:
[email protected]
Bastounis, Elias A., MD, PhD First Department of Surgery Athens University Medical School Athens, Greece (E-mail:
[email protected])
Anagnostopoulos, Constantine E., MD, ScD Department of Cardiothoracic Surgery Athens University Medical School Athens, Greece and Columbia University St. Luke’s/Roosevelt Hospital New York New York, USA (E-mail:
[email protected])
Bell, Sir Peter, MD University of Leicester Department of Surgery Robert Kilpatrick Building Leicester Royal Infirmary Leicester, UK (E-mail:
[email protected])
Anagouras, Dimitrios C., MD, FETCS Department of Cardiothoracic Surgery University of Athens School of Medicine Attikon Hospital Center Athens, Greece (E-mail:
[email protected]) Balas, Panagiotis E., MD P. Psihico, Greece (E-mail:
[email protected]) Balzer, Klaus, MD Department of Vascular Surgery Evanglisches Krankenhaus Mülheim Mülheim/Ruhr, Germany (E-mail:
[email protected])
Benedetti-Valentini, Fabrizio, MD Department of Vascular Surgery University of Rome “La Sapienza” Rome, Italy (E-mail:
[email protected]) Berg, Patrick, MD Department of Vascular Surgery Centre Hospitalier Luxembourg (E-mail:
[email protected]) Bergqvist, David, MD, PhD, FRCS Department of Surgical Sciences Uppsala University, Hospital Uppsala, Sweden (E-mail:
[email protected])
XXX
Contributors
Biasi, Giorgio M., MCHiR, FACS, FRCS Department of Surgical Sciences and Intensive Care School of Medicine, University of Milan-Bicocca San Gerardo Hospital Monza, Italy (E-mail:
[email protected])
Carmo, Michele, MD Division of Vascular Surgery Ospedale S. Carlo Borromeo University of Milan Milan, Italy (E-mail:
[email protected])
Björck, Martin, MD, PhD Department of Vascular Surgery Academic Hospital Uppsala Uppsala, Sweden (E-mail:
[email protected])
Cau, Jérôme, MD Vascular Surgery Service University Hospital Jean Bernard Poitiers, France (E-mail:
[email protected])
Black, Stephen A., MD Regional Vascular Unit St. Mary’s Hospital London, UK (E-mail:
[email protected])
Chamogeorgakis, Themistocles, MD Department of Cardiothoracic Surgery University of Athens School of Medicine Attikon Hospital Center Athens, Greece (E-mail:
[email protected])
van Bockel, J. Hajo, MD, PhD Department of Vascular Surgery Leiden University Medical Centre Leiden, The Netherlands (E-mail:
[email protected]) Brooks, Marcus J., MD Regional Vascular Unit St. Mary’s Hospital London, UK (E-mail:
[email protected]) Cairols, Marc, MD Servei d’Angiologia I Cirurgia Vascular Hospital Universitari de Bellvitge University of Barcelona Barcelona, Spain (E-mail:
[email protected]) Camesasca, Valter, MD School of Medicine University of Milan-Bicocca San Gerardo Hospital Monza, Italy (E-mail:
[email protected])
Cormier, Jean-Michel, MD Division Vascular Surgery St. Joseph-Hospital Paris, France (E-mail:
[email protected]) Daenens, Kim, MD Department of Vascular Surgery University Hospital Gasthuisberg Leuven, Belgium (E-mail:
[email protected]) Dallatana, Raffaello, MD Division of Vascular Surgery Ospedale S. Carlo Borromeo Milan, Italy (E-mail:
[email protected]) Daskalopoulos, Marios E., MSC, DIC, MD Department of Vascular Surgery University of Athens Medical School Athens, Greece (E-mail:
[email protected])
Contributors
Daskalopoulou, Stella S., MsC, DIC, MD, FASA Department of Vascular Surgery University of Athens Medical School Athens, Greece and Department of Clinical Biochemistry and Surgery Royal Free Hospital London, UK (E-mail:
[email protected]) De Angelis, Gianni A. T., MD Division of Vascular Surgery Ospedale S. Carlo Borromeo University of Milan Milan, Italy (E-mail:
[email protected]) Defraigne, Jean-Olivier, MD Department of General and Human Biochemistry and Physiology, Centre Hospitalier Universitaire du Sart Tilman University of Liège, Belgium (E-mail
[email protected]) Deleo; Gaetano, MD School of Medicine University of Milan-Bicocca San Gerardo Hospital Monza, Italy (E-mail:
[email protected]) Dimakakos, Panos B., MD Vascular Department-B Surgical Clinic Aretaeion Hospital University of Athens, Athens, Greece (E-mail:
[email protected]) Dzsinich, Csaba, MD, PhD Department of Cardiovascular Surgery Semmelweis University Budapest, Hungary (E-mail:
[email protected]) Farghadani, Hirad, MD Department of Vascular Surgery Centre Hospitalier Luxembourg (E-mail:
[email protected])
Febrer, Guillaume, MD Department of Vascular Surgery University Hospital Poitiers, France (E-mail:
[email protected]) Fernandes e Fernandes, José, MD Professor of Surgery and Chief of Service Department of Vascular Surgery Hospital Santa Maria and Faculty of Medicine Director Instituto Cardiovascular de Lisboa Lisbon, Portugal (E-mail:
[email protected];
[email protected]) Fourneau, Inge, MD Department of Vascular Surgery University Hospital Gasthuisberg Leuven, Belgium (E-mail:
[email protected]) Fraedrich, Gustav, MD Department of Vascular Surgery Medical University of Innsbruck Innsbruck, Austria (E-mail:
[email protected]) Froio, Alberto, MD Vascular Surgery Unit University of Milano-Bicocca San Gerardo Hospital Monza, Italy (E-mail:
[email protected]) Geelkerken, Robert H., MD Medisch Spectrum Twente Enschede, The Netherlands (E-mail:
[email protected]) Georgopoulos, Sotiris E. First Department of Surgery Athens University Medical School Athens, Greece (E-mail:
[email protected])
XXXI
XXXII
Contributors
Gerasimidis, Thomas, MD Professor of Vascular Surgery Head of the Fifth Surgical Clinic Aristotle University of Thessaloniki Hippokrateio Hospital Thessaloniki, Greece (E-mail:
[email protected]) Giamarellou, Helen, MD, PhD 4th Department of Internal Medicine and Infectious Diseases Athens University Medical School University General Hospital “ATTIKON” Athens, Greece (E-mail:
[email protected]) Giannopoulos, Aris M., MD First Urology Department University of Athens Medical School, Laiko Hospital Athens, Greece (E-mail:
[email protected]) Golematti, Spyretta, MD, PhD Biomedical Simulations and Imaging Laboratory Faculty of Electrical and Computer Engineering National Technical University of Athens Athens, Greece (E-mail:
[email protected]) Gossetti, Bruno, MD Department of Vascular Surgery Policlinico Umberto 1° University of Rome “La Sapienza” Rome, Italy Goulao, J., MD Hospital Garcia de Orta Servico de Angiologia e Cirurgia Vascular Almada, Portugal (E-mail:
[email protected]) Guillou, Matthieu, MD Department of Vascular Surgery Hospital Jean Bernard Poitiers, France (E-mail:
[email protected])
Heikkinen, Maarit A., MD Division of Vascular Surgery Tampere University Hospital and Tampere University Tampere, Finland (E-mail:
[email protected]) Horrocks, Michael, MD Academic Department of Surgery Royal United Hospital Bath, UK (E-mail:
[email protected]) Horsch, Svante, MD Department of Vascular and Endovascular Surgery Krankenhaus Porz am Rhein Porz, Germany (E-mail:
[email protected]) Kakisis, John D., MD 3rd Department of Surgery Attikon Hospital Athens, Greece (E-mail:
[email protected]) Karamanos, Dimitrios Vascular Surgeon Fifth Surgical Clinic Aristotle University of Thessaloniki Hippokrateio Hospital Thessaloniki, Greece (E-mail:
[email protected]) Katsilambros, Nicholas, MD First Department of Propaedeutic Medicine Athens University Medical School Laiko University Hospital Athens, Greece (E-mail:
[email protected]) Kiskinis, Dimitrios A., MD, PhD Papageorgiou General Hospital Department of Vascular Surgery Aristotle University of Thessaloniki Thessaloniki, Greece (E-mail:
[email protected])
Contributors
Klocker, Josef, MD Department of Vascular Surgery Medical University of Innsbruck Innsbruck, Austria (E-mail:
[email protected])
Laurito, Antonella, MD Department of Vascular Surgery and Service of Nuclear Medicine Policlinico Umberto I, “La Sapienza” University Rome, Italy
Konstantinidis, Konstantinos Vascular Surgeon Fifth Surgical Clinic Aristotle University of Thessaloniki Hippokrateio Hospital Thessaloniki, Greece
Lecis, Alexandre, MD Department of Vascular Surgery University Hospital Jean Bernard Poitiers, France (E-mail:
[email protected])
Kostakis, Alkiviadis, MD Department of Surgery Athens University Medical School Laiko Peripheral General Hospital Athens, Greece (E-mail:
[email protected]) Kotsis, Thomas E., MD Vascular Department-B Surgical Clinic Aretaeion Hospital School of Medicine, University of Athens Athens, Greece (E-mail:
[email protected]) Ktenidis, Kiriakos, MD, PhD, EBSQ-VASC. Papageorgiou General Hospital Ass.Prof. Dr. K. Ktenidis Aristotle University of Thessaloniki 1st Department of Surgery-Vascular Surgery Thessaloniki, Greece (E-mail:
[email protected]) Lamont, Peter, MD, FRCS-EBSQ-VASC Consultant Vascular Surgeon Bristol Royal Infirmary Bristol, UK (E-mail:
[email protected]) Largiadèr, Jon, MD Universitätsspital Zurich Zurich, Switzerland (E-mail:
[email protected])
Lens, Vincent, MD Department of Radiology and Neuroradiology Centre Hospitalier Luxembourg (E-mail:
[email protected]) Liapis, Christos D., MD, FACS, FRCS Department of Vascular Surgery University of Athens Medical School Athens, Greece (E-mail:
[email protected]) Liloia, Angela, MD Department of Surgical Sciences and Intensive Care, School of Medicine University of Milan-Bicocca San Gerardo Hospital Monza, Italy (E-mail:
[email protected]) Limet, Raymond R., MD Department of Cardiovascular Surgery University Hospital of Liège CHU Sart-Tilman Liège, Belgium (E-mail:
[email protected]) Lindahl, Anne-Karin, MD Sykehuset Asker og Baerum HF, Norway (E-mail:
[email protected]) Ljungman, Christer, MD, PhD Department of Surgical Sciences, Section Surgery Academic University Hospital Uppsala, Sweden (E-mail:
[email protected])
XXXIII
XXXIV
Contributors
Makrilakis, Constantinos, MD First Department of Propaedeutic Medicine Athens University Medical School Laiko University Hospital Athens, Greece (E-mail:
[email protected]) Mallios, Alexandros Resident in Surgery Fifth Surgical Clinic Aristotle University of Thessaloniki Hippokrateio Hospital Thessaloniki, Greece Mambrini, Simone, MD Unit of Vascular and Endovascular Surgery University Hospital “San Martino” Genoa, Italy (E-mail:
[email protected]) Mansilha, Armando, MD Porto, Portugal (E-mail:
[email protected]) Mantas, Dimitrios, MD Department of Surgery Athens University Medical School Laiko Peripheral General Hospital Athens, Greece (E-mail:
[email protected]) Marchand, Christophe, MD Vascular Surgery Service University Hospital Jean Bernard Poitiers, France (E-mail:
[email protected])
Mataigne, Frédéric, MD Department of Radiology and Neuroradiology Centre Hospitalier Luxembourg (E-mail:
[email protected] Melas, N., MD First Department of Surgery and Vascular Surgery Aristotle University of Thessaloniki Papageorgiou General Hospital Thessaloniki, Greece Menezes, J. Daniel, MD Servico de Angiologia e Cirurgia Vascular Hospital Garcia de Orta Almada, Portugal (E-mail:
[email protected]) Mercandalli, Giulio, MD Division of Vascular Surgery Ospedale S. Carlo Borromeo University of Milan Milan, Italy (E-mail:
[email protected]) Metcalfe, James, MD Academic Department of Surgery Royal United Hospital Bath, UK (E-mail:
[email protected]) Metz René, MD Department of Neurology Centre Hospitalier Luxembourg (E-mail:
[email protected])
Martinelli, Ombretta, MD Department of Vascular Surgery Policlinico Umberto I° University of Rome “La Sapienza” Rome, Italy
Mikhailidis, Dimitri P., MD, FASA, FFPM, FRCP, FRCPATH Department of Clinical Biochemistry (Vascular Disease Prevention Clinics) and Department of Surgery, Royal Free Hospital London, UK (E-mail:
[email protected])
Massa, Rita, MD Department of Vascular Surgery and Service of Nuclear Medicine, Policlinico Umberto I° University of Rome “La Sapienza” Rome, Italy (E-mail:
[email protected])
Mitropoulos, Fotios, MD, PhD Department of Cardiothoracic Surgery University of Athens School of Medicine Attikon Hospital Center Athens, Greece (E-mail:
[email protected])
Contributors
Moreno, Rosa M., MD Hospital Clinico Universitario San Carlos Madrid, Spain (E-mail:
[email protected]) Nachbur, Bernhard, MD, FMH Ittingen, Switzerland (E-mail:
[email protected]) Nevelsteen, Andre, MD, PhD, FRCS Department of Vascular Surgery University Hospital Gasthuisberg Leuven, Belgium (E-mail:
[email protected]) Nikita, Konstantina S., MD Biomedical Simulations and Imaging Laboratory Faculty of Electrical and Computer Engineering National Technical University of Athens Athens, Greece (E-mail:
[email protected]) Nyman, Rickard, MD, PhD Department Diagnostic Radiology Academic University Hospital Uppsala, Sweden (E-mail:
[email protected]) Palombo, Domenico, MD Unit of Vascular and Endovascular Surgery University Hospital “San Martino” Genoa, Italy (E-mail:
[email protected]) Parsson, Hakan N., MD Department of Surgery Uppsala University Helsingborgs Lasarett Helsingborg, Sweden (E-mail:
[email protected]) Pedro, Luis Mendes, MD Faculty of Medicine University of Lisbon Consultant in Vascular Surgery Hospital de Santa Maria Lisbon, Portugal (E-mail:
[email protected])
Piazzoni, Claudia, MD Department of Surgical Sciences and Intensive Care School of Medicine University of Milan-Bicocca San Gerardo Hospital Monza, Italy (E-mail:
[email protected]) Poulakou, Garyphallia, MD 4th Department of Internal Medicine and Infectious Diseases, Athens University Medical School University General Hospital “ATTIKON” Athens, Greece (E-mail:
[email protected]) Pozzi, Grazia, MD Department of Surgical Sciences and Intensive Care, School of Medicine University of Milan-Bicocca San Gerardo Hospital Monza, Italy (E-mail:
[email protected]) Riera, S, MD Servei d’Angiologia I Cirurgia Vascular Hospital Universitari de Bellvitge Barcelona, Spain (E-mail:
[email protected]) Ricco, Jean-Baptiste, MD, PhD Vascular Surgery Service University Hospital Jean Bernard Poitiers, France (E-mail:
[email protected]) Rokkas, Chris K., MD Department of Cardiothoracic Surgery University of Athens School of Medicine Attikon Hospital Center Athens, Greece (E-Mail:
[email protected]) Saarinen, Jukka P., MD Division of Vascular Surgery Tampere University Hospital and Tampere University Medical School Tampere, Finland (E-mail:
[email protected])
XXXV
XXXVI
Contributors
Salenius, Juha-Pekka, MD Division of Vascular Surgery Tampere University Hospital and Tampere University Medical School Tampere, Finland (E-mail:
[email protected])
Skalkeas, Gregory D., Professor Emeritus, Academician President of the Foundation of Biomedical Research of the Academy of Athens Athens, Greece (E-mail:
[email protected])
Sampaio, Sérgio, MD Porto, Portugal (E-mail:
[email protected])
Sosa, Tomislav, MD (deceased) University Hospital Merkur Zagreb, Croatia
Saratzis, A., MD Department of Vascular Surgery Aristotle University of Thessaloniki Thessaloniki, Greece (E-mail:
[email protected])
Soucacos, Panayotis N., MD, FACS Department of Orthopaedic Surgery University of Athens, School of Medicine “K.A.T.” Accident Hospital Athens, Greece (E-mail:
[email protected])
Saratzis, Nikos A., MD Department of Vascular Surgery Aritstotle University of Thessaloniki Thessaloniki, Greece (E-mail:
[email protected]) Schmitz, Serge, MD Department of Vascular Surgery Centre Hospitalier Luxembourg (E-mail:
[email protected]) Schulte, Stefan, MD, PhD Department of Vascular Surgery Krankenhaus Porz am Rhein Porz, Germany (E-mail:
[email protected]) Sechas, Michael N., MD, FACS Athens, Greece (E-mail:
[email protected]) Sefranek, Vladimir, MD, PhD Slovak Institute of Cardiovascular Diseases Bratislava Bratislava, Slovakia (E-mail:
[email protected]) Settembrini, Piergiorgio G., MD Division of Vascular Surgery Ospedale S. Carlo Borromeo University of Milan Milan, Italy (E-mail:
[email protected])
Stamou, Sotiris, MD, PhD Department of Cardiothoracic Surgery Athens University Medical School Athens, Greece (E-mail:
[email protected]) Stravodimos, Konstantinos G., MD First Urology Department University of Athens, Medical School Laiko Hospital Athens, Greece (E-mail:
[email protected]) Stumpo, Regina, MD Department of Vascular Surgery Policlinico Umberto 1° University of Rome “La Sapienza” Rome, Italy Tentolouris, Nicholas, MD First Department of Propaedeutic Medicine Athens University Medical School Leiko University Hospital Athens, Greece (E-mail:
[email protected]) Toumpoulis, Ioannis K., MD Department of Cardiothoracic Surgery University of Athens School of Medicine Attikon Hospital Center Athens, Greece (Email:
[email protected])
Contributors
Tsapogas, Panagiotis, MD First Department of Propaedeutic Medicine Athens University Medical School Leiko University Hospital Athens, Greece (E-mail:
[email protected]) Vidjak, Vinko, MD University Hospital Merkur Zagreb, Croatia (E-mail:
[email protected])
Wanhainen, Anders, MD, PhD Department Diagnostic Radiology Academic Hospital Uppsala Uppsala, Sweden (E-mail:
[email protected]) Wolfe, John H. N., MD Regional Vascular Unit St. Mary’s Hospital London, UK (E-mail:
[email protected])
XXXVII
Vascular Surgery and the Vascular Patient
3
1.1 The History of Vascular Surgery in Europe Panagiotis E. Balas
To study the texts of the illustrious personalities of the past. GALEN
1.1.1 Introduction Writing the history of a medical specialty necessitates extensive historical and bibliographic research and the collection of data from various other sources such as information from medical people. The author must be experienced in collecting, evaluating and crosschecking the historical data in a scientific way to preserve objectivity. Undertaking this task of presenting the history of vascular surgery in Europe is difficult within the allotted time constraints, which necessarily are in conflict with being comprehensive and objective. My major concern however is that by studying and working exclusively in the field of angiology and vascular surgery for almost 40 years, by participating in the foundation of relevant scientific societies and by organizing congresses and other activities at home and abroad, I was part of the evolution of this medical field during the last half of the twentieth century and this could lead to a lack of objectivity. Therefore, my goal is to maintain the objectivity of this work while avoiding, as far as possible, any bias due to continental, national and personal scientific and professional preoccupations and interests. In this historical review, the development, evolution and recognition of the specialty of vascular surgery in Europe, including references to the associated medical specialties, will be presented, followed by an account of the various national contributions to this field.
1.1.2 The Origin and the Foundations of European Vascular Surgery The first interventions of Man on the blood vessels are lost in the depth of history, although some descriptions exist in ancient Indian and Greek texts. All the great
classical physicians, such as Hippocrates (fifth century b.c.), Aurelius Celsus (first century a.d.), Galen (second century a.d.) and Paulus Aegineta (sixth century a.d.), described various methods of treating varicose veins by ligation, cauterization and even stripping of the dilated long saphenous vein [14, 38]. The Greek Antyllus of the third century a.d., the most famous surgeon of antiquity, applied the well-known Antyllus’ method, an operation for aneurysm in which he applied two ligatures to the artery and cut between them. This was the accepted method of dealing with aneurysms until the work of Jon Hunter in the eighteenth century. Antyllus was the first to recognize two forms of aneurysm: the developmental, caused by dilatation, and the traumatic, following arterial trauma [38]. The famous surgeon-philosopher René Leriche (1879– 1955) credits four people who, with their ideas, practice and findings, influenced the development and evolution of knowledge in order to establish vascular surgery and to a certain extent its destination in Europe and the world all over. These four people were Ambroise Paré, William Harvey, Jean-Louis Petit and John Hunter [38].
Ambroise Paré
In 1546, Ambroise Paré performed the first arterial ligation during leg amputation in the midst of a combat and said “without having seen this attempt by any other person, nor heard or read but God advised me to tie the artery of the amputee”. He also introduced the first arterial forceps, the “bec de corbin”.
William Harvey
William Harvey (1578–1657), an Englishmen, went to the University of Padova, the most prestigious Institute at that time, and he studied under Hieronymus Fabricius. In 1603, Fabricius, an ardent anatomist, published the first
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1.1 The History of Vascular Surgery in Europe
treatise on the valves of the heart and the great veins of the body, entitled De venarum ostiolis and observed the one-way valves in veins, but had not figured out exactly what their role was [10]. Harvey became Professor of Anatomy and Surgery at St. Bartholomew’s Hospital in London and, after 9 years of experimentation on living animals and cadavers, proved that the blood was circulating in a circuit system including the heart, arteries and veins. The connection between arteries and veins through the capillaries was discovered later by the Italian Marcello Malpighi, by using the microscope. He presented his findings in 1628 in his book Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus (An Anatomical Study on the Motion of the Heart and Blood in Animals) (Figs. 1.1.1 and 1.1.2). Thus 1300 years after the Greek physician Galen had concluded that the cardiovascular system carried blood and not air, Harvey disclosed the circulation [38].
The end of the eighteenth and the beginning of the nineteenth century marked a golden age in which many surgeons contributed to knowledge on vascular diseases and surgery. There follows a brief description of their contributions. Hallowel applied the first arterial suture, an idea proposed by Lambert around 1770. In 1774 Morel, a
John Hunter
John Hunter was born in 1728 in Scotland and at the age of 23 arrived at St. Bartholomew’s Hospital to work with Percivall Pott. He worked on comparative and human anatomy and described the exposition of the arteries in the human body. His books and publications had a profound impact on the medical and surgical practice of that time. He described, famously, the very proximal ligation of the femoral artery, for the preservation of the collateral branches, in the treatment of popliteal aneurysm. One such surgical specimen is exhibited at the renowned museum of the Royal College of Surgeons of England in London. In 1757, William Hunter, John’s older brother, described and properly analysed the development of arterio-venous aneurysms [38].
Jean-Louis Petit
Jean-Louis Petit (1731) was the first surgeon to study haemostasis [38]. The famous English surgeon Sir Astley Cooper, at Guy’s Hospital, made two important contributions: a successful ligation of the common carotid artery for aneurysm in 1805 and in 1817 his attempt to treat an aneurysm of the iliac artery by ligation, for the first time, of the aorta above the bifurcation. He was also the first to use the extraperitoneal approach to the abdominal aorta, which was reintroduced by C. Rob in 1963 [56].
Fig. 1.1.1 William Harvey, Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus [Anatomical Exercise on the Motion of the Heart and Blood in Animals]. Edition, Roterdami, A pud Arnoldum Leers A 1661. (From author’s personal collection)
1.1.2 The Origin and the Foundations of European Vascular Surgery
military surgeon, applied the haemostatic tourniquet to the extremities in the battlefield. During the eighteenth century 123 studies had been conducted on aneurysms and their treatment with arterial ligation and the discussion on this topic continued until the middle of the twentieth century [38]. The pathologist Rudolf Virchow, the “Pope of German medicine”, described in 1852 the existence of arterial embolism. He also coined the terms thrombosis and embolism and later described the aetiological triad of venous thrombosis known as Virchow’s triad. In 1859 Karl Hueter in Germany reported the first case of venous gangrene of the extremities [25].
The pioneer of vascular surgery in Russia was N. I. Pirogov who, in 1865, developed surgical approaches to the aorta and peripheral arteries, arguing against the dogmatic views that a vascular suture was not promising. P. Girsztowt of Warsaw recommended in 1868 the excision of the large varicose veins. Eugene Koeberle, a surgeon in Strasburg, invented a simple haemostatic clamp and applied it in surgery in 1868. It was the first operation actually ushering in our present technique of clamping and tying, which was carried out and popularized by J. Pean with a clamp he invented in 1869 [38]. N. V. Ekk, an outstanding Russian surgeon and physiologist in Pavlov’s laboratory in St. Petersburg, performed in
Fig. 1.1.2 This illustration depicts one of William Harvey’s experiments included in the book Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus. Harvey shows that venal blood flows only towards the heart. He ligatured an arm to make obvious the veins and their valves, then pressed blood away from the heart and showed that the vein would remain empty because it was blocked by the valve
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1877 the first experimental vascular anastomosis between the portal vein and the inferior vena cava (Ekk’s fistula) [54]. Rudolf Matas, born in Louisiana USA and trained in the USA (with additional training in Paris and Barcelona), made history in 1888 by performing the first endoaneurysmorraphy for a traumatic aneurysm of the brachial artery [22]. In 1895 the Russian surgeon I. F. Sabaneyev made the first attempt in the world to remove an embolus from the femoral artery while the Russian R. R. Vreden performed in 1897 the first retrograde embolectomy of the aorta with limited success [54]. In 1896 the Lyon veterinarian M. Jaboulay proposed in the journal Lyon Medical an inverted suture of the arteries, known as the mattress-suture. Interestingly, this suture technique was clinically applied 50 years later by A. Blalock in Baltimore, USA [23]. In 1897 the Turkish Cemil Topuzlu Pacha, Pean’s pupil, repaired an axillary artery with five stitches [3]. Jaboulay’s technique was improved by one of his pupils, Alexis Carrel, who in 1902 published the technique of suturing the vessels in Lyon Medical. Also during this period Carrel performed outstanding research work in Lyon on arterial suturing and transplantation of arteries and organs. He successfully performed the first experimental cardiac homo-transplantation in the world, transplanting the heart of an animal to the neck of another by joining the carotid arteries (!). He published his work in the journal Lyon Medical in 1902 [24]. Carrel left Lyon in 1904 for Canada and the USA later, following political-religious turmoil due to his testimony of a miracle at Lourdes. In Chicago as Director of the Hull Laboratory of Physiology at the University of Chicago in collaboration with Charles C. Guthrie, he mastered his suturing techniques as the well-known Carrel’s Triangulation Techniques, and also the venous patch grafts made to enlarge the diameter of arteries. Later as Director of the Department of Experimental Surgery, at the Rockefeller Institute for Medical Research in New York, he worked on the preservation of arterial and venous segments for replacement of arteries and veins. He performed canine transections and end-to-end anastomosis of the descending aorta, or inserted a segment of preserved vena cava between the divided segments of the aorta. He also experimented with the insertion of a paraffined tube as an internal shunt within the aortic lumen in order to prolong the time of safe occlusion [24]. In addition to transplanting vessels and organs, Carrel worked on tissue cultures and organ preservation. The Norwegian R. Ingebrigtsen participated in this work and performed later interesting scientific work on arteriovenous fistulae in his country. In
1906, Carrel wrote the following instructions which are still valid a century later: “The vessels must be handled very gently and the endothelium must be protected…No dangerous metallic forceps are used. Great care is exercised to obtain accurate and smooth approximation of the endothelium of the vessel without invagination. Sutures should be made with very fine needles while the wall is somewhat stretched. Stenosis or occlusion only occurs as a result of faulty technique” [24]. Carrel received the Nobel Prize in Physiology and Medicine in 1912 for his spectacular experimental work [24]. During the ceremony of presentation of the Prize, the President of the Committee J. Ackerman among other things also said “To the great intelligence you have received from your mother country, France, to whom humanity owes so many great things, is united the energy and resolve of your adapted country. Your miraculous operations are the evident result of this happy collaboration…”. With his associate C. A. Lindbergh (famed for making the first solo airplane transatlantic flight in 1927) he developed in 1935 the first mechanical heart, a pump for circulating blood or fluids through preserved organs, namely the precursor of the extra-corporeal circulation which is in use today [24]. C. A. Lindbergh wrote in 1974 “medical scientists evaluating his work in the light of modern developments have said that he was fifty to a hundred years ahead of his time” [24]. In 1901, the Austrian Erwin Payr performed a vascular anastomosis with absorbable magnesium rings. Also arterial suturing was applied experimentally by Stich and Makkas (Germany) and many others [38]. In 1902 Tuffier attempted the resection of a syphilitic aneurysm of the ascending aorta but the patient died on the 13th day. Joe Goyanes of Madrid in 1929, after excision of a popliteal aneurysm, used an adjacent segment of popliteal vein to successfully bridge the defect (the first in situ vein graft) [27]. Six months later Erich Lexer at the University Hospital in Konigsberg, Germany performed excision of an axillary aneurysm and restored the arterial continuity by using a segment of the great saphenous vein [43]. This case was reported in the prestigious journal Archiv für Klinische Chirurgie which was read assiduously by prominent surgeons in Europe and in the United States. Among them was the American William S. Halsted, the famous first Professor of Surgery at the Johns Hopkins Medical School and Hospital, who had trained in Europe and, besides pioneering radical surgery of breast cancer, was also interested in vascular surgery, establishing a school of experimental vascular surgery. He studied various types of
1.1.3 Europe, Cradle of the World’s Vascular Surgery
arterial ligatures, among which was banding to achieve progressive arterial occlusion in order to reduce the size of distal aneurysms. In 1892 he successfully ligated the first part of the subclavian artery for the treatment of a huge distal aneurysm. Georges Labey, in 1911, performed the first successful arterial embolectomy of the extremities in the world [41], although there is information that in the same year the Hungarian surgeon J. Bakay performed a direct femoral embolectomy (D. Dzsinich, personal communication). In 1914 in Innsbruck, Austria, Hans von Haberer was the first surgeon to excise a false aneurysm of the carotid artery and to restore its continuity by an end-to-end anastomosis. He also published a monograph on “Kriegsaneurysmen” reporting on 72 operated cases of aneurysms [26]. During the First World War the pioneer Polish vascular surgeon Romuald Weglowski recommended the direct arterial reconstruction of arterial injuries, also using venous grafts for arterial bridging [57]. Vojislav Soubbotich, a pioneer vascular surgeon in Serbia during the Balkan wars (1912–14), performed repair, instead of ligation, of the injured vessels and of the post-traumatic aneurysms by using circular and lateral sutures, an experience commented on favourably by R. Matas [45, 59]. It is ironic that nearly 40 years passed before similar efforts were successful during the latter part of the Korean conflict [55]. Friedrich Trendelenburg, in Leipzig Germany, introduced an operation for varicose veins and in 1907 attempted a pulmonary embolectomy; however, he saw his pupil W. Kirchner perform a successful embolectomy in 1924, which was popularized later by many surgeons in Europe and the USA [40]. I was fortunate to attend the first pulmonary embolectomy under extra-corporeal circulation by Denton Cooley and A. Bell in 1960 at Saint Luke’s Hospital in Houston, Texas. The great breakthrough in the diagnosis of arterial diseases was the introduction of arteriography, namely the opacification of the arterial lumen, disclosing the abnormalities and even the occlusion of the artery, by intra-arterial injection of a liquid opacified by X-rays, which was first performed by J. Coapody in 1925 [13]. In Lisbon in 1926 Egaz Moniz, a Portuguese neurosurgeon, performed the first intra-carotid injection of thorium dioxide for the opacification of the carotid artery in a case of brain tumour [49]. Reynaldo dos Santos, a professor of urology in Lisbon, had performed the first translumbar aortography in 1929 [20] (Fig. 1.1.3). The first successful replacement of a semi-occluded femoral artery with a segment of the large saphenous
Fig. 1.1.3 A copy of the original aortograph performed by Reynaldo dos Santos in 1929, kindly given to the author by his son Joao Cid dos Santos in Lisbon in 1969
vein was performed by the Russian N. A. Bogoraz in 1935 (cited by A. N. Filatov) [54].
1.1.3 Europe, Cradle of the World’s Vascular Surgery European vascular surgery has been developed by the work of the above-mentioned pioneers and by European surgeons and medical angiologists since the 1930s and after the Second World War. During the second part of the twentieth century vascular surgeons were trained in Europe and many in the USA.
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1.1.3.1 The Nursery of Vascular Surgery in Europe in the 1930s was the René Leriche School in Strasburg, France The identity of vascular surgery as a specialty in the major field of surgery, not only in Europe but also internationally, started emerging in the 1930s in the famous School of René Leriche in Strasburg. In this Clinic many young European surgeons and the American Michael E. DeBakey had their training and were indoctrinated with the impressive ideas and experience of Leriche concerning the pathophysiology and treatment of arterial diseases. Among Leriche’s pupils were Michael E. DeBakey (USA), Nicolas Christeas (Greece) (both were my teachers), Joao Cid dos Santos (Portugal) and the French René Fontaine, Jean Kunlin and others (Fig. 1.1.4). René Leriche, from Lyon, became director of a surgical clinic in Strasburg and later in Paris. He described
the occlusion of the terminal aorta, a condition which was coined Leriche syndrome [38]. For the treatment of occlusion of the abdominal aorta he performed lumbar sympathectomies with or without excision of the occluded aortic segment. Certainly he thought that the proper treatment should be resection of the occluded aorta and its replacement with an arterial substitute, as Carrel has done experimentally, but no arterial substitute for Man was available at the time [37]. He performed with R. Fontaine, his successor in Strasburg, stellate ganglion block for the release of arterial spasm in pulmonary embolism, in angina pectoris and in vasospastic conditions, such as Raynaud’s syndrome (Fig. 1.1.5). These methods were used for many years in our angiological practice [46]. In 1947 René Leriche proposed the establishment of the specialty of vascular surgery by stating “Arterial surgery is a special discipline of general surgery. The diagnostic investigation and the operations exist and the material is
Fig. 1.1.4 An historic picture of Leriche and his pupils in Strasburg in 1938. First row from left to right: (starting third from left) M. E. DeBakey (USA), René Leriche, N. Christeas (Greece), C. Eliades (Greece), J. Kunlin (France). Second row: from left to right: Joao Cid dos Santos (Portugal). (Picture from author’s personal collection)
1.1.3 Europe, Cradle of the World’s Vascular Surgery
abundant” [38]. His proposal was realized in the European Union countries after 57 years, in 2004 [42]. It is important to mention that many prominent American vascular surgeons had obtained their “portions” of training in Europe before the Second World War, e.g. Michael E. DeBakey, or after the war, e.g. Denton A. Cooley. The author owes a personal debt of gratitude to their two cardiovascular centres for the training he received. They are the Methodist Hospital-Texas Medical Center of Michael E. DeBakey and the St. Luke’s Hospital-Texas Heart Institute of Denton A. Cooley. A very large series of European surgeons was trained and many hundreds of European cardiovascular surgeons have visited these centres, obtaining experience in vascular and/or cardiac surgery, bringing it back to their home institutions. Most of these trainees and many other cardiovascular surgeons from all over the world became members of the M. E. DeBakey International Cardiovascular Society which I established in
Fig. 1.1.5 Leriche performing operation with Christeas on his left. Strasburg 1938. (Picture from author’s personal collection)
Fig. 1.1.6 Audience to the President of the Hellenic Republic, Professor Constantinos Tsatsos. From left to right : H. Eascott (UK), E. Malan (Italy), The President, M. E. DeBakey (USA), A. Senning (Switzerland), P. Balas (Greece)
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Athens, Greece in 1976 (Fig. 1.1.6). Also, a similar Society of Denton A. Cooley was established. Many prominent American vascular surgeons were born in Europe and, after immigrating to the USA, developed leading vascular centres. Among them are the following: R. Linton born in Scotland, who was Director of Vascular Service in the Massachusetts General Hospital in Boston; Emeriick Szilagyi, born in Hungary, who was Director of Vascular Service in the Henry Ford Hospital, in Detroit; and Gega de Takats, also born in Hungary, who was Director of the Vascular Service in the University of Illinois, Chicago. Henry Haimovici from Tulcea Romania grew up and went to Medical School in Marseille, France. He moved to New York and became Head of Vascular Surgical Service Montefiore Hospital and Medical Center. It is very interesting that after his donation in 1976 the Rumanian Vascular Surgical Society was established. John Dormandy, born in Hungary, was Consultant Vascular Surgeon at St. George Hospital, London, UK. Peter Gloviczki, born in Hungary, is Professor and Chairman of the Department of Vascular Surgery, Mayo Clinic, Rochester, Minnesota, USA. Christopher K. Zarins, born in Latvia, is Director of Vascular Service in Stanford University Medical Center, Stanford, California. C. Rob moved from St. Mary’s Hospital in London, UK to the USA and became Chairman of the Department of Surgery at the Rochester University Medical School in Rochester, New York. In these centres many European surgeons were trained in vascular surgery, bringing about a reciprocal exchange of knowledge and experience among the surgeons and vascular surgical centres of Europe and the USA, starting from the old continent.
use of heparin for prevention of thrombosis, performed in 1947 the first successful thrombo-endarterectomy of the femoral artery with a silver ophthalmic spatula [40] (Fig. 1.1.7). During the next few years, open disobliteration was performed mainly by French surgeons, such as Bazy, Reboul and Huguier. Despite initial enthusiasm, it was apparent that the long-term results were not satisfactory. However, this technique revived following the introduction of patch graft angioplasty and extension of disobliteration of long occluded arterial segments by introducing the metallic ring strippers for semi-closed thrombo-endarterectomy. This was done first by the Americans Cannon and Baker and later by the Russian B. V. Petrovsky in 1959 [54] and in 1966 by the German J. Vollmar [61] using their own metallic ring strippers. Jean Kunlin, Leriche’s pupil, performed the first femoro-popliteal autologous saphenous venous by-pass in Paris in 1948 [36].
1.1.3.2 Reference to European Surgeons who Through their Pioneering Work Developed Vascular Surgery in their Continent with International Influence Clarence Crafοord, Director of Cardiovascular Surgery at the Karolinska Hospital in Stockholm, was a pioneer in performing pulmonary embolectomies and in 1944 performed the first successful correction of coarctation of the aorta. After the excision of the stenotic segment of the aorta he performed an end-to-end anastomosis, using Carrel’s triangulation technique [9]. In Russia V. F. Gudov, in 1945, designed and applied clinically the first vascular suturing apparatus [54]. Joao Cid dos Santos, taking advantage of the development of arteriography and the
Fig. 1.1.7 Jean Natali (France, left) and Joa Cid dos Santos (Portugal) in the early 1970s
1.1.3 Europe, Cradle of the World’s Vascular Surgery
In Paris Jacques Oudot performed experimental work in vascular surgery and the preservation of arterial homografts with the assistance of Jean Natali, who later became one of the leaders of French vascular surgery [50]. In 1950 Oudot was the first to replace the occluded abdominal aorta with a preserved aortic bifurcated homograft. Later on, due to occlusion of the right leg of the graft, he performed, also for the first time, a cross-over iliac–iliac by-pass with an arterial homograft [51, 53]. René Fontaine in 1951, established in Strasburg the first arterial bank in Europe, followed by similar banks in many European centres. The Russian N. I. Makhow performed in 1950 the world’s first implantation of femoral lymphatic channels into the femoral vein of a patient with secondary lymphoedema [54]. In 1951 Charles Dubost in Paris performed the monumental operation of excision of an abdominal aortic aneurysm and replacement with a 14-cm-long preserved segment of thoracic aorta [21]. In 1953 at St. Mary’s Hospital in London, UK, H. H. G. Eastcott together with Professor Charles Rob performed reconstruction of the occluded left carotid artery – the first time this had been done in Europe [23]; a similar procedure had been performed a few months earlier by M. E. DeBakey in Houston, Texas [18]. G. Arnulf in Lyon France published a book on carotid surgery [1]. In 1952, at St. Thomas’ Hospital in London, Sir John Kinmonth, who was a pioneer in the study and treatment of lymphatic diseases, introduced lymphangiography to image the lymphatic vessels of the extremities [35]. The Czech J. Dvorak and his collaborators were the first in Europe to manufacture cloth arterial prostheses of knitted terylene followed by other kinds of material [12]. These prostheses were first used in 1951 at New York’s
Fig. 1.1.8 B. V. Petrovsky, Russia
Columbia-Presbyterian Hospital, by Arthur Voorhees, who conceived the idea by chance on observing that silk sutures placed in a canine heart became completely covered with connective tissue. L. V. Lebedev and L. L. Plotkin in Leningrad in 1959 developed arterial prostheses from synthetic lavsan and later from fluorolon [54]. The most celebrated of Russian vascular surgeons Β. V. Petrovsky, Founder and Director until his mid-eighties of the All Union Research Center of Surgery (AURCS) in Moscow and past Minister of Public Health of the USSR, performed in 1947 the first successful resection of post-traumatic aneurysm in Europe [54] (Fig. 1.1.8). In 1959, the German pioneer in cardiovascular surgery Georg Heberer was the first in Europe to perform an intervention on a post-traumatic rupture of the thoracic aorta [5]. R. van Dongen, a prominent Dutch vascular surgeon and I. Boerema’s pupil, designed a specific table and used a special needle for aortography in the 1950s and later on published an impressive book with illustrations of vascular procedures [31, 60] (Fig. 1.1.9). In 1959 Karl Victor Hall, Professor of Surgery at the National Hospital of Oslo, applied in Europe, at about the same time as Cartier in Canada, in situ venous by-pass in the lower extremities. He later developed Hall’s valve stripper [30]. In 1962 A. V. Pokrovsky in Moscow was the first in the world to use retroperitoneal thoraco-abdomi-
Fig. 1.1.9 Presentation of a Diploma of Honorary Distinction of IUA, by P. Balas, Secretary of the Union (left), to R. J. A. M. van Dongen in Amsterdam in 1986 during the Eighth Course of Vascular Surgery organized by the honouree
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nal access to the thoraco-abdominal aorta and visceral arteries [54]. In 1953 F. Cockett in London described the perforator veins in the leg as Cockett’s perforators [15] and also iliac compression syndrome in 1965 [16]. This syndrome was also described by R. May in Innsbruck [14]. Around 1954 the first vascular surgical clinics of England were set up in London, one by C. Rob and F. Eascott at St. Mary’s Hospital and the other by F. Cockett and J. Kinmonth at St. Thomas’ Hospital; another was established in Manchester by Michael Boyd (F. B. Cockett, communication by correspondence, 2004). A famous Polish vascular surgeon Jan Nielubowicz, in co-operation with Waldemar Olszewski, introduced in 1967 the surgical lymphatico-venous shunt in patients with secondary lymphoedema [52]. Later a Scandinavian plastic surgeon T. Ipsen and colleagues performed, with the use of a microscope, a lymph–venous anastomosis [32]. After the introduction of microvascular surgery in the USA by Julius Jacobson II in 1960 [33], this field was extended in Europe by the work of Victor Krylov in the early 1970s at AURCS in Moscow [2] and by M. Gazi Yasargil in Switzerland [19]. E. Malan, Director of a Cardiovascular Institute in Milan, proposed a “classification of the vascular malformations” and established in the 1970s and 1980s an important centre of vascular surgery in Italy. In 1967 in Athens, Greece, P. Balas performed the first replantation of a completely amputated upper extremity in Europe, which is functioning satisfactorily up to the present date [11]; this was followed by a successful case carried out by the Swiss Bruno Vogt in 1979. Jorg Vollmar in Germany developed a rigid endoscope in 1969 to inspect the luminal surface after closed arterial endarterectomy [61]. The Czech V. Michal in 1973–78 developed procedures for vasculogenic impotence (femoro-pudendal by-pass, internal iliac thrombo-endarterectomy and direct arterial anastomosis to the cavernous body) [48].
1.1.3.3 Medical and Interventional Vascular Contributions to the Development of Vascular Surgery in Europe and Worldwide Christian Doppler was a mathematician born in Salzburg, Austria. In 1842 he wrote a paper entitled “Concerning the colored light of double stars”, the substance of which is now known as the Doppler effect. He hypothesized that the pitch of a sound would change if the source of the
sound was moving. This hypothesis was tested in 1845. The Japanese Shige and Satomiga applied the Doppler effect to the diagnostic investigation of the cardiovascular system using ultrasound techniques. The resulting valuable tools for the study of the cardiovascular system include Doppler ultrasonography, which uses audio and graphic measurements to hear and measure blood flow, and duplex ultrasonography, with or without colour imaging. In the early 1950s, Swedish physicians, following the work of the Swede Gunnar Bauer in 1940, developed both ascending and descending phlebography and they also started the use of heparin for the treatment of venous thrombosis [4]. Sven Ivar Seldinger, a radiologist at the Karolinska Hospital in Stockholm, applied in 1952 a technique for peripheral arteriography; the procedure is now coined with his name [56] and is used at present for all endovascular procedures. In the 1960s the Swedes Carl Arnodi, Knut Haeger, Goran Nylander and others contributed to the study of venous disorders of the lower extremities (G. Hagmueller, communication by correspondence 2004). James S. T. Yao, working as research fellow at the vascular laboratory W. T. Irving at St. Mary’s Hospital in London in 1968, did pioneering work in the study of peripheral arterial circulation by using strain gauge plethysmography and ultrasound Doppler and developed the ankle/brachial blood pressure index (ABI), which has been and still is used extensively [62]. In the 1960s I. Boerema, father of modern hyperbaric medicine, applied hyperbaric oxygen therapy in cases of critical limb ischaemia and gangrene and in anaerobic infections of the extremities, and he also performed minor procedures in the hyperbaric facility in the University Hospital in Amsterdam [7] (Fig. 1.1.10). However, the largest and very impressive hyperbaric medical facility in Europe, and probably the world, was established in AURCS in Moscow in 1975, where Victor Krylov performed carotid endarterectomy and B. A. Konstantinov and others performed cardiac operations in 1998. In 1998 I visited this centre, which was under the direction of a senior professor specializing in hyperbaric medicine and included many sections such as surgical, obstetrics, gynaecology and others [2] (Fig. 1.1.11). In the early 1970s in London V. V. Kakkar made a breakthrough in the prevention of venous thromboembolism by introducing the subcutaneous injection of a low dose of heparin for the prophylaxis of deep vein thrombosis (DVT) [34].
1.1.3 Europe, Cradle of the World’s Vascular Surgery
Fig. 1.1.10 Hyperbaric Chamber, University Hospital of Amsterdam
A. Nikolaides contributed through original works to the study of venous diseases [6]. S. I. Seldinger, a radiologist at the Karolinska hospital in Stockholm, applied in 1952 a technique for periph-
Fig. 1.1.11 Performance of minor surgery in the chamber
eral arteriography; the procedure is now coined with his name [58]. In 1971 E. Zeitler, a German radiologist, started popularizing in Europe the American Charles Dotter’s technique of transcutaneous arterial disoblitaration. Andreas Gruntzig of the Angiological Clinic of Alfred Bollinger in Zurich, Switzerland, after his work with Zeitler, developed in 1974 the monumental method of arterial dilatation by using a balloon catheter for dilatation of the peripheral and coronary arteries, introducing percutaneous transluminal angioplasty (PTA) [28]. In 1976 Gruntzig performed the first PTA on the coronary arteries with the back-up of cardiac surgeons [28]. In 1977 Felix Mahler from the Department of Angiology of the University of Berne was the first to perform PTA of the renal arteries, for renovascular hypertension, with the back-up of vascular surgeons. The application of Gruntzig’s method (PTA) was one of the greatest breakthroughs in the treatment of cardiovascular diseases in the twentieth century. The radiologist I. K. Rabkin at AURCS in Moscow performed the first transcatheter intravascular procedure in
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the USSR and was the first in the world to perform, in 1984, dilatation and endovascular prosthetic grafting of an external iliac artery [54]. N. L. Volodos was the world pioneer in devising and clinically applying endoprostheses in the aorta and iliac arteries in the Ukraine in 1985, before J. Parodi [54]. Claude Mialhe from France was a world pioneer, performing in 1995 endovascular abdominal aortic aneurysm repair by using a modular stent graft [47], followed immediately by Wolf J. Stelter in Frankfurt, Germany (personal communication, 1964). The Leicester group under Sir Peter Bell and the radiologist A. Bolia contributed to the advancement of endoluminal treatment by applying subintimal angioplasty to the lower extremities [8]. In the 1970s Herbert Ehringer in Vienna introduced intravenous thrombolysis for arterial occlusions. The German angiologist Hans Hess in Munich in the early 1980s introduced intra-arterial thrombolysis in peripheral arterial occlusive disease, followed by the Swede D. D. Do (1987).
1.1.4 European Vascular Surgical and Angiological Societies and Congresses Since the 1970s the following events have played an essential role in the development of European vascular surgery. The European Society of Vascular Surgery (ESVS) was founded by leading vascular surgeons R. Greenhalgh, Sir Peter Bell (UK), P. Fiorani (Italy), H. Mhyre (Norway), H. Van Urk (The Netherlands) and others. The inaugural meeting of the Society was held in May 1987, with the first President being Hans Myhre, during the International Symposium of the Charing Cross Hospital in London; it was organized by Greenhalgh, who had written the first constitution of the Society. Preceding the formation of the Society, the European Journal of Vascular Surgery was started by a European Editorial Board chaired by Greenhalgh and became the official journal of the Society [44] (Fig. 1.1.12). Concerning the establishment of vascular surgery as an independent specialty in the European Union (EU), credit has to be given, among others, to Domenico Palombo, an Italian vascular surgeon who organized a meeting of a working group of representatives of vascular surgical societies of the 12 EU countries at that time, in St. Vincent (Aosta-Italy) on March 1991, to discuss the perspectives of European vascular surgery. Through many meetings of representatives of European vascular surgical societ-
Fig. 1.1.12 Presentation by P. Balas, President of the ESVS, of a Diploma of Honorary Member of the Society to Roger Greenhalgh (UK) during the Congress of the Society in Berlin in 1993
ies, who formed the Council of Vascular Surgeons in the EU (Aosta group), a statute was attested by a notary and was drawn, defining the specialty of vascular surgery and the objectives of the Council, signed by the following: M. D’Addato (Italy), P. C. Maurer (Germany), H. G. Nicaise (France), R. Vanmaele (Belgium), J. Barbosa (Portugal), J. Buth (The Netherlands), P. L. Harris (UK), M. A. Cairols (Spain), P. Balas (Greece) and W. P. Paaske (Denmark). The Council approached the European Union of Medical Specialists (UEMS) and after long discussions, together with the help of the ESVS, a Division of Vascular Surgery in the Section of General Surgery of the UEMS was established in 1992 in Edinburgh. The Division organized a European Board of Vascular Surgical Qualification (EBSQ-VASC) to provide a European certification in vascular surgery for the vascular surgeons of the countries of the EU, following proper assessment. The first assessment took place in Venice in 1966 and subsequently each year in conjunction with the annual meeting of the ESVS. Following successful examinations a diploma is provided with the title Fellow of the European Board of Vascular Surgery [44]. On 15 October 2004 vascular surgery was recognized by the UEMS as an independent specialty in the EU (Fig. 1.1.13). People who over the years contributed to the recognition of the specialty were R. Greenhalgh (UK), P. Harris (UK), J. Buth (The Netherlands), W. P. Paaske (Denmark), C. Liapis (Greece), F. Benedetti-Val-
1.1.4 European Vascular Surgical and Angiological Societies and Congresses
Fig. 1.1.13 Creation of Section of Vascular Surgery, 15 October 2004. From left: F. Benedetti-Valentini, President UEMS Section of Vascular Surgery; R. Greenhalgh, President European Board of Surgery and UEMS Representative, Surgical Specialties; H. Halila, President UEMS; and C. Liapis, President ESVS
entini (Italy), J. Fernandes e Fernandes (Portugal), J. Wolfe (UK), G. Biasi (Italy), D. Bergqvist (Sweden) and others [44]. A crucial factor in the development and evolution of the field of endovascular therapies for peripheral arterial diseases in Europe was the establishment in 1992 in Bordeaux, France, of the International Society of Endovascular Surgery. Among the eight founders members of the Society four were Europeans: P. Balas (Greece), P. Bergeron (France), J. Busques (France) and J. Bleyn (Belgium) [17]. During the Congress of the European Society for Vascular Surgery (ESVS 1992), which I had organized in Athens (Fig. 1.1.14), we organized with Edwards Dietrich, from the Arizona Heart Institute, a spectacular satellite, live broadcast of endovascular procedures from his Institute to the Athens Hilton Hotel, an event that I am convinced was decisive for the decision of the European Society of Vascular Surgery and its journal to change their names to include the endovascular component [2]. European angiology played a pivotal role in the development of world angiological disciplines, among which was vascular surgery. The promotion of European and international angiology has been achieved by the International Union of Angiology (IUA) and its journal International Angiology, which started in 1982 with P. Balas as Editor-in-Chief, and essential to this process has been the co-operation of prominent European angiologists and vascular surgeons such as F. Pratesi, A. Strano and G.
Fig. 1.1.14 P. Balas, President of the Congress of the ESVS in Athens in 1992 and P. Fiorani (Italy), President of ESVS and Mrs P. Fiorani
Biasi (Italy), P. Maurer (Germany), H. Boccalon, L. Castellani (France), D. Clement (Belgium), A. Nicolaides (UK), L. Norgren (Sweden) and others. In 1988 The Mediterranean League of Angiology and Vascular Surgery (MLAVS) was established by P. Balas (Greece), A. Strano, G. Biasi (Italy), L. Castellani (France), A. Angelides (Cyprus), E. Hussein (Egypt), J. Fernandes e Fernandes (Portugal) and representatives from other European countries, under the patronage of the IUA, for the promotion of angiology in the Mediterranean countries [2]. The contribution of the angiological schools of Fernando Martorell (Barcelona, Spain), J. Merlen (Lille, France), C. Olivier (Paris), Franco Pratesi (Florence), A. Strano (Palermo-Rome, Italy), Alfred Bollinger (Zurich) and Bent Fagrell (Stockholm) should also be emphasized. In 1959 Max Ratschow, an outstanding German angiologist in Heidelberg, published an important book Angiologie. Among Ratschow’s pupils were outstanding German angiologists Hans Hess and W. Schoop and the Swiss Leo Widmer (Basel). All these contributed to the development of the major field of angiology in Europe, paving the way for the development of vascular surgery.
15
16
1.1 The History of Vascular Surgery in Europe
The following leading European cardiovascular surgeons George Arnulf (France), J. Kinmonth (UK), Edmondo Malan (Italy), R. Fontaine, Jean Natali (France), J. C. Dos Santos (Portugal), Jean Van Der Stricht (Belgium) and others were the founders of The European Chapter of the International Society for Cardiovascular Surgery in 1951 and of its official journal Journal of International Cardiovascular Surgery in the 1960s, playing a crucial role in the development of cardiovascular surgery in Europe [29]. Since the 1960s many international, European and national congresses, conferences, work-shops and other scientific activities have been organized in Europe, contributing significantly to the continuing education of trainees
in angiology-vascular surgery and of the vascular surgeons. Among them were the 25 annual Charing Cross Symposia in London, the annual congresses of the ESVS in various European countries since 1988 and the international and the European congresses of the IUA [2]. In Fig. 1.1.15, during the 15th World Congress of Angiology in Rome in 1989 are depicted the past, present and the future presidents of the IUA. From left to right: P. Balas (Greece), D. Clement (Belgium), P. Glovinczki (USA), P. Maurer (Germany), Cs. Dzsinich (Hungary), A. Strano (Italy), President of the Congress, L. Castellani (France), H. Boccalon (France), A. Schirger (USA) and G. Parulkar (India). Fourteen Annual Mediterranean
Fig. 1.1.15 The Presidents of the IUA, during the 15th World Congress of Angiology, Rome, 1989
1.1.5 Epilogue
Congresses have been organized so far. Also, 14 Annual Congresses of the MLAVS have also been organized (Fig. 1.1.16). Tables 1.1.1 and 1.1.2 present various national data concerning vascular surgery in various European countries. It was possible to collect these through personal communications with leading vascular surgeons and/or from publications. Some omissions are due to lack of information.
1.1.5 Epilogue This historical review is a tribute to the personalities who contributed to some extent to the progress of vascular surgery in Europe, both those who are among us at present and those who are fondly remembered (Fig. 1.1.17). However, from this short historical account many important persons and their work have not been mentioned due to limited space, but the interested reader can find them in other more extensive historical treatises.
Table 1.1.1 National data concerning vascular surgery in Europe. (A The existence of the independent speciality of vascular surgery and date of establishment, B the existence of vascular surgical clinics and date of establishment, B1 number of state clinics, B2 number of university clinics, B3 total number, C date of establishment of a vascular surgical society and/or angiological society, D the publication of vascular surgical and/or angiological journals, E the publication of books on vascular surgery and/or angiology, + existence, – existence, ? no information available) Country
A
B B1
B2
C
D
E
–
+
–
B3
Austria
+ (1983)
1 (1972)
4
–
Bulgaria
+ (1994)
1 (1964)
–
7
Croatia
?
9 (1964)
13
19
Cyprus
+ (1987)
–
–
–
–
+
–
+ (1996)
–
?
–
–
–
Czech Republic
+ (1986)
3
1
4
?
+
+
Denmark
+ (2004)
4
5
9
–
–
–
Germany
+ (1978)
?
?
100
+ (1984)
+
+
Greece
+ (1989)
2
4
6
+ (1982)
+
+
Hungary
+
?
?
?
+
+
+
Iceland
–
1 (1994)
–
–
–
–
–
Ireland
–
1 (Late 50s)
–
–
+ (With UK)
–
–
Italy
+ (1974)
28
79
107
+
?
+
Norway
+ (1986)
–
–
–
+ (1990)
+
–
Poland
+ (2001)
–
–
–
+ (2001)
+
+
Serbia
+ (1992)
1 (1989)
–
–
–
–
–
Slovak Republic
+ (1988)
1 (1978)
–
–
–
–
–
Spain
+ (1978)
1 (1963)
–
42
?
+
+
Switzerland
+ (2002)
–
–
–
+ (1989, 2000)
+
+
The Netherlands
–
–
–
–
+ (1981)
–
–
Turkey
–
1 (1961)
–
–
+ (1982)
+
+
UK
+ (1966)
?
?
?
+
–
+
Ukraine
–
1 (1972)
?
?
+ (2001)
+
+
17
?
?
1961
1966
?
1968
1966
1958
1957
1956
1953
Turkey
1957
Switzerland
? 1967
The Netherlands Yes
? 1962
?
Serbia
Spain
1947
Russia
Slovak Republic
1979 ?
Poland
?
Ireland
Norway
1954 ?
Iceland
Early 70s 1958
Greece
Hungary
Early 60s Early 60s ?
Czech Republic
1978
?
?
?
?
?
?
?
?
?
?
?
?
1964
?
?
1988
?
1960
Cyprus
?
Bulgaria
?
A3
?
A2
Austria
A1
A
?
Yes
?
1963
1961
1965
?
1963
1958
1956
1973
1969
1963
Early 60s
1981
1962
1962
B
?
?
?
?
1953
?
?
1958
1955
?
?
1949
Early 70s
Early 60s
?
?
?
C
?
Yes
?
?
1964
1966
1959
?
?
1959
1960
1967
1963
?
?
?
1958
D
?
1962
?
E2
?
?
?
1959
?
1956
?
Late 50s
?
?
?
1951
1962
?
?
?
?
1960
?
?
Late 50s
?
1954
?
?
1961
Middle 50s 1958
?
?
1952
E1
E
?
?
?
?
1981
1970
1999
1992
?
?
?
1986
?
1979
?
1974
?
F
?
?
?
?
G3
?
?
?
?
?
?
?
?
Early 2000 1997
?
?
?
?
G2
?
1994
?
?
?
?
?
?
?
?
?
?
?
?
?
?
?
?
?
?
?
Last years Last years ?
1995
?
?
1997
1996
1994
2000
?
?
G1
G
Table 1.1.2 Dates that various vascular surgical procedures started. (A Excision of aneurysms, A1 thoracic, A2 abdominal, A3 peripheral, B carotid endarterectomy, C arterial endarterectomy, D aortic by-pass, E femoro-popliteal by-pass, E1 with vein, E2 with plastic arterial prosthesis. F venous reconstruction, G endovascular aneurysm repair, G1 abdominal, G2 thoracic, G3 peripheral, ? no information available). The dates indicate the first performed operation
18 1.1 The History of Vascular Surgery in Europe
1.1.5 Epilogue
I trust that the new generations of vascular surgeons, inspired by the achievements of the important and leading personalities in angiology and vascular surgery of the past, will continue to carry the torch of progress of vascular surgery with enthusiasm and vision, to pioneer scientific work and carry out excellent medical practice for the benefit of our fellow humans afflicted by vascular diseases.
Fig. 1.1.16 The President of the MLAVS, P. Balas, presenting a Diploma of Honorary Member to G. Biasi (Italy), former Secretary of the League
Fig. 1.1.17 Galene’s Dictum in Greek (To study the texts of the illustrious personalities of the past)
Acknowledgements I greatly appreciate the following colleagues for providing important historical data concerning the development and evolution of vascular surgery in their countries: • V. Anastasov, Plovdiv, Bulgaria • Nicos Angelides, Nicosia, Cyprus • Sir Peter Bell, Leicester, UK • Patrice Bergeron, Marseille, France • David Bergqvist, Uppsala, Sweden • Giorgio Biasi, Milan, Italy • Andrea Brunner, Nuremberg, Germany • Murat Byazit, Turkey • Josep M. Capdevila, Barcelona, Spain • Lazar B. Davidovic, Belgrade, Serbia • R. J. A. M. van Dongen, Amsterdam, The Netherlands • Csaba Dzsinich, Budapest, Hungary • H. H. G. Eastcott, London, UK • Bert Eiklboom, Utrecht, The Netherlands • Georg Hagmueller, Vienna, Austria • William P. Hederman, Dublin, Ireland • A. V. Gavrilenko, Moscow, Russia • Roman Jaworski, Wroclaw, Poland • Kiriaki Kalligianni, Athens, Greece • Milan Krajicek, Praha, Czech Republic • William MacGowan, Dublin, Ireland. • Zygmunt Mackiewicz, Bydgoszcz, Poland • Nikolay Muz, Ukraine • Hans O. Myhre, Trondheim, Norway • Bernhard Nachbur, Ittigen, Switzerland • Jean Natali, Paris, France • Anatoly Pokrovsky, Moscow, Russia • V. Riambou, Barcelona, Spain • Einar Stranden, Oslo, Norway • Vladislav Treska, Plezen, Czech Republic • James Yao, Chicago, USA • F. Zernovicky, Bratislava, Slovak Republic I would also like to thank my friends Professor Julius Jacobson, II, New York, N. Y., USA and Mr. L. H. Brown, Athens, Greece, for their editorial assistance.
19
20
1.1 The History of Vascular Surgery in Europe
References 1. Arnulf G (1957) Pathologie et chirurgie des carotids. Masson et Cie, Paris 2. Balas P (2003) Memoirs of an angiologist and vascular surgeon. Zita, Athens 3. Batirel HF, Yuksel M (1997) Our surgical heritage. Ann Thorac Surg 64:1201–1203 4. Bauer G (1940) Venographic study of thromboembolic problems. Acta Chir Scand 84 (Suppl) 61:1–75 5. Becker HM (2000) In memoriam Prof. Dr. Georg Heberer. Gefasschirurgie 5:4–5 6. Bergqvist D, Comerota JA, Nicolaides A, Scurr JH (1994) Prevention of venous thromboembolism. Med-Orion, London 7. Boerema I (1961) An operating room for high oxygen pressure. Surgery 47:291–298 8. Bolia A, Miles KA, Brennan J, Bell PRF (1990) Percutaneous transluminal angioplasty of occlusions of the femoral and popliteal arteries by subintimal dissection. Cardiovasc Intervent Radiol 13:357 9. Bjork VO (1984) Clarence Crafoord (1900–1984) The leading European thoracic surgeon died. J Cardiovasc Surg 25:473 10. Caggiati M, Rippa M, Bonati A, Pieri A, Riva A (2004) Four centuries of valves. Eur J Vasc Endovasc Surg 28:439–441 11. Christeas N, Balas P, Giannikas A (1969) Replantation of amputated extremities. Report of two successful cases. Am J Surg 118:68–73 12. Chvapil M, Krajicek N (1963) Principle and construction of a highly-porous collagen-fabric vascular graft. J Surg Res 5:358–364 13. Coapody J (1925) Arterienphotographien vermittels, Lipiodol. Klin Wehnschr 4:2327 14. Cockett FB (1990) A historical outline of varicose vein surgery up to the present day. Flebolinfologia 1:3–5 15. Cockett FB, Jones DE (1953) The ankle blow-out syndrome. A new approach to the varicose ulcer problem. Lancet [Jan 3] 1:17–23 16. Cockett FB, Thomas ML (1965) The iliac compression syndrome. Br J Surg 52:816–821 17. Criado F (1998) ISES: the first five years 1992–1997. J Endovasc Surg 5:XXI–XXII 18. DeBakey ME (1975) Successful carotid endarterectomy for cerebrovascular insufficiency. J Am Med Assoc 233:1083–1085 19. Donaghy RMP, Yasargil MG (1967) Micro-vascular surgery. Mosby, St Louis; Georg Thieme, Stuttgart
20. Dos Santos R, Lamas A, Pereirgi CJ (1929) L’arteriographie des members de l’aorte et ses branches abdominal. Bull Soc Nat Chir 55:587 21. Dubost C, Allary M, Oeconomos N (1951) A propos du traitement des aneurysmes de l’aorte. Ablation de l’aneurysme, retablissment de la continuité par greffe de l’aorte humaine conservée. Mem Acad Chir 77:381 22. Eascott HHG (1969) Arterial surgery. Lippincott, Philadelphia 23. Eascott HHG, Pickering GW, Rob CG (1954) Reconstruction of internal carotid artery in a patient with intermittent attacks of hemiplegia. Lancet ii:994–996 24. Edwards WS (1974) Alexis Carrel. Visionary surgeon. Charles C Thomas, Springfield 25. Encyclopaedia Britannica On line. Virchow (12/9/2004) www.britannica.com. 26. Fraedrich G (2004) From Hippocrates to Palmaz-Schatz. The history of carotid surgery. Eur J Vasc Endovasc Surg 28:455 27. Goyanes J (1929) Nuenos trabajos de cirugia vascular. Substitucion plastica de las arterias por las venas, o atrerioplastica venosa, applicada como nuevo metodo, al tratamiento de los aneurismas. El Siglo Med Sept pp 346–561 28. Gruntzig A, Holff H (1974) Perkutaene rekanalisation chronischer arterieller verschluess mit einem neuen dilatationskatheter. Dtsch Med Wochenschr 99:2502 29. Haimovici H (1977) The history of the International Cardiovascular Society. J Cardiovasc Surg 18:207–240 30. Hall KV (1962) The great saphenous vein used in situ as an arterial shunt after extirpation of the vein valves. Surgery 51:492–495 31. Heberer G, van Dongen RJAM (1989) Vascular surgery. Springer, Berlin Heidelberg New York 32. Ipsen T, Pless J, Fredriksen PB (1990) Experience with microlymphaticovenous anastomoses for the treatment of obstructive lymphedema. Plast Reconstr Surg 85:562–571 33. Jacobson J, II, Suarez EL (1960) Microsurgery in anastomosis of small vessels. Surgical Forum XI:243 34. Kakkar VV, Spindler J, Flute PT et al (1972) Efficacy of the low doses of heparin in prevention of deep venous thrombosis in blind randomized trail. Lancet 2:101 35. Kinmonth JB (1952) Lymphangiography in man; a method of outlining lymphatic trunks at operation. Clin Sci 11:13–20 36. Kunlin J et al (1951) Le traitement de l’ischémie artéritique par la greffe veineuse longue. Rev Chir 15:206–235 37. Landry P (1999) Biographies, William Harvey. www.blupete.com/Literature/Biographies/Science/Harvey.htm
References
38. Leriché R (1923) Des oblitérations artérielles hautes (obliteration de la terminaison de l’aorte) comme causes des insuffisances circulatoires des membres inferieurs. Bull Mem Soc Chir Paris 49:401–404 39. Leriche R (1940) De la resection du carefour aorto-iliaque avec double sympathectomie lombaire pour thrombose arteritique de l’aorte: le syndrome de l’obliteration terminoaortique par arterite. Presse Med 48:601 40. Leriche R (1943) Physiologie pathologique et chirurgie des artères des membres. Masson et Cie, Paris 41. Leriche R (1947) Les embolectomies de l’artere pulmonaire et des artères des membres. Masson Cie, Paris 42. Leriche R (1947) Rapport. Sur la desobstraction des thromboses artérielles anciennes, par M. Jean Cid dos Santos (de Lisbone). Mem Acad Chir 73:409–411 43. Lexer E (1907) Die ideale operation des arteriellen und des arteriell-venosen aneurysma. Arch Klin Chir 83:459 44. Liapis CD, Paaske WP (2004) Status of vascular surgery in Europe. Elsevier, Amsterdam 45. Matas R (1903) An operation for the radical cure of aneurism based upon arteriography. Ann Surg 37:161–196 46. Mellière D (2000) Petite histoire du traitement des maladies artérielles et de ses pionniers. Europeene D’ Editions, Paris 47. Mialhe C, Amicabile C (1995) Traitement endovasculaire des aneurysmes de l’aotre sous-renal par endoprothese Stentor, Serie preliminaire. J Mal Vasc 20:290–295 48. Michal V, Kramar R, Pospichal J (1974) Femoro-pudendal by-pass, internal iliac thromboendarterectomy and direct arterial anastomosis to the cavernous body in the treatment of impotence. Bull Soc Int Chir 33:343–350 49. Moniz E (1934) L’angiographie cerebrale. Masson et Cie, Paris
50. Natali J (1992) L’apport de Jacques Oudot a la chirurgie de la bifurcation aortique. Ann Chir Vasc 6:185–192 51. Natali J (2002) The Lèriche Memorial Lecture. In: The 50th International Congress of the European Society for Cardiovascular Surgery, June 20–23, 2001, Budapest, Hungary. Endocardiovascular WEB Magazine 6:7–17 52. Nielubowicz J, Olszewski W (1968) Surgical lymphatico-venous shunts in patients with secondary lymphoedema. Br J Surg 55(6):440 53. Oudot J (1951) La greffe vasculaire dans les thromboses du carrefour aortique. Presse Med 59:234 54. Pokrovsky A, Bogatov YP ( 2000) Vascular surgery in Russia. J Angiol Vasc Surg 6(3):8–20 55. Rich NM, Clagett PG, Salander JM, Piscevic S (1983) The Matas/Soubbotitch connection. Surgery 93:17–19 56. Rob C (1963) Extraperitoneal approach to the abdominal aorta. Surgery 53:87–89 57. Schumacker HB (1987) Romuald Weglowski: neglected pioneer in vascular surgery. J Vasc Surg 6:95–97 58. Seldinger SI (1953) Catheter replacement of the needle in percutaneous arteriography. A new technique. Acta Radiol 39:368–376 59. Soubbotitch V (1913) Military experience of traumatic aneurysms. Lancet 2:720 60. Van Dongen RJAM (1970) Photographic atlas of reconstructive arterial surgery. Stenfert Kroesse, Leiden 61. Vollmar J, Storz L (1974) Vascular endoscopy: possibilities and limits of its clinical application. Surg Clin North Am 54:111–122 62. Yao JST, Hobbs JT, IrvineWT (1968) Ankle pressure measurement in arterial diseases of the lower extremities. Br J Surg 55:859–860
21
23
1.2 Development of Atherosclerosis for the Vascular Surgeon Jean-Olivier Defraigne
1.2.1 Introduction Atherosclerosis is a complex disease involving various vascular segments and blood vessels such as the aorta, carotid, coronary and/or peripheral arteries. Taken together, the thrombotic or thromboembolic complications arising from this systemic process (stroke, myocardial infarction and gangrene) are the leading causes of morbidity and mortality in United States, Europe and also Asia. A high plasma cholesterol level is known to be a major risk factor for the development of atherosclerotic lesions. As a consequence, atherosclerosis is too often considered as a simple overload of lipids within the intimal layer of blood vessels [3]. Nevertheless, a revolution in the concept of atherosclerosis occurred after the recognition that the intrinsic vascular wall cells are not merely passive responders to inflammatory stimuli but can elaborate various mediators implicated in the initiation of an inflammatory process [41, 42]. Thus, although it is clear that the accumulation of lipids in macrophages and smooth muscle cells is a prominent aspect of the disease, numerous sequential cellular events leading to an inflammatory disease of the blood vessels play a central role in atherogenesis. Untreated or poorly treated atherosclerosis has significant medical consequences. So, better knowledge of both the atherosclerotic disease course and of factors favouring the onset of complications will help in improving not only medical treatment but also the selection, indications and adequacy of surgical interventions.
1.2.2 Physiopathology of Atherosclerosis
and adventitia. Endothelial cells (EC) lineate the intima and are in contact with the blood flow. Smooth muscle cells (SMC) are encountered in the media. Based on their fibre content and on cell composition, two main types of arteries are distinguished. Besides collagen fibres, elastic arteries contain a high proportion of elastic fibres in the media. Located proximally to the heart, these arteries store energy within their wall during the heart systole. Thereafter, during the diastole period, they recoil and reinstate this energy, thus transforming pulsatile flow into a continuous one. In contrast, more distal arteries exhibit a larger amount of SMC in the media. These latter arteries provide the resistive properties to the arterial tree, thus contributing to vascular tone [14]. Molecular signals and complex interactions between EC and SMC are implicated in the preservation of normal blood flow and vascular patency [42]. Regarding its total surface and its metabolic activities, the endothelium may be considered as a whole organ [7]. EC indeed produce and release several mediators implicated in the local control and regulation of vascular tone, blood flow, vessel patency and SMC activities (Table 1.2.1). By expressing cell adhesion molecules, EC also regulate cell traffic through the vascular wall. ECs are implicated in blood coagulation, notably by acting on platelet aggregation. For example, in response to local thrombotic events, EC secrete vasodilating substances such as prostacyclin (PGI2), prostaglandin E2 (PGE2), nitric oxide (NO) and endothelial-dependent relaxing factor (EDRF). In addition, as listed in Table 1.2.1, EC are also implicated in matrix product elaboration, as well as immunological and growth regulatory functions.
1.2.2.2 Initiation of Atherosclerosis and Role of Endothelial Dysfunction
1.2.2.1 Normal Blood Vessel Morphology From the lumen to the external side, normal arteries are made up of three concentric layers named intima, media
Atherosclerotic lesions develop progressively with a succession of events leading to the constitution of mature lesions named atheromatous plaques (Fig. 1.2.1). These lat-
24
1.2 Development of Atherosclerosis for the Vascular Surgeon
Table 1.2.1 Products released by endothelial cells Function
Products secreted
Elaboration of matrix components
Fibronectin, laminin, collagen (type I, II, III, IV), proteoglycans
Control of vascular tonus
NO, prostacyclin (PGI2), prostaglandin E2 (PGE2), angiotensin-converting enzyme (ACE), thromboxane (TXA2), leukotrienes, endothelin-1
Control of cell proliferation
Platelet-derived growth factor (PDGF), endothelial-derived growth factor (EDGF), fibroblast growth factor (FGF), insulin-like growth factor-1 (IGF-1), transforming growth factor-β (TGF-β), granulocyte-monocyte-colony stimulating factor (GM-CSF)
Control of coagulation
Von Willebrand factor (vWF), thromboplastin, platelet activating factor (PAF), plasminogen activator inhibitor 1 and 2 (PAI-1 and PAI-2), high molecular weight kininogen (HMWK), thombomodulin, antithrombin III, heparan sulfate, adenosine diphosphatase, tissue plasminogen activator, protein C
Control of inflammatory processes and immunological function
Interleukins-1, -6, -8, leukotrienes B4, C4, D4, E4, cell adhesion molecules (CAM), major histocompatibility complex II (MHC II)
Fig. 1.2.1 Steps and processes observed during atheromatous plaque formation and maturation
1.2.2 Physiopathology of Atherosclerosis
ter are composed mainly of: (1) cells (monocyte-derived macrophages, T lymphocytes and SMC); (2) connective tissue and extracellular matrix (collagen, proteoglycans, fibronectin and elastic fibres); and (3) lipid deposits (crystalline cholesterol, cholesteryl esters and phospholipids). Due to varying proportions of these components, a spectrum of lesions may be observed, giving rise to stable, fibrous or vulnerable plaques. The fatty streak forming yellow streaks on the luminal surfaces of blood vessels is often considered to be a lesion preceding the development of a more advanced plaque [46]. Aside from SMC and T lymphocytes, monocyte-derived macrophages are a major component of this highly cellular lesion that represents a primitive inflammatory response. Nevertheless, the relationship between fatty streaks and the ultimate development of atherosclerosis is not completely elucidated. For examples, fatty streaks may be observed in fetuses and in children and may regress spontaneously. In addition, they are more frequent in females whereas atherosclerosis is more frequent in males.
To explain the process of developing atherosclerosis, several theories have been proposed. For example, the plaque cluster could result from the monoclonal proliferation of modified SMC originating from a single progenitor (monoclonal theory) [2]. Another theory considers the role of a small accumulation of SMC, which acts as a primordial stage of stem cells prone to playing a role in the development of atherosclerosis (intimal cell hypothesis) [49]. Although some isolated cases are perhaps relevant, none of these theories is able to completely explain all the aspects of ongoing atherosclerosis. This suggests that the eventual onset of atherosclerosis is also determined by superimposed extrinsic factors such as increased cholesterol levels, smoking, etc. Whereas, as mentioned previously, EC normally express anticoagulant and vasodilatative properties, in some circumstances (ischaemia, stimulation by humoral factors, influence of various pathological processes), EC may modify their activities and exhibit procoagulant and vasoconstrictive properties (Fig. 1.2.2). In this latter per-
Fig. 1.2.2 Consequences of endothelial dysfunction. Normal endothelium displays antiaggregant, anticoagulant and vasodilatative properties, along with inhibition of cell proliferation. After exposure to various agents causing endothelial dysfunction, these functions are modified toward procoagulant and vasoconstrictive activities together with stimulation of cell recruitment and proliferation. (LDL Low density lipoprotein, PAF platelet activating factor, PAI-1 plasminogen activator inhibitor-1, PGI2 prostacylin, TXA2 thromboxane A2, SMCs smooth muscle cells)
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spective, numerous observations of animal models and in clinical situations led to the concept of the responseto-injury hypothesis, which takes into account the different steps involved in atherosclerosis. A first version of this hypothesis proposed that endothelial denudation or abrasion was the initial event. At the present time, rather than endothelial denudation, endothelial dysfunction is considered a keystone in the triggering and progression of the atherosclerotic process [41, 42]. So, injury to the endothelium layer and to underlying SMC initiate a protective compensatory response, ultimately altering the normal homeostatic properties of endothelium. During these compensatory responses, aside the release of growth factors and cytokines, expression of adhesion molecules on the endothelial surface is simultaneously increased, resulting in increased adhesiveness for leukocytes and platelets. So increased vascular permeability, altered control of the vascular tone and altered balance between pro- and antithrombotic factors follow EC dysfunction. Finally, a chronic inflammatory response is installed, leading to healing or to a fibroproliferative response and eventually to an advanced, complicated lesion.
1.2.2.3 Evolution of the Atherosclerotic Plaque Adhesion and Migration of White Blood Cells Cellular adhesion molecules (CAMs) are implicated in the interactions between EC and circulating leukocytes, monocytes or T lymphocytes. After injury, the adhesiveness of the EC increases progressively and several adhesion molecules are sequentially expressed on the luminal surfaces of EC, such as members of the immunoglobulin super family VCAM-1 (vascular cell adhesion molecule-1), ICAM-1 (intercellular adhesion molecule-1) or membrane glycoprotein E-selectin [11, 42]. VCAM-1 is the ligand for VLA-4 (very-late forming antigen-4) and ICAM-1 binds to LFA-1 or Mac-1. The latter are integrins present at the surface of different kinds leukocytes. E-selectin is involved in interaction with leukocytes and platelets, since E-selectin binds P-selectin and to L-selectin, expressed by platelets and leukocytes, respectively [7]. The pattern of expression of each CAM (onset after injury, time course and duration, and degradation) is variable, thus conferring a specific role to each of them and providing an insight into the understanding of their specific role in leukocyte adhesion. For example, E-selectin is
the first to be expressed after stimulation and initiates the process of leukocyte rolling. In a second step, ICAM-1 and probably VCAM-1 are expressed, thus contributing to stronger and permanent adhesion. These latter interactions precede the leukocyte infiltration of the intima, starting the atherosclerotic process. Adhesion of circulating monocytes to the surface of the EC is effectively an early event in the development of an atherosclerotic plaque. In response to a chemoattractant (monocyte chemoattractant protein-1, MCP-1, produced by EC), monocytes adhere to, and insinuate themselves between, the tight junctions of the EC, to enter the subendothelial space [33, 40]. Inside the intima, they transform and differentiate into a phagocyte state (macrophages). They ingest modified lipids [primarily oxidized lipids coming from low-density lipoprotein (LDL), see below] and attempt to remove these lipids from the intima. As their lipid content increases, these macrophages take on a foamy appearance (“foam cells”) and accumulate locally. The process of “scavenging” lipoproteins by macrophages also leads to the release of cytokines, which stimulate smooth muscle migration and proliferation (see below). Immune mechanisms also appear to play a role in the process. Albeit in small numbers in human plaques, T lymphocytes (implicated in the cell-mediated immune response) are present in both young and advanced fibrous lesions. A suggested role for T lymphocytes during atherogenesis is help in mobilizing macrophages, which is similar to their role in immune responses [14, 26].
Influence of Haemodynamic Factors Haemodynamic forces imposed on the endothelium influence its biological response. High shear stress (tangential drag force) appears to reduce the incidence of early intimal lesions by affecting the migration, proliferation and biological functions of ECs [31, 51]. For example, it has been shown that cultured ECs submitted to a flow still present an alignment parallel to the direction of flow. When high shear stress is applied, change in the endothelial cytoskeleton is observed and the actin microfilament bundles are aligned. In contrast, the latter remain dense and nonaligned in areas where shear stress is low and the flow nonlaminar and turbulent. In addition, high shear stress increases the production of vasodilating and anti-aggregating prostacyclin (PGI2). These findings imply a mechanism that may contribute to increased atherogenicity in areas of low shear stress. Moreover, mitotic
1.2.2 Physiopathology of Atherosclerosis
division of EC is more frequent in areas of turbulent flow than in contiguous areas [50]. At atherosclerotic lesion-prone sites of the circulatory system, the expression of VCAM on the endothelium can be altered by abrupt changes in the direction and force of local blood flow. An element responsive to shear stress has been identified in the regulatory region of several genes (one coding for platelet-derived growth factor, PDGF) and promotes the expression of adhesion molecules as well as other molecular factors that participate in atherogenesis. It is supposed that a transcription factor produced in response to abnormal shear forces can induce the expression of genes contributing to the development of atherosclerosis. As a consequence, intimal lesions preferably develop in areas of low levels of shear stress. If one considers laminar flow in a straight, un-branching segment of a vessel, the flow velocity is greatest at the centre of the vessel and, because of friction, is least at the blood–endothelium interface. Depending on fluid viscosity, mean velocity and blood vessel diameter, bifurcations and other geometric changes result in turbulent flow, with random and erratic flow profiles. The velocity vector of blood flow in these areas becomes nonlinear. These changes in haemodynamic factors that occur at bifurcations account for the topographical distribution of atherosclerosis [14, 58]. So in the vessels particularly prone to atherosclerosis (coronary arteries, major branches of the aortic arch, abdominal aorta, major visceral and lower extremity branches), the plaque localizations are not strictly randomly determined. In the carotid territory for example, plaque formation occurs frequently at the origin of the proximal internal carotid artery. The area of the carotid sinus opposite the flow divider between the external and internal carotid arteries exhibits lower shear stress and is thus subjected to changes in haemodynamic forces that promote atherosclerosis. Maximal intimal thickness occurs on the side opposite the flow divider and intimal thickening is minimal on the inner wall while flow remains laminar. Such data may be transposed to other vascular territories.
factor (HB-EGF), vascular endothelial cell growth factor (VGEF)]. All of these have been detected in atherosclerotic plaques [29, 42, 43]. In response to these chemoattractants, SMC migrate from the media to the intima. Migrating SMC are morphologically different from the native SMC found in the media and their growth and proliferation are stimulated. Where denudation of endothelium is noted, other factors are also implicated. Coagulation factors and other products released by platelets forming micro-thrombi also contribute to the evolution of the plaque [39]. Simultaneously, neo microvascularization originating from the vasa vasorum develops within the plaque and the vessel wall, and allows local delivery of substances contributing to the evolution of the atheroma. Like PDGF, thrombin released by focal haemorrhages in the plaque area is a modulator of SMC activity [24]. So whereas EC dysfunction is the key factor initiating the plaque, SMC are implicated in its progression [43]. Nevertheless, the rate of SMC proliferation within the plaques is not uniform and slow progression may be observed for a long period of time, interspersed with transient bouts of increased cell proliferation. Within the plaques, local cytostatic mediators such as transforming growth factor-β (TGF-β) and interferon-γ (IFN-γ) may be implicated in the regulation of cell proliferation [32]. As the plaque matures, SMC display high secreting activities, producing various constituents of the extracellular
The Role of Smooth Muscle Cells (SMC) Leukocytes and ECs produce and release numerous cytokines and potent mitogens [interleukin-1 (IL-1), tumour necrosis factor-α (TNF-α), macrophage-colony stimulating factor (M-CSF)] or growth factors [fibroblast growth factor (FGF), heparin-binding epidermal growth
Fig. 1.2.3 Atherosclerotic plaque. This mature plaque is characterized by a fibrous cap and by the presence of cholesterol clefts in the vessel wall
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1.2 Development of Atherosclerosis for the Vascular Surgeon
matrix (such as type I and type III collagen, elastin and proteoglycans). As a consequence, more mature plaques are characterized by increased fibrous and less cellular architecture [42, 58] (Fig. 1.2.3).
1.2.3 Contributive Factors to Endothelial Dysfunction and Plaque Formation Several potential factors leading to endothelial dysfunction have been identified and include smoking, diabetes mellitus, hypertension, increased plasma level of oxidized modified lipoprotein (LDL, low density lipoprotein), hyper homocysteinemia, infectious microorganisms (Herpes virus or Chlamydia pneumoniae), or combinations of these or other factors.
pounds. Besides effects on lipid metabolism (stimulation of lipolysis and increase in LDL levels), nicotine contributes to the conversion of SMC from a contractile to a synthetic phenotype. Increased levels of fibrinogen, increased platelet activity and blood viscosity together with decreased prostacyclin levels also contribute to altering the vascular wall. Homocysteinemia is an autosomal recessive disease that is the consequence of a deficiency of the enzyme cystathione β-synthase [5]. Elevated levels of homocysteine are correlated with an increased risk of coronary heart disease, stroke and peripheral vascular disease [52]. Homocysteine causes EC dysfunction, SMC proliferation and collagen production. Increased LDL oxidation and inhibition of endogenous anticoagulant activity are associated features of the disease.
1.2.3.2 The Oxidized LDL Hypothesis 1.2.3.1 Miscellaneous Factor Hypertension is associated with increased vascular permeability resulting in enhanced migration of lipoproteins and macromolecules into the intima. In the presence of hypertension, cyclic strain and pulsatile stretching of the vessel wall are increased, which lead to repetitive, circumferential, pulsatile pressure distension being conferred to the vascular wall [57]. In response to cyclic strains, signal transduction pathways in ECs are activated with resulting changes in morphology and proliferation. As mentioned previously, expression of cellular adhesion molecules (ICAM-1 for example) is increased. In addition, production of toxic oxygen species (hydrogen peroxide, superoxide anion, hydroxyl radical) is increased by hypertension, with reduction of endothelial nitric oxide release resulting in increased peripheral resistance [9]. Cyclic strains also affect the arterial sub endothelium, with changes in SMC shape, orientation and proliferation and the secretion of extracellular matrix contributing to the development of atherosclerotic lesions. Notably, collagen production is increased when SMC are submitted to cyclic strains. Finally, angiotensin II promotes SMC hypertrophy and its levels are frequently elevated during hypertension. Smoking is damaging for the vascular wall, resulting in swelling and luminal surface projections of ECs [53]. Cigarette smoke contains several potentially toxic compounds including nicotine, aromatic hydrocarbons, sterols, aldehydes, nitriles, cyclic ethers and sulfur com-
Low density lipoproteins (LDL) are plasma particles that contain in association with protein several types of lipids with a predominance of phospholipids, free and esterified cholesterol, for a total of about 1200 unsaturated fatty acid chains. In the presence of high levels of LDL – a well-recognized risk factor for developing atherosclerosis – influx of cholesterol and LDL into the intima is increased. In addition to binding to connective tissue elements (such as proteoglycans), accumulated LDL is progressively oxidized [36–38, 56] (Fig. 1.2.4). This increased oxidation gives rise to the production of several toxic products. For example, free radicals chain reaction within the lipid chains form hydroperoxides that easily break down, generating aldehydes (malonaldehyde, 4-hydroxynonenal) and other toxic substances that can react with lysine moieties in the B-apoprotein part of the LDLs. Other toxic products include for example 7-β-hydroperoxycholesterol, 7-ketocholesterol, lysophosphatidylcholine, oxidized fatty acid and epoxy sterols [18]. Native (nonoxidized) LDLs are collected by the extremely specific LDL receptors, and then cleared by a nonatherogenous process. In contrast, the oxidatively modified LDLs are not recognized by these receptors. They are metabolized in an unregulated way by scavenger receptors expressed by the macrophages present in the vascular wall and derived from the circulating monocytes, as mentioned previously [48]. Removal and sequestration of modified LDLs by macrophages may be considered a protective role minimizing the effects of modified
1.2.3 Contributive Factors to Endothelial Dysfunction and Plaque Formation
Fig. 1.2.4 Role of LDL oxidation in atheromatous plaque formation. After oxidation, LDLs exert toxic effects on endothelial cells with resultant expression of cell adhesion molecules and release of growth factors. Oxidized LDL also stimulates smooth muscle cell proliferation. After endocytosis of oxidized LDL, macrophages transform into foam cells. (E-selectin Endothelial selectin, GM-CSF granulocyte-monocyte-colony stimulating factor, ICAM-1 intercellular adhesion molecule-1, LDL low density lipoprotein, Lyso-PC lysophosphatidylcholine, MCP-1 monocyte chemoattractant protein-1, ox-chol oxidized cholesterol VCAM-1 vascular cell adhesion molecule)
LDL. Nevertheless, this route is atherogenous, since the internalization of LDL by macrophages leads to the formation of lipid peroxides and facilitates the transformation of macrophages into foam cells [60]. Vitamins C and E protect LDLs against oxidation and protective effects of vitamin E supplementation have been suggested in some reports [17]. In addition to their ability to injure macrophages, oxidized LDLs contribute to the perpetuation of the inflammatory reaction and to progression of the plaque, mainly for two reasons [35]. First, oxidized LDLs are implicated in the recruitment and proliferation of monocytes and lymphocytes, notably via upregulation of gene expression for MCP-1 and for M-CSF. This inflammatory response
increases the inward movement of lipoprotein within the artery, leading to a positive feedback. This induces a vicious cycle favouring development and progression of the plaque. Second, autoantibodies directed toward modified LDLs are produced. Along with scavenging of LDL, immune complexes taken up by macrophages stimulate the release of cytokines and growth factors by macrophages, thus contributing to stimulation of SMC migration and proliferation. Diabetes is often associated with an accelerated course and a diffuse character of atherosclerosis, especially in peripheral arteries, with devastating cardiovascular complications. In this case, the nonenzymatic glycosylation process of LDL impairs binding of LDL to its receptor and
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increases the formation of foam cells [22]. This process is facilitated since vascular permeability is increased subsequent to alteration of the components of the extracellular matrix and to thickening of the basement membrane [54].
1.2.4 Plaque Instability and Complicated Plaques Generally, atherosclerotic plaques remains asymptomatic because of the development of a collateral circulation heralded by chronic or subacute episodes of hypoxia and because of a compensatory enlargement of the blood vessel, thus trying to maintain adequate blood flow and constant lumen diameter (vascular remodelling) [23]. Increasing the vessel size is effective until the narrowing is approximately less than 40% of the normal lumen [59]. However, during its maturation process the plaque may become vulnerable and predisposed to ulceration and/or rupture [12, 19]. Once a plaque becomes ulcerated and disrupted, the coagulation cascade is initiated, with formation of platelet-rich white thrombi, that differ from the red thrombi formed in regions of stasis or low flow. Despite simultaneous endogenous thrombolysis, the initial small mural thrombus may evolve to a major, near-occlusive thrombus. It may also embolize, resulting in distal small vessel occlusion leading eventually to massive arterial occlusion. In these circumstances, acute clinical conditions may occur, with the onset of a wide range of symptoms including rapidly installing unstable angor pectoris, myocardial infarction, transient ischaemic attack, or toe gangrene. Several factors influencing plaque stability have been identified, such as the extent of the lipid core, the fibrous cap and its thickness, and the amount of inflammation within the cap. Thin or ruptured fibrous caps with lack of SMC-mediated healing, a large lipidic core (with a predominance of cholesterol esters) and intense cell infiltration with inflammatory activity render the plaque more vulnerable [6]. In other words, dense and uniform fibrous caps are generally associated with stable plaques. Usually, erosion and thinning of the plaque are uneven and rupture frequently occurs at the shoulder of the lesion where the fibrous cap is the thinnest and more susceptible to physical forces causing rupture [21]. In the areas of rupture, the plaque is also massively infiltrated by macrophage-derived foam cells and SMC proliferation seems impaired, with a high frequency of apoptosis of
these latter cells [4]. Once immunologically activated by T lymphocytes, these macrophages massively release matrix metalloproteases (such as collagenases, elastases and stromelysins) [16]. Although metalloproteases probably exert a regulatory action by breaking down extracellular matrix formation during the early stage of plaque formation, these serine and cysteine proteases degrade the various components of the extracellular matrix, further destabilizing the plaques [15, 27, 44]. Simultaneously, production of tissue-factor procoagulant and other haemostatic factors further increase the possibility of thrombosis. Along with intrinsic factors, extrinsic factors also influence the plaque stability. Low or oscillatory shear stress promotes plaque complication. Cyclic blood pressure changes may cause circumferential bending of eccentric soft plaques, which may weaken them. In addition, large deposits of calcium found on atheromatous plaques can be directly mediated by interaction with collagen. This massive calcification of the plaque alters the elastic properties and has significant haemodynamic consequences.
1.2.5 Classification of Atherosclerotic Plaques The American Heart Association Committee on Vascular Lesions has proposed a classification of atherosclerotic plaques [46, 47]. This classification is based on the plaque’s evolution and maturation stages. Phase I lesions correspond to early arterial changes that will progress in a stable fashion for several years. Phase II lesions are lipid-rich plaques that are prone to rupture. Phase III and phase IV lesions refer to acutely complicated plaques with formation of a nonocclusive (phase III) or an occlusive (phase IV) thrombus. Phase V lesions consist of an organized and fibrotic thrombus. From a histological perspective and according to their cell and lipid contents, different types (I, II and III) are distinguished in phase II lesions. The vulnerable type IV (lesion with intermixed lipids and fibrous tissue) and Va (lesion with an increased lipid core covered by a thin fibrous cap) lesions are the most relevant to acute ischaemic lesions. Disruption of a type IV or type Va lesion leads to the formation of a thrombus or “complicated” type VI lesion. Type VI lesions consist of confluent cellular lesions with a great deal of extracellular lipid intermixed with fibrous tissue covered by a fibrous cap. The complicated type VI is reserved for phase III and IV lesions causing acute syndromes. These lesions are more the consequence
1.2.7 General Therapeutic Measures
of an occlusive thrombus rather than being characterized by a small mural thrombus.
1.2.6 Assessment and Evaluation of the Risk of an Atherosclerotic Plaque As shown above, the sequence of events characterizing atherosclerosis is associated with an active inflammation process. This explains the elevation of plasma concentrations of various markers, such as fibrinogen, C-reactive protein and E-selectin, which may indicate ongoing atherosclerosis. Elevated levels of circulating metalloproteases have also been found in patients with unstable and complicated carotid plaques [42]. Description of the various technical methods available to evaluate an atherosclerotic patient presenting with clinical symptoms is outside the scope of this chapter and is reported elsewhere. Nevertheless, when considering atherosclerosis development and complications, an essential goal is to identify or recognize a vulnerable or unstable plaque prone to thrombosis and rupture. This is essential if one is to eventually decrease the complication rate of atherosclerosis and to prevent acute complications. Several invasive (e.g. X-ray angiography, intravascular ultrasound and angioscopy) and noninvasive (surface Bmode ultrasound and ultrafast computed tomography) imaging techniques may provide information on morphological characteristics of the disease, such as lumen diameter, degree of stenosis or wall thickness [8, 34]. Nevertheless, some of these techniques are limited in the evaluation of the evolutionary tendency of atherosclerosis. For example, measurement of luminal stenosis from digital subtraction techniques does not adequately reflect disease burden in carotid atherosclerosis. Vessel wall remodelling may produce normal luminal measurements despite a large atheromatous plaque in situ. Moreover, although an assessment of the relative risk associated with the atherosclerotic disease may be obtained with some techniques, these techniques do not give information on the composition of the plaque and are therefore incapable of identifying unstable plaques. In this context, noninvasive high-resolution magnetic resonance imaging (MRI) is an alternative for atherosclerotic plaque characterization, as shown by animal and human studies [30]. MRI differentiates plaque components on the basis of biophysical and biochemical parameters such as chemical composition and concentration, water content, physical state, molecular motion, or diffusion…
Initial studies were performed ex vivo and focused on lipid assessment with nuclear magnetic resonance spectroscopy and chemical shift imaging [45]. With the improvement of the MRI techniques, high resolution and contrast imaging became possible and therefore allowed the in vivo study of different plaque components [10]. As shown in vivo on human carotid, coronary and peripheral arteries, MRI allows characterization of the plaque components, such as lipid core, neovascularization, fibrous cap, necrotic cores, intraplaque haemorrhage and thrombus, with very high overall sensitivity and specificity [28]. Correlation is excellent with histopathology in grading the lesion shape and type. The concentration of serum markers of inflammation also correlates with MR markers of atherosclerosis, as shown in patients presenting with plaques in the aorta and common carotid artery [55]. The patients with MRI markers of unstable plaques have higher values of IL-6, C-reactive protein and VCAM-1 than those without MRI markers. Finally, in the thoracic aorta, MRI and trans-oesophageal echocardiography cross-sectional aortic images show a strong correlation for estimation of the plaque composition and of the mean maximum plaque thickness [20]. Along with monitoring of basic studies of atherosclerotic disease, MRI may thus be used to follow the progression of atherosclerosis in a given patient (hypercholesterolemic patient for example) or to detect atherosclerosis prospectively and its location in a given population. For example, an MRI study of asymptomatic patients from the Framingham Heart Study (FHS) showed that atherosclerotic disease prevalence and burden (i.e. plaque volume/aortic volume) significantly increased with age and was higher in the abdominal aorta compared with the thoracic aorta. So, in vivo, high-resolution, multi-contrast MR imaging is a promising method for imaging vulnerable plaques, characterizing plaques in term of lipid and fibrous content, and identifying the presence of thrombus or calcium in all arteries including the coronary arteries. MRI also allows serial evaluation assessment of the progression and/or regression of atherosclerosis over time.
1.2.7 General Therapeutic Measures Since atherosclerosis is a systemic disease frequently associated with several risk factors, hygieno-dietetic measures must be recommended in addition to drug therapies. Smoking must be discontinued with the help
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of smoking cessation programmes and antidepressant therapy, if necessary. Lipid-lowering drugs are especially indicated, with the use of HMG-CoA reductase inhibitors. Statins not only decrease cholesterol levels but also exert pleiotropic effects on the vascular wall limiting the inflammatory process within the plaques [1, 13]. Plaque regression with lipid-lowering therapy has been reported in both the aorta and carotids. An LDL cholesterol level less than 100 mg/dl should be attained. The incidence of cardiac event may be minimized by appropriate control of heart rate and blood pressure. Diabetic patients should be adequately treated and monitored. Haemoglobin A1c should be less than 7%. Dietary supplementation of vitamin B12 and folic acid should be prescribed, especially in patients with hyperhomocysteinemia [25]. Exercise decreases LDL cholesterol and all patients should maintain a regular exercise regimen. Lastly, the use of anti-platelet drugs may reduce the risk of fatal and nonfatal ischaemic events in patients with vascular disease. Several drugs are available and aspirin and clopidogrel are quite effective.
1.2.8 Conclusion Knowledge about atherosclerosis has increased dramatically over the last 20 years. Despite significant improvements in medical and surgical treatment, atherosclerosis remains a serious disabling and sometimes life-threatening disease. Perhaps in the future the development of gene therapy will provide a new mode of therapy able to modify not only the initiation but also the progression of the plaque. Nevertheless, at the present time, general therapeutic, preventive and adjunctive measures are the only way to limit the progression and consequences of atherosclerosis. In addition, a screening programme is also useful in order to detect the unstable plaques prone to rupture and to complications. References 1. Bellosta S, Via D, Canavesi M (1998) HMG-CoA reductase inhibitors reduce MMP-9 secretion by macrophages. Arterisocler Thromb Vasc Biol 18:1671–1678 2. Benditt EP, Benditt JM (1973) Evidence for a monoclonal origin of human atherosclerotic plaque. Proc Natl Acad Sci USA 70:1753–1756 3. Berliner JA, Navab M, Fogelman AM, Frank JS, Demer LL, Edwards PA, Watson AD, Lusis AJ (1995) Atherosclerosis: basic mechanisms: oxidation, inflammation and genetics. Circulation 91:2488–2496
4. Bjorkerud S, Bjorkerud B (1996) Apoptosis is abundant in atherosclerotic lesions, especially in inflammatory cells (macrophages and T-cells), and may contribute to the accumulation of gruel and plaque instability. Am J Pathol 149:367–380 5. Boushey CJ, Beresdorf SA (1995) A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increased folic acide intakes. J Am Med Assoc 274:1049–1057 6. Boyle JJ (1997) Association of plaque rupture and atherosclerotic inflammation. J Pathol 181:93–99 7. Burrig KF (1991) The endothelium of advanced arteriosclerotic plaques in humans. Arterio Thromb 11:1678–1689 8. Celermajer DS (1998) Noninvasive detection of atherosclerosis. N Engl J Med 339:2014–2015 9. Chobanian AV (1983) The influence of hypertension and other hemodynamic factors in atherogenesis. Cardiovasc Dis 26:177–196 10. Choi CJ, Kramer CM (2002) MR imaging of atherosclerotic plaque. Radiol Clin North Am 40:887–898 11. Davies MJ, Wollf N (1993) Atherosclerosis: what is it and why does it occur? Br Heart J 69 (Suppl):S3–S11 12. Davies MJ, Richardson PD, Woolf N, Katz DR, Mann J (1993) Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content. Br Heart J 69:377–381 13. Davignon J, Mabile L (2002) Mécanismes d’action des statines et leurs effets pléiotropiques. Ann Endocrinol 62:101–112 14. De Palma RG, Gallagher GL (1997) In: Sidawy AN, Sumpio BE (eds) The basic science of cardiovascular disease. Futura, Armonk, N.Y., pp 151–186 15. Defawe O, Colige A, Lambert C, Munaut C, Delvenne P, Nusgens B, Lapière C, Limet R, Sakalihasan N (2003) TIMP2 and PAI-I mRNA levels are lower in aneurysmal as compared to atheroocclusive abdominal aortas. Cardiovasc Res 60:205–213 16. Dollery CM, McEwan JR, Henney AM (1995) Matrix metalloproteinases and cardiovascular disease. Circ Res 77:863–868 17. Esterbauer H, Rotheneder M, Striegl G, Waeg G, Ashy A, Sattler W, Jurgens G (1989) Vitamin E and other lipophilic antioxidants protect LDL against oxidation. Fat Sci Technol 91:316–324 18. Esterbauer H, Dieber-Rotheneder M, Waeg G, Striegl G, Jurgens G (1990) Biochemical structural and functional properties of oxidized low density lipoprotein. Chem Res Toxicol 3:77–92 19. Falk E (1992) Why do plaques rupture? Circulation 86 (Suppl III):III30–III42
References
20. Fayad ZA, Tamana N, Badimon JJ, Goldman M, Weinberger J, Fallon JT, Aguinaldo G, Shinnar M, Chesebro JH, Fuster V (1998) In vivo MR characterization of plaques in the thoracic aorta. Circulation 98:I515 21. Fuster V (1999) Plaque stabilization: present and future trends. In: Fuster V (ed) The vulnerable atherosclerotic plaque: understanding, identification and modification. American Heart Association, Armonk, N.Y., pp 393–412 22. Ginsberg HN (1991) Lipoprotein physiology in non-diabetic and diabetic states: relationship to atherosclerosis. Diabetes Care 14:839–845 23. Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ (1987) Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 316:1371–1375 24. Heldin CH, Westermark B (1990) Platelet-derived growth factor: mechanism of action and possible in vivo function. Cell Regul 1:555–556 25. Jacques PF, Selhub J et al (1999) The effect of folic acid fortification on plasma folate and total homocysteine concentration. N Engl J Med 340:1449–1454 26. Jonasson L, Holm J, Skalli O, Bjonders G, Hansson GK (1986) Regional accumulations of T cells, macrophages and smooth muscle cells in the human atherosclerotic plaque. Arteriosclerosis 6:131–138 27. Konx JB, Sukhova GK, Whittemore AD, Libby P (1995) Evidence for altered balance between matrix metalloproteinases and their inhibitors in human aortic diseases. Circulation 95:205–212 28. Kramer CM, Cerilli LA, Hagspiel K, DiMaria JM, Epstein FH, Kern JA (2004) Magnetic resonance imaging identifies the fibrous cap in atherosclerotic abdominal aortic aneurysm. Circulation 109:1016–1021 29. Libby P, Ross R (1996) Cytokines and growth regulatory molecules. In: Fuster V, Ross R, Topol E (eds) Atherosclerosis and coronary artery disease. Lippincott-Raven, Philadelphia, pp 585–594 30. Martin AJ, Gotlieb AI, Henkelman RM (1995) High-resolution imaging of human arteries. J Magn Reson Imaging 5:93–100 31. Matsushita H, Lee KH, Tsao PS (2001) Cyclic strain induces reactive oxygen species production via an endothelial NAD(P)H oxidase. J Cell Biochem 36 (Suppl):99–106 32. Moses HL, Yang EY, Pietenpol JA (1990) TGF-beta stimulation and inhibition of cell proliferation: new mechanistic insights. Cell 63:245–247 33. Nelken N, Coughlin S, Gordon D ( 1991) Monocyte chemoattractant protein-1 in human atherosclerotic plaques. J Clin Invest 88:1121–1127
34. Nissen SE, DeFranco AC, Tuzcu EM, Moliterno DJ (1995) Coronary intravascular ultrasound: diagnostic and interventional applications. Coron Artery Dis 6:355–367 35. Parthasarathy S, Steinberg D, Witzum JL (1992) The role of oxidized low-density lipoprotein in the pathogenesis of atherosclerosis. Annu Rev Med 43:219–255 36. Pincemail J, Defraigne J-O, Limet R (1996) Oxidative stress in clinical situations: fact or fiction? Eur J Anaesthiol 13:219–234 37. Pincemail J, Lecomte J, Castiau JP, Collard E, Vasankari T, Cheramy-Bien J-P, Limet R, Defraigne J-O (2000) Evaluation of autoantibodies against oxidized LDL and antioxidant status in top soccer and basketball players after four months of competition. Free Radic Biol Med 28:559–565 38. Pincemail J, Bovy JC, Chapelle JP, Gielen J, Defraigne J-O, Rorive G (2001) Markers of oxidative stress linked to increased risk of cardiovascular diseases in chronic hemodialysis patients. Free Radic Biol Med (Suppl 1) 31(A345) 39. Rauch U, Osende JI (2001) Thrombus formation on atherosclerotic plaques in humans. Ann Intern Med 134:224–238 40. Rollins BJ, Yoshimura T, Leonard EJ (1990) Cytokine-activated human endothelial cells synthesize and secrete a monocyte chemoattractant, MCP-1/JE. Am J Pathol 136:1229–1233 41. Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362:801–809 42. Ross R (1999) Atherosclerosis – an inflammatory disease. N Engl J Med 340:115–126 43. Ross R, Glomset JA (1973) Atherosclerosis and the arterial smooth muscle cell: proliferation of smooth muscle is a key event in the genesis of the lesions of atherosclerosis. Science 180:1332–1339 44. Shah PK, Falk E, Badimon JJ, Fernandez-Ortiz A, Mailhac A, Villareal-Levy G, Fallon JT, Regnstrom J, Fuster V (1995) Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic fibrous caps. Potential role of matrix-degrading metalloproteinases and implications for plaque rupture. Circulation 92(6):1565–1569 45. Shinnar M, Fallon JT, Wehrli S, Levin M, Dalmacy D, Fayad ZA, Badimon JJ, Harrington E, Fuster V (1999) The diagnostic accuracy of ex vivo magnetic resonance imaging for human atherosclerotic plaque characterization. Arterioscler Throm Vasc Biol 19:2756–2761 46. Stary HC, Chandler AB, Glagov S, Guyton JR, Insull W, Ronsefeld ME, Schaffer SA, Schwartz CJ, Wagner WD, Wissler RW (1994) A definition of initial, fatty streak, and intermediate lesions of atherosclerosis: a report from the Committee on Vascular Lesions of the Council of Arteriosclerosis, American Heart Association. Circulation 89:2462–2478
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47. Stary HC, Chandler AB, Dinsmore RE, Fuster V, Glagov S, Insull W, Ronsefeld ME, Schwartz CJ, Wagner WD, Wissler RW (1995) A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on a Arteriosclerosis, American Heart Association. Circulation 92:1355–1374 48. Steinberg D, Parthasarathy S et al (1989) Modification of low-density lipoprotein that increases its atherogenicity. N Engl J Med 320:915 49. Strong JP (1993) Natural history of aortic and coronary atherosclerotic lesions in youth: findings from the PDAY study. Arterio Thromb 13:1291–1298 50. Sumpio BE (1989) Mechanical stress ands cell growth. J Vasc Surg 10:570–571 51. Sumpio BE (1993) In: Sumpio BE (ed) Hemodynamic and vascular cell biology. RG Landes, Austin 52. Tsai JC, Perella MA (1994) Promotion of vascular smooth muscle cell growth by homocysteine: a link to atherosclerosis. Proc Natl Acad Sci USA 91:6369–6373 53. Villablanca AC, McDonald JM, Rutledge JC (2000) Smoking and cardiovascular disease. Clin Chest Med 21:159–172
54. Vlassara H, Bucal R, Stiker L (1994) Pathogenesis effect of advanced glycosylation: biochemical and biologic implication for diabetes and aging. Lab Invest 70:138–151 55. Weiss CR, Arai AE, Bui MN (2002) Arterial wall MRI characteristics are associated with elevated serum markers of inflammation in humans. J Magn Reson Imaging 2001:698–704 56. Witzum JL, Berliner JA (1998) Oxidized phospholipids and isoprostanes in atherosclerosis. Curr Opin Lipidol 9:441–442 57. Xu C, Lee S et al (2001) Molecular mechanisms of aortic wall remodeling in response to hypertension. J Vasc Surg 33:570–578 58. Zarins CK, Glagov S (1982) Aneurysms and obstructive plaques: differing local responses to atherosclerosis. In: Bergan JJ, Yao JS (eds) Aneurysms. Diagnosis and treatment. Grune and Stratton, New York, p 61 59. Zarins CK, Weisenberg E, Glagov S (1988) Differential enlargement of artery segments in response to enlarging atherosclerotic plaques. J Vasc Surg 7:386–394 60. Zhang H, Basra HJK, Steinbrecher UP (1990) Effects of oxidatively modified LDL on cholesterol esterification in cultured macrophages. J Lipid Res 31:1361–1369
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1.3 Lipids and Peripheral Arterial Disease Stella S. Daskalopoulou, Marios E. Daskalopoulos, Christos D. Liapis, Dimitri P. Mikhailidis
1.3.1 Introduction Peripheral arterial disease (PAD) is associated with a high risk of vascular events [1, 2, 14, 18, 19, 31, 32]. This is true whether PAD is symptomatic or asymptomatic. This risk is so high that PAD is considered as a coronary heart disease (CHD) equivalent [5, 13]. It follows that these patients need to have their modifiable vascular risk factors controlled. Dyslipidaemia, a modifiable vascular risk factor, should be treated aggressively with lipid-lowering drugs, according to international guidelines [5, 13, 16, 37]. The earlier low density lipoprotein-cholesterol (LDL-C) targets {European LDL-C target <96 mg/dl (2.5 mmol/l) [5] and National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III [13] LDL-C target <100 mg/dl (2.6 mmol/l)} have been revised recently. Thus, the UK guidelines set the LDL-C goal to ≤2.0 mmol/l (77 mg/dl) for high-risk patients (March 2004) [37]. Furthermore, the revised NCEP ATP III guidelines proposed the optional target of ≤70 mg/dl (1.8 mmol/l) for very highrisk patients (July 2004) [16]. Other lipid variables, such as high density lipoproteincholesterol and triglycerides, are also important and they have recently attracted more attention [11]. However, the guidelines still focus on LDL-C levels as the main target for treatment [5, 13, 16, 37]. In this review, we consider the evidence showing the effect of lipid-lowering drugs on: • Prevention of PAD • Improvement of symptoms associated with PAD • Reduction of the risk of vascular events [e.g. myocardial infarction (MI), stoke or revascularization] associated with PAD.
1.3.2 Effect of Lipid Lowering on PAD 1.3.2.1 Prevention of PAD A post-hoc analysis of the Scandinavian Simvastatin Survival Study (4S) found that new or worsening intermittent claudication was significantly (p = 0.008) reduced (by 38%) in those taking the statin when compared with the group assigned to placebo [30]. All the patients (n = 4444) participating in this trial had CHD and were followed-up for a median of 5.4 years. In the Program on the Surgical Control of Hyperlipidemias (POSCH) [9] the effect of cholesterol-lowering induced by partial ileal by-pass in patients (n = 838) with a previous MI and hyperlipidaemia was assessed. The incidence of new cases of claudication was significantly lower [relative risk (RR): 0.66, 95% confidence interval (CI): 0.20–0.90; p = 0.009] in the intervention group when compared with the control (nonintervention) group 4 years after the closure of the trial.
1.3.2.2 Improvement of Symptoms Associated with PAD As mentioned above, new or worsening intermittent claudication was significantly (p = 0.008) reduced (by 38%) in the active treatment group of the 4S trial [30]. In another study [24] patients (n = 354) with intermittent claudication were assigned to placebo or active treatment with atorvastatin 10 mg or 80 mg daily. Maximal walking time after 12 months of treatment did not change significantly. However, there was a significant (p = 0.025) improvement in pain-free walking time in the 80 mg group compared with placebo. A physical activity questionnaire showed improvement (p = 0.011) in ambulatory ability for the 10 and 80 mg groups, whereas two quality of life questionnaires did not show significant changes.
36
1.3 Lipids and Peripheral Arterial Disease
Another study [21] included 392 patients with an ankle brachial pressure index (ABPI) <0.90 and 249 with ABPI 0.90–1.50. After adjusting for age, sex, ABPI, co-morbidities, cholesterol and other confounders, those taking statins had significantly better walk performance indices than participants not taking statins. Positive associations were slightly attenuated after additional adjustment for C-reactive protein (CRP) level but remained statistically significant for walking velocity and the summary performance score. These findings suggest that both the cholesterol-lowering and non-cholesterol-lowering actions of statins may favourably influence functioning in persons with and without PAD. The effect of short-term therapy with simvastatin on walking performance was assessed in hypercholesterolaemic (>220 mg/dl; 5.7 mmol/l) patients (n = 86) with PAD [25]. The patients were assigned either to simvastatin 40 mg (n = 43) or to a placebo (n = 43). At 6 months, the mean pain-free walking distance increased by 90 m (95% CI: 64–116; p < 0.005) more in the simvastatin group than in the placebo group. Similar results were seen for the mean total walking distance (increased by 126 m; 95% CI: 101–151; p < 0.001). The ABPI at rest increased by 0.09 (95% CI: 0.06–0.12; p < 0.01) and after exercise by 0.19 (95% CI: 0.14–0.24; p < 0.005) in those taking simvastatin. There was also a greater improvement in claudication symptoms among patients treated with simvastatin. In the Lower Extremity Arterial Disease Event Reduction (LEADER) trial [22], bezafibrate 400 mg daily (n = 783 men) or placebo (n = 785 men) were compared (median follow-up of 4.6 years). Bezafibrate reduced the severity of intermittent claudication for up to 3 years. The changes in symptoms may be related to the angiographic improvement documented in several studies.
1.3.2.3 Reduction of the Risk of Vascular Events Associated with PAD The Heart Protection Study (HPS) [17] confirmed that statin treatment reduces the risk of death and adverse cardiovascular events in patients with coronary and noncoronary atherosclerosis, including patients with PAD but without diagnosed CHD (n = 2701). There was a significant reduction (approximately 25%) in the first major vascular event (major coronary event, stroke or revascularization) among patients with PAD, with or without prior CHD (both p < 0.0001). In HPS there was a significant 16% [standard error (SE) 6.0, 95% CI: 5.0–26.0)] propor-
tional reduction in the rate of noncoronary revascularization (4.4% versus 5.2%; p = 0.006). Half of that difference involved a definite reduction in carotid endarterectomy or angioplasty (0.4% versus 0.8%; p = 0.0003). In the Mohler et al. study [24], mentioned above, there was a significant (p = 0.003) reduction in vascular events after 12 months. There were 3 events in the 240 patients (1.3%) assigned to atorvastatin (10 and 80 mg/day) and 9 events in the 114 patients (7.9%) assigned to placebo. Statin use has also been shown to decrease the risk of vascular events in diabetics with and without prior MI [2]. In a comparison of 318 PAD patients treated with statins versus 342 patients not on lipid-lowering drugs there were significant changes in the event rates after a mean follow-up of 39 months [1]. Sudden coronary death, fatal MI and new coronary events were all significantly reduced (p = 0.0005, p = 0.007 and p < 0.0001, respectively). In the LEADER trial [22], bezafibrate had no effect on the incidence of CHD and of stroke combined. However, the incidence of nonfatal coronary events was reduced (RR: 0.60, 95% CI: 0.36–0.99; p = 0.05), particularly in those aged <65 years at entry, in whom all coronary events may also be reduced (RR: 0.38, 95% CI: 0.20–0.72). In this trial plasma fibrinogen levels fell by 13% (p < 0.0001) in the bezafibrate group. It is well established that elevated plasma levels of this coagulation factor contribute to whole-blood viscosity and to an increased risk of vascular events in patients with PAD.
1.3.3 Peripheral Vascular Surgery and Statins Graft patency and limb salvage were improved in patients taking statins before infra-inguinal by-pass surgery [18]. Aggressive lipid lowering may reduce the high mortality and morbidity (mainly from coronary events) associated with vascular surgery in PAD and other patients [14, 29]. Coronary events are the most important cause of long-term morbidity and mortality after peripheral vascular surgery [12, 14]. Even PAD patients without overt CHD are at significant risk of long-term cardiac events. The effect of atorvastatin compared with placebo on the occurrence of a composite of cardiovascular events after vascular surgery was assessed [12]. Patients (n = 100) were randomly assigned to atorvastatin 20 mg once daily (n = 50) or placebo (n = 50) for 45 days, irrespective of
1.3.6 Concluding Comments
their serum cholesterol concentration. Vascular surgery was performed on average 30 days after randomization. During the 6-month follow-up, the incidence of cardiac events was higher in the placebo compared with the atorvastatin group [13 (26.0%) versus 4 (8.0%); p = 0.031]. In a case-control study, among patients (n = 2816) who underwent major vascular surgery, 160 (5.7%) died during their hospital stay [32]. After adjustments, statin therapy was significantly less common in the patients who died than in controls (8% versus 25%; p < 0.001). The adjusted OR for peri-operative mortality among statin users as compared with nonusers was 0.22 (95% CI = 0.10–0.47).
1.3.4 Additional Potential Actions of Lipid-lowering Drugs that may Benefit PAD Patients Statins exert pleiotropic effects, which may be independent of LDL-C lowering. These effects may appear even before a change in lipid level occurs [26, 35]. Statins increase nitric oxide (NO) production and improve endothelial function (e.g. increased flow-mediated dilatation). They have antioxidant properties and they inhibit the migration of macrophages and smooth muscle cell proliferation, leading to an antiproliferative effect and the stabilization of atherosclerotic plaques. Statins have anti-inflammatory effects including a reduction in the circulating levels of CRP, inflammatory and proinflammatory cytokines [e.g. interleukin-6 (IL-6), IL8], adhesion molecules [e.g. intercellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1)] and other acute phase proteins. They reduce tissue factor expression and platelet activity, whereas fibrinolysis can be enhanced. Statins improve microalbuminuria, renal function, hypertension and arterial wall stiffness. A significant reduction of the carotid and femoral intima-media thickness was also reported early after statin treatment. In the GREACE trial, the effect [3, 4] of atorvastatin on serum creatinine and uric acid in patients with CHD was rapid and it was reversed equally rapidly if patients happened to discontinue atorvastatin. The fall in creatinine was greater in both those with higher baseline serum levels of this indicator of the glomerular filtration rate and at the higher doses of atorvastatin. Simvastatin can also significantly reduce serum creatinine and serum
uric acid (p < 0.0001) in patients with PAD treated for 3–4 months [38]. The difference in the creatinine levels was more pronounced in the tertile of patients with the highest baseline creatinine levels. Statins can reduce circulating CRP levels [6, 20]. Other lipid-lowering drugs (e.g. ciprofibrate [33], fenofibrate [36] and ezetimibe [7, 34]) can also decrease circulating CRP levels. However, the potential relevance of lowering CRP levels to a greater or lesser extent remains unclear. Furthermore, recent evidence suggests that circulating CRP levels may only be a moderate predictor of CHD risk. Patients with the metabolic syndrome have a clustering of many risk factors, such as hypertension, insulin resistance/type 2 diabetes mellitus, dyslipidaemia and obesity [11]. Therefore, it not surprising that these patients are at increased risk of developing PAD [15, 28]. The prevalence of the metabolic syndrome in PAD patients in a crosssectional survey [15] was 58%.
1.3.5 Are all Statins the Same? Statins are of proven efficacy in secondary prevention in high-risk groups such as PAD patients. However, we do not know if all statins are equally effective. This question can only be answered by “head to head” comparison trials that incorporate clinical endpoints. Potential differences between statins can conveniently be considered in the context of: • LDL-C lowering potency, and • Pleiotropic actions. So far, “head to head” comparisons clearly show that some statins are considerably more potent, in terms of LDL-C lowering, than others [10, 27]. However, potency must not be considered in the decision-making process at the expense of safety and event-based evidence. What is less clear is whether statins differ in properties that may not be exclusively due to variations in their LDL-C-lowering capacity, the so-called pleiotropic actions [8].
1.3.6 Concluding Comments Trial-based evidence shows that lipid-lowering treatment is beneficial in patients with PAD. However, these
37
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1.3 Lipids and Peripheral Arterial Disease
patients are often under-treated despite their high risk for vascular events [19, 23]. It is also not widely appreciated that lipid lowering can improve PAD-related symptoms. The time has come for those looking after PAD patients to use aggressive preventive treatment. Although statins can improve both clinical outcomes and symptoms in PAD, it is possible that further benefit can be obtained if LDL-C levels are lowered beyond the “older” targets for high-risk patients [from 96–100 mg/ dl (2.5–2.6 mmol/l) to 70–77 mg/dl (1.8–2.0 mmol/l)]. However, we do not know if these “new” LDL-C targets provide further symptomatic improvement or a more effective prevention of events in PAD. These issues need to be resolved by appropriately designed trials. References 1. Aronow WS, Ahn C (2002) Frequency of new coronary events in older persons with peripheral arterial disease and serum low-density lipoprotein cholesterol ≥125 mg/dl treated with statins versus no lipid-lowering drug. Am J Cardiol 90:789–791 2. Aronow WS, Ahn C (2003) Elderly diabetics with peripheral arterial disease and no coronary artery disease have a higher incidence of new coronary events than elderly nondiabetics with peripheral arterial disease and prior myocardial infarction treated with statins and with no lipid-lowering drug. J Gerontol A Biol Sci Med Sci 58:573–575 3. Athyros VG, Mikhailidis DP, Papageorgiou AA, Symeonidis AN, Pehlivanidis AN,Bouloukos VI, Elisaf M (2004a) The effect of statins versus untreated dyslipidaemia on renal function in patients with coronary heart disease: a subgroup analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) Study. J Clin Pathol 57:728–734 4. Athyros VG, Elisaf M, Papageorgiou AA, Symeonidis AN, Pehlivanidis AN, Bouloukos VI, Milionis HJ, Mikhailidis DP; GREACE Study Collaborative Group (2004b) Effect of statins versus untreated dyslipidemia on serum uric acid levels in patients with coronary heart disease: a subgroup analysis of the GREek Atorvastatin and Coronary-heartdisease Evaluation (GREACE) study. Am J Kidney Dis 43:589–599 5. De Backer G, Ambrosioni E, Borch-Johnsen K, Brotons C, Cifkova R, Dallongeville J, Ebrahim S, Faergeman O, Graham I, Mancia G, Manger Cats V, Orth-Gomer K, Perk J, Pyorala K, Rodicio JL, Sans S, Sansoy V, Sechtem U, Silber S, Thomsen T, Wood D: Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (2003) European guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 24:1601–1610
6. Balk EM, Lau J, Goudas LC, Jordan HS, Kupelnick B, Kim LU, Karas RH (2003) Effects of statins on nonlipid serum markers associated with cardiovascular disease: a systematic review. Ann Intern Med 139:670–682 7. Ballantyne CM, Houri J, Notarbartolo A, Melani L, Lipka LJ, Suresh R, Sun S, LeBeaut AP, Sager PT, Veltri EP; Ezetimibe Study Group (2003) Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Circulation 107:2409–2415 8. Bonetti PO, Lerman LO, Napoli C, Lerman A (2003) Statin effects beyond lipid lowering – are they clinically relevant? Eur Heart J 24:225–248 9. Buchwald H, Bourdages HR, Campos CT, Nguyen P, Williams SE, Boen JR (1996) Impact of cholesterol reduction on peripheral arterial disease in the program on the surgical control of the hyperlipidemias (POSCH). Surgery 120:672–679 10. Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM; Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators (2004) Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 350:1495–1504 11. Daskalopoulou SS, Mikhailidis DP, Elisaf M (2004) Prevention and treatment of the metabolic syndrome. Angiology 55:589–612 12. Durazzo AE, Machado FS, Ikeoka DT, De Bernoche C, Monachini MC, Puech-Leao P, Caramelli B (2004) Reduction in cardiovascular events after vascular surgery with atorvastatin: a randomized trial. J Vasc Surg 39:967–975 13. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001) 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). J Am Med Assoc 285:2486–2497 14. Farkouh ME, Rihal CS, Gersh BJ, Rooke TW, Hallett JW Jr, O’Fallon WM, Ballard DJ (1994) Influence of coronary heart disease on morbidity and mortality after lower extremity revascularization surgery: a population-based study in Olmsted County, Minnesota (1970-1987). J Am Coll Cardiol 24:1290–1296
References
15. Gorter PM, Olijhoek JK, van der Graaf Y, Algra A, Rabelink TJ, Visseren FL; For the SMART Study Group (2004) Prevalence of the metabolic syndrome in patients with coronary heart disease, cerebrovascular disease, peripheral arterial disease or abdominal aortic aneurysm. Atherosclerosis 173:361–367 16. Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, Pasternak RC, Smith SC Jr, Stone NJ; National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association (2004) Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 110:227–239 17. Heart Protection Study Collaborative Group (2002) MRC/ BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360:7–22 18. Henke PK, Blackburn S, Proctor MC, Stevens J, Mukherjee D, Rajagopalin S, Upchurch GR Jr, Stanley JC, Eagle KA (2004) Patients undergoing infrainguinal bypass to treat atherosclerotic vascular disease are underprescribed cardioprotective medications: effect on graft patency, limb salvage, and mortality. J Vasc Surg 39:357–365 19. Hirsch AT, Gotto AM Jr (2002) Undertreatment of dyslipidemia in peripheral arterial disease and other high-risk populations: an opportunity for cardiovascular disease reduction. Vasc Med 7:323–331 20. Kinlay S, Schwartz GG, Olsson AG, Rifai N, Leslie SJ, Sasiela WJ, Szarek M, Libby P, Ganz P; Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering Study Investigators (2003) High-dose atorvastatin enhances the decline in inflammatory markers in patients with acute coronary syndromes in the MIRACL study. Circulation 108:1560–1566 21. McDermott MM, Guralnik JM, Greenland P, Pearce WH, Criqui MH, Liu K, Taylor L, Chan C, Sharma L, Schneider JR, Ridker PM, Green D, Quann M (2003) Statin use and leg functioning in patients with and without lower-extremity peripheral arterial disease. Circulation 107:757–761 22. Meade T, Zuhrie R, Cook C, Cooper J (2002) Bezafibrate in men with lower extremity arterial disease: randomised controlled trial. Br Med J 325:1139–1141 23. Meijer WT, Grobbee DE, Hunink MG, Hofman A, Hoes AW (2000) Determinants of peripheral arterial disease in the elderly: the Rotterdam study. Arch Intern Med 160:2934–2938 24. Mohler ER, Hiatt WR, Creager MA (2003) Cholesterol reduction with atorvastatin improves walking distance in patients with peripheral arterial disease. Circulation 108:1481–1486
25. Mondillo S, Ballo P, Barbati R, Guerrini F, Ammaturo T, Agricola E, Pastore M, Borrello F, Belcastro M, Picchi A, Nami R (2003) Effects of simvastatin on walking performance and symptoms of intermittent claudication in hypercholesterolemic patients with peripheral vascular disease. Am J Med 114:359–364 26. Napoli C, Sica V (2004) Statin treatment and the natural history of atherosclerotic-related diseases: pathogenic mechanisms and the risk-benefit profile. Curr Pharm Des 10:425–432 27. Nissen SE, Tuzcu EM, Schoenhagen P, Brown BG, Ganz P, Vogel RA, Crowe T, Howard G, Cooper CJ, Brodie B, Grines CL, DeMaria AN; REVERSAL Investigators (2004) Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. J Am Med Assoc 291:1071–1080 28. Olijhoek JK, van der Graaf Y, Banga JD, Algra A, Rabelink TJ, Visseren FL; the SMART Study Group (2004) The metabolic syndrome is associated with advanced vascular damage in patients with coronary heart disease, stroke, peripheral arterial disease or abdominal aortic aneurysm. Eur Heart J 25:342–348 29. Pasceri V, Patti G, Nusca A, Pristipino C, Richichi G, Di Sciascio G; ARMYDA Investigators (2004) Randomized trial of atorvastatin for reduction of myocardial damage during coronary intervention: results from the ARMYDA (Atorvastatin for Reduction of MYocardial Damage during Angioplasty) study. Circulation 110:674–678 30. Pedersen TR, Kjekshus J, Pyorala K, Olsson AG, Cook TJ, Musliner TA, Tobert JA, Haghfelt T (1998) Effect of simvastatin on ischemic signs and symptoms in the Scandinavian simvastatin survival study (4S). Am J Cardiol 81:333–335 31. Peripheral Arterial Diseases Antiplatelet Consensus Group (2003) Antiplatelet therapy in peripheral arterial disease. Consensus statement. Eur J Vasc Endovasc Surg 26:1–16 32. Poldermans D, Bax JJ, Kertai MD, Krenning B, Westerhout CM, Schinkel AF, Thomson IR, Lansberg PJ, Fleisher LA, Klein J, van Urk H, Roelandt JR, Boersma E (2003) Statins are associated with a reduced incidence of perioperative mortality in patients undergoing major noncardiac vascular surgery. Circulation 107:1848–1851 33. Rizos E, Bairaktari E, Kostoula A, Hasiotis G, Achimastos A, Ganotakis E, Elisaf M, Mikhailidis DP (2002) Effect of ciprofibrate on lipoproteins, fibrinogen, renal function, and hepatic enzymes. J Cardiovasc Pharmacol Ther 7:219–226 34. Sager PT, Melani L, Lipka L, Strony J, Yang B, Suresh R, Veltri E; Ezetimibe Study Group (2003) Effect of coadministration of ezetimibe and simvastatin on high-sensitivity C-reactive protein. Am J Cardiol 92:1414–1418
39
40
1.3 Lipids and Peripheral Arterial Disease
35. Tsiara S, Elisaf M, Mikhailidis DP (2003) Early vascular benefits of statin therapy. Curr Med Res Opin 19:540–556 36. Tsimihodimos V, Kostoula A, Kakafika A, Bairaktari E, Tselepis AD, Mikhailidis DP, Elisaf M (2004) Effect of fenofibrate on serum inflammatory markers in patients with high triglyceride values. J Cardiovasc Pharmacol Ther 9:27–33
37. Williams B, Poulter NR, Brown MJ, Davis M, McInnes GT, Potter JF, Sever PS, Thom SM; BHS guidelines working party, for the British Hypertension Society (2004) British Hypertension Society guidelines for hypertension management 2004 (BHS-IV): summary. Br Med J 328:634–640 38. Youssef F, Gupta P, Seifalian AM, Myint F, Mikhailidis DP, Hamilton G (2004) The effect of short-term treatment with simvastatin on renal function in patients with peripheral arterial disease. Angiology 55:53–62
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1.4 Clotting Disorders: What Should the Vascular Surgeon Know About Hypercoagulation States in Venous Diseases? Rosa M. Moreno
1.4.1 Introduction In daily clinical practice, the vascular surgeon frequently has to evaluate and manage patients who present with venous thrombosis. Identifying the cause of this disease along with its risk factors has several interesting implications, which are reviewed in this chapter concerned with abnormalities in the blood clotting mechanism that generates hypercoagulation states.
1.4.2 Venous Thrombosis Venous thrombosis is a significant cause of morbidity and mortality in western countries, and is estimated to affect between 1 and 3 persons per 1000 each year [36]. A hypercoagulation, or hypercoagulable, state is defined as an abnormal situation of the circulating blood, in which a smaller stimulus is required to induce the onset of thrombosis compared to the normal coagulation state. It most commonly manifests as thromboembolic disease, deep vein thrombosis (DVT), pulmonary thromboembolism (PTE) or post thrombotic syndrome. However, venous thrombosis can affect any body site such as the retina, veins of the arm, or the mesenteric, hepatic or cerebral veins. Venous thrombosis seems to be age-related, since rates during childhood according to some authors are as low as 1 per 100,000 annually, while the incidence could reach 1% per year in elderly subjects [38]. The thrombotic state is produced by an upset in the normal balance of procoagulant, anticoagulant and fibrinolytic factors. An inherited tendency for thrombosis, irrespective of the causative factor, has been denoted primary or hereditary thrombophilia. Situations in which thrombosis is acquired are known as secondary hypercoagulable states. In
these cases, thrombosis is the final consequence of several factors making the precise definition of its physiopathological basis extremely difficult.
1.4.2.1 Risk Factors Acquired risk factors and predisposing conditions for the development of DVT have been described by an ad hoc team on behalf of The Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter [42] (Table 1.4.1). The factors classically defined are: a previous history of DVT, immobilization, the postoperative state, age, heart disease, trauma to the lower limbs, a concurrent malignancy, hormone therapy, pregnancy, the postpartum period and obesity. Familial thrombophilia, a genetic risk factor, has been known since 1965 when Egeberg [10] identified an inherited tendency for thrombosis caused by an antithrombin III deficiency in a Norwegian family. It was not until almost two decades later that protein C [16] and protein S [44] deficiencies were identified, and anomalies such as factor V Leiden thrombophilia, mutation of the prothrombin gene or dysfibrinogenemia have been only recently described.
Acquired or Environmental Risk Factors Previous History of DVT
A previous episode of DVT in the lower limb is the most significant risk factor for developing a subsequent DVT episode. Specific phlebographic findings or the results of noninvasive tests are considered sufficient to confirm a previous DVT episode. A patient with post thrombotic syndrome yet no history of DVT should be suspected of having undergone a previous episode.
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1.4 Clotting Disorders: What Should the Vascular Surgeon Know About Hypercoagulation States in Venous Diseases?
Table 1.4.1 Risk factors for venous thrombosis Acquired
Congenital
Mixed
Previous thrombosis
Antithrombin III deficiency
Hyperhomocysteinaemia
Immobilization
Protein C deficiency
High factor VIII levels
Postoperative period
Protein S deficiency
High factor IX levels
Age
Factor V Leiden
High factor XI levels
Heart disease
Prothrombin gene mutation
Acquired PC resistance
Lower limb trauma
Blood group
Dysfibrinogenemia
Malignant tumour
Methylenetetrahydrofolate reductase
Hormone treatment
Dysfibrinogenemia
Pregnancy/postpartum Obesity Antiphospholipid syndrome
Immobilization
All situations affecting the action of the calf muscular pump are associated with DVT. Several situations are related to immobilization, such as bed rest, in turn produced by conditions such as acute myocardial infarction, cardiac insufficiency, respiratory insufficiency, paralysis or trauma, or even prolonged periods of sitting when travelling long distances. The duration and cause of immobilization affect the risk of DVT [37]. Since 1954, when Homans [18] reported the first case of DVT after a long commercial flight, this subject has generated much interest among both the medical and general population, with the so-called tourist class syndrome frequently appearing in the general press. Several publications reflect the interest in this topic [27, 43]. Some have reported findings such as sudden death being more common in airport arrivals than departure lounges [43]. Attention has also been paid to the possible influence that the length of the flight might have. Hence, the risk of DVT is 50 times higher in flights of distance longer than 10,000 km compared to flights covering a distance of 5000 km [27]. Other studies, some controlled, find no conclusive data regarding the size of possible risks, and attribute travel-related DVT to a multifactorial predisposition [11, 26]. In 2002, the World Health Organization launched its WRIGHT study (WHO Research into Global Hazards of Travel) to try to more precisely define these concepts. This investigation aims to establish the mechanisms through which thrombosis is induced and identify the roles of hypoxia and hypobaria. These
factors appear to act as triggers for coagulation, although these results have not yet been published.
The Postoperative State
The duration of surgery and the type of anaesthesia are related to the postoperative onset of DVT. These risks are particularly high in patients undergoing orthopaedic procedures [6, 19] at the level of the pelvis, hip or legs, with risks estimated at 30% to 50%. Further variables considered risk factors are neurosurgery procedures, any intraabdominal procedure, and gynaecological and urological surgery, especially radical prostatectomy [29].
Age
The risk of thrombosis increases with age. This may be explained by a combination of factors such as reduced mobility, diminished muscle tone, increased morbidity and the deterioration of the venous system itself. The age effect is considerable and should always be considered before making any clinical decision. When this risk is weighed up against the undesirable effects of treatment, the cost of screening or the disadvantages of not prescribing treatment, the management option selected can vary tremendously depending on the patient age group.
1.4.2 Venous Thrombosis
Heart Disease
The severity of a heart condition seems to increase the risk of developing DVT and, according to the New York Heart Association (NYHA) functional class, a correlative risk score is assigned [37, 42].
Trauma to the Lower Limbs
Major trauma is an important risk factor for thrombosis, which occurs in 50% to 60% of patients with cranial, or spinal cord trauma and fractures of the pelvis, femur or tibia [13].
A Concurrent Malignancy
DVT is more common in patients with a malignant tumour, an observation made for the first time by Trousseau [47] in 1865. DVT can be the first sign of cancer and is taken as a warning sign for malignant disease. The thrombogenic effect of cancer arises from the production of humoral factors (procoagulants), mechanical factors (vein compression or local infiltration) and general factors indicated by the presence and increased levels of acute phase reactants [5]. Indirectly, thrombosis may also be induced by reduced patient mobility and diminished uptake of vitamins such as folates. Finally, thrombosis may be promoted by the treatment received by the patient including radiotherapy and chemotherapy [31, 49], and may also be triggered by postsurgery fibrosis. The prevalence of cancer in patients with DVT has been estimated at 3% to 18% by different studies. In a Swedish population study [34], 19% of patients with DVT already had a diagnosis of cancer and 1 year later this proportion had increased by 5%. The type of tissue affected may also be related to the development of DVT [37], adenocarcinoma (especially mucinous) and cerebral malignant glioma being associated with the greatest risk.
Hormone Therapy
Several publications [50] have reported that oral contraceptives (OC), including those containing mini hormone doses, are linked to an increased risk of thrombosis of about fourfold. Most OC contain an oestrogen and progesterone. Over the years, the amount of oestrogen has been steadily reduced until the present dose of 30 μg or even less of ethinyloestradiol. However, there is still no convincing evidence that this dose reduction has managed to decrease the risk of thrombosis. Both early and
recent studies have shown a 4% to 8% increased risk of thrombosis among women using OC, yet comparisons between OC containing 30 μg and 50 μg have not yielded conclusive results [14]. Progestagens are also thought to affect the risk of thrombosis. Third-generation progestagens (desogestrel and gestodene) have been related to a risk of thrombosis of up to two times that of preparations containing second-generation progestagens [22, 51]. Hormone replacement therapies (HRT) based exclusively on oestrogens increase the risk of endometrial cancer, to the extent that there is a tendency to prescribe oestrogen and progesterone HRT except in hysterectomized women. There are reports indicating a two- to fourfold increased risk of DVT in women on HRT [9, 15]; this should be taken into account when evaluating menopausal women. It should also be kept in mind that a large number of epidemiological studies conclude that Asian women, because of their diet rich in soy, reach the menopause in better condition than Occidental women and have a lower incidence of undesirable effects. Moreover, and despite the large number of published reports focusing on isoflavones (a Medline search of the term isoflavones yields over 7500 citations), there is no mention in the literature of an increased risk of thrombosis linked to the uptake of these components of soy.
Pregnancy and the Postpartum Period
It has been estimated that 1 in 2000 women develop thrombosis during pregnancy. This risk increases 10 times when compared with nonpregnant women of the same age [23, 30]. This risk also goes up in the postpartum period. Pregnancy leads to increased levels of the blood clotting factors I, VII, VIII, IX, X, XI and XII, an increased platelet count and reduced protein S and antithrombin concentrations. Further, the fibrinolytic pathway may be blocked by the increased levels of activated plasminogen inhibitors 1 and 2, produced in the placenta. These factors, combined with the venous stasis produced by compression by the uterus of draining leg veins, can increase the risk of thrombosis during the prepartum period by up to 20 times. Some 2 months after childbirth, fibrinolytic and coagulation systems return to their normal state.
Obesity
Severe obesity can be an independent risk factor for developing thrombosis, especially if 175% of the ideal weight is surpassed [37].
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1.4 Clotting Disorders: What Should the Vascular Surgeon Know About Hypercoagulation States in Venous Diseases?
Genetic Risk Factors
risk of thrombosis by 3- to 8-fold in heterozygous carriers and by 50- to 80-fold in homozygous carriers [24].
Antithrombin III Deficiency
This condition is produced by point mutations in the antithrombin III (AT-III) gene and shows an autosomal dominant transmission pattern. AT-III is an α2 globulin that inhibits factors XIIa, XIa, IXa, Xa, IIa and plasmin. Its prevalence is less than 1 in 1000 people [45]. The homozygous state is incompatible with life. Heterozygotes show 40% to 60% the normal functional activity of AT-III. An acquired AT-III deficiency may occur in cases of its reduced production (in liver disorders or following the administration of OC), enhanced excretion (nephrotic syndrome, protein-losing enteropathy), excessive consumption, or disseminated intravascular coagulation (DIC).
Prothrombin Gene Mutation 20210A
This anomaly described in 1996 is caused by a mutation in nucleotide 20210 of the prothrombin gene (guanine replaced by adenine). The heterozygous state occurs in 1% to 4% of the general population and in up to 6% to 10% of subjects with venous thrombosis. The risk of thrombosis increases 2–3 times with respect to the population at large, and seems to be mediated by increased prothrombin levels [35]. It has even been suggested that prothrombin gene and factor V Leiden mutations occur in 63% of families with thrombophilia [3].
Blood Group Protein C Deficiency
Protein C is vitamin K dependent. It acts by inactivating factors Va and VIIIa and requires the presence of protein S as a cofactor, activated by thrombin and thrombomodulin. Protein C deficiency is a hereditary disorder of autosomal dominant transmission. The prevalence [39, 46] of an asymptomatic heterozygous deficiency is low at 1/300–500, with 1/16,000–36,000 showing clinical signs. A homozygous protein C deficiency manifests as neonatal purpura fulminans progressing with thrombosis in the microcirculation and DIC.
Protein S Deficiency
Protein S is a vitamin-K-dependent glycoprotein that acts as a cofactor to protein C in the degradation of factors Va and VIIIa. Its pattern of transmission is autosomal dominant. Its prevalence is similar to those of protein C and AT-III deficiencies.
Resistance to Activated Protein C
This anomaly is the consequence of the substitution of the amino acid arginine 506 by glutamine in the factor V molecule. This mutated factor V, designated factor V Leiden, is resistant to the catalytic action of activated protein C. This disorder, first described in 1993 by Dahlbäck [8], has an autosomal dominant pattern of transmission and is the most common deficiency in the general Caucasian population linked to thrombosis. Its prevalence [4, 41] is high at 5% to 15%, yet it is relatively uncommon in populations of other races. Factor V Leiden increases the
Non-O blood groups are associated with a 2- to 4-fold increased risk of venous thrombosis [21].
Methylenetetrahydrofolate Reductase 677T
A variation in the gene coding for methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in homocysteine metabolism, has been associated with slightly elevated homocysteine levels in the blood [12], increasing the risk of thrombosis.
Other Plasma Anomalies Related to the Risk of Thrombosis Hyperhomocysteinemia
Homocysteine is an amino acid that metabolizes cysteine (with vitamin B6 acting as cofactor) or methionine (with vitamin B12 as cofactor). Its blood levels can rise as the result of either a congenital deficiency in one of the enzymes involved in these processes or a nutritional deficiency of folate, vitamin B6 or vitamin B12. High blood homocysteine levels induce endothelial damage and are associated with an increase in tissue factor, and the enhanced activity of factors V and XII, and protein C. Homocysteine levels above 18 μmol/l are linked to an increased risk of thrombosis [32]. Patients with hyperhomocysteinemia have a 3.5 times higher risk of presenting with thrombosis. This risk increases by over 20-fold if the patient also has factor V Leiden. Treatment with folate and vitamins B6 and B12 reduces homocysteine concentrations.
1.4.3 What Should a Surgeon do when Faced with Hypercoagulation?
Antiphospholipid Antibodies
Antiphospholipid syndrome (APS) is a commonly acquired cause of hypercoagulation. It appears in 1% to 15% of the population, this rate increasing with age (to 50% in patients over the age of 80 years) [28]. APS affects patients with lupus anticoagulant or anticardiolipin antibodies. These antibodies react with endothelial cells, platelets and phospholipids. Recurrent venous thrombosis is one of its clinical manifestations [20]. Thrombotic complications, estimated to be as high as 50%, have also been reported after vascular reconstruction procedures [1]. A further common manifestation of APS is miscarriage. Its diagnosis should include the identification of lupus anticoagulant and anticardiolipin antibodies. Treatment consists of eliminating risks such as avoiding pregnancy and taking OC. If venous thrombosis has already been provoked, heparin or urokinase should be immediately given followed by oral anticoagulation with warfarin adjusted to maintain the international normalized ratio (INR) between 2 and 3. Patients with a history of DVT or miscarriage who are pregnant should be treated with heparin throughout pregnancy and switched to oral anticoagulation after giving birth.
High Coagulation Factor Levels
Augmented levels of prothrombin (factor II), factor VIII, factor IX, or factor XI have been linked to a high risk of thrombosis [25]. Although little is known about the aetiology of these abnormalities, they have been described as a combination of congenital and acquired alterations.
1.4.3 What Should a Surgeon do when Faced with Hypercoagulation? When confronted with an episode of DVT, several uncertainties immediately come to mind. First, should we search for evidence of thrombophilia? How should this be done and when? Also important to the vascular surgeon is the question of whether to consider special therapeutic options in patients who are carriers of thrombophilia.
1.4.3.1 Should a Search for Thrombophilia be Undertaken? All acquired risk factors can be controlled to a certain extent whether at the level of prophylaxis or treatment. The major worry is evaluating a genetic hypercoagulable state because its presence can be well demonstrated but its treatment not yet well defined. There are several arguments in favour of embarking on a search for thrombophilia. Its discovery could benefit relatives. Prophylaxis may be started in situations of added risk. It is well known that both pregnancy and OC are associated with factor V Leiden or a mutation in prothrombin gene 20210A, increasing the risk of thrombosis by 4–8 times. A similar situation arises owing to the link with HRT or treatment with tamoxifen. In contrast, if, in an elderly patient presenting an idiopathic venous thrombosis, thrombophilia is discovered, this will avoid worry and an exhaustive, sometimes unforthcoming, search for neoplastic disease.
Defects in the Fibrinolytic System
A drop in fibrinolytic activity and a predisposition to thrombosis may be secondary to diminished plasminogen levels, to reduced activity of plasminogen activator or to the increased action of the plasminogen inhibitor. Reduced fibrinolytic activity occurs in acquired disease states (myocardial infarction, generalized arteriosclerosis, diabetes, scleroderma, thrombocytopenic purpura, ulcerative colitis, Crohn’s disease) [7]. Congenital plasminogen deficiency is transmitted in an autosomal dominant manner. Thrombotic events usually occur when plasminogen levels fall below 40% of those related to normal biological activity [17]. This disorder is extremely rare with reports of only a few isolated cases [33].
1.4.3.2 How Should the Search be Done? As mentioned previously, the most recently discovered deficiencies (factor V Leiden and prothrombin gene mutation 20210A) are highly prevalent, thus generating an increased number of patients whose venous thrombosis could be attributed to an inherited thrombophilia. The first step of diagnosis will involve drawing up a careful clinical record, a meticulous physical examination and a basic laboratory routine check to characterize the severity of the thrombotic process, and determine the presence of any of the causes of hypercoagulability. Obviously, an objective test for the diagnosis of venous thrombosis will also have to be conducted. The second step will be to screen for the causes of hereditary thrombophilia, which if identified will mean
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1.4 Clotting Disorders: What Should the Vascular Surgeon Know About Hypercoagulation States in Venous Diseases?
adopting a specific management plan. Screening should be performed, especially if DVT appears before the age of 50 years in cases of DVT recurrence and if there is a family history of DVT. If one or more of these conditions are met, a complete evaluation will be needed to rule out thrombophilia.
1.4.3.3 Diagnosing Thrombotic Disease in Patients with Thrombophilia All patients presenting juvenile, idiopathic, recurrent thrombosis with a family history of thrombosis should be assessed for possible deficiencies. Once a suspicion of thrombophilia has been established, the following factors may be determined during the episode of thrombosis: anticardiolipin antibodies, homocysteine, factor V Leiden and prothrombin gene mutation. Other factors may be consumed during the coagulation process or be reduced by anticoagulant therapy, or because of hepatic insufficiency or sepsis. For this reason, the clinician should wait until the end of the 6-month treatment period and then leave a further treatment-free interval (proposed by some as ideally 2 months), before determining the presence of the remaining possible deficiencies (protein C, protein S, antithrombin III).
1.4.3.4 Treating Thromboembolic Disease in Patients with Thrombophilia The treatment regime for a patient with DVT and pulmonary thromboembolism is usually heparin initially and oral anticoagulant for 3–6 months, adjusted to keep the INR between 2 and 3. According to several randomized trials, after a first episode, the incidence of recurrent venous thromboembolism is between 5% and 15% in the first year and from 20% to 30% at 4 years [2]. At the same time, it should be taken into account that the risk of haemorrhage is estimated at 2% to 3% per year. This yearly risk in young patients, with no added risks for the haemorrhage, is unimportant but may give rise to a series of contraindications for treatment in patients with multiple associated diseases and an advanced age. In general there is scarce information on thrombotic recurrence in nonselected patients. Most studies have been based on select populations with generally very high recurrence rates. For the most prevalent abnormalities, factor V Leiden and prothrombin mutation 20210A, the available data fail to indicate a higher recurrence after
a first episode [38]. The current consensus is that there is no need to prolong treatment in the presence of these anomalies. However, the risk of recurrence is probably high in the heterozygous population simultaneously having both anomalies. It is also important to keep in mind that interaction between an acquired and a congenital risk factor can substantially increase the risk threshold. A clear example is the increased relative risk produced when the use of OC is added to the presence of factor V Leiden [48] (RR increases from 6 to 35), or if HRT is added to this factor (RR increases from 4 to 15) [40]. When these anomalies are detected in asymptomatic carriers (relatives of the patient), in the presence of additional risk factors, these subjects might benefit from a selective prophylaxis regimen. These subjects could be rejected by insurance companies. Indefinite anticoagulation is only considered appropriate for patients categorized as high risk, meaning two or more events; a spontaneous (without another DVT risk factor) severe event; or a patient with a spontaneous event and documented antiphospholipid antibodies. When patients are categorized as having moderate risk, i.e. in the absence of symptoms or if the stimulus for a thrombotic event has been identified, prophylaxis would only be given in a risk situation.
1.4.3.5 Specific Considerations in Treating Thromboembolic Disease Related to Thrombophilia Antithrombin III Deficiency The treatment of this deficiency consists of infusions of fresh plasma or preferably antithrombin concentrate. Long-term treatment involves oral anticoagulation provided there have been past thrombotic episodes. Heparin is given during pregnancy or in other risk situations (e.g. surgery, trauma, sepsis).
Protein C Deficiency Intravenous infusion of fresh plasma can restore functional levels of protein C. Heparin prophylaxis (during pregnancy) or treatment should be given in risk situations such as after surgery, trauma or sepsis. Lifetime oral anticoagulation is required for recurrent or life-threatening thrombosis.
References
Protein S Deficiency The management of this deficiency is the same as for protein C deficiency.
Activated Protein C Resistance Heparin prophylaxis is given in high-risk situations for thrombosis. Lifetime anticoagulation therapy is required for recurrent or life-threatening thrombosis.
Prothrombin Gene Mutation The treatment for this condition remains to be clearly defined. Long-term oral anticoagulation therapy is also recommended in patients with recurrent thrombosis.
1.4.4 Summary • The occurrence of venous thrombosis is the result of interaction between both genetic and acquired factors. • Screening should be based on characterizing patients according to their clinical history. • Tests should be undertaken 2 months after the end of anticoagulation therapy. • Asymptomatic carriers do not require treatment yet should undergo prophylaxis in situations of risk. • Treatment of a first episode of DVT with proven thrombophilia is the same as for the general population. • There is a need for greater insight into all possible risk factors and in particular the interactions produced among several risk factors, since this will synergistically potentiate the risks involved. • Future data will enable the physician to gauge this risk in each individual patient and design the tools needed to prevent the thromboembolic state. References 1. Ahn SS, Kalunian K, Rosove M, Moore WS (1988) Postoperative thrombotic complications in patients with the lupus anticoagulant: increased risk after vascular procedures. J Vasc Surg 7:745–756
2. Anderson FA, Wheeler HB, Goldberg RJ et al (1991) A population based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT study. Arch Intern Med 151:933–938 3. Bertina RM (1997) Factor V Leiden and other coagulation factor mutations affecting thrombotic risk. Clin Chem 43:1678–1683 4. Bertina RM, Koeleman RPC, Koster T et al (1994) Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 369 (117):750–753 5. Bick RL (1992) Coagulation abnormalities in malignancy: a review. Semin Thromb Hemost 18:353–369 6. Cohen SH, Ehrlich GE, Kaufman MS, Cope C (1973) Thrombophlebitis following knee surgery. J Bone Surg 55:106–111 7. Colleen D, Juhan-Vaghe I (1988) Fibrinolysis and atherosclerosis. Semin Thromb Hemost 14:180–183 8. Dahlbäck B, Carlsson M, Svensson PJ (1993) Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C. Proc Natl Acad Sci USA 90:1004–1008 9. Daly E, Vessey MP, Hawkins MM, Carson JL, Gough P, Marsh S (1996) Risk of venous thromboembolism in users of hormone replacement therapy. Lancet 348:977–980 10. Egeberg O (1965) Inherited antithrombin deficiency causing thrombophilia. Thromb Diath Hemorrh 13:516–530 11. Ferrari E, Cevallier T, Chapelier A, Baudouy M (1999) Travel as a study. Chest 115:440–444 12. Frosst P, Bloom HJ, Milos R et al (1995) A candidate genetic risk factor for vascular disease a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10:111–113 13. Geerts WH, Code KI, Jay RM, Chen E, Szalai JP (1944) A prospective study of venous thromboembolism after major trauma. N Engl J Med 331:1601–1606 14. Gertsman BB, Piper JM, Tomita DK, Ferguson WJ, Stadel BV, Laundin FE (1991) Oral contraceptive estrogen dose and the risk of deep venous thromboembolic disease. Am J Epidemiol 133:32–37 15. Grady D, Furberg C (1997) Venous thromboembolic events associated with hormone replacement therapy. J Am Med Assoc 278:477 16. Griffin JH, Evatt B, Zimmerman TS, Kleiss AJ, Wideman C (1981) Deficiency of protein C in congenital thrombotic disease. J Clin Invest 68:1370–1373 17. Hasegawa DH, Tyler BJ, Edson JR (1982) Thrombotic disease in three families with inherited plasminogen deficiency. Blood 60:213–217 18. Homans J (1954) Thrombosis of the leg veins due to prolonged sitting. N Engl J Med 250:148–149
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19. Hull RD, Raskob GE (1986) Prophylaxis of venous thromboembolic disease following hip and knee surgery. J Bone Surg 68:146–150 20. Insko EK, Haskal ZJ (1997) Antiphospholipid syndrome: patterns of life-threatening and severe recurrent vascular complications. Radiology 202:319–326 21. Jick H. Slone D, Westernholm B et al (1969) Venous thromboembolic disease and ABO blood type. Lancet i:539–542 22. Kemmeren JM, Algra A, Grobee DE (1995) Third generation oral contraceptives with differing progression components. Lancet 346:1589–1593 23. Kierkegaard A (1983) Incidence and diagnosis of deep vein thrombosis associated with pregnancy. Acta Obstet Gynecol Scand 62:239–243 24. Koster T, Rosendaal FR, De Ronde H, Briët E, Vandenbroucke JP, Bertina RM (1993) Venous thrombosis due to a poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. Lancet. 342:1503–1506 25. Koster T, Blann AD, Riét E, Vandenbroucke JP, Rosendaal FR (1995) Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet 345:152–155 26. Kraaijenhaghen RA, HaverKamp D, Koopman MM, Prandoni P, Piovella F, Büller HR (2000) Travel and risk of venous thrombosis. Lancet 356:1492–1493 27. Lapostolle F, Surget V, Borron SW et al (2001) Severe pulmonary embolism associated with air travel. N Engl Med 345:779–783 28. Manoussakis MN, Tzioufas AG, Silis MP, Pange PJ, Goudevenos J, Moutsopoulos HM (1987) High prevalence of anticardiolipin and other autoantibodies in a healthy elderly population. Clin Exp Inmunol 69:557–565 29. Mayo M, Halil T, Browse NL (1971) The incidence of deep vein thrombosis after prostatectomy. Br J Urol 43:738–742 30. McColl MD, Ramsay JE, Tait RC et al (1997) Risk factors for pregnancy associated venous thrombosis. Thromb Hemost 78:1183–1188 31. Meier CR, Jic H (1998) Tamoxifen and risk of idiopathic venous thromboembolism. Br J Clin Pharmacol 45:608–612 32. Mudd SH, Skovby F, Levy HL et al (1985) The natural history of homocystinuria due to cystathionine beta-synthetase deficiency. Am J Hum Genet 37:1–31 33. Nilsson IM, Tengborn LA (1984) A family with thrombosis associated with high level of tissue plasminogen activator inhibitor. Haemostasis 14:24–27 34. Nordstrom M, Lindblad B, Anderson H, Bergqv D, Kjellströ T (1994) Deep venous thrombosis and occult malignancy: an epidemiological study. BMJ 308:891–894
35. Poort SR, Rosendaal FR, Reitsma PH, Bertina RM (1996) A common genetic variation in the 3’-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 88:3698–3703 36. Porter JM, Moneta GL (1995) Classification and grading of chronic venous disease. A consensus statement. J Vasc Surg 21:635–645 37. Porter JM, Moneta JL (1995) Reporting standards in venous disease: an update. J Vasc Surg 21:635–645 38. Rosendal FR (1997) Thrombosis in the young: epidemiology and risk factors, a focus in venous thrombosis. Thromb Hemost 78:1–6 39. Rosendaal FR, Koster T Vandenbroucke JP, Reitsma PH (1995) High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance). Blood 85:1504–1508 40. Rosendal FR, Vessey M, Rumley A et al (2002) Hormonal replacement therapy, prothrombotic mutations and the risk of venous thrombosis. Br J Haematol 116:851–854 41. Rees DC, Cox M, Clegg JB (1995) World distribution of factor V Leiden. Lancet 346:1133–1134 42. Rutherford RB, Clagett GP, Cranley JJ, O’Donell TF, Raju S, Zierler RE, Browse N, Nicolaides A (1988) Reporting standards in venous disease. J Vasc Surg 8:172–181 43. Savesvaan R (1986) Sudden natural deaths associated with commercial air travel. Med Sci Law 26:35–38 44. Schwarz HP, Fischer M, Hopmeier P, Batard MA, Griffin JH (1984) Plasma protein S deficiency in familial thrombotic disease. Blood 64:1297–1300 45. Tait RC, Walker ID, Perry DJ et al (1994) Prevalence of antithrombin deficiency in the healthy population. Br J Haematol 87:106–112 46. Tait RC, Walker ID, Reitsma PH et al (1995) Prevalence of protein C deficiency in the healthy population. Thromb Haemost 73:87–93 47. Trousseau A, Phegmasia Alba Dolens (1865) Clinique Médicale de l‘Hötel-Dieu de Paris. Vol. 3.Ballière, Paris, pp 652–695 48. Vandenbroucke JP, Koster T, Briët E, Reitsma PH, Bertina RM, Rosendaal FR (1994) Increased risk of venous thrombosis in oral contraceptives users who are carriers of factor V Leiden mutation. Lancet 344:1453–1457 49. Weijl NL, Rutten MF, Zwinderman AH et al (2000) Thromboembolic events during chemotherapy for germ cell cancer: a cohort study and review of the literature. J Clin Oncol 18:2169–2178
References
50. World Health Organization (1995) Venous thromboembolic disease and combined oral contraceptives: results of international multicentre case control study. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet 346:1575–1582
51. World Health Organization (1995) Effect of different progestagens in low estrogen oral contraceptives on venous thromboembolic disease. World Health Organization Collaborative Study of Cardiovascular and Steroid Hormone Contraception. Lancet 346:1582–1588
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1.5 Noninvasive Diagnosis of Vascular Diseases P. Berg, H. Farghadani, V. Lens, R. Metz, F. Mataigne, S. Schmitz
Noninvasive vascular laboratory findings remain important in the diagnosis of peripheral arterial disease (PAD). In many circumstances they are as accurate as invasive imaging and have the advantage of being quick and inexpensive. The two basic modalities of evaluation are the indirect methods (ankle brachial pressure index, Doppler wave forms, treadmill exercise) that provide location and functional severity of disease, and the direct method of evaluation, colour duplex imaging (CDI), which provides more specific anatomical and physiological information.
• Platelet count: changes may precipitate or aggravate the symptoms of PAD. Associated haematological disease may influence treatment. • Blood glucose or haemoglobin HbA1c, urea, creatinine: diabetes and chronic renal insufficiency are important risk factors in PAD, for interpretations of results and for further treatment. • Lipid profile: elevated low-density lipoprotein (LDL), triglycerides and low high-density lipoprotein (HDL) represent major risk factors for PAD and have to be treated. Lipid modification can be associated with stabilization or regression of femoral atherosclerosis. • Hypercoagulability screen and homocysteine levels should be performed selectively in patients with a family history or atypical events.
1.5.1.2 Physical Examination
1.5.1.4 Special Investigations, Other Than Imaging
In the majority of patients, diagnosis can usually be made on the basis of the history. Chronic arterial insufficiency of the lower extremity causes two very characteristic types of pain: intermittent claudication and ischaemic rest pain. Information may be obtained in the case of sudden worsening of limb perfusion in acute limb ischaemia. Physical examination should include: • Palpable pulses. • Audible bruits. • Changes in colour and temperature. • Presence of ulcers or gangrene.
Pressure and Volume Measurements
1.5.1 Peripheral Arterial Disease 1.5.1.1 Introduction
1.5.1.3 Basic Haematological and Biochemical Tests The following blood tests are most frequently used and are those that should be performed for all new patients presenting with PAD: • Complete blood count (haemoglobin, haematocrit, white cell count).
Ankle Brachial Pressure Index (ABPI)
• The ABPI serves as a baseline for comparing the patient with him or herself at different times. • Widely standard in the evaluation of patients with PAD. • It is calculated for each extremity by dividing the highest ankle pressure by the highest arm pressure. The ABPI provides important basic information; the following indices are consistent with the following clinical diagnoses: • 1.0–1.2: normal. • 0.5–0.9: claudication. • <0.5: markedly decreased (often to less than 0.30). Seen in patients with rest pain, ischaemic ulcer or gangrene [11, 29, 33]. • >1.3: abnormally high. Secondary to noncompressible vessels due to medial calcification.
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1.5 Noninvasive Diagnosis of Vascular Diseases
• For calcified arteries, the use of digital pressures or flow velocity recording in the pedal arteries is needed to supplement pressure recordings. • Specificity of this index is 100% for all reports. • Sensitivity is 92–94% [39].
Segmental Limb Systolic Pressure Measurements (SLP)
• Routinely used because of accurate haemodynamically significant detection of occlusive lesions between the heart and the measuring point. • The cuffs are placed in standard locations: high-thigh, low-thigh, below the knee, ankle and metatarsal. • Direct measurement is obtained by placing a Doppler probe over the artery just below the inflated cuff, or the probe can be placed over one of the pedal arteries giving a pressure gradient between the different cuffs. • A gradient greater than 20 mmHg suggests occlusive disease between the two cuffs.
Digital Pressure Measurement and Toe Brachial Index
• Digital pressures are useful in arterial occlusive disease within the foot or hand and in instances of falsely elevated ankle pressures secondary to medial calcification. • Using a small cuff (2.0 or 2.5 cm) and a photo electrode placed on the finger or toe as the pulse sensor, the digital pressure is obtained in the same way as for the ankle pressure. • The normal toe brachial index is 0.8–0.9. • An index of 0.35 ± 0.15 is consistent with claudication. • An index of 0.11 ± 0.10 is consistent with ischaemic rest pain [27]. • For absolute pressure, it is generally considered that a toe pressure less than 30 mmHg is indicative of severe ischaemia. • There is no difference between the mean values for diabetic and nondiabetic patients.
Segmental Plethysmography or Pulse Volume Recording (PVR)
• Any instrument measuring the change in volume of the limb during each cardiac cycle by a plethysmographic sensor may be used; for example, sphygmomanometer, mercury-in-silastic tube strain gauge or impedance captors.
• The pulse volume recording is obtained by a plethysmograph connected to these devices placed at selected locations of the limb [26]. • In addition a brachial cuff reflects the undampened cardiac contribution to arterial pulsatility. • Comparing each PVR reveals an eventual significant occlusive lesion. • The accuracy of each SLP and PVR alone is reported to be 85%. • These two measurements used together have an accuracy of over 95%. • This combination could help to recognize diabetic patients.
Doppler Velocity Waveform (VWF)
• Arterial VWF is recorded by a continuous-wave Doppler over the femoral, popliteal, posterior tibial and dorsalis pedis arteries. • Qualitative differences of the VWF between two adjacent recording points identify the presence of an occlusive lesion in the intervening arterial segment. • In normal individuals the VWF is triphasic, with reverse flow seen. • When atherosclerotic changes are present in the arteries, turbulence may be seen at the high-frequency peak or on the descending phase of the forward flow. • Dampened reverse flow suggests the presence of stenosis and with severe stenosis or occlusion the reverse flow is absent. In addition, the systolic acceleration of the forward flow becomes flattened. • In severe ischaemia the waveform becomes continuous and nonpulsatile. • In a patent but dilated artery, the flow waveform shows a widening of the systolic forward flow. • Visual inspection of these waveforms recorded over the different arteries described can detect and localize arterial occlusive disease in most cases. • These tests are painless, inexpensive, quick and accurate enough. VWF is more accurate than SLP alone. It has been reported [20] that VWF was 97% accurate (75% for SLP alone) in detecting superficial femoral artery lesions with over 50% luminal narrowing and 91% accurate (54% for SLP alone) in detecting similar lesions in the popliteal artery.
1.5.1 Peripheral Arterial Disease
Functional Testing Treadmill Exercise (TE)
• At rest, variation of flow in the lower limb requires an 80% stenosis, which is due to low flow and high resistance of its circulation. • Despite that, during exercise, a 20% stenosis is enough for significant haemodynamic changes because of high flow and low resistance of the circulation. • For practical reasons only brachial and ankle cuffs are routinely used. • The standard usually used is walking at 3.5 km/h on a 12% incline for 5 min. The ABPI is measured before exercise, at 1 or 2 min, at 5 min and then every minute until back to initial values. • Thus, the onset of claudication, the maximum walking distance, the percentage decrease in pressure and its absolute value during the post-exercise period (10–15 min) and recovery time are obtained. • In patients with multiple occlusions, the ankle pressure is often decreased to zero, with longer recovery time than patients with a single occlusion.
•
•
•
•
•
• Inducing Limb Hyperaemia (ILH)
• For the ILH, the pressure cuff is placed on the lower thigh and inflated to a level of 50 mmHg above the systolic pressure for 3–5 min. • Reactive hyperaemia occurs after the pressure cuff is abruptly deflated. • Ankle systolic pressure (AP) is then recorded at 1-min intervals until it returns to the resting level. • The decrease in AP 30 s after cuff deflation is equivalent to that observed 1 min after walking to the point of claudication on a treadmill [10, 14, 38]. • It is reported elsewhere [23] that ABPI and the treadmill test are widely superior to this test; nevertheless, ILH can be proposed if the treadmill is not possible. • Unfortunately, many patients do not tolerate the discomfort associated with this degree and duration of cuff inflation.
Microcirculatory Investigations Transcutaneous Oxygen Measurements (TcpO₂)
• TcpO2 provides valuable metabolic data which may be used to supplement the haemodynamic data provided
• • •
•
by other noninvasive tests. It provides a measure of the adequacy of the arterial oxygen supply to the tissues. An oxygen-sensing electrode is placed on the skin, which contains a small heating unit that warms the skin to a temperature of 44°C, conducive to efficient oxygen diffusion. The quantity of oxygen available for diffusion to the skin is a function of the arterial flow to the area and the amount of oxygen extracted from the blood to meet the metabolic requirements of the tissues. When arterial occlusive disease is severe, the tissue perfusion becomes marginal and capillary oxygen perfusion decreases as the proportion of oxygen extraction must increase to meet the metabolic demands of the tissue. TcpO2 is usually measured at the dorsum of the foot, medial aspect of the calf, and the thigh, with a reference electrode placed in the infraclavicular region. Comparing the values obtained at the lower extremity and the chest yields an index that can be compared to the normal value with regard to the patient’s age, cardiac output and arterial oxygen tension. The measurement should be done in a supine and in a sitting position; the difference between both values provides information about the microcirculatory reserve supply. The results are expressed in mmHg. There are important variations, essentially in older patients and in concomitant cardiopulmonary disease. In general, a TcpO2 <30 mmHg suggests ischaemia and nonhealing. As there is an admitted error range of ±10 mmHg, it is admitted that if TcpO2 <20 mmHg, healing will not occur and if TcpO2 >40 mmHg healing will be probable. There is a high positive predictive value (77–87%) [6, 34–37].
Laser Doppler Fluxmetry (LDF), Capillary Microscopy (CM)
• CM enables visualization of the nailfold capillaries of the big toe in the sitting position and provides information about capillary morphology, density and velocity. • LDF measurements on the pulp of the big toe give information about total skin perfusion, including capillaries, deeper vessels and arteriovenous anastomoses, which are mainly involved in thermoregulation.
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1.5 Noninvasive Diagnosis of Vascular Diseases
• The reactive hyperaemia response after a 3-min arterial occlusion can be measured to assess the reserve capacity of skin blood supply. • In a Dutch multicentre study, clinical and Doppler systolic pressure parameters were found to be inadequate for predicting imminent amputation, because all patients met these criteria but only 44% of them underwent amputation.
• Enhancement of vascular structure requires high contrast flow rates of 3–5 ml/s of 300–350 mg/ml iodic contrast with a total amount of 120–150 ml. • Irradiation is inevitable and particular precautions have to be taken to reduce the irradiation dose as much as possible.
Aorta Conclusion
The combination of all three techniques – TcpO2, LDF and CM – showed the highest specificity (87%), but a rather low sensitivity (46%). The conclusion is that TcpO2 measures provide microcirculatory classification and are the easiest measurement to perform [36].
1.5.1.5 Imaging Techniques Duplex Scanning • Colour duplex imaging incorporates real-time B-mode imaging, and pulsed and colour Doppler. • Duplex scanning can provide most of the essential anatomical information plus some functional information; for instance, velocity gradients across stenoses. • The arterial tree of the lower extremities can be visualized, with the extent and degree of occlusive lesions accurately assessed and arterial velocities measured. • It can characterize specific lesions in regard to their suitability for endovascular treatment. Arterial reconstructive surgery can be performed on the basis of duplex scanning alone in some cases. • Real-time B-mode imaging is the best mode for determining the anatomical detail of a vessel (e.g. plaque characterization, intimal flap, mural thrombus, diameter measurements).
• Applications for evaluation of the aorta with CTA are: dissection, aneurysm, traumatic injury, atherosclerotic pathology and other inflammatory and congenital diseases. • Abdominal aneurysm disease, including diagnosis and post-operative follow-up, is well explored by CTA, providing information about the extent of the aneurysm formation and other extraluminal pathology. • Thoraco-abdominal aortic exploration can be achieved with CTA with the new multirow scanner in a single exploration of 20 s. • Due to its fast access, high availability and short examination time, CTA is the preferred method for diagnosis of aortic dissection and traumatic aortic injury. CTA gives direct visualization of the aortic traumatism.
Renal Arteries
• CTA is routinely used for the evaluation of renal artery stenosis, and evaluation of renal transplant donors. • Excellent information regarding renal lesions and renal arteries can be provided with appropriate exploration (section thickness of 0.625–1.25 mm).
Lower Limb CTA
• New MDCT allows study of the arterial system of the lower extremity with only one examination.
Multiple Detector Computer Tomography (MDCT)
Studies Comparing MDCT and CT Angiography
• Recent advances in CT scanner technology, mainly multiple detector rows and high gantry rotation speed, as well as developments in reformatting technique allow the CT scan to be used as a noninvasive method to explore the “deep” arterial system (including aorta and visceral arteries) as well as the lower limb arteries. • CTA is a “noninvasive” imaging modality, but it still requires injection of contrast media.
• Particular attention should be paid to the study of the axial native images including all the diagnostic information. • 3D reconstruction and post-processing images are highly operator dependent. • Inadvertent 3D manipulations could “create” or “ignore” pathological conditions.
1.5.1 Peripheral Arterial Disease
Fig. 1.5.1. Male 65 years, 76-mm-diameter infrarenal abdominal aortic aneurysm (AAA), stenosis of right common iliac artery. Postoperative CTA after endovascular aneurysm repair (EVAR)
Magnetic Resonance Angiography • MRA is a noninvasive and nonirradiating technique. • Its limitation is mainly due to the electromagnetic field, which creates the images but prohibits the use of this methodology on patients wearing pacemakers and other ferromagnetic foreign bodies. • As in ultrasound, “flow images” can be acquired without the use of contrast medium. • Use of non nephrotoxic intravenous contrast agent (gadolinium) enhances the MRA result. The bolus injection is done at a rate of 1.5–2 ml/s. • Enhanced MRA results in reduction of flow artefacts and enhanced image resolution. • Gadolinium-enhanced MRA has a reported sensitivity that ranges from 75% to 100% for assessment of extracranial carotid stenosis compared to conventional angiography. • MRA is used to image preoperative evaluation of endovascular aortic repair.
• The main limiting factor is low image resolution compared to CT. • MRA is used for imaging vessels of the lower extremity and visceral aortic branches (renal, mesenteric arteries). • For renal arteries MRA with contrast enhancement has a reported sensitivity of 96%. • With regard to the lower extremity vessel, MRA is a preoperative noninvasive tool mainly useful in planning peripheral intervention or surgery.
1.5.1.6 Conclusion Colour duplex imaging associated either with CT angiography or MR angiography allows, in most cases, conventional angiography to be avoided, which should be reserved for when there is a discrepancy between noninvasive imaging techniques or when an endovascular treatment is likely to be performed during the session.
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Fig. 1.5.2. Female 71 years, occlusion of a left femoro-popliteal by-pass, patency of a stent of the right superficial femoral artery (SFA)
1.5.2 Disease of Arteries Supplying the Brain 1.5.2.1 Introduction • Stroke represents the third leading cause of death in industrialized countries today. • Macro-angiopathies are responsible for nearly onethird of all ischaemic strokes. • In extracranial disease, the correct diagnosis of the degree of carotid stenosis in combination with clinical findings is the key to deciding whether patients require carotid endarterectomy. • Digital subtraction intra-arterial angiography (DSA) is mostly considered to be the gold standard but different noninvasive methods are giving quite comparable results [24].
1.5.2.2 Imaging Techniques • Visualizing the intracerebral circulation is also more and more accurately done by noninvasive techniques. • Three noninvasive approaches for visualizing the brain-supplying arteries will de discussed: the first based on Doppler ultrasound, the second based on magnetic resonance and finally the third based on computer tomography.
Doppler Ultrasound • High-resolution ultrasound combined with colourcoded Doppler flow analysis (Duplex sonography) has become a clinical tool of great value permitting bedside noninvasive diagnosis of the extracranial and intracranial vessel pathology.
1.5.2 Disease of Arteries Supplying the Brain
Fig. 1.5.3. Male 74 years, asymptomatic stenosis of the right internal carotid artery (ICA). Velocity criteria correspond to a stenosis of 70–80%
• The accuracy of the description of the degree of carotid stenosis has been demonstrated in several studies. • Each neurosonology laboratory uses several standardized criteria which are refined according to the technical advances in Doppler ultrasound techniques combined with regular auto-evaluation. • Velocity criteria [2], pre- and post-stenotic Doppler spectrum and collateral flow allow the best evaluation of the degree of stenosis. • The detection of a floating thrombus and some characterization of the atheromatous plaque consistency is also used in evaluating the degree of instability of the arterial lesion. • Microembolic signals (HITS) in the post-stenotic flow also permit the prediction of stroke risk in high-grade stenosis.
• Recently, echocontrast agents have been shown to improve Doppler ultrasound image quality, permitting a better diagnosis of pseudo-occlusions and intracranial vessel disease [8]. • Doppler ultrasound techniques have the advantage that they can be repeated easily and even allow continuous monitoring of the acute stroke patient [7]. • Transcranial Doppler can also be applied during carotid surgery to help decide whether a shunt should be placed and verify its patency.
Magnetic Resonance Angiography • The first MR angiographic images were 2D and 3D time-of-flight (TOF) and had a low accuracy because of the tendency to often overestimate the lesion.
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Fig. 1.5.4. MR angiography of the same patient as in Fig. 1.5.2. Eighty percent stenosis of the ostium of the right ICA. Reconstruction of the Circle of Willis demonstrating an absence of the segment A1 of the left anterior cerebral artery
• More recently, 3D contrast-enhanced MR angiography increased confidence in MRA and shows a good correlation with conventional DSA for extracranial and intracranial vessels. • MR imaging also permits the brain parenchyma to be visualized and thus shows the extent of the associated vascular lesions. • MR diffusion imaging techniques are a unique window to see, very early after stroke, the cytotoxic oedema provoked by an ischaemic injury. • MRA combined with MR diffusion and MR perfusion imaging has the advantage of giving the clinician a comprehensive analysis of the stroke in evolution and hints at its aetiology.
Computed Tomographic Angiography • Spiral CT angiography has demonstrated its clinical effectiveness in the assessment of narrowing of the lumen of the extracranial carotid artery bifurcation and is even more accurate than conventional CT angiography. • CT also permits extra- and intracranial vessels to be analysed as well as the brain parenchyma. Perfusion mapping is feasible and allows one to accurately determine the brain tissue at risk in acute stroke. • The practical advantages of CT imaging are the short scanning times with fewer motion artefacts, the easier handling of agitated and unstable stroke patients and the wide availability of CT machines.
1.5.3 Diseases of the Venous Circulation
Fig. 1.5.5. CT angiography of the same patient. Confirmation of a high-grade calcified stenosis of the right ICA
1.5.2.3 Conclusion • Doppler ultrasound, MRA and CTA all show similar accuracy in the diagnosis of occlusive diseases of the brain-supplying arteries [21]. • No noninvasive technique on its own is accurate enough to replace DSA. Especially in carotid stenosis, the combination of two techniques, with the addition of a third if the first two disagree, appears to be the best approach. Thus, invasive DSA before carotid endarterectomy can be avoided in the majority of patients. • For intracranial imaging, combined MRA and CTA is equal to the accuracy of DSA in most cases [12]. • Transcranial Doppler ultrasound is a bedside procedure, is easy to perform, and allows monitoring of brain haemodynamics, detection of microemboli as well as evaluation of collateral flow and may even enhance vessel reopening during thrombolysis [1].
1.5.3 Diseases of the Venous Circulation 1.5.3.1 Introduction • Venous problems are common. • They include chronic venous insufficiency and acute deep venous thrombosis. • Chronic venous insufficiency refers to both superficial varicosities and postphlebitic syndrome.
1.5.3.2 Chronic Venous Insufficiency Investigations When special tests with instruments have not satisfactorily explained the nature of the venous disorder, the following techniques for studying the vein can be used.
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Fig. 1.5.6. Female 21 years, symptomatic chronic venous insufficiency of the left leg. Duplex ultrasound demonstrates normal respiratory movements on the right side and absence of reflux after blocking respiration. Normal photoplethysmography (red curve). On the left side, prolonged reflux after Valsalva, short venous filling time
Photoplethysmography
• By this method the number of red cells is estimated in the skin capillary bed using a photoelectrical transducer. • The signals are recorded as a line tracing on a chart recorder or a computerized display. • It has been shown that the degree of congestion of red cells in skin capillaries bears a close relationship to the venous pressure in the limb, and thus the signal from the photoplethysmograph closely parallels the venous pressure changes. • With exercise, in an upright position, the venous pressure within the limb generally falls, and it takes at least 20 s before the original pressure is regained (venous refilling time: VRT). • In states of superficial or deep vein valvular incompetence the refilling time may be decisively shortened by reflux of venous blood down the limb.
• A diminished refilling time demonstrates incompetent venous valves, but cannot differentiate whether this incompetence is within the superficial or deep venous system. Two successive recordings may be done, with and without saphenous occlusion, by finger or cuff pressure. • If RFT is corrected after saphenous occlusion, this means that incompetence is due to the superficial system. Placing the cuff successively over the thigh and the calf may make the same comparison. This differentiates between incompetence of the short and long saphenous veins.
Volume Plethysmography
• The limb volume closely parallels the venous pressure so that when the patient is standing still it is maximal but afterwards, when blood has been expelled from the limb, both venous pressure and limb volume will fall.
1.5.3 Diseases of the Venous Circulation
• The time taken for the volume to return to its original value is a good indication of valve competence. With fully competent valves, this will be at least 20 s, but when superficial or deep vein incompetence is present this will be shortened according to the severity of condition.
predictive values. Even if ascending venography has been described as the gold standard for the diagnosis of DVT, Duplex ultrasonography has become the method of choice, combined with plasma D-dimer assay.
Investigations Doppler Flowmeter
Duplex Scanning
• According to the direction and speed of movement of red cells, there is a Doppler shift in the phase of the signal which is recognized by the machine and made apparent. • Only speed and direction are represented by the signal, not the volume. • Abnormal flow in direction indicates that the valves are incompetent or absent. • The probe is placed over the vein to be examined while the patient is standing and the response to coughing, to calf compression, to exercise and to an occluded saphenous (long or short) vein is studied.
• Duplex scanning is a practical method of assessing blood flow in veins and valve cusp movements. • It can differentiate between acute and chronic thrombosis. • All the major deep veins of the lower limb can be assessed. • The technique is less accurate for the small veins of the calf and cannot demonstrate the presence of thrombi in these small veins. However, in many cases this depends on the ability and the experience of the technician. • The vein is scanned in transverse and sagittal planes. • The presence of thrombosis is evaluated by the compressibility of the vein. • In addition, a vein without thrombus should show Doppler evidence of flow, variation with respiration and increase when distal veins are compressed. • Recent thrombi tend to be anechoic and only later will show characteristic internal echoes.
Ultrasonography
• Ultrasonography provides a much more sophisticated demonstration by giving an image of veins and their valves on a display screen. It will show the movement in these structures and also the direction and speed of blood flow within them. • The vein walls and lumen can be outlined and studied, clot may be recognized by absence of flow and immobile vein walls, and the structure of valves and their competence can be scrutinized. • The anatomy of veins can be visualized preoperatively. Individual deep veins and their branches can be distinguished and their flow pattern displayed, so that, for instance, incompetence in gastrocnemius vein can be recognized and the reflux within it estimated to assess its significance. In the popliteal vein this will indicate the effectiveness of the musculovenous pump below the knee or, conversely, the severity of reflux in the deep veins at that level.
Volume Plethysmography
• Pulse volume recorders are used to assess venous outflow. • Two components of the curves are used: first, the circumference changes after the inflation of the cuff; second, the downslope of the curve after immediate deflation. • In the case of thrombosis, the downslope will be slow. • For calculation, two values are used: the maximum increase in calf volume and the maximum venous outflow during the first second after deflation of the cuff. • Both of these values are decreased in patients with DVT [4].
1.5.3.3 Deep Vein Thrombosis 1.5.3.4 Conclusion • The clinical diagnosis of deep vein thrombosis (DVT) is unreliable in more than 50% of cases, and, in recent years, plasma D-dimer assays have been used to predict the presence of DVT with high sensitivity and negative
Duplex scanning of the superficial and deep veins is the preferred imaging technique to asses venous disorders of the legs.
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References 1. Alexandrov AV, Molina CA, Grotta JC, Garami Z, Ford SR, Alvarez-Sabin J, Montaner J, Saqqur M, Demchuk AM, Moyé LA, Hill MD, Wojner AW, the CLOTBUST Investigators (2004) Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N Engl J Med 351:2170–2178 2. Archie JP Jr, Ranke C, Trappe H-J, Creutzig A, Becker H (1999) Standardization of carotid ultrasound. Stroke 30:402–406 3. Baker JD, Dix DE (1981) Variability of Doppler ankle pressures with arterial occlusive disease: an evaluation of ankle index and brachial-ankle pressure gradient. Surgery 89:134–137 4. Barnes RW, Collicot RE, Mozerski DI et al (1973) Noninvasive quantitation of venous reflux in postphlebitic syndrome. Surg Gynecol Obstet 136:769–773 5. Bunt TJ, Holloway GA (1996) TcPO2 as an accurate predictor of therapy in limb salvage. Ann Vasc Surg 10:224–227 6. Cassilas JM, Becker F, Roux J, Raup JC, Didier JP (1985) TCPO2 et viabilité du moignon d’amputaion. J Mal Vasc 10:71–72 7. Chernyshev OY, Garami Z, Calleja S, Soon J, Campbell MS, Noser EA, Shaltoni H, Chen C-I, Iguchi Y, Grotta JC, Alexandrov AV (2005) Yield and accuracy of urgent combined carotid/transcranial ultrasound testing in acute cerebral ischemia. Stroke 36:32–37 8. Droste DW, Metz RJ (2004) Clinical utility of echocontrast agents in neurosonology. Neurol Res 26:754–759 9. Feigelson HS, Criqui MH, Fronek A, Langer RD, Molgaard CA (1994) Screening for peripheral arterial disease: the sensitivity, specificity, and predictive value of noninvasive tests in a defined population. Am J Epidemiol 140:526–534 10. Fox MJ, Tripolitis A, Kirby S (1977) A comparison of reactive hyperemic test with a standard exercise test in the evaluation of peripheral vascular disease. Br J Surg 64:290 11. Gahtan V (1998) The noninvasive vascular laboratory. Surg Clin North Am 78:507–518 12. Hirai T, Korogi Y, Ono K, Nagano M, Maruoka K, Uemura S, Takahashi M (2002) Prospective evaluation of suspected stenoocclusive disease of the intracranial artery: combined MR angiography and CT angiography compared with digital subtraction angiography. Am J Neuroradiol 23:93–101 13. Jamieson CW (1982) The definition of critical limb ischaemia of the limb. Br J Surg 69 [Suppl]:S1 14. Johnson WC (1975) Doppler ankle pressure and reactive hyperemia in the diagnosis of arterial insufficiency. J Surg Res 18:177–180
15. Kohler TR, Nance DR, Cramer MM, Vandenburghe N, Strandness DE Jr (1987) Duplex scanning for diagnosis of aortoiliac and femoropopliteal disease: a prospective study. Circulation 6:460–469 16. Kohler TR, Nicholls SC, Zierler RE, Beach KW, Schubart PJ, Strandness DE Jr (1987) Assessment of pressure gradient by Doppler ultrasound: experimental and clinical observations. J Vasc Surg 6:460–469 17. Kohler TR, Andros G, Porter JM et al (1990) Can duplex scanning replace arteriography for lower extremity arterial disease? Ann Vasc Surg 4:280–287 18. Langsfeld M, Nepute J, Hershey FB et al (1988) The use of deep duplex scanning to predict hemodynamically significant aortoiliac stenoses. J Vasc Surg 7:395–399 19. Lezack JD, Carter SA (1970) Systolic pressures in the extremities of man with special reference to the toes. Can J Physiol Pharmacol 48:469–474 20. Moneta GL, Yeager RA, Antonovic R, Hall LD, Caster JD, Cummings CD et al (1992) Accuracy of arterial duplex mapping. J Vasc Surg 15:275–284 21. Nonent M, Serfaty J-M, Nighoghossian N, Rouhart F, Derex L, Rotaru C, Chirossel P, Guias B, Heautot J-F, Gouny P, Langella B, Buthion V, Jars I, Pachai C, Veyret C, Gauvrit JY, Lamure M, Douek PC for the CARMEDAS Study Group (2004) Concordance rate differences of 3 noninvasive imaging techniques to measure carotid stenosis in clinical routine practice: results of the CARMEDAS multicenter study. Stroke 35:682–686 22. Olsson AG, Ruhn G, Erikson U (1990) The effect of serum lipid regulation on the development of femoral atherosclerosis in hyperlipidaemia: a non-randomized controlled study. J Int Med 227:381–390 23. Ouriel K, McDonnell AE, Metz CE, Zarins CK (1982) Critical evaluation of stress testing in the diagnosis of peripheral vascular disease. Surgery 91:686–693 24. Patel SG, Collie DA, Wardlaw JM, Lewis SC, Wright AR, Gibson RJ, Sellar RJ (2002) Outcome, observer reliability, and patient preferences if CTA, MRA, or Doppler ultrasound were used, individually or together, instead of digital subtraction angiography before carotid endarterectomy. J Neurol Neurosurg Psychiatry 73:21–28 25. Pourcelot L (1982) L’examen doppler des vaisseaux périphériques. ACD Productions, Paris 26. Raines JK (1993) The pulse volume recorder in peripheral arterial disease. In: Bernstein EF (ed) Non-invasive diagnostic techniques in vascular disease. Mosby, St Louis, pp 534–543
References
27. Ramsey DE, Manke DA, Sumner DS (1983) Toe blood pressure. A valuable adjunct to ankle pressure measurement for assessing peripheral arterial disease. J Cardiovasc Surg (Torino) 24:43–48 28. Rittenhouse EA, Maixner W, Burr JW, Barnes RW et al (1976) Directional arterial flow velocity: a sensitive index of changes in peripheral vascular resistance. Surgery 79:350–355 29. Rutherford RB (1986) Suggested standards for reports dealing with lower extremity ischemia. Prepared by the Ad Hoc Committee on Reporting Standards, Society for Vascular Surgery/North American Chapter, International Society for Cardiovascular Surgery. J Vasc Surg 4:80–94 30. Rutherford RB (1997) Recommended standards for reports dealing with lower extremity ischemia: revised version. Prepared by the Ad Hoc Committee on Reporting Standards, Society for Vascular Surgery/North American Chapter, International Society for Cardiovascular Surgery. J Vasc Surg 26:517–538 31. Rutherford RB, Lowenstein DH, Klein MF (1979) Combining segmental systolic pressures and plethysmography to diagnose arterial disease of the legs. Am J Surg 138:211–218 32. Strandness DE Jr, Bell JW (1965) Peripheral vascular disease: diagnosis and objective evaluation using a mercury strain gauge. Ann Surg Suppl 161::3–35
33. TransAtlantic Inter-Society Consensus (TASC) (2000) Management of peripheral arterial disease (PAD), investigation of patients with intermittent claudication. J Vasc Surg 31(Part 2):S62–S72 34. TransAtlantic Inter-Society Consensus (TASC) (2000) Management of peripheral arterial disease (PAD), investigations for critical limb ischemia. J Vasc Surg 31(Part 2):S178–S183 35. Ubbink DT, Tulevski II, den Hartog D, Koelemay MJ, Legemate DA, Jacobs MJ (1997) The value of non-invasive techniques for the assessment of critical limb ischaemia. Eur J Vasc Endovasc Surg 13:296–300 36. Ubbink DT, Spincemaille GH, Reneman RS, Jacobs MJ (1999) Prediction of imminent amputation in patients with non-reconstructible leg ischemia by means of microcirculatory investigations. J Vasc Surg 30:114–121 37. Ubbink DT, Gersbach PA, Berg P, Amann W, Gamain J (2003) The best TcpO2 parameters to predict the efficacy of spinal cord stimulation to improve limb salvage in patients with inoperable critical limb ischemia. Int Angiol 22:356–363 38. Wilbur BG, Olcott C (1978) A comparison of three modes of stress on Doppler ankle pressures. In: Dietrich EB (ed) Non-invasive cardiovascular diagnosis: current concepts. University Park Press, Baltimore 39. Yao JS, Flinn WR, Bergan JJ (1984) Noninvasive vascular diagnostic testing: techniques and clinical applications. Prog Cardiovasc Dis 26:459–494
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1.6 Invasive Diagnosis of Vascular Diseases Luís Mendes Pedro and José Fernandes e Fernandes
1.6.1 Introduction Angiography is the most used invasive technique to study vascular disorders. It consists of the introduction of iodinated contrast material into the vascular system, through percutaneous direct injection or catheterization of the vessels, allowing its visualization by X-rays. It followed the discovery by Roentgen of the capability of using radiation to visualize the bodily structures. The first “in vivo” angiogram was obtained in 1927 by the Portuguese neurologist Egas Moniz (Fig. 1.6.1a), through direct injection following surgical exposure of the common carotid artery. The original discovery was immediately adapted by Reynaldo dos Santos (Fig. 1.6.1b) to study the peripheral arterial circulation by direct injection into the abdominal aorta [22]. Major technical developments since the 1950s have improved the safety and utilization of this technique for the entire vasculature, such that angiography is now the gold standard method for studying vascular diseases and planning conventional surgical treatment, and is the basic and fundamental tool for new endovascular interventions. Arteriography comprises visualization of the arterial system and, despite the development of new noninvasive technologies for diagnosis of arterial diseases, it continues to be used not only for confirmation of the diagnosis, but as the first step of modern therapeutic intervention. The visualization of the venous system is called phlebography, and it was also initiated in Lisbon in 1933, by João Cid dos Santos (Fig. 1.6.1c); following the introduction of new noninvasive imaging technologies its use became very selective and new interest in it was regained with the introduction of new modalities of endovascular treatment for some venous disorders [4]. Lymphography was started in Porto in 1931 by Hernâni Monteiro, an anatomist, to study the lymphatic system “in vivo”, but it was the contribution of Kinmonth [14], with direct injection of a liposoluble radio-opaque
contrast, that promoted its clinical utilization to study lymphatic disorders. Its practical use declined and is restricted to the study and treatment of lymphoedemas in selected centres.
1.6.2 History The first ex vivo angiogram was obtained in 1896 by Haschek and Lindenthal [10] by injecting contrast in the arteries of an amputated upper limb. In 1923 Berberich and Hirsch [1] reported the first experimental in vivo human angiograms using radio-opaque contrast and in the following year Barney Brooks [2] conceived a potential clinical use for this procedure to determine the amputation level by injecting the lower limb arteries with sodium iodinated contrast. The discovery of angiography of the entire vascular system and the demonstration of its clinical relevance represents a major contribution made by Portugal to the medical sciences. The early experiences with X-rays to visualize the vessels stimulated Egas Moniz, a neurologist facing the clinical problem of diagnosing cerebral tumours, to conceive a technique of visualizing the arteries in the brain that would be displaced by a tumour, thus providing an objective method for its diagnosis. The first in vivo cerebral angiogram was performed in 1927 [19] by surgical exposure of the common carotid artery and intra-arterial injection of a sodium iodinated contrast. Its value as a major diagnostic tool to be used in several clinical settings was immediately recognized by Moniz and co-workers, who reported the first cases of in vivo internal carotid occlusion in patients with strokes [20]. The initial technique carried a higher incidence of contrast-related complications (2.6% of the 302 cases performed between 1927 and 1931) [29], leading to the use of torotrast as a radiological marker.
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Fig. 1.6.1a–c a First cerebral angiograph. b First translumbar aortograph. c João Cid dos Santos and the first phlebography
1.6.2 History
Fig. 1.6.2 Translumbar aortography
Modifications of the original technique were introduced and in 1936 Loman and Myerson [21] demonstrated the feasibility of cerebral arteriography by direct percutaneous injection into the common carotid artery. Demonstration of occlusive lesions in the cervical arteries by arteriography was a major development in the understanding of the importance of these lesions in both intra- and extracranial vessels in the pathogenesis of stroke. Reynaldo dos Santos in 1929 conceived the application of the Moniz technique to the study of lower limb arterial circulation by direct injection into the abdominal aorta via the translumbar approach, starting a new era for the comprehension of the role of occlusive lesions in the arterial system of the lower limbs in the pathogenesis of gangrene [22] (Fig. 1.6.1b). Modern arteriography followed the development of new methods for distant contrast injection as proposed
by Loman and Myerson (1936), Fariñas (1941) and Radner (1948). These contributions led to the method of percutaneous retrograde catheterization described by Sven-Ivar Seldinger [27] in 1953, through the common femoral artery, which became the standard arteriographic technique. Other arteries were used as entry points into the arterial system, such as the axillary, brachial and popliteal arteries. The association of computer technology with angiographic equipment enabled new digital subtraction techniques, leading to great improvements in image quality and safety of the procedure. Visualization of the veins in a cadaveric arm was first reported by Berberich and Hirsch [1] in 1923, but the first in vivo phlebogram was obtained by J. Cid dos Santos in 1933, by direct exposure and injection of the long saphenous vein (Fig. 1.6.1c). The technique was modified subsequently with percutaneous vein puncture to inject the
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contrast material, and several techniques were described using direct free-flow ascending visualization and descending techniques with retrograde filling of the venous system to study valvular function [16, 27].
garded in modern vascular practice as the first step of surgical or interventional treatment. • Therefore, arteriography should only be indicated when aggressive treatment is planned or if there is disagreement between clinical and noninvasive evaluation.
1.6.3 Arteriography Translumbar Aortography 1.6.3.1 Techniques Arteriography • Arteriography provides detailed visualization of the arterial segments and is an essential tool for planning revascularization by conventional or endovascular techniques. • Noninvasive technology combining new vascular imaging modalities with flow assessment has reduced the diagnostic importance of arteriography, which is re-
Fig. 1.6.3 Lower limb arteriography by direct femoral access
• Translumbar aortography (Fig. 1.6.2) was the first technique available. It is performed with the patient lying ventrally. • Under local anaesthesia percutaneous insertion of a long needle is performed aimed at the second or third lumbar vertebra and then shifted anteriorly to enter the lateral aspect of the aorta. • It provided good visualization of the aorto-iliac segment. • For the femoral and crural arteries successive pictures were obtained during a 50–70 ml injection of contrast. • Visualization of the distal arteries was poor, and required a complementary study by femoral percutaneous injection to obtain adequate information, particularly in patients with critical limb ischaemia and diabetes, where patency of crural and foot vessels may be of paramount importance to promote a limb-saving revascularization (Fig. 1.6.3). • The limitations of translumbar aortography related mainly to the discomfort of the patient, failure to obtain a clear visualization of the visceral vessels (which required more proximal puncture of the aorta with increased risk of iatrogenic lesions), risk of aortic and/or visceral arterial dissection (a rare but serious complication) and retroperitoneal haematoma, usually selfcontained and limited. • Popliteal arteriography can also be obtained by percutaneous puncture in the popliteal fossa under Duplex-scan guidance or contrast visualization obtained by injection elsewhere in the arterial system using a mobile radiological table. • Arteriography can still be required for the study of tumour vascularization and adequate planning of surgical resection. • Pain and moderate discomfort can be associated with contrast injection, but the new nonionic agents are much better tolerated, allowing the performance of arteriography under local anaesthesia and sedation.
1.6.3 Arteriography
• The major contraindications for arteriography are a history of previous severe allergic reaction to contrast media, pulmonary insufficiency and severe renal function impairment. • New low osmolarity contrasts are better tolerated with fewer gastrointestinal side-effects (nausea and vomiting) and cause fewer allergic reactions (although the risk of serious reactions may always be present). • Proper hydration of the patients and new pharmacological agents such as acetylcysteine seem to reduce the renal risk associated with arteriography.
• Interruption of anticoagulant treatment with warfarin at least for 48 h and normalization of INR. • Evaluation of renal and coagulation function. • Adequate control of arterial hypertension. • Absence of oral intake for 4 h before the exam. • Insertion of venous access. • Adequate hydration of the patient to promote maintained diuresis and reduce the risk of renal impairment. • Light sedation with benzodiazepines. • Correct selection of entry point according to pulse amplitude, presence of arterial disease and previous arteriograms.
Contrast Media [3, 8, 9] • The contrast media that are in use contain iodine; they vary according to the quantity of iodine and its osmolarity. • They are divided into two main groups: high osmolarity (ionic contrasts) and low osmolarity (ionic or nonionic contrasts). The amount of iodine is a major contributor to its global osmolarity. • Low osmolarity contrasts are better tolerated, with less severe gastrointestinal reactions (nausea and vomiting) and fewer allergic reactions. However, they are more expensive. • On the other hand, nonionic contrasts are less painful when injected in the peripheral circulation, being the preferred choice for limb arteriography. • Usually, the use of low osmolarity contrast media in cerebral arteriography is recommended during endovascular procedures in patients with a previous history of allergies and/or asthma, heart failure, pulmonary hypertension or a previous history of allergy to the contrast media, as well as in old patients and in those with known renal dysfunction.
1.6.3.2 Pre-procedure Evaluation and Preparation The indications for arteriography should be carefully evaluated and previous imaging studies should be reviewed. Medical history of the patient should also be complete, including history of allergic reactions and coagulation disorders. Proper management before arteriography requires the following steps: • Discontinuation of oral antidiabetic treatment replaced by rapid action insulin, until resumption of oral feeding.
1.6.3.3 Technique Vascular Access The choice of the site for access to the arterial system is an essential step for a successful arteriogram. It should facilitate good access to the area under study and ideally the arterial pulse should be normal, to exclude significant proximal occlusive disease. The most common access site is the femoral artery but in selected cases a brachial, radial, popliteal or even translumbar technique must be used. With the exception of the translumbar approach, arterial access is based on the Seldinger technique.
Seldinger Technique
• The skin and perivascular tissues are infiltrated with a local anaesthetic (10 ml lidocaine 20%) and a small (1 mm) incision is performed. • A needle is inserted at an angle of 45° until the blood comes out and an introduction guidewire is passed and the needle removed. • The introducer sheath and dilator is then inserted over the guidewire. • Finally, the dilator and the guidewire are removed and the sheath is flushed with heparinized solution. • This procedure should be performed meticulously to avoid dissection of the proximal arterial segment, which can lead to thrombosis. An alternative method to enter the artery is by transfixation puncture, access being obtained by the retrograde movement of the needle. This technique is associated with
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a higher rate of haemorrhagic complications, because of a double (anterior and posterior) arterial orifice. This method provides retrograde access to the arterial system using the femoral artery as the entry point, and, through selective catheterization of different arteries, allows adequate visualization of the iliac system, aorta, visceral abdominal aortic branches, supra-aortic trunks, upper limb and cerebrovascular arteries. Access to the arteries of the contralateral lower limb can be achieved by a cross-over technique at the aortic bifurcation (antegrade access in the contralateral limb) and is usually adequate to carry out interventional procedures.
have used this approach to monitor intra-sac pressure following endovascular treatment of abdominal aortic aneurysms and to identify type II endoleaks [7].
Upper Limb Access
When the femoral route cannot be used, access from the upper extremity, using the brachial or less frequently the radial artery, can be adequate. This approach can also be helpful for retrograde endovascular treatment of proximal subclavian stenosis.
Catheters Antegrade Femoral Access
• The antegrade femoral technique through the ipsilateral common or superficial femoral artery provides access, for diagnostic or endovascular purposes, to the femoro-popliteal and tibio-peroneal arterial segments. • It is obtained through an antegrade, flow-directed percutaneous approach proximal to the femoral pulse with orientation of the needle appropriate for entry into the common femoral artery. • Care should be taken to avoid dissection and to orientate the guidewire in the proper direction to the femoro-popliteal segment.
Translumbar Aortic Access
In selected cases of complete aortic occlusion or bilateral iliac occlusion and when upper limb access cannot be used, arteriography can be obtained through a direct aortic puncture using a suitable needle. • The patient has to be in ventral decubitus. • After skin infiltration with a local anaesthetic and a small incision is made, the needle is inserted with an angulation of 45° in a point located in the left dorsal region 7–10 cm lateral to the midline and 2–3 cm below the 12th rib. • The needle is advanced tangential to the vertebral body, the transmission of the aortic pulsation can be felt, and the aorta usually entered through its lateral wall. Translumbar aortography is rarely used, except for extensive occlusive disease when retrograde catheterization is either impossible or difficult. However, some authors
• The choice of the appropriate angiographic catheter is essential and it depends on the artery that has to be studied and the type of angiographic examination. • A large number of different catheters are available and the main differences are related to their length, calibre, tip configuration and location of distal holes (single terminal or multiple lateral).
1.6.3.4 Post-procedure Care After removal of the angiographic sheath it is important to follow some essential steps in order to prevent the occurrence of complications: 1. Adequate manual compression at the puncture site should be maintained until there is a clear haemostasis. 2. The patient should maintain bed rest for 4 h in the case of a 4F or 5F introducer sheath and for a longer period (8–12 h) if a larger introducer sheath had been used. 3. Close surveillance of the puncture site should be maintained. 4. Surveillance of vital signs and peripheral pulses. 5. Maintenance of adequate hydration usually using the intravenous access.
1.6.3.5 Complications • Complications related to angiography occur in 5–8% of cases but only 1–2% require treatment [11]. However, angiography can be associated with potential life-threatening complications in 0.05–0.1% of instances [6].
1.6.3 Arteriography
• Angiography-related complications may arise from arterial lesions at the access site and allergic (pseudoallergic?) reactions or may be related to direct toxicity of the contrast agent.
Access Site Complications • Complications related to the access site may occur in about 1.7% of cases when the femoral artery is used and in about 7% when the entry point is the brachial artery. • The most common complications are the formation of a haematoma or even a pseudo-aneurysm that can become apparent only days after the procedure. Haematomas are usually treated conservatively; small pseudo-aneurysms may thrombose spontaneously but frequently require surgical or ultrasound-guided compression with associated thrombin injection. • The insertion of the introducer sheath can cause local dissection of the arterial wall which can lead to arterial thrombosis or distal embolization. • The incidence of access site complications is higher in an endovascular intervention setting than in diagnostic procedures, because there is a need to use larger diameters for the introducers and guiding sheaths. • The incidence of complication is also higher when anticoagulant, antiplatelet and thrombolytic drugs are used during the procedure. • The prevention of haematoma and pseudo-aneurysm formation includes a strict control of arterial hypertension during and after the procedure, careful access site compression and bed rest for 4–6 h in diagnostic procedures and 8–12 h when larger sheaths have been used. • The use of access site occlusion devices seems to be associated with fewer complications and needs less resting time after the procedure. • The prevention of arterial dissection includes the utilization of strictly correct technical principles and fluoroscopic control during sheath, guidewire and catheter introduction.
Pseudo-Allergic Reactions • Anaphylactoid reactions are also called pseudo-allergic because they are histamine mediated and not related to antigen–antibody reactions [24].
• They are common and range from simple urticaria or bronchospasm to severe laryngeal oedema or shock. • They are independent of the dose of contrast used and are more common in patients with a history of asthma and previous contrast reactions. • In patients at risk prophylactic medication with antihistamine drugs and corticosteroids is indicated to reduce the frequency and severity of these allergic complications.
1.6.3.6 Direct Toxicity Gastrointestinal Reactions • The most common gastrointestinal reactions are nausea and vomiting, related to osmolarity, and seem to be less frequent when low osmolar contrasts are used.
Renal Function Impairment Impairment of renal function after contrast injection is not common after diagnostic angiography. It can be relevant if previously there has been any degree of renal failure, in aged or diabetic patients and when high volumes of contrast are used [13, 23, 25]. The occurrence or worsening of renal dysfunction after angiography can be prevented or limited by some measures that must be taken into account in every patient, with special emphasis in those at risk: 1. Adequate hydration of the patient. 2. Use of low osmolarity contrast. 3. Limitation of the amount of contrast used. 4. Active maintenance of diuresis during and after the procedure. 5. Oral administration of acetylcysteine 400–600 mg b.d. 2 days before the procedure [13].
Pain During Injection • Burning pain after arterial injection of contrast is common during aortic and lower limb angiographic procedures. • It involves gluteal and thigh regions in aortic injections and the leg and foot in femoral injections, where it is usually more severe.
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• The use of nonionic contrasts is associated with better tolerance and less pain during arteriography.
1.6.4 Phlebography • This became the most accurate method for evaluating lower limb veins and has been applied to patients with deep venous obstruction, post-thrombotic syndrome, superficial vein insufficiency as well as chronic deep venous reflux [15]. • The use of the new noninvasive imaging and flow assessment methods for the study of vascular diseases introduced in the 1980s provided adequate and reliable information for the diagnosis of venous disorders, reducing the scope of phlebography as a major diagnostic tool. • Its pitfalls were recognized, i.e. its invasive nature, the need to use contrast material and radiation exposure, and the publication of several reports of acute deep vein thrombosis associated with the contrast injection particularly in the lower limb veins. • As phlebography requires injection of iodinated material, the contrast-related complications are the same as described previously for arteriography. The same preventive measures should also be taken before the examination. • These reasons have led to a reduction in the number of phlebograms performed and its clinical indications have been reduced and limited to certain clinical situations where noninvasive information is inadequate, or in the presence of discrepancy between clinical and noninvasive evaluations, and prior to surgical or interventional treatment of the deep venous system.
1.6.4.1 Indications Current indications for the clinical use of phlebography are the following: • Atypical varicose veins the origin of which is not well documented by colour-flow Duplex scan. • Recurrent varicose veins without clear evidence of the sites of reflux by colour-flow Duplex scan. • Discrepancy between the clinical examination and the results of colour-flow Duplex scan. • Deep venous thrombosis with extension to the inferior vena cava when placement of a filter or other endovascular interventions may be considered.
• High clinical suspicion of deep venous thrombosis when noninvasive evaluation is doubtful or negative. • Planning of direct deep venous reconstructions such as venous crossover by-pass, venous valve transplantation or repair.
1.6.4.2 Techniques Ascending or Free-flow Phlebography • Ascending or free-flow phlebography is performed with the patient in the supine position; access is usually obtained through a dorsal vein of the foot and a tourniquet is applied at the ankle to block the superficial system thus directing the flow of contrast into the deep venous system. • An injection of 80 ml is often necessary to obtain adequate visualization of the entire deep venous system of the lower limbs, and its progression along the limb followed by fluoroscopy. • This allows the assessment of partial or complete obstruction of the deep venous system and the identification of sites of incompetence at different levels in the leg and thigh, and visualization of incompetent perforators.
Descending or Retrograde Phlebography • The main objective of this technique is the study of venous valve function and evaluation of venous reflux in both the deep and superficial venous system, and for detailed study of insufficiency at the sapheno-femoral and sapheno-popliteal junctions. • The initial technique of descending phlebography was through puncture of the femoral vein with the patient standing; it was developed subsequently by Cid dos Santos [18] to study sapheno-femoral incompetence and abnormal patterns of venous reflux in complex recurrent varicose veins. • It is performed with the patient in a 60° upright position using a tilting radiological table or with the patient in the standing position supported by a rigid frame. • The access is made by puncture of the common femoral vein, followed by cannulation using a standard Seldinger technique and a multiple side hole catheter inserted in the external iliac vein, to allow the injection of 40 ml iodinated contrast.
1.6.4 Phlebography
• Reflux of contrast is stimulated by a Valsalva manoeuvre in order to test the valve function and to diagnose deep system valvular incompetence and also deep to superficial reflux. • The extension of reflux into the deep system was classified according to its extension to the thigh and leg veins [26] and its clinical relevance seems to be associated with the involvement of popliteal and crural veins, the popliteal valve playing an essential protective role [28]. • Abnormal patterns of reflux in complex recurrences were clearly demonstrated by descending phlebography (Fig. 1.6.4) and this technique may be useful in pre-operative evaluation of varicose vein recurrences.
Popliteal phlebography was an additional descending technique promoted by Cid dos Santos and co-workers [5] to study the sapheno-popliteal junction and to diagnose abnormal patterns of reflux into the saphenous system. • With the patient standing, and supported by a frame, local anaesthesia was applied in the popliteal fossae and direct puncture of the popliteal vein obtained. • Injection of contrast initially during free-flow provided visualization of the superficial and common femoral vein; then, a Valsalva manoeuvre was performed to promote venous reflux and successive anterior and lateral pictures were obtained to visualize the popliteal and leg veins and assess the presence of abnormal venous reflux.
Fig. 1.6.4 Different phlebographic aspects of popliteal reflux (adapted from [30])
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• Initial clarification of the variability of the anatomy of the short saphenous vein and its junction in the deep system were achieved by this technique. • Incompetence of the gastrocnemius vein as a cause of varicose veins in the leg was recognized [17] and insufficiency of the Giacomini vein associated with short saphenous incompetence as a source of reflux into the long saphenous vein was clearly demonstrated. Popliteal and femoral descending phlebography provided the anatomical basis for the understanding of venous physiology and the “road-map” for the subsequent use of noninvasive imaging modalities such as colour-flow Duplex-scan evaluation. Its use in modern practice is very limited to the study of deep valvular incompetence to plan reconstructive venous surgery and for difficult situations of recurrence where the colour-flow Duplex scan has not provided clear demonstration of the source of reflux. Popliteal phlebography may still play a role in clarifying recurrences following short saphenous surgery to facilitate surgical planning. Its main goal was to determine the exact location of the sapheno-popliteal junction before surgery, an objective that can be obtained by carefully performed Duplex-scan evaluation or more easily and directly by table phlebography and direct injection of the short saphenous vein [12]. References 1. Berberich J, Hirsh S (1923) Roentgenography of blood vessels. Klin Wochenschr 2:2226–2228 2. Brooks B (1924) Intra-arterial injection of sodium iodide. J Am Med Assoc 82:1016–1019 3. Bush WH, Swanson DP (1991) Acute reactions to intravascular contrast media: types, risk factors, recognition, and specific treatment. AJR Am J Roentgenol 157:1153–1161 4. Cid dos Santos J (1938) La phlebographie directe. Conception technique, premiers resultats. J Int Chir 35:625–669 5. Cid dos Santos J (1973) Introduction anatome-phisiopathologique à la technique phlébographique. Phlebologie 26:359–360 6. Coley BD, Roberts AC, Fellmeth BD, Valji K, Bookstein JJ, Hye RJ (1995) Postangiographic femoral artery pseudoaneurysms: further experience with US-guided compression repair. Radiology 194:307–311 7. Dias NV, Ivancev K, Malina M, Hinnen JW, Visser M, Lindblad B, Sonesson B (2004) Direct intra-aneurysm sac pressure measurement using tip-pressure sensors: in vivo and in vitro evaluation. J Vasc Surg 40:711–716
8. Gomes AS, Lois JF, Baker JD, McGlade CT, Bunnell DH, Hartzman S (1989) Acute renal dysfunction in high-risk patients after angiography: comparison of ionic and nonionic contrast media. Radiology 170:65–68 9. Greenberger PA, Patterson R, Tapio CM (1985) Prophylaxis against repeated radiocontrast media reactions in 857 cases. Adverse experience with cimetidine and safety of beta-adrenergic antagonists. Arch Intern Med 145:2197–2200 10. Haschek E, Lindenthal O (1896) A contribution to the practical use of the photography according to Roentgen. Wien Klin 9:63–64 11. Hessel SJ, Adams DF, Abrams HL (1981) Complications of angiography. Radiology 138:273–281 12. Hobbs J (1980) Per-operative venography to ensure accurate sapheno-popliteal vein ligation. Br Med J 2:1578 13. Kay J, Chow WH, Chan TM, Lo SK, Kwok OH, Yip A, Fan K, Lee CH, Lam WF (2003) Acetylcysteine for prevention of acute deterioration of renal function following elective coronary angiography and intervention: a randomized controlled trial. J Am Med Assoc 289:553–558 14. Kinmonth JB (1952) Lymphangiography in man; a method of outlining lymphatic trunks at operation. Clin Sci (Lond) 11:13–20 15. Kistner RL, Kamida CB (1995) Update on phlebography and varicography. Dermatol Surg 21:71–76 16. Lea Thomas M, Treweeke PS (1987) The assessment of deep vein valve incompetence by ascending phlebography with a Valsalva manoeuvre: a comparison with descending phlebography. Vasa 16:274–277 17. Marques JS (1975) Varices of long saphenous system due to valvular insufficiency of short saphena’s cross. Folia Angiologica XXIII:135–144 18. Marques JS, Cid dos Santos J, Coito A (1970) Flebografia vertical directa. Progressos técnicos da prova popliteia. J Med 1406:5–19 19. Moniz E (1927) L’éncephalographie artérielle: son importance dans la localization des tumeurs cérébrales. Rev Neurol 2:172 20. Moniz E, Lima A, Lacerda R (1937) Hemiplegies par thrombose de la carotide interne. Presse Med 45:977 21. Pedro LM (2003) A window to atherosclerosis: high definition ultrasonography in the study of the arterial wall. University of Lisbon, Lisbon 22. Reynaldo dos Santos, Lamas A, Caldas JP (1931) L’arteriographie des membres et de láorte abdominale. Masson, Paris
References
23. Rihal CS, Textor SC, Grill DE, Berger PB, Ting HH, Best PJ, Singh M, Bell MR, Barsness GW, Mathew V, Garratt KN, Holmes DR Jr (2002) Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation 105:2259–2264 24. Routh WD (1995) Contrast angiography. In: Dean RH, Yao JS (eds) Current diagnosis and treatment in vascular surgery. Lange, Stamford 25. Rudnick MR, Berns JS, Cohen RM, Goldfarb S (1997) Contrast media-associated nephrotoxicity. Semin Nephrol 17:15–26 26. Rutherford RB, Padberg FT Jr, Comerota AJ, Kistner RL, Meissner MH, Moneta GL (2000) Venous severity scoring: an adjunct to venous outcome assessment. J Vasc Surg 31:1307–1312
27. Seldinger SI (1953) Catheter replacement of the needle in percutaneous arteriography. Acta Radiol 39:368–376 28. Shull KC, Nicolaides AN, Fernandes JF et al (1979) Significance of popliteal reflux in relation to ambulatory venous pressure and ulceration. Arch Surg 114:1304 29. Wickbom I (1948) Angiography of the carotid artery. Acta Radiol Supl LXXII:1–90 30. Diniz LT, Marques JS, Coito A, Pinto FO, Korn M (1979) A doença venosa dos membros inferiores. Bial, Porto
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1.7 Computer-Aided Diagnosis of Vascular Disease Spyretta Golemati, Konstantina S. Nikita
1.7.1 Introduction To diagnose vascular disease, physicians usually base their decision on clinical history and physical examination of the patient, as well as visual inspection of medical images. In some cases, confirmation of the diagnosis is particularly difficult because it requires specialization and experience, or even the application of interventional methodologies (e.g. arteriography). While advances in medical imaging technology have greatly contributed to early detection and diagnosis of vascular disease, the selection of patients to whom surgery is offered remains one of the most challenging tasks in the management of vascular disease. In medical imaging, the accurate diagnosis and/or assessment of a disease depends on both image acquisition and image interpretation. Modern imaging devices based on fundamental concepts in physical science (e.g. X-ray, magnetic resonance, nuclear physics and acoustics) and incorporating the latest innovations in computer technology and data processing techniques have proved extremely useful for early diagnosis of vascular disease. More recent advances in imaging technology include advanced imaging possibilities (3D reconstruction, functional imaging, magnetic resonance angiography, elastography), novel imaging techniques (e.g. virtual angioscopy) and registration of images obtained with different modalities. The image interpretation process, however, has only recently begun to benefit from computer technology. Interpretation of medical images, usually performed by radiologists, is often limited due to the nonsystematic search patterns of humans, the presence of structure noise (camouflaging normal anatomical background) in the image, and the presentation of complex disease states requiring the integration of vast amounts of image data and clinical information. Computer-aided diagnosis (CAD) – defined as a diagnosis made by a physician who uses the output from a computerized analysis of medical data as a “second opinion” in detecting lesions, assess-
ing disease severity and making diagnostic decisions – is expected to enhance the diagnostic capabilities of physicians and reduce the time required for accurate diagnosis. With CAD, the final diagnosis is made by the physician. Thus, the computer output needs to be at a sufficient level of sensitivity and specificity, and in addition the output must be displayed in a user-friendly format for effective and efficient use by the clinician. This chapter reviews the field of CAD in vascular imaging, including aspects of image processing and presents an example of an in-house-developed CAD system.
1.7.2 Computer-Aided Diagnosis in Vascular Imaging The main steps in the diagnosis process include lesion detection, characterization and assessment. Lesion detection refers to the definition of possible pathological structures from image data. Lesion characterization involves the assessment of the status of the lesion, e.g. the likelihood that the lesion, such as a plaque, is malignant (symptomatic). Features that characterize normal and pathological tissue may be extracted from medical images. These include measurements of the size and shape of regions of interest (ROIs) within the tissue, texture features [20] and elasticity indices estimated from sequences of images [15]. In the case of vascular disease, the location and size of the lesion, namely the atheromatous plaque, need to be determined in order to estimate the degree of stenosis. Additional plaque characteristics, including texture and motion features, are important to assess disease severity. Lesion assessment refers to assigning a lesion to a class of a predefined set of classes. Symptomatic or asymptomatic plaques would be candidate classes in the case of arterial wall disease. Currently, CAD systems are being developed to detect, characterize and potentially diagnose lesions on vascular images. Such systems may take the digital image data as
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input, process the data using computer vision and artificial intelligence techniques, and then output clinically relevant information, including locations of suspect lesions, characterizations of suspect lesions, estimates of the probabilities of malignancy of suspect lesions and/or numerical indices of risk of clinical symptoms. The typical structure of a CAD system includes the following procedures: • image pre-processing, • definition of regions of interest (ROIs), • extraction and selection of characteristic features, • classification.
1.7.2.1 Image Pre-processing To improve image quality, linear or nonlinear filters can be applied to the image. Image filtering is particularly important in the case of noisy images, such as ultrasound images. Histogram equalization is often used to enhance the appearance of ultrasound images. Histogram equalization modifies the dynamic range and contrast of an image by altering that image such that its intensity histogram has a desired shape [14].
development of computer vision methods requires a priori knowledge of the physical imaging properties of the digital image acquisition system and morphological information concerning the abnormal (e.g. atheromatous plaque) and normal tissue. Computer vision techniques usually include image processing (e.g. texture analysis, motion analysis) and feature extraction.
Texture Analysis Image texture may be defined as a function of the spatial variations in pixel intensity (grey values), which are generally due to some underlying physical variation in the sample. In medical image analysis, automatic extraction of texture features can be used for a variety of classification tasks, such as distinguishing normal from abnormal tissue or classifying different types of abnormal tissues. The most frequently used texture analysis techniques in medical imaging include: • First-order statistics • Second-order statistics • Neighbourhood grey tone difference matrix • Grey level difference statistics • Laws’ texture energy • Fractal dimension.
1.7.2.2 Definition of Regions of Interest – Automatic Segmentation First-order Statistics
Regions corresponding to suspect lesions (e.g. plaques) can be detected from medical images using either (1) manual and semi-automatic methodologies where the user interacts with the system in order to define a possible pathological region or (2) fully automated methodologies where suspect regions are detected with appropriate digital image processing techniques [4]. Several techniques for segmentation of arterial wall and plaques from images of various modalities have evolved recently. Examples include the segmentation of coronary plaques from intravascular ultrasound (IVUS) images [29], and the segmentation of carotid plaques from B-mode ultrasound using active contour models [24].
First-order statistics measure the likelihood of observing a grey value at a randomly chosen location in the image. First-order statistics can be computed from the histogram of pixel intensities in the image. These depend only on individual pixel values and not on the interaction or co-occurrence of neighbouring pixel values. A total of 16 first-order statistical features can be estimated from the normalized grey-level histogram of the selected region of the image, including minimal grey level, maximal grey level, median grey level, mean grey level, standard deviation of grey levels, coefficient of variation, grey level skewness, grey level kurtosis, grey level energy, grey level entropy, 10th percentile, 25th percentile, 50th percentile, 75th percentile, 90th percentile and histogram width.
1.7.2.3 Extraction and Selection of Characteristic Features
Second-order Statistics
Automatic extraction of features, which may or may not be visible to the human observer, from digital images is possible with the use of computer vision methods. The
Second-order statistics are defined as the likelihood of observing a pair of grey values occurring at endpoints of a dipole (or needle) of random length placed in the image at a random location and orientation. These are properties
1.7.2 Computer-Aided Diagnosis in Vascular Imaging
of pairs of pixels. Second-order statistics are derived from angular nearest-neighbour spatial-dependence matrices, also known as co-occurrence matrices [16]. The relative frequencies P(i, j, d, θ) with which two neighbouring pixels with grey levels i and j at a given distance d and orientation θ occur on the image are used to construct the cooccurrence matrices. A total of 14 textural measures can be estimated from the co-occurrence matrix, including angular second moment, contrast, correlation, variance, inverse difference moment, sum average, sum variance, sum entropy, entropy, difference variance, difference entropy, information measures of correlation (two features) and maximum correlation coefficient.
Neighbourhood Grey Tone Difference Matrix
For each ROI, information about spatial changes in intensity can be obtained by looking at the difference between each pixel and the grey tones of its surrounding neighbours. A one-dimensional (1D) matrix can be estimated for each ROI, in which the ith entry corresponds to the summation of the differences between the grey level of all pixels with grey level i, and the average grey level of their surrounding neighbours. The size of the neighbourhood depends on the selected distance, i.e. a distance equal to 1 results in a 3×3 neighbourhood. Five features are derived from this 1D matrix, namely coarseness, busyness, contrast, complexity and texture strength.
Grey Level Difference Statistics
First-order statistics of the local property values can be obtained using the grey level difference statistics method [32]. The computation of the local properties is based on the absolute difference between pairs of grey levels or of the average grey levels. For any given displacement δ=(Δx, Δy) the following four texture measures can be estimated: contrast, angular second moment, entropy and mean.
Laws’ Texture Energy
Laws’ texture energy measures [23] are derived from three simple vectors of length 3, L3 − − (1, 2, 1), E3 − − (–1, 0, 1) and S3 − (–1, 2, –1), which represent the 1D operations of centre-weighted local averaging, symmetric first differencing for edge detection, and second differencing for spot detection. If these vectors are convolved with themselves or with each other, five vectors of length 5 are obtained, L5 − − (1, 4, 6, 4, 1), S5 − − (–1, 0, 2, 2, –1), R5 − − (1, –4, 6, –4, 1), E5 − (–1, –2, 0, 2, 1) and W5 − (–1, 2, 0, –2, 1). If the col-
umn vectors of length 5 are multiplied by row vectors of the same length, then Laws’ 5×5 masks are obtained. To describe texture in an image using the obtained masks, the masks are convolved with the image and statistics (e.g. energy) of the results are used as texture properties.
Fractal Dimension
Many natural surfaces have a statistical quality of roughness and self-similarity at different scales. Fractals, first proposed by Mandelbrot [25], are very useful in modelling these properties in image processing. The definition of the fractal dimension is based on the concept of selfsimilarity. Given a bounded set A in a Euclidean n-space, the set A is said to be self-similar when A is the union of N distinct (nonoverlapping) copies of itself, each of which has been scaled down by a ratio of r. The fractal dimension D is related to the number N and the ratio r as follows: D = log N / log (1/r). The fractal dimension gives a measure of the roughness of a surface. For an image, the fractal dimension is a noninteger number between 2 and 3. Intuitively, the larger the fractal dimension, the rougher the texture. Image texture has been widely used to characterize biological tissue. In computer-aided diagnosis of vascular disease, the grey scale median (GSM), estimated from Bmode ultrasound images, was found to be significantly lower for symptomatic plaques [9, 30] and for high degrees of stenosis [9]. Echogenic plaques, defined as plaques with GSM > 50, were associated with a 9% incidence of ipsilateral brain CT infarction, whereas echolucent plaques, defined as plaques with GSM < 50, were associated with a 40% incidence of ipsilateral brain CT infarction [5]. The GSM was found to be lower for soft material (blood, lipid) and higher for fibrous tissue and calcific deposits [10, 22]. Furthermore, the mean pixel value (MPV) was found to decrease as the soft (fat and blood) content of the plaque increased, and to increase as the fibrocalcific tissue content increased [1, 26]. First-order statistics have been used to characterize texture in various areas of a typical B-mode ultrasound image of a diseased carotid artery (e.g. atheromatous plaque, blood and surrounding tissue) and were found to be significantly different for different areas [13]. Furthermore, symptomatic and asymptomatic atheromatous plaques have been characterized using the previously described texture analysis techniques [2, 8, 33]. In addition to this, analysis of image texture has been used to characterize coronary plaques from intravascular ultrasound images [31, 35]. These studies have shown
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that quantitative information extracted from ultrasound images can be useful in the diagnosis of atherosclerosis and enable decision-making about disease management. Estimates of tissue texture may be used in a number of studies, including: (1) modelling of the mechanical behaviour of normal and abnormal tissue, and (2) drug assessment. In combination with estimates of tissue strain obtained from motion analysis, texture information may be used to estimate the stresses exerted on tissue [34]. In studies of drug treatment assessment, it is assumed that texture may change after treatment with specific drugs [7], and thus, texture estimates may be used to evaluate the performance of drug treatment.
Motion Analysis Motion analysis from sequences of images allows the estimation of mechanical strain experienced by the tissue. In the case of arterial walls, strain is due to stresses caused by blood pressure, blood flow and tethering to surrounding tissue. To estimate motion, temporal sequences of images need to be recorded at high frame rates. The estimation of motion patterns of biological tissue may provide useful insight into the mechanical properties of different types of tissue. In particular, in the case of atherosclerosis, the analysis of plaque motion may provide new insight into plaque modelling as well as into mechanisms of plaque rupture with subsequent embolism. The following techniques can be used to analyse arterial wall and plaque motion from sequences of images: • Region tracking and block matching • Optical flow.
Region Tracking and Block Matching
The method is described in detail elsewhere [12]. Briefly, a ROI can be selected in the first frame of the sequence and its position is automatically tracked in subsequent frames. Automatic tracking is based on matching ROI pixel intensities in each frame with those in the first frame. Rectangular ROIs can be tracked if their co-ordinates and dimensions are given by the user or can be defined using the mouse. The result of the motion analysis consists of waveforms showing radial and axial displacements, velocities and accelerations of the selected ROIs as well as correlation coefficients. The difference waveforms for the radial and axial displacement can be used to analyse relative motion between selected sites. The vectors of
maximum displacements for each ROI can be displayed superimposed on the B-mode image.
Optical Flow
The calculation of the apparent velocity field, i.e. optical flow, relies on the estimation of the spatiotemporal changes in pixel intensities throughout an image sequence. An implementation of a validated motion estimation algorithm [17], using a minimization of sum-of-squared differences between images, was used in this work to estimate optical flow. Results of motion estimation between consecutive frames are propagated, i.e. vector end points are used as starting co-ordinates for the next frame evaluation. The final result is a dense vector map where each pixel is represented by a vector corresponding to its velocity between two frames. Motion of the carotid artery wall has been estimated from sequences of two-dimensional B-mode ultrasound images [12] as well as from ultrasound radiofrequency images [3]. Image speckle patterns were tracked between successive frames using the correlation coefficient as the matching criterion. The results showed expected cyclical motion in the radial direction and some axial movement of the arterial wall. Meairs and Hennerici [27] studied carotid plaque motion using 4D ultrasonography and optical flow. They expressed plaque surface motion in terms of two parameters: (1) maximal surface velocity (MSV) and (2) maximal discrepant surface velocity (MDSV), defined as the maximum of differences between maximal and minimal surface velocities of successive 3D frame volumes. Asymptomatic plaques showed a homogeneous orientation and magnitude of computed velocity vectors corresponding to a global pattern of arterial motion without evidence of inherent plaque movement. Symptomatic plaques showed signs of inherent plaque motion, irrespective of arterial wall motion.
1.7.2.4 Classification Classification is possible through artificial intelligence techniques, which can be used to merge the mathematical descriptors of the image features into a diagnostic output. The process is similar to the decision-making task of a physician who weighs up different aspects of vascular imaging findings. Many computer analysis methods involve the use of classifiers to distinguish between actual lesions and false-positive detections, or between malignant and benign lesions, including rule-based methods, discrimi-
1.7.2 Computer-Aided Diagnosis in Vascular Imaging
nant analysis, Bayesian methods, artificial neural networks and fuzzy logic [19]. The features for input to these classifiers are selected using a variety of computer techniques such as stepwise methods and genetic algorithms [21].
1.7.2.5 ANALYSIS: a Modular Software System to Support Diagnosis of Vascular Disease ANALYSIS is a CAD system designed and developed in the Biomedical Simulations and Imaging Laboratory, School of Electrical and Computer Engineering, National Technical University of Athens, Greece. The system incorporates the main parts of a typical CAD system and has been used to support the diagnosis of vascular disease (carotid atherosclerosis). ANALYSIS can be installed
Fig. 1.7.1 User interface of ANALYSIS
on PC-based platforms operating under the Microsoft Windows operating system. Minimum requirements in processor speed and RAM are 600 MHz and 256 MB, respectively. Using these minimum requirements, motion analysis of two ROIs using block-matching takes 20 min. The main user interface of ANALYSIS is shown in Fig. 1.7.1. The two main windows of the interface are designed to support motion and texture analysis. Tool buttons and menu bars allow the user to select the parameters of the analysis, e.g. the number of investigated ROIs, the size and shape of ROIs, the inter-pixel distance for the calculation of second-order statistics and neighbourhood grey tone difference matrix, etc. The system includes a friendly wizard for importing results files, which can be subsequently analysed using ANOVA statistics and clustered into predefined groups using fuzzy c-means.
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An important feature of ANALYSIS is the possibility of on-line tele-collaboration between health care professionals under a secure framework. The continuous advances in telecommunications allow exchange of information not only throughout but also beyond the hospital as well as real-time collaboration between remote users [6]. Thus, with the introduction of computer-aided diagnosis, a wide area of possible telematics applications for vascular disease can be identified. These include support of the diagnosis procedure [11, 28] and continuous medical education in arterial wall disease [28]. The collaborative environment of ANALYSIS extends the capabilities of the stand-alone CAD system, giving local and remote health care professionals the opportunity to co-operate for the delineation and image analysis of ROIs in ultrasound images. The implementation is based on a pointto-point communication scheme following the “What You See Is What I See” (WYSIWIS) paradigm. To support the collaborative environment, both asynchronous (off-line transfer of data sets) and synchronous (on-line collaboration) data exchange schemes are employed. The term “off-line” indicates the absence of user’s interaction with ANALYSIS and involves the transfer of large datasets. A sequence of B-mode ultrasound images after lossless compression requires 5–20 MB of storage depending on the number of images.
1.7.3 Conclusion CAD systems are expected to be useful tools in the diagnosis of vascular disease, because they can assist the interpretation of vascular images through a user-friendly interface. Their ultimate acceptance in clinical practice will depend not only on the performance of the computerized method alone, but also on how well the clinician performs the task when the computer output is used as an aid and on the ability to integrate the computerized analysis method into routine clinical practice [18]. Issues such as a friendly user-interface, a short system response time and low cost are critical for the daily routine use of CAD systems. References 1. Aly S, Bishop CC (2000) An objective characterization of atherosclerotic lesion. Stroke 31:1921–1924
2. Asvestas P, Golemati S, Matsopoulos GK, Nikita KS, Nicolaides AN (2002) Fractal dimension estimation of carotid atherosclerotic plaques from B-mode ultrasound: a pilot study. Ultrasound Med Biol 28:1129–1136 3. Bang J, Dahl T, Bruinsma A, Kaspersen JH, Hernes TAN, Myhre HO (2003) A new method for analysis of motion of carotid plaques from rf ultrasound images. Ultrasound Med Biol 29:967–976 4. Bankman I (2000) Handbook of medical imaging: processing and analysis. Academic Press, San Diego 5. Biasi GM, Sampaolo A, Mingazzini P, De Amicis P, El-Barghouty N, Nicolaides AN (1999) Computer analysis of ultrasonic plaque echolucency in identifying high risk carotid bifurcation lesions. Eur J Vasc Endovasc Surg 17:476–479 6. Caramella D, Reponen J, Fabbrini F, Bartolozzi C (2000) Teleradiology in Europe. Eur J Radiol 33:2–7 7. Cesarone MR, Belcaro G, Nicolaides AN, Geroulakos G, Bucci M, Dugall M, DeSanctis MT, Incandela L, Griffin M, Sabetai M (2001) Increase in echogenicity of echolucent carotid plaques after treatment with total triterpenic fraction of Centella asiatica: a prospective, placebo-controlled, randomized trial. Angiology 52 [Suppl 2]:S19–S25 8. Christodoulou CI, Pattichis CS, Pantziaris M, Nicolaides A (2003) Texture-based classification of atherosclerotic carotid plaques. IEEE Trans Med Imaging 22:902–912 9. Elatrozy T, Nicolaides A, Tegos T, Griffin M (1998) The objective characterisation of ultrasonic carotid plaque features. Eur J Vasc Endovasc Surg 16:223–230 10. El-Barghouty NM, Levine T, Ladva S, Flanagan A, Nicolaides AN (1996) Histological verification of computerized carotid plaque characterization. Eur J Vasc Endovasc Surg 11:414–416 11. Endean ED, Mallon LI, Minion DJ, Kwolek CJ, Schwarcz TH (2001) Telemedicine in vascular surgery: does it work? Am Surg 67:334–340 12. Golemati S, Sassano A, Lever MJ, Bharath AA, Dhanjil S, Nicolaides AN (2003) Carotid artery wall motion estimated from B-mode ultrasound using region tracking and blockmatching. Ultrasound Med Biol 29:387–399 13. Golemati S, Tegos TJ, Sassano A, Nikita KS, Nicolaides AN (2004) Echogenicity of b-mode sonographic images of the carotid artery – work-in-progress. J Ultrasound Med 23:659–669 14. Gonzalez RC, Woods RE (1993) Digital image processing. Addison-Wesley, New York 15. Greenleaf JF, Fatemi M, Insana M (2003) Selected methods for imaging elastic properties of biological tissues. Annu Rev Biomed Eng 5:57–78
References
16. Haralick RM, Shanmugam K, Dinstein I (1973) Textural features for image classification. IEEE Trans Syst Man Cybern SMC:610–621 17. Horn BKP, Schunck BG (1981) Determining optical flow. Artificial Intelligence 17:185–203 18. Hunt D, Haynes RB, Hanna S, Smith K (1998) Effects of computer-based clinical decision support systems on physician performance and patient outcomes. J Am Med Assoc 280:1339–1346 19. Jain AK, Duin RPW, Jianchang M (2000) Statistical pattern recognition: a review. IEEE Trans Pattern Anal Machine Intell 22:4–37 20. Kerut EK, Given M, Giles TD (2003) Review of methods for texture analysis of myocardium from echocardiographic images: a means of tissue characterization. Echocardiography 20:727–736 21. Kupinski MA, Giger ML (1999) Feature selection with limited datasets. Med Phys 26:2176–2182 22. Lal BK, Hobson RW, Pappas PJ et al (2002) Pixel distribution analysis of B-mode ultrasound scan images predicts histologic features of atherosclerotic carotid plaques. J Vasc Surg 35:1210–1217 23. Laws KI (1980) Rapid texture identification. Proc SPIE Conf Missile Guidance 238:376–380 24. Loizou CP, Pattichis CS, Istepanian RSH, Pantziaris M, Nicolaides AN (2004) Atherosclerotic carotid plaque segmentation. In: Proceedings of the 26th Annual International Conference of the IEEE EMBS, pp 1403–1406 25. Mandelbrot BB, Van Ness JW (1968) Fractional Brownian motion, fractional noises and applications. SIAM Rev 10:422–438 26. Mazzone AM, Urbani MP, Picano E et al (1995) In vivo ultrasonic parametric imaging of carotid atherosclerotic plaque by videodensitometric technique. Angiology 46:663–672
27. Meairs S, Hennerici M (1999) Four-dimensional ultrasonographic characterization of plaque surface motion in patients with symptomatic and asymptomatic carotid artery stenosis. Stroke 30:1807–1813 28. Ricci MA, Knight SJ, Nutter B, Callas PW (1998) Desktop telemedicine in vascular surgery: some preliminary findings. Telemed J 4:279–285 29. Sonka M, McKay CR, von Birgelen C (1997) Computer analysis of intravascular ultrasound images. In: Leondes CT (ed.) Medical imaging techniques and applications. Gordon and Breach, Amsterdam, pp 183–226 30. Tegos TJ, Stavropoulos P, Sabetai MM, Khodabakhsh P, Sassano A, Nicolaides AN (2001) Determinants of carotid plaque instability: echoicity versus heterogeneity. Eur J Vasc Endovasc Surg 22:22–30 31. Vince DG, Dixon KJ, Cothren RM, Cornhill JF (2000) Comparison of texture analysis methods for the characterization of coronary plaques in intravascular ultrasound images. Comput Med Imag Grap 24:221–229 32. Weszka JS, Dyer CR, Rosenfeld A (1976) A comparative study of texture measures for terrain classification. IEEE Trans Syst Man Cyber SMC 6:269–285 33. Wilhjelm JE, Grønholdt MLM, Wiebe B, Jespersen SK, Hansen LK, Sillesen H (1998) Quantitative analysis of ultrasound B-mode images of carotid atherosclerotic plaque: correlation with visual classification and histological examination. IEEE Trans Med Imaging 17:910–922 34. Zhao SZ, Xu XY, Collins MW (1998) The numerical analysis of fluid-solid interactions for blood flow in arterial structures. Part 1: A review of models for arterial wall behaviour. Proc Inst Mech Eng [H] 212:229–240 35. Zhang X, McKay CR, Sonka M (1998) Tissue characterization in intravascular ultrasound images. IEEE Trans Med Imaging 17:889–899
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1.8 Preoperative Evaluation of a Vascular Patient Michael Horrocks, James Metcalfe
1.8.1 Introduction The purpose of preoperative evaluation is to identify and, if necessary, implement measures to prepare higher risk patients for surgery. Preoperative evaluation can decrease the length of hospital stay as well as minimize postponed or cancelled surgeries [4]. With the high likelihood of underlying coronary artery disease and the high degree of haemodynamic cardiac stress with profound alteration in heart rate, blood pressure, vascular volume, bleeding and clotting tendencies, vascular surgery represents an intermediate (1–5%) to high (>5%) mortality risk. Surgical morbidity and mortality generally falls into one of three categories: cardiac, respiratory and infectious complications. A good history and physical examination, focusing on risk factors for cardiac, pulmonary and infectious complications, and determination of a patient’s functional capacity are essential in the general evaluation process. With respect to the type of surgery, urgent and emergency procedures constitute higher risk situations than elective, nonurgent surgery and present a limited opportunity for preoperative evaluation and treatment.
daemia) are also risk factors for coronary artery disease (CAD). The incidence of CAD in patients with peripheral vascular disease is around 60%. The usual symptomatic presentation in this group of patients may be obscured by exercise limitations due to advanced age or intermittent claudication.
Risk Stratification The goal of risk stratification is to reduce overall morbidity and mortality associated with the surgical procedure. The information gathered from the history and examination will help to stratify the patient as at high, intermediate, or low risk for peri-operative cardiac complications. Consideration of further testing is based on the risk category at which the patient is placed. An example of risk stratification is shown in Table 1.8.1. For patients who have undergone coronary artery bypass grafting within the last 5 years, and whose clinical status has remained stable without recurrent symptoms or sign of ischaemia, further cardiac testing is not necessary. If a patient has had adequate coronary evaluation in the last 2 years and the findings were favourable, it is not usually necessary to repeat the tests unless there are new symptoms.
1.8.2 Systemic Evaluation Diagnostic Procedures A thorough systemic evaluation is appropriate in all patients undergoing vascular surgery. Specific areas of importance are discussed here.
Recommended European Standard Low Risk
• Electrocardiography (ECG) • Plain chest radiograph. 1.8.2.1 Cardiovascular System Intermediate Risk and High Risk
Cardiac complications are the leading cause of morbidity and death in patients undergoing vascular surgery [1]. Many of the risk factors contributing to peripheral vascular disease (diabetes mellitus, smoking, dyslipi-
• Exercise electrocardiography – in most ambulatory patients the test of choice is exercise electrocardiography, which provides an estimate of functional capacity and can detect myocardial ischaemia.
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Table 1.8.1 A guide to risk stratification Low Risk
Intermediate Risk
High Risk
Advanced age
Prior myocardial infarction
Recent myocardial infarction
Abnormal electrocardiogram
Diabetes mellitus
Unstable or severe angina
Rhythm other than sinus
Compensated or prior congestive heart failure
Decompensated congestive heart failure
Low functional capacity
Mild angina pectoris
Severe valvular disease
History of stroke
Significant arrhythmias in the presence of underlying heart disease
Uncontrolled hypertension
Supraventricular arrhythmias with uncontrolled ventricular rate
Advanced age
• Stress echocardiography – useful in patients with a major abnormality or uninterpretable ECG, or patients who cannot meet the physical requirements of the exercise portion of an exercise ECG. Patients with positive results have an 8–38% risk of cardiac death or myocardial infarction (MI) within 30 days after surgery.
Treatment Recommended European Standard Low Risk
• β-Blockade – the ability of β-blockers to reduce the peri-operative risk of cardiac complications has been extensively documented [2]. Atenolol is often administered intravenously or orally beginning 2 days preoperatively and continuing for 7 days postoperatively; this intervention reduced the incidence of peri- and postoperative myocardial ischaemia by 30–50% in randomized controlled trials [7]. In the absence of contraindications all patients undergoing major vascular surgery should benefit from β-blockade. Intermediate and High Risk
Therapy in these groups should be based upon the results of noninvasive testing: • If negative – β-blockade only. • If positive – consider cardiac catheterization, the results of which may lead to either percutaneous coronary angioplasty (PTCA) or coronary artery by-pass grafting (CABG).
Useful Additional Therapeutic Strategies
For the small percentage of patients who are at high risk and have symptoms of unstable angina or residual angina after recent MI it may be appropriate to proceed directly to coronary angiography rather than noninvasive studies. PTCA or CABG should only be performed in patients who meet the criteria for the respective procedures independent of the proposed vascular surgery. The benefit of prophylactic coronary revascularization has never been proven in a randomized controlled trial (RCT); however, several retrospective studies have shown that patients who have undergone CABG have the same morbidity and mortality from cardiac complications as those with no clinical signs of coronary artery disease [3]. Figure 1.8.1 shows an algorithm for cardiac evaluation and management of vascular surgical patients.
1.8.2.2 Respiratory System The major pulmonary complications in the peri-operative period are atelectasis, pneumonia and bronchitis. Predisposing risk factors include cough, dyspnoea, smoking, a history of lung disease and obesity. Vascular surgery of the abdomen or chest has a far higher rate of pulmonary complications compared to vascular surgery in places other than the abdomen.
1.8.2 Systemic Evaluation
Vascular Surgical Patient
Risk Stratify
Intermediate / High Risk
<1yrs Since Favorable Evaluation of Coronary Arteries and Asymptomatic
Low Risk
Non Invasive Testing
Positive
Negative
Cardiac Catherterisation
Left Main Stem or Three Vessel Disease
1 or 2 Vessel Disease
CABG
PTCA
Negative
Peri-operative β Blockade
Vascular Procedure
Fig. 1.8.1 Algorithm for cardiac evaluation and management of vascular surgical patients
Coronary Revascularisation Within 5 yrs and Asymptomatic
Emergency Presentation
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Diagnostic Procedures Recommended European Standard
• Plain chest radiograph – appropriate for patients with signs or symptoms of chest disease who have not had a chest radiograph in the previous year. • There is no RCT evidence that more complex respiratory function testing leads to changes in the management of patients with pre-existing respiratory disease.
Treatment Recommended European Standard
• Pharmacological – patients with respiratory disease may benefit from peri-operative use of bronchodilators or steroids. • Physiotherapy – patients at increased risk of pulmonary complications should receive instruction in deep breathing exercises or incentive spirometry.
Useful Additional Diagnostic Strategies
• Duplex ultrasound – 98% sensitivity and specificity of diagnosing significant RAS, however is dependent on a skilled user. Should be carried out in all patients where there is clinical suspicion of RAS. • Arteriography – the obvious advantages of conventional angiography are its ability to determine the clinical importance of suggestive lesions and the ability to concurrently perform endovascular therapy. However, specialists should weigh these advantages against the higher cost and greater morbidity of conventional angiography, and the risks of nephrotoxic contrast agents. • Magnetic resonance angiography (MRA) – the slightly inferior variability of MRA in diagnostic interpretation further supports the use of this technique as potentially the most appropriate tool for screening patients strongly suggested to have atherosclerotic renovascular disease.
Treatment Useful Additional Therapeutic Strategies
• Smoking cessation – the patient should cease smoking 8 weeks or more before surgery to minimize the surgical risk associated with smoking. This interval allows the mucociliary transport mechanism to recover, the secretions to decrease and the carbon monoxide levels in the blood to drop.
1.8.2.3 Renal System Patients with vascular disease have a high prevalence of renal dysfunction secondary to atherosclerotic renal artery stenosis (RAS). Early diagnosis of RAS is important in ensuring successful correction of any dysfunction.
Diagnostic Procedures Recommended European Standard
• Creatinine clearance – estimation of creatinine clearance should be performed to evaluate renal function in all patients undergoing vascular surgery, especially in the presence of co-existing hypertension.
All patients with bilateral stenoses and stenosis in a solitary functioning kidney are candidates for revascularization, regardless of whether they have renal insufficiency. When renal insufficiency is present, patients with unilateral stenosis are also possible candidates for revascularization prior to other major vascular surgery being performed. Table 1.8.2 Aneurysm screening Size
Aneurysm screening
<4 cm
Yearly USS
4–5.5 cm
Six-monthly USS
>5.5 cm
Elective repair
Rapidly expanding >1 cm/ Urgent elective surgery year or symptoms of tenderness
1.8.3 Evaluation of Specific Vascular Disease
1.8.3 Evaluation of Specific Vascular Disease 1.8.3.1 Aneurysmal Disease: Abdominal Aortic Aneurysm The decision to perform elective abdominal aortic aneurysm (AAA) repair is made on the balance of the operative risk of morbidity and mortality versus the risk of rupture and death associated with conservative treatment. The UK Small Aneurysm Trial showed no benefit from early surgery of asymptomatic infrarenal AAA between 4 cm and 5.5 cm when compared to regular ultrasound screening surveillance [5, 6].
Diagnostic Procedures Recommended European Standard
• Duplex ultrasound – rapid, cheap, noninvasive test, good for diagnosis and an important screening tool. Its may be difficult to interpret in obese patients or those with lots of bowel gas. It cannot easily diagnose rupture. • CTA and MRA – give excellent detail on size and configuration of the aneurysms necessary for surgical and endovascular treatment. • Intra-arterial digital subtraction angiography (IADSA) – limited role with improvement in MRA and CTA.
Treatment Recommended European Standard
• Open surgical repair – overall mortality from open repair should be less than 5% (nearer 2% in some centres). Inflammatory aneurysms increase risk of mortality to 3–20%. • Endoluminal repair – 70% of infrarenal AAA can be managed endovascularly. This type of repair minimizes haemodynamic insult but may increase the risk of distal embolization. Subject of many ongoing large multicentre studies – EUROSTAR, EVAR, RETA. Initial reports have suggested a problem with high re-intervention rates. At present it is to be considered for inflammatory aneurysms and patients unfit for open surgery.
Useful Additional Therapeutic Strategies
• Laparoscopic AAA repair – aims to reduce the complications associated with a large surgical incision; little RCT evidence to show proven benefit.
Aneurysmal Disease: Ruptured Abdominal Aortic Aneurysm A ruptured AAA should be suspected in anyone over the age of 50 years presenting as an emergency with sudden onset of severe pain in the abdomen, back or flank. This pain may be associated with collapse and shock. • Avoid palpating the abdomen more than necessary. • Note the presence or absence of distal pulses for future reference. • Do not waste time on investigations. • If the diagnosis is in doubt, and the situation is less acute and the patient is haemodynamically stable, computerized tomography should be performed straight away. • During the resuscitation of a suspected ruptured AAA you should avoid attempts to bring the blood pressure up as it may precipitate rupture and add to worsening anaemia and coagulopathy through haemodilution.
1.8.3.3 Peripheral Vascular Disease: Chronic Lower Limb Ischaemia Lower limb ischaemia is by far the most common form of symptomatic peripheral vascular disease. Most lower limb ischaemia is chronic due to atherosclerosis of the abdominal aorta, the iliac vessels and the lower limb vessels. Other causes include vasculitides, such as Buerger’s disease; haematological disorders and collagen diseases. When assessing an ischaemic limb it is important to identify both the severity and site(s) of the arterial tree that is affected. It is also important to exclude other causes of leg pain such as lumbar sacral nerve root compression, osteoarthritis and venous claudication of the post thrombotic limb. Diabetics are at greatly increased risk of limb ischaemia, with increased limb loss and mortality. Affected arteries can be heavily calcified making reconstruction difficult. Tibio-peroneal disease with occlusions at multiple levels is usually seen in these cases and is difficult to manage.
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Diagnostic Procedures
• Endarterectomy • By-pass surgery.
Recommended European Standard
• Ankle brachial pressure index – maybe falsely elevated in diabetic patients due to medial sclerosis of the vessels. • Resting and post exercise Doppler pressures – exercise Doppler pressures are measured before and after a treadmill test using a standard protocol. A fall in Doppler pressure of >15 mmHg suggests that the cause is due to arterial insufficiency. • Duplex USS – noninvasive, inexpensive and repeatable and good at evaluating stenosis. • IADSA – allows intervention if required but carries the risk of arterial puncture.
Useful Additional Diagnostic Strategies
• CTA and MRA – can be used in patients with femoral artery occlusion. • Vein mapping – identification of a suitable autogenous vein graft is appropriate where surgical reconstruction is being considered.
Treatment Recommended European Standard
Conservative treatment for nondisabling claudication would include: • Smoking cessation • Correct/control • Cholesterol/triglyceride abnormality • Hypertension • Diabetes mellitus • Weight control • Exercise – to encourage collateral circulation development.
Useful Additional Therapeutic Strategies
In up to 20% of patients, arterial reconstruction is not feasible. Other treatments of critical limb ischaemia include: • Lumbar sympathectomy • Epidural spinal cord stimulation • Drug therapies such as prostanoids treatment. Results from these treatments are often disappointing and there is little proven overall benefit; amputation may still be required.
1.8.3.4 Peripheral Vascular Disease: Acute Limb Ischaemia Acute limb ischaemia is a surgical emergency. Prompt, accurate evaluation and management are important to reduce mortality and limb loss. Acute ischaemia is usually caused by either thrombosis on an atherosclerotic plaque or embolism. A embolic cause should be suspected where there is a history is a sudden onset of pain in the affected limb without any previous claudicant symptoms. Specifically a history of palpitations or known atrial fibrillation should be sought or whether the patient has had a recent MI. Examining the affected limb may not help to distinguish between an acute embolic and an acute on chronic condition. Examining the other limb for signs of chronic ischaemia is more useful. The popliteal fossa, femoral region and abdomen should be examined for evidence of aneurysmal disease.
Diagnostic Procedures The prognosis is that about 65% of patients will respond to conservative management; other progress and require more aggressive treatment. Surgery is indicated for disabling claudication or critical limb ischaemia. The procedure undertaken will depend on the state of the arterial tree as assessed by arteriography, which aims to identify the level and character of occlusion, and the quality of the proximal and distal arterial tree. Options for reconstruction include: • Balloon angioplasty ± intravascular stenting
Eighty to ninety percent of all emboli are of cardiac origin, secondary to atrial fibrillation, post MI mural thrombosis, prosthetic or diseased heart valves.
Recommended European Standard
• ECG – to identify arrhythmias • Urgent echocardiography – to identify mural thrombosis or valvular disease
1.8.3 Evaluation of Specific Vascular Disease
• Urgent abdominal USS – to exclude a AAA. • Urgent arteriography to localize stenosis, embolus and assess for reconstruction or thrombolysis.
Treatment Recommended European Standard
• Aspirin • Intravenous heparin • If embolus is suspected: • Embolectomy • If thrombosis suspected: • Limb viable: thrombolysis and treatment of the underlying lesions. Thrombolysis usually takes 4–24 h to dissolve the thrombus, therefore a limb which is unlikely to remain viable for this long is not appropriate for this therapy. • Limb threatened: urgent surgical thrombectomy ± reconstruction.
Useful Additional Therapeutic Strategies
Revascularization of an advanced acutely ischaemic limb is hazardous with a 30-day mortality of 15%. Late presentation (over 24 h) indicates a high risk and amputation may be safer in these circumstances. Signs of advanced ischaemia include: anaesthesia, muscle tenderness and swelling. The level of amputation should be considered carefully, below knee or above knee are most commonly performed with unreconstructable disease or advanced ischaemia. In a mobile patient preservation of the knee joint improves the use of the prosthesis and subsequent mobility. In patients who are unlikely to walk again an above-knee amputation may be more suitable.
Diagnostic Procedures Clinical examination may reveal nothing, and a carotid bruit is an unreliable sign of disease severity. Neurological and eye signs may be transient. Examination of the visual fields may reveal defects and fundoscopy may reveal evidence of previous emboli. Any residual paraesthesia or weakness will be on the opposite side to the carotid lesion.
Recommended European Standard
• Duplex ultrasound – to confirm carotid artery disease, bilateral colour Doppler ultrasound imaging (Duplex) of the carotid arteries should be performed. This is a very accurate method of diagnosing carotid artery stenosis. Its limitation is in the differentiation of a very tight stenosis and an occlusion of the artery where operation is contraindicated. • CT or MRI of the brain – to exclude neoplastic and other serious pathology. • IADSA – give additional information to that found on Duplex scanning, but there is a 1% stroke rate when the carotid is directly accessed.
Useful Additional Diagnostic Strategies
• MRA or CTA – indicated where the diagnosis of occlusion is uncertain on ultrasound. MRA and CTA can give information on the carotid disease at the same time as assessing for brain pathology.
Treatment Recommended European Standard
1.8.3.5 Carotid Disease Carotid surgery started in the 1950s and is of proven benefit to those with symptomatic disease of the internal carotid artery. The symptoms are usually caused by the atherosclerotic plaque usually located at the bifurcation of the common carotid artery undergoing ulceration, thrombus formation and distal embolization resulting in a transient ischaemic attack (TIA) or a stroke.
All patients should undergo risk factor modification to decrease the risk of disease progression. Asymptomatic Patients
• Stenosis of 70%, treat with low-dose aspirin. • Stenosis of 70–99%, most clinicians would treat conservatively although there are ongoing clinical trials to determine whether surgery would be beneficial. Patients with History of TIA
• Less than 20% stenosis, treat with anti-platelet drugs. • 20–69%, most surgeons would treat conservatively with anti-platelet drugs.
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• 70–99%,defined benefit for surgery. • 100% occlusion, surgery contraindicated. Carotid Endarterectomy
• Can be performed under general or loco-regional anaesthesia. • The GALA trial is currently looking for differences in the morbidity, mortality and patient experience following either local or general anaesthesia.
• Exclusion of pelvic pathology – venous obstruction with secondary varicose veins can be the first sign of a pelvic malignancy, therefore clinical history and examination should take this into account, including internal examination.
The decision over which is the most appropriate treatment to use depends on local experience with surgical and radiological procedures.
There are many rudimentary methods for eliciting the site of incompetence, including cough impulses, percussive tests, calf squeezes and tourniquet tests. It is the authors’ opinion that the results from these tests should not be used as a guide to choice of surgical procedure. Often perforators or communicating veins can complicate clinical diagnosis and therefore where possible all patients undergoing varicose vein surgery should undergo a Duplex USS. This will identify unusual anatomy, such as Duplex long saphenous vein, thigh and calf perforators. It will also show competence and patency of the deep venous system. Where there is a history of previous deep vein thrombosis Duplex studies must be performed to confirm the status of the deep veins prior to any surgery.
1.8.3.6 Venous Disease
Treatment
The commonest vascular surgical procedure is varicose veins treatment: 1 in 1000 people undergo surgery for varicose veins every year in the western world.
The management of varicose veins depends mainly on the symptoms and the presence or absence of complications.
Carotid Stenting
• There has been a recent trend of performing balloon angioplasty of the internal carotid artery usually with the placement of a stent. However, there is a lack of RCT evidence on the benefit of this technique, unlike endarterectomy.
Diagnostic Procedures The clinician’s task is to determine if the patient’s symptoms are due to the varicosities and to determine the site of reflux from the deep to the superficial system. Preoperative evaluation of the status of the venous system in the affected leg is the key to reducing recurrence and avoiding unnecessary surgery.
Recommended European Standard Conservative Treatment
Advised if the varices are not severe or if intervention is contraindicated. Losing weight, skin care and graduated compression hosiery are the mainstay of conservative treatment. Compression hosiery has proven benefit, although patient compliance with this treatment, especially in the summer months, is poor. Surgical Treatment
Recommended European Standard
Patients should always be examined standing where possible. • Skin changes – the skin can reveal signs of lipodermatosclerosis or haemosiderin deposition, eczema and ulceration. • Varicose distribution – examination of the anterior and posterior aspects of the thigh and leg will review the distribution of dilated veins. • Peripheral pulses should be palpated.
The indications for intervention are severe disfiguring varices, aching or pain, the presence of skin changes or ulceration. Intervention may be contraindicated if there is any evidence of deep venous occlusion. • Historically stripping of the clinically incompetent vein with phlebectomies for dilated varicosities was the gold standard. This procedure however has always had a significant morbidity and recurrence rate. It may be more appropriate where bilateral treatment is required to operate on one limb at a time to encourage postoperative mobilization.
References
Useful Additional Therapeutic Strategies
• Endovenous thermal techniques can be easily performed under local anaesthesia in an office or daycase setting. They reduce the morbidity attached to stripping of the vein whilst reporting successful treatment in approximately 90% of patients at 2–5 years. Recently some evidence has been presented to suggest that new varicose formation occurs in approximately 30% of cases treated endovascularly at 5 years, similar to traditional surgery. • Recently endovenous foam sclerotherapy is gaining popularity, however there is little randomized controlled evidence of its efficacy or safety, although case series suggest a favourable outcome. • Subfascial endoscopic perforator surgery (SEPS) can be utilized where multiple calf perforators are the cause of reflux, especially in patients with overlying ulceration making direct access undesirable.
Authors Note Since this chapter was written there has been continuing debate on the appropriateness of peri-operative use of β-Blockade in patients undergoing surgery. The most significant development in this area is the POISE trial(1), a blinded, randomised, and controlled trial of controlled release metoprolol versus placebo in 10,000 patients at risk for a peri-operative cardiovascular event who are undergoing non-cardiac surgery. This trial has so far recruited more than 6300 patients of which 42% underwent vascular surgery, and should provide level one evidence. A recent 2006 Guidance update from the ACC and AHA (2) continues to recommend the use of peri-operative β Blockade in high risk surgical patients, a group to which most arterial patients belong. The author stands by the treatment algorithms presented in this chapter based upon a consensus of expert opinion in this field.
1. (2006) Rationale, design, and organisation of the Peri-Operative Ischemic Evaluation (POISE) Trial: A randomised controlled trial of metoprolol versus placebo in patients undergoing non-cardiac surgery. Am Heart J 152(2):223-230 2. Fleisher LA (2006) ACC/AHA 2006 Guideline Update on Peri-operative Cardiovascular Evaluation for Non-cardiac Surgery: Focused Update on Peri-operative β-Blocker Therapy. A Report of the American College of Cardiology / American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 47(11):2343-2355
References 1. Abir F, Kakisis I, Sumpio B (2003) Do vascular surgery patients need a cardiology work-up? A review of pre-operative cardiac clearance guidelines in vascular surgery. Eur J Vasc Endovacs Surg 25:110–117 2. Boersm E, Poldermans D, Bax JJ, Steyerberg EW, Thomson IR (2001) Predictors of cardiac events after major vascular surgery: role of clinical characteristics, dobutamine echocardiography, and beta blocker therapy. J Am Med Assoc 285:1965–1873 3. Reul GJ Jr, Cooley DA, Duncan JM et al (1986) The effect of coronary artery bypass on the outcome of peripheral vascular operations in 1093 patients. J Vasc Surg 3:788–798 4. Turnbull JM, Buck C (1987) The value of preoperative screening investigations in otherwise healthy individuals. Arch Intern Med 147:1101–1105 5. UK Small Aneurysm Trial (1998) Mortality results for randomised controlled trial of early elective surgery or ultrasonographic surveillance for small abdominal aortic aneurysms. Lancet 352:1649–1655 6. UK Small Aneurysm Trial (1998) Health service costs and quality of life for early elective surgery or ultrasonic surveillance for small abdominal aortic aneurysms. Lancet 352:1656–1660 7. Wallace A, Llayug B, Tateo L et al (1998) Prophylactic atenolol reduces post-operative myocardial ischaemia. Anesthesiology 88:7–17
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1.9 Peri-operative Care of the Vascular Patient Anne Karin Lindahl
1.9.1 Introduction The vascular patient is at high risk of complications in the peri-operative period, due to the generalized nature of the atherosclerotic disease and other concomitant diseases. The aim of peri-operative care for the vascular patient is to minimize the risk of complications by: • careful pretreatment • peri- and postoperative monitoring • optimized anaesthesia • postoperative pain treatment. In this chapter, these aspects will be reviewed in the light of available scientific evidence.
1.9.2 Preoperative Planning The patient’s medical status must be evaluated preoperatively, and all documented preoperative measures to prevent peri-operative ischaemia need to be taken. Initiation of β-blockers and platelet inhibitors is particularly important, as are smoking cessation and the implementation of preoperative optimal regulation of blood pressure and blood glucose. Also, the use of statins seems to be associated with reduced peri-operative mortality in major noncardiac surgery, probably due to their anti-inflammatory, plaque-stabilizing effects [57, 65]. These preoperative considerations should be made in good time before admission for planned surgery, in order to optimize the high-risk vascular patient. In many centres, preoperative cardiac screening and overall evaluation are performed by a specialized anaesthetist, with or without a cardiologist, in addition to the vascular surgeon, to ensure the best preoperative medical treatment. This treatment will not only improve the peri-operative mortality and morbidity, but also the patients’ long-term
outcomes. This must be emphasized, in order to motivate the patient to be compliant and make the necessary lifestyle changes. Detailed written and oral information should be given in advance to the patient regarding the procedure and possible complications, and what to expect during the recovery period. The information should be clear and understandable, in order for the patient to give his or her informed consent to the procedure. In addition to the patient’s right to information, good preoperative information reduces preoperative anxiety, thereby decreasing stimulation of the sympathetic nerve system. Preoperative anxiety, cigarette smoking and other stimulation of the sympathetic nervous system, in addition to the surgical trauma, lead to an increase in peri-operative coronary thrombosis and vasospasms. The importance of good communications skills to convey this kind of information needs to be emphasized, as does the need to include communication skills in the education of surgeons and anaesthetists [30].
1.9.3 Effects of Anaesthesia The use of epidural anaesthesia may favourably influence early graft patency in patients undergoing infra-inguinal revascularization [12], but the evidence is not unequivocal [64]. An improved early graft patency may be explained by an increase of fibrinolysis, which has been reported with regional anaesthesia (RA), possibly mediated by a reduction in plasminogen activator inhibitor (PAI) [24, 61]. There is no evidence of beneficial effects on cardiac mortality of using RA alone for peripheral vascular surgery. For peripheral surgery, RA may be used alone, or in combination with general anaesthesia, in an attempt to dilate peripherally for best possible tissue perfusion in the
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1.9 Peri-operative Care of the Vascular Patient
symptomatic leg [12, 24]. However, the improved blood flow with RA was more pronounced in patients who did not suffer from peripheral arterial disease, and the improvement of blood flow was the least prominent in patients with both atherosclerosis and diabetes mellitus [28]. For aneurysm surgery, general anaesthesia with opiates and a potent inhalational agent is most often used, combined with thoracic epidural anaesthesia for the perioperative effects and also for postoperative pain relief. Some procedures, most often carotid thromboendarterectomy (TEA) and acute peripheral embolectomy, may be performed under local anaesthesia. Due to the known cardiac risk of the vascular patient, it is important to treat the anxiety of a patient who is awake during surgery. However, some surgeons prefer to have the patient awake to be able to assess their level of consciousness, especially during carotid surgery, and to avoid unnecessary use of a shunt during the procedure. The choice of method of anaesthesia is often traditionbound to the hospital or even to the country. In some countries, the use of local anaesthesia for carotid TEA is very rare, while local anaesthesia is used routinely for this procedure in other countries.
1.9.4 Peri-operative Monitoring A minimum for peri-operative cardiac monitoring of the vascular patient is continuous electrocardiogram (ECG), preferably with computerized analysis of ST changes, measurements of arterial O2, end-tidal CO2, blood pressure, diuresis and body core temperature. In many hospitals, the monitoring of the hypnotic depth is also routine. For abdominal surgery or in high-risk patients, continuous central venous pressure and intra-arterial pressure should be monitored and kept as stable as possible. Continuous monitoring of O2 in mixed venous blood can be considered in patients with highly symptomatic cardiac disease, and is performed through a pulmonary artery catheter (Schwan-Ganz catheter). Some centres use transoesophageal echocardiography in order to detect myocardial ischaemia early.
1.9.4.1 Monitoring for Cardiac Ischaemia There are three major ways to monitor for cardiac ischaemia:
1. Surface ECG 2. Transoesophageal echocardiography 3. Pulmonary artery catheterization.
Due to the complexity and the possible side-effects of the two latter methods, the most practical and most used form is surface ECG. It is considered important to monitor ischaemia during and after the operation and to take measures to resolve the ischaemia if possible, to prevent myocardial infarction, although it is not shown to reduce peri-operative morbidity in controlled trials [51]. Subendocardial ischaemia is the most common type of ischaemia, and is detected by ST depression [37], while transmural ischaemia causing ST segment elevation in the leads facing the lesion is less common. In noncardiac surgery patients, 96% of ischaemic episodes were detected with a three-lead system (leads II, V4 and V5) [38]. ECG changes consistent with ischaemia are difficult to detect in patients with right bundle branch block, left ventricular hypertrophy with a strain pattern or with atrial fibrillation, and impossible in patients with left bundle branch block or on a pacemaker – this affects about 15% of vascular surgery patients [58]. The most reliable way to monitor for ischaemia is to follow the trend for ST segment elevation or depression over time by computerized ST segment analysis [51], which is now automated in most monitoring equipment. Pulmonary artery catheterization has not been proven to reduce complications or mortality in a meta-analysis [1]. Elevation of troponin postoperatively has been shown to be prognostic of both short-term mortality and long-term mortality. However, a recent report contradicted these findings, and did not identify troponin elevation to be prognostic of 2-year all-cause mortality or of major cardiac events in noncardiac surgery [18].
1.9.4.2 Peri-operative Temperature Control Although hypothermia may be of benefit in some aspects of the peri-operative period, and may provide some protection against cerebral and myocardial hypoxia, the results of hypothermia (below 36°C) may also harm the patient. Hypothermia affects blood coagulation by reducing the effect of extrinsic pathway activation (measured by the prothrombin time), slightly reducing the platelet count, and increasing peri-operative bleeding and the need for transfusion [34, 63]. Upon wakening from anaesthesia, a hypothermic patient will also use energy and increase their myocardial and total O2 consumption due
1.9.5 Prevention of Cardiac Ischaemia
to shivering to increase their body temperature. This may increase the risk of cardiac complications postoperatively [19, 20].The anaesthetic drugs profoundly impair thermoregulatory responses, but the protective mechanisms are reactivated as the anaesthetics are withheld [53]. It is therefore important to reduce temperature loss during the operation to a minimum, and to use devices such as the “bear hugger” upper body warm air blanket, in addition to warming the intravenous fluids and inspired air, to effectively warm the patient during surgery. It has also been documented that the use of warming devices and avoiding hypothermia during surgery improve survival, and reduce the stay in the intensive care unit and the hospital [8, 35].
1.9.4.3 Level of Hypnotic Depth Hypnotic depth may be measured by electroencephalogram (EEG) and quantified by Bispectral Index®, for instance, and such measurements may be used to dose the anaesthetic drugs more exactly, thus reducing cardiovascular side-effects caused by overdosage [7]. This not only affects the immediate peri-operative period – in a multivariate model of demographic, preoperative clinical and intraoperative variables, cumulative deep hypnotic time, patient co-morbidity and intraoperative systolic hypotension were found to be predictors of 1-year mortality [47].
1.9.5 Prevention of Cardiac Ischaemia 1.9.5.1 Preoperative Revascularization The preoperative cardiac evaluation will reveal the need for preoperative revascularization. The benefits of coronary artery by-pass graft (CABG) and percutaneous coronary intervention (PCI) accrue gradually; subsequent surgery should ideally be delayed for at least 6 weeks and longer, after such reconstructive procedures, if possible [72].
1.9.5.2 Good Peri-operative Haemodynamic Control Myocardial ischaemia results from an imbalance between myocardial oxygen supply and demand. Such imbalance may have many causes in the peri-operative period. The
most detrimental changes are tachycardia, hypovolaemia and anaemia – and if they occur at the same time, the oxygen demand increases as the oxygen supply decreases. Tachycardia increases oxygen demand by increasing the myocardial workload. At the same time, myocardial oxygen supply decreases due to a shorter diastole, the period during which most coronary blood flow occurs.
1.9.5.3 Anaemia This will result in both reduced oxygen supply and demand. Reduced oxygen content reduces the supply, and tachycardia and increased cardiac output as a result of anaemia will increase oxygen demand. However, a liberal transfusion policy may be more harmful than beneficial, and even for patients at risk of cardiac ischaemia haemoglobin levels of 7–9 g/l are considered adequate, except in patients with acute myocardial infarcts and unstable angina [31].
1.9.5.4 Adrenergic Tone Myocardial ischaemia and infarction occur more frequently postoperatively than pre- or peri-operatively (Table 1.9.1). Although the vascular patients have more ischaemia peri-operatively than other patient groups, the problem is even more frequent postoperatively. This intriguing discrepancy is probably due to the careful haemodynamic monitoring and balancing of the patient’s oxygen demand and supply preoperatively [51]. During the operation, the anaesthetist suppresses the adrenergic tone by β-blockade or a thoracic epidural with bupivacaine or another local anaesthetic [5]. Some advocate liberal use of β-blockers during the operation to keep the heart rate under 80 beats/min [51], while the American College of Cardiology (ACC) guidelines suggest a target heart rate of 50–60 beats/min in those with inducible ischaemia [16]. Boersma et al. [3] showed that the relative risk reduction from peri-operative β-blockade depends on the number of clinical risk factors (age >70 years, a history of current or previous angina, myocardial infarct, stroke or heart failure) and the presence or absence of inducible ischaemia. In patients with one or two clinical risk factors, the incidence of death or myocardial infarct was lower in β-blocked patients (0.9%) than in those who were not βblocked (3%). However, in patients with three or more risk factors and inducible ischaemia, the incidence of adverse cardiac events was 10% despite β-blockade [3].
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1.9 Peri-operative Care of the Vascular Patient
Table 1.9.1 Incidence (percentage) of myocardial ischaemia detected by continuous Holter monitoring and ST segment analysis during preoperative, peri-operative and postoperative periods in vascular patients. Modified after Norris [51] Study
Preoperative
Peri-operative
Postoperative
Overall
Aortic/lower extremity
40
38
48
61
Carotid
38
41
54
68
Oyang et al. [54]
13
21
63
–
McCann and Clements [46]
14
–
38
–
Mangano et al. [41, 42, 43]
Pasternack et al. [56]
20
25
41
–
Raby et al. [59]
–
18
30
–
Christopherson et al. [12]
8
11
40
40
Boylan et al. [4]
–
–
35
–
Norris et al. [52]
3
4
15
16
19
23
40
46
Average
The scientific evidence for the benefit of β-blockade and α2-agonists during vascular operations to reduce ischaemia, myocardial infarction and cardiac death are unequivocal, while the evidence for the benefits of using calcium channel blockers is less clear [68]. Survival is also higher 1–2 years postoperatively when continuing such treatment. Despite the convincing evidence for the benefits of β-blockade, both peri-operatively and in the long-term, only 57% of Canadian anaesthesiologists reported in a study that they always or usually administered β-blockers to patients with known coronary disease. Only 34% of these regular users continued β-blockade beyond the early postoperative period, while 95% of the respondents were aware of the peri-operative β-blocker literature [74]. This emphasizes the importance of a specially trained and aware anaesthetist, who is also involved in preoperative patient evaluation, in order to understand the high-risk vascular patient’s need for intensive peri-operative titration of vasoactive therapies [30]. Also, the vascular surgeon should be aware and ensure that his or her patient receives optimal and evidence-based peri-operative pharmacological treatment.
1.9.5.5 Postoperative Ischaemia Prevention In the immediate postoperative period, an increased oxygen demand may be due to pain, tachycardia, hyperten-
sion, sympathetic discharge and hypercoagulability [5]. Transfer from the operating room to the intensive care unit may be made under less surveillance than peri-operatively, despite transportable monitors, and in a less controllable state. Most postoperative ischaemia and infarctions are silent, due to masking by postoperative pain and opioids, and are usually associated with an increased heart rate [36, 42]. Peri-operative blood pressure control is also important in relation to cardiac ischaemia, and a maximum 20% variation from baseline is recommended [51]. If the ratio between mean arterial pressure and the heart rate, the pressure/rate quotient, is less than 1.0, there is an increased risk of ischaemia [6].
1.9.6 Aneurysm Surgery 1.9.6.1 Effects of Clamping and Declamping Even clamping below the renal arteries reduces renal perfusion by 38%, with resulting renal failure in 2–3% of patients [21]. Therefore, most surgeons want mannitol to be given before cross clamping, although the effect of this is not documented, and the mechanism of this presumed beneficial effect is not known. Also, effects of administering calcium blockers and dopamine in low dose on renal perfusion have been tested extensively, but no conclusive beneficial effects have been found. During clamping, va-
1.9.7 Heparin
sodilatation therapy is important to avoid an abrupt increase in blood pressure. Such an abrupt increase may lead to a steep increase in left ventricular filling pressure, which may induce subendocardial hypoxia due to the pressure-induced hypoperfusion. Agents most often used for vasodilatation are nitroglycerin or nitroprusside. The latter may also improve the intestinal circulation [24]. Perfusion of the kidneys and intestines may suffer during clamping above the renal arteries. Different peri-operative measures are used to avoid ischaemic injury, including perfusion of cold Ringer’s acetate solution to the kidneys, shunting through a side branch of the graft or a temporary by-pass to circulate the distal aorta and the lower limbs during the operation [17]. On cessation of cross clamping, close cooperation between the surgeon and the anaesthetist is needed, in order to keep the blood pressure from dropping too quickly and too low. The anaesthetist can manipulate the vasoactive drugs and reduce the vasodilatation drugs before unclamping, in addition to keeping the patient filled up with fluid. It is beneficial to avoid vasopressor drugs, which add to the stress and oxygen demand of the heart. In vulnerable patients, the surgeon may want to unclamp gradually by manual external pressure on the aorta. The aim is always to keep the patient’s arterial pressure as stable as possible, in order to prevent cardiac events.
1.9.6.2 Prevention of Spinal Cord Ischaemia in Thoracic Aortic Surgery Spinal cord ischaemia resulting in postoperative paraplegia is a devastating complication of thoracoabdominal aortic aneurysm repair. To prevent spinal cord compartment syndrome, cerebrospinal fluid drainage, as well as various other methods, including hypothermia, distal aortic perfusion, reattachment of intercostals arteries and more, have been used as adjuncts to thoracoabdominal aortic aneurysm repair [70].
1.9.6.3 Autotransfusion During Surgery Autotransfusion during aortic surgery is widely used and is considered to reduce the need for allogeneic blood transfusion [25, 69]. Especially in complicated cases, where blood loss may be great, cost-effectiveness has been shown [13, 26]. Spark et al. has shown that autotransfusion reduced hospital stay and infective complications [67]. The method of autotransfusion may also be
important [60], and autotransfusion of washed red blood cells is now routinely used in most centres. These washing systems may also have the benefit and possibility of producing homologous thrombocyte/fibrin glue from the normally discarded plasma, which can be used peri-operatively.
1.9.7 Heparin 1.9.7.1 Peri-operative Heparin During most vascular surgical procedures, heparin is given intravenously or intra-arterially to prevent clotting of the temporarily clamped arteries. For intra-arterial instillation of heparin in peripheral surgery, 10–20 ml of a solution of 10 U/ml unfractionated heparin is instilled in the efferent and afferent arteries immediately after clamping. There is no documentation of the beneficial or detrimental effects of this heparin treatment, although the heparin concentration theoretically should be well above therapeutic anticoagulation treatment levels in the clamped arteries. The dose of heparin given intravenously before cross clamping varies from a standardized fixed dose to weightadjusted doses. Some surgeons neutralize part of or the whole heparin effect with protamine after declamping the arteries. Most often this is done after larger doses of heparin (e.g. 7500 or 10,000 IU in a single dose). For lower doses, 2500–5000 IU, most surgeons think the patient benefits from the heparin after the surgery and refrain from neutralizing it. Administration of intravenous heparin before cross clamping in elective aortic surgery is widely used, and is considered to reduce peripheral thrombotic complications. This has however not been proven in a randomized trial of heparin versus placebo, where there was no difference in blood loss, blood transfusion or distal thrombosis. However, this study did show a benefit of heparin administration on peri-operative myocardial infarction – 5.7% in the placebo group versus 1.4% in the heparinized group [71]. The anticoagulant effect of a single dose of 5000 IU during aortic surgery was monitored, and found to be surprisingly high even 1 h after surgery [60]. This prolonged heparin effect is probably beneficial for the clotting tendency of the arteries operated on, but may increase the frequency of bleeding episodes. Especially in aortic aneurysm surgery, where bleeding may be a major
99
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1.9 Peri-operative Care of the Vascular Patient
obstacle, the prolonged heparin effect may be a problem of some significance. Intravenous heparin is most often not used for emergency aortic surgery. The rationale for this is the bleeding tendency resulting from consumption of coagulation factors and fibrin upon rupture. Pushing the haemostatic system further towards bleeding in this situation is considered more risky than beneficial. This is despite the well-known risk of patients with acute aneurysm rupture to experience embolic episodes peripherally.
1.9.7.2 Prophylaxis of Deep Leg Vein Thrombosis Standard regimens of deep leg vein thrombosis prophylaxis should be followed after vascular surgery. The vascular patients are not considered at particular risk of vein thrombosis, but risk factors such as thrombophilia, previous vein thrombosis, obesity, abdominal surgery, long operating time, etc. should be considered when deciding upon whether to give a low or high dose of low-molecular-weight heparin for prophylaxis of deep leg vein thrombosis. Due to the frequent use of unfractionated heparin during the operation, most surgeons prefer to wait until after the procedure to start this treatment.
1.9.8 Peri-operative Monitoring after Arterial Reconstructions During vascular surgery, quality control of the performed reconstruction is required. The options for such quality control are: • intravascular ultrasound (to visualize intima flaps and stenoses) • intraoperative angiography • Doppler flow measurements • intraoperative duplex scanning. Most surgeons use one or more such measurements of quality control, but the choice of method depends on: • the type of reconstruction • the resources available • the independent preference of the surgeon. Injections of a potent vasodilatation agent, e.g. papaverine, may be applied during such quality control, to measure the maximal flow of the reconstruction.
1.9.9 Prophylactic Antibiotic Administration The use of prosthetic grafts for vascular surgery prompts the use pf prophylactic antibiotic treatment to avoid graft and skin infections. The skin bacteria, e.g. Staphylococcus aureus or Staphylococcus albicans, cause most such infections. Most centres use prophylaxis with a cephalosporin 24 h peri-operatively. Prolonged treatment is saved for cases with known infectious focus or when infections are diagnosed. In addition to skin infections and graft infections, the vascular patient is at risk of pulmonary infection (see below) and urinary infection after urethra catheterization. For open abdominal aortic surgery, postoperative septicaemia may be one of several possible complications [23]. There is no evidence that prophylactic treatment with antibiotics peri-operatively prevents postoperative septicaemia.
1.9.10 Postoperative Pain Treatment The control of postoperative pain is vital for reducing catecholamine release [5], and the more the pain, the more stressful it is for the patient. Knowing the catecholamine effect on an already strained heart, the benefits regarding prevention of cardiac events postoperatively and of good postoperative pain control are obvious. In the immediate postoperative period, epidural analgesia with bupivacaine and morphine are associated with lower postoperative morbidity than “on demand” general opiate analgesia, especially after surgery involving the abdominal or thoracic aorta [73]. It is considered obligatory postoperative pain treatment to apply a base of paracetamol, and in patients without manifest or imminent renal insufficiency, a nonsteroidal anti-inflammatory drug. Since vascular patients are at particular risk of cardiac ischaemia, cyclooxygenase-2 (COX-2) antagonists should be avoided.
1.9.11 Pulmonary Complications, Prophylaxis and Treatment All surgical patients may suffer from pulmonary complications. The rate of complications depends on the patient’s
1.9.14 Pre- and Postoperative Gut Function and Nutrition
respiratory status preoperatively, as well as on the nature of the surgery and the speed of the recovery. To reduce pulmonary complications it is important to implement the following: • preoperative smoking cessation • general exercise • optimization of bronchodilatational therapy and preoperative information • specific breathing exercises. Postoperatively, mobilization of the patient and pulmonary physiotherapy are imperative, as are a focus on general fluid mobilization and avoidance of the development of heart failure and pulmonary oedema after larger surgery.
1.9.12 Peri-operative Care and Endovascular Surgery Patients treated with endovascular procedures need the same preoperative optimization of medical treatment, smoking cessation, etc. as those undergoing conventional open surgery, for lowest peri- and postoperative morbidity and mortality, but more so for the long-term results. Patients treated with endovascular therapy peripherally, e.g. percutaneous transluminal angioplasty or iliac or carotid stent implantation, as well as peripheral fibrinolysis are most often cared for in a postoperative unit with close monitoring, but there is usually no need for admission to the intensive care unit. Patients treated for aneurysmal disease with stent graft usually have a much easier recovery and fewer postoperative complications than those treated with open repair. Thus the need for peri- and postoperative monitoring is less extensive in these patients. There are fewer cardiac complications both peri- and postoperatively when comparing patients with the same degree of preoperative heart disease. This is probably due to the much smaller total surgical trauma, but in particular the fact that aortic cross clamping is not needed during the procedure. However, patients not fit for conventional surgical aortic aneurysm repair due to a combination of co-morbid conditions are now receiving aortic stent graft treatment, and these patients are at increased risk of postoperative complications [15]. The level of postoperative monitoring will naturally reflect the patient’s preoperative condition and possible adverse events during stent grafting.
In these patients in particular, postoperative monitoring of renal function is warranted, due to the use of relatively large quantities of nephrotoxic contrast media, to the problems that may occur upon placing the upper part of the stent above the renal arteries or due to the dislocation of the aneurysm neck thrombosis into the renal arteries [45]. The need for postoperative dialysis must be considered when the patient is suffering from prolonged renal failure. Renal failure is in these patients, as in patients with open repair, associated with a higher postoperative mortality rate [45].
1.9.13 Intensive Care Ward is Needed Only for Selected Patients There is an ongoing discussion about the need for intensive care treatment postoperatively in patients undergoing vascular surgery. While some centres practise the routine use of the intensive care unit (ICU) for one or more days after major vascular surgery, there is now a trend for selecting patients for ICU treatment, rather than admitting all vascular patients, even after larger operations such as open aortic aneurysm surgery. Several studies document the need for ICU care for some patients. In one of these, 109 out of 502 patients surviving the first 48 h needed a prolonged ICU stay [23]. Preoperative risk factors predicting the need for a prolonged ICU stay were elevated creatinine indicating renal failure, and operation for ruptured aneurysm.
1.9.14 Pre- and Postoperative Gut Function and Nutrition Some centres favour peri-oral fluids until 2–4 h preoperatively, and some advocate carbohydrate supplement to increase the gut recovery after intra-abdominal surgery [2]. The evidence for the beneficial effects of such regimens in open aortic surgery remains to be documented [66]. Immediate, transient postoperative nausea and vomiting is very common, but may be avoided using prophylactic anti-nausea treatment, particularly in vulnerable patients. The use of guidelines for the treatment of postoperative nausea has been shown beneficial [22]. In some patients undergoing abdominal surgery, postoperative gastrointestinal tract dysfunction may persist
101
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1.9 Peri-operative Care of the Vascular Patient
beyond the first 72 h postsurgery, and may reflect injury due to manipulation of the intestines leading to postoperative paralytic ileus, or reflect more serious conditions such as multiorgan failure or ischaemic bowel [33, 49]. The postoperative dysfunction may be caused by an inflammatory response due to reperfusion injury of the intestines, e.g. in aortic surgery, but other trauma, hypoxia or infection may also induce this inflammatory response [11]. Analgesics, mainly opioids, used during and after anaesthesia may contribute to a relative gut paralysis [40]. Newer drugs with selective peripheral opioid antagonist effects have demonstrated earlier resolutions of ileus after intra-abdominal surgery, with effects on the quality of postoperative analgesia [62]. Pain itself may also contribute to postoperative gastrointestinal tract dysfunction, either directly through noxious stimuli affecting gut perfusion, or indirectly by gut pain contributing to delayed mobilization, delayed eating and breathing difficulty [27, 39]. Postoperative gastrointestinal tract dysfunction may be induced more easily upon a reduction in circulating blood volume, as in acute aortic surgery with bleeding [29], whereas replacement with larger volumes of fluid improves gut perfusion and outcome [50]. Collis et al. [14] advocate the use of hydroxyethyl starch for such plasma expansion due to its possible anti-inflammatory effects, shown by reduced rolling and sticking of white cells to vascular endothelium. Routine placement of a nasogastric tube as a preventative measure postoperatively is associated with an increase in morbidity, and thus not recommended. The nasogastric tube should be placed selectively upon post-
operative bloating and vomiting [9]. Pharmacological treatment to speed up the recovery of the bowel after the surgical trauma has not been very effective [32]. Multiple drugs have been tried, and although some have shown effects in some studies, others have not been able to reproduce these effects (Table 1.9.2). Studies on early nutrition suggest that it is associated with a more rapid return of gastrointestinal tract function regardless of the site of surgery [55]. Early nutrition is also associated with improved outcome, measured as reduced morbidity and length of hospital stay [44].
1.9.15 Discharge Planning As the length of hospital stay is shorter, most of the recovery period is at home. While patients routinely receive much information before and after cardiac surgery, the information given after vascular procedures varies [10]. • The patients need to know what to expect regarding wound healing, leg swelling, progressive ambulation and medication. • Most patients need to stop smoking and use the perioperative period as a starting point, often requiring nicotine replacement therapy and support. • The use of nicotine replacement therapy should be discouraged in patients treated for critical ischaemia, as it may induce vasospasm in the smaller vessels and aggravate the peripheral ischaemia.
Table 1.9.2 Pharmacological therapeutic possibilities for treating postoperative ileus. Table adapted from Holte and Kehlet [32] Agent
Mechanism of action
Effect on duration of postoperative ileus
Propranolol
ß-receptor antagonist
Decreased or none
Dihydroergotamine
α-receptor antagonist
Decreased or none
Neostigmine
Acetylcholinesterase inhibitor
Decreased or none
Erythromycin
Motilin agonist
None
Cisapride
Acetylcholine agonist Serotonin receptor agonist
Decreased or none
Metoclopramide
Cholinergic stimulant Peripheral dopamine antagonist
None
Cholecystokinin
Prokinetic peptide
None
Ceruletide
Cholecystokinin
Decreased
Vasopressin
Stimulation of defecation
None
References
• Information on diet, need for physical exercise and general change of lifestyle should ideally be given before, but needs to be stressed at discharge, as the patients may be especially receptive to these changes after surgery to maintain a good operative result. For cardiac surgery patients, a shorter length of stay and fewer postoperative complications have been shown to result from the preoperative teaching and predischarge preparations [48]. There is reason to believe that similar results will be valid for vascular patients as well. The most frequent postdischarge concerns for CABG patients were leg incision healing, pain, medication, leg swelling, gastrointestinal disturbance, activities, cold symptoms and sleep. Most of these occurred within the first 14 days.
1.9.16 Summary Vascular patients are at high risk of complications during surgery. Good planning, preoperative preparation and pretreatment, the right level of monitoring related to the patient’s preoperative condition and the extent of the procedure performed may all influence the outcome of the vascular surgical treatment favourably. The cooperation of several medical professions is needed round the vascular patient for the best possible outcome. Early recognition and treatment of complications are imperative. The best peri-operative treatment gives fewer complications, better survival and reduces the need for intensive care treatment and hospital stay. References 1. Barone JE (2001) Routine perioperative pulmonary artery catheterization has no effect on rate of complications in vascular surgery: a meta analysis. Am Surgeon 67:674–679 2. Basse L et al (2000) A clinical pathway to accelerate recovery after colonic resection. Ann Surg 232:51–57 3. Boersma E et al (2001) Predictors of cardiac events after major vascular surgery – role of clinical characteristics, dobutamine echocardiography and beta-blocker therapy. J Am Med Assoc 285:1865–1873 4. Boylan JF et al (1998) Epidural bupivacaine-morphine analgesia versus patient-controlled analgesia following abdominal aortic surgery: analgesic, respiratory and myocardial effects. Anesthesiology 89:585–593 5. Breslow MJ et al (1993) Determinants of catecholamine and cortisol responses to lower extremity revascularization. The PIRAT study group. Anesthesiology 79:1202–1209
6. Buffington CW (1985) Hemodynamic determinants of ischaemic myocardial dysfunction in the presence of coronary artery stenosis in dogs. Anesthesiology 63:651–662 7. Buhre W, Rossaint R (2003) Perioperative management and monitoring in anesthesia Lancet 362:1839–1846 8. Bush H Jr et al (1995) Hypothermia during elective abdominal aortic aneurysm repair: the high price of avoidable morbidity. J Vasc Surg 21:392–402 9. Cheatham ML et al (1995) A meta-analysis of selective versus routine nasogastric decompression after elective laparotomy. Ann Surg 221:469–476 10. Chien-Yun W (1995) Assessment of post discharge concerns of coronary artery bypass graft patients. J Cardiovasc Nurs 10:1–7 11. Chieveley-Williams S, Hamilton-Davies C (1999) The role of the gut in major postoperative morbidity. Int Anesthesiol Clin 37:81–110 12. Christopherson R et al (1993) Perioperative morbidity in patients randomized to epidural or general anesthesia for lower extremity vascular surgery. Anesthesiology 79:422–434 13. Clagett GP et al (1999) A randomized trial of intraoperative autotransfusion during aortic surgery. J Vasc Surg 29:22–30 14. Collis RE et al (1994) The effect of hydroxyethyl starch and other plasma volume substitutes on endothelial cell activation: an in vitro study. Intensive Care Med 20:37–41 15. Cuypers P et al (1999) On behalf of the EUROSTAR collaborators. Realistic expectations for patients with stentgraft treatment of abdominal aortic aneurysms. Results of a European Multicentre Registry. Eur J Vasc Endovasc Surg 17:507–516 16. Eagle KA et al (2002) ACCAHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery – executive summary. A report of the American College of Cardiology/American Heart Association Task force on practice guidelines Circulation 105:1257–1267 17. Eide TO et al (2003) Shunting of the coeliac and superior mesenteric arteries during thoracoabdominal aneurysm repair. Eur J Vasc Endovasc Surg 26:602–606 18. Filipovic M et al (2005) Predictors of long-term mortality and cardiac events in patients with known or suspected coronary artery disease who survive major non-cardiac surgery. Anesthesia 60:5–11 19. Frank SM (1997) Perioperative maintenance of normothermia reduces the incidence of morbid cardiac events. A randomized clinical trial. J Am Med Assoc 277:1127–1134 20. Frank SM, Christopherson R (1993) Unintentional hypothermia is associated with postoperative myocardial ischaemia. Anesthesiology 78:468–476
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21. Gamulin Z et al (1984) Effects of infrarenal aortic crossclamping on renal hemodynamics in humans. Anesthesiology 61:394–399 22. Gan TJ et al (1993) Consensus guidelines for managing postoperative nausea and vomiting. Anesth Analg 2003 97:62–71 23. Gefke K et al (1994) Abdominal aortic aneurysm surgery: survival and quality of life in patients requiring prolonged postoperative intensive therapy. Ann Vasc Surg 8:137–143 24. Gelman S (1993) General versus regional anaesthesia for peripheral vascular surgery. Is the problem solved? Anesthesiology 79:415–418 25. Glazier DB et al (1998) Elective aortic surgery with minimal banked blood. Am Surg 64:171–174 26. Goodnough LT et al (1996) Intraoperative salvage in patients undergoing elective abdominal aortic aneurysm repair: an analysis of cost and benefit. J Vasc Surg 24:213–218 27. Grundy D (2002) Neuroanatomy of visceral nociception: vagal and splanchnic afferent. Gut 51 8 (Suppl 1):i2–i5 28. Haljamae H, Holm FJ, Akerstrom G (1988) Epidural vs. general anesthesia and leg blood flow in patients with occlusive atherosclerotic disease. Eur J Vasc Surg 2:395–268 29. Hamilton-Davies C et al (1997) Comparison of commonly used indicators of hypovolaemia with gastrointestinal tonometry. Intensive Care Med 23:276–281 30. Hepner DL, Bader AM (2001) The perioperative physician and professionalism: the two must go together! Anesth Analg 93:1088–1090 31. Herbert PC et al (2001) Is a low transfusion threshold safe in critically ill patients with cardiovascular diseases? Crit Care Med 29:227–234 32. Holte K, Kehlet H (2002) Postoperative ileus: progress towards effective management. Drugs 62:2602–2615 33. Kalff JC et al (1998) Surgical manipulation of the gut elicits an intestinal muscularis inflammatory response resulting in postsurgical ileus. Ann Surg 228:652–663 34. Kettner SC et al (2003) The effect of graded hypothermia (36°C – 32°C) on hemostasis an anesthetized patients without surgical trauma. Anesth Analg 96:1772–1776 35. Kurz A et al (1996) Perioperative normothermia to reduce the incidence of surgical wound infection and shorten hospitalization. Study of Wound Infection and Temperature Group. N Engl J Med 334:1209–1215 36. Landesberg et al (2001) Myocardial infarction after vascular surgery. The role of prolonged stress-induced ST-depression type ischaemia. J Am Coll Cardiol 37:1839–1845 37. London MJ (1991) Monitoring for myocardial ischaemia. In Kaplan JA (ed) Vascular anesthesia. Churchill Livingstone, New York, pp 249–287
38. London MJ et al (1988) Intraoperative myocardial ischaemia: localization by 12-lead electrocardiography. Anesthesiology 69:232–241 39. Mackaway-Jones K et al (1999) Modification of the cardiovascular response to hemorrhage by somatic afferent nerve stimulation with special reference to gut and skeletal muscle blood flow. J Trauma 47:481–485 40. Manara L, Bianchetti A (1986) The central and peripheral influences of opioids on gastrointestinal propulsion. Annu Rev Pharmacol Toxicol 25:249–273 41. Mangano DT et al (1990) Association of perioperative myocardial ischaemia with cardiac morbidity and mortality in men undergoing noncardiac surgery N Engl J Med 323:1781–1788 42. Mangano DT et al (1991) Perioperative myocardial infarction in patients undergoing noncardiac surgery – I: incidence and severity during the 4 day perioperative period. The Study of Perioperative Ischaemia (SPI) Research Group. J Am Coll Cardiol 17:843–850 43. Mangano DT et al (1991) Perioperative myocardial infarction in patients undergoing noncardiac surgery – II: Incidence and severity during the 1st week after surgery. The Study of Perioperative Ischaemia (SPI) Research Group. J Am Coll Cardiol 17:851–857 44. Mangesi L, Hofmeyer GJ (2002) Early compared with delayed oral fluids and food after caesarean section. Cochrane Database Syst Rev CD 003516 45. May J et al (1999) Adverse effects after endoluminal repair of abdominal aortic aneurysms: a comparison of two successive periods of time. J Vasc Surg 29:32–39 46. McCann RL, Clements FM (1989) Silent myocardial ischaemia in patients undergoing peripheral vascular surgery: incidence and association with perioperative cardiac morbidity and mortality. J Vasc Surg 9:583–587 47. Monke TG et al (2005) Anesthetic management and oneyear mortality after noncardiac surgery. Anesth Analg 100:4–10 48. Mullen P et al (1992) A metaanalysis of controlled trials of cardiac patient education. Patient Educ Counsel 19:143–162 49. Mythen MG (2005) Postoperative gastrointestinal tract dysfunction. Anesth Analg 100:196–204 50. Mythen MG, Webb AR (1995) Perioperative plasma volume expansion reduces incidence of gut mucosal hypoperfusion during cardiac surgery. Arch Surg 130:423–429 51. Norris EJ (2003) Anesthesia for vascular surgery. In: Miller RD (ed) Miller’s anesthesia, Vol 2. Elsevier, Amsterdam, pp 2051–2125
References
52. Norris EJ et al (2001)Double-masked randomized trial comparing alternate combinations of intraoperative anesthesia and postoperative analgesia in abdominal aortic surgery. Anesthesiology 95:1054–1067 53. Okuyama K et al (2003) Doxapram produced a dose-dependent reduction in the shivering threshold in rabbits. Anesth analg 97:759–762 54. Oyang P et al (1989) Frequency and significance of early postoperative silent myocardial ischaemia in patients having peripheral vascular surgery. Am J Cardiol 64:1113–1136 55. Page CP (1989) The surgeon and gut maintenance. Am J Surg 159:485–490 56. Pasternack PF et al (1989) The value of silent myocardial ischaemia monitoring in the prediction of perioperative myocardial infarction in patients undergoing peripheral vascular surgery. J Vasc Surg 10:617–625 57. Poldermans D et al (2003) Statins are associated with a reduced incidence of peri-operative mortality in patients undergoing major noncardiac vascular surgery. Circulation 107:1848–1851 58. Raby KE et al (1989) Correlation between preoperative ischaemia and major cardiac events after peripheral vascular surgery. N Engl J Med 321:1296–1300 59. Raby KE et al (1992) Detection and significance of intraoperative and postoperative myocardial ischaemia in peripheral vascular surgery. J Am Med Assoc 268:222–227 60. Roald et al (1996) Reduced rate of complications with autotransfusion of washed blood as compared to unwashed blood during surgery for abdominal aortic aneurysms. Circulation 94:235 61. Rosenfeld BA et al (1993) The effects of different anaesthetic regimens on fibrinolysis and the development of postoperative arterial thrombosis. Anesthesiology 79:435–443 62. Schmidt WK (2001) (ADL8-2698) is a novel peripheral opioid antagonist. Am J Surg 182:27–38 63. Schmied H et al (1996) Mild intraoperative hypothermia increases blood loss and allogenic transfusion requirements during total hip arthroplasty. Lancet 347:289–292
64. Schunn CD et al (1998) Epidural versus general anesthesia: does anesthetic management influence early infrainguinal graft thrombosis? Ann Vasc Surg 12:65–69 65. Shouten O, Poldermans D (2005) Statins in the prevention of perioperative cardiovascular complications. Curr Opin Anaesthesiol 18:51–55 66. Smedley F et al (2004) Randomized clinical trial of the effects of preoperative and postoperative oral nutritional supplements on clinical course cost of care. Br J Surg 91:983–990 67. Spark JL et al (1997) Allogenic versus autologous blood during abdominal aortic aneurysm surgery. Eur J Vasc Endovasc Surg 14:482–486 68. Stevens RD, Burri H, Tramer MR (2003) Pharmacologic myocardial protection in patients undergoing noncardic surgery: a quantitative systematic review. Anesth Analg 97:623–633 69. Szalay D, Wong D, Lindsay T (1999) Impact of red cell salvage on transfusion requirements during elective abdominal aortic aneurysm repair. Ann Vasc Surg 13:576–581 70. Tabayashi K (2005) Spinal cord protection during thoracoabdominal aneurysm repair. Surg Today 35:1–6 71. Thompson JF et al (1996) Intraoperative heparinisation. Blood loss and myocardial infarction during aortic aneurysm surgery: a joint vascular research group study. Eur J Vasc Surg 12:86–90 72. Thompson JP (2004) Ideal perioperative management of patients with cardiovascular disease: the quest continues. Anaesthesia 59:417–421 73. Tuman KJ et al (1991) Effects of epidural anesthesia and analgesia on coagulation and outcome after major vascular surgery. Anesth Analg 73:696–704 74. VanDen Kerkhof EG, Milne B, Parlow JL (2003) Knowledge and practice regarding prophylactic perioperative β blockade in patients undergoing noncardiac surgery: a survey of Canadian anesthesiologists. Anesth Analg 96:1558–1565
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1.10 Training of the Vascular Surgeon for Endovascular Procedures Giorgio M. Biasi, Claudia Piazzoni, Gaetano Deleo, Alberto Froio, Valter Camesasca, Angela Liloia, Grazia Pozzi
In the last two decades the most crucial event in the evolution of vascular surgery has been the advent of endovascular techniques. The introduction of endovascular therapies has had an extraordinary impact on vascular surgery, widening and transforming the horizons of vascular surgeons in many important ways. The number of endovascular procedures has increased in the last few years and the need to gain endovascular skills has become necessary, as changing trends strongly indicate that endovascular procedures will replace traditional open operations in many vascular territories. On the other hand, even though surgeons were the first to introduce catheter-derived procedures to the vascular field, other specialists with a historically greater experience of catheter manoeuvring and the ability to treat vascular diseases stepped into the scene of the treatment of peripheral vascular diseases. The question inevitably arose as to which specialist was most qualified to treat these cases through endoluminal access. The question remains unresolved and in some cases turf battles are conducted to assert the supremacy of one specialist over the others and to identify who is responsible for the procedure. In any case, the trend seems to be that endoluminal procedures will increasingly represent the treatment of choice for many vascular diseases and that these must be performed by appropriately trained vascular surgeons who have endoluminal devices as part of their armamentarium. It also seems that the numbers of vascular surgeons who are not inclined, or do not intend, to enter the endoluminal field will eventually diminish. A primary mission of vascular surgery is to give the best possible care to the population, offering all types of treatment. To be successful with these radical modifications, vascular surgeons need to transform their traditional methods to face and treat vascular pathologies, adopting the knowledge and skill typical of other specialists (interventional radiologists, cardiologists, etc.) [2].
This dramatic change is only partly related to new techniques and procedural manoeuvres; it mostly concerns new indications [3]. This represents an inevitable evolution for vascular surgeons, consequently it has enormous implications for vascular fellowship organization. There is currently a pressing need for full reform of traditional methods of training and certification. A dedicated training is therefore mandatory to prepare the specialist with competence to treat patients with a full range of vascular diseases: a new specialist with competence in vascular open surgery, catheter-manoeuvring ability and experience in imaging [6]. Some fellowship programmes in the USA are changing by replacing the year normally dedicated to research training with endovascular training. Other programmes have partnered with an interventional radiology fellowship to make their trainees more familiar with vascular imaging, catheters and guidewires. Others have been changed to incorporate an entire year of interventional radiology into vascular surgery training [7]. Newer methods are being explored, including computer simulation [8, 9]. The advantage of training by computer simulation is the ability to place a trainee in a graphic scenario and provide real-time feedback and discussion of actions and consequences without risk of harm. It represents an emergent approach that has yet to be validated, but it could be considered an important and realistic tool for residency training. These can be partial solutions to the problem of the educational training of the “new” vascular surgeon but many other steps have yet to be taken to create this new type of hybrid specialist [4, 10]. The association of vascular surgeons and interventional radiologists, working as partners in groups or institutes, is a sensible but less than perfect manner in which to address the question of retraining vascular surgeons. Probably the most important benefit derived from these partnerships will be to
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facilitate the education of a new generation of vascular surgeons for whom these techniques will be as familiar as the conventional open ones. In Europe the organization and practice of vascular surgical services vary, and depend on local, regional and national traditions and needs, thus presenting a highly complex and often confusing, disorganized pattern. The training to become a vascular surgeon varies all over Europe, both in duration and content. The length of vascular training varies between 5 and 11 years, and the number of procedures undertaken by the trainees varies hugely among trainees and countries [1, 5, 11]. In several countries the training programmes are currently under revision, with formal incorporation of training in endovascular procedures as a hallmark. However, this poses some difficulties that must be solved to train the specialist for the future: • When should endovascular skill be acquired? • Will other competences have to be sacrificed to give way to endovascular training or should endovascular training just be added to the present vascular training programme? • Will endovascular training be performed only by vascular surgeon trainers or is it necessary for other specialists to be involved in the training process with the consequent need for some reciprocity? • On the other hand, are radiologists and cardiologists presently being adequately trained to perform endovascular procedures and face their potential complications? During the academic year 2001–2002 at the University of Milano-Bicocca, in Milan, Italy, Giorgio Biasi’s team started a University-certified Master in Endovascular Techniques (MET), open to vascular surgeons, interventional cardiologists and radiologists who have received the specialization or relative certification of completion of the training programme (Fig. 1.10.1). The year-long MET course, now in its fourth year, starts on 1 November of each year and ends on 31 October of the following year, divided into two semesters. The training programmes are highly professional and different according to the background of the trainee: a vascular surgeon will spend 6 months in an interventional radiology department and 6 months in an interventional cardiology department. Reciprocal programmes have been devised for radiologists and cardiologists. The programme seems to have great success, with many applications from all over the world.
Fig. 1.10.1 Master in Endovascular Techniques
The intention is to provide the formation of a new figure: the “Endovascular Specialist”. This is an extremely ambitious project considering that there is still no clear definition of an endovascular specialist, his/her limits and duties. Ideally, the training programme for the creation of such a specialist should start immediately after obtaining the medical degree. The programme should be divided into three different stages [3]: Stage 1: Two years of this new vascular fellowship could be dedicated to vascular anatomy and physiology, angiology, diagnostic vascular lab and minor general, venous and arterial surgery procedures. The young vascular surgeons should also be trained in preventive medicine in order to treat lifestyles and risk factors. At this stage basic science training should also be considered that permits intelligent interpretation of emerging knowledge and technologies, such as genetic risk factors, gene therapy, drug-eluting stents, etc.
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Fig. 1.10.2 “Endovascular specialist” training programme, Certificate of Completion of Speciality Training (CCST)
1.12.3 Lower Extremity By-pass
Table 1.12.3 Factors contributing to graft occlusion with time Cause
Time from implant 0–30 days
1–18 18 months months to 5 years
Operative technique
++++
–
–
Graft surface thrombogenicity
++
+
–
Poor outflow
++
+
–
Obstructive venous disease ++
+
–
Neointimal fibroplasias
–
+++
–
Graft structural abnormalities (vein)
–
+++
++
Graft structural abnormalities (prosthetic graft)
–
–
++
Progressive atherosclerosis
–
+
++++
Modified from [35]
As shown in Table 1.12.3, these factors act at different times; in the early postoperative period technical errors undoubtedly play the major role in jeopardizing the patency [1]. Moreover, even if patency can be restored in occluded grafts, long-term results are rarely achieved if the occlusion occurred in the early postoperative period [27]. Therefore, any measure providing improvement of immediate results needs to be considered. Different methods have been used to obtain intraoperative quality control to ensure the adequacy of the arterial reconstructions. These are: • flowmetry • IVUS • duplex • angiography • angioscopy.
1.12.3.1 Angiography The introduction of the angiographic intraoperative control in the intraoperative field was justified by an early experience from Renwick et al. [26]: when routinely used on any type of lower extremity surgical operation, it showed technical defects in 27% of the patients. This dramatically
Fig. 1.12.1 A below-knee femoropopliteal by-pass done a few months before it thrombosed acutely. At reintervention patency was restored by using Fogarty catheters. Completion angiography showed a patent tibioperoneal trunk. Run-off was provided through the tibialis posterior and peroneal
decreased the early thrombosis rate from 18% to 0%. A landmark paper from Courbier et al. [7] reported on more than 1800 arterial procedures where a completion angi-
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1.10 Training of the Vascular Surgeon for Endovascular Procedures
Stage 2: Progress to three years of training in major open vascular procedures obtaining the Certificate of Completion of Specialist Training (CCST) in Vascular Surgery. Although the appearance of endovascular techniques demands the addition of new elements of training, it has not diminished the need for advanced skills in open surgical repair; conversely, it emphasizes the need for such skills – the skill required for conversion of a failed endovascular procedure into an open repair is greater than that required for primary surgical repair. Stage 3: The next step should be a 1-year training programme for acquiring skill and experience of catheterderived endovascular procedures, as well as imaging. Possession of such knowledge will not be in conflict with open traditional surgery but will be an adjunctive and complementary part of the training (Fig. 1.10.2). Stage 3 could represent a sort of common trunk, a part of the training programme that can apply to other specialists (radiologists and cardiologists). This new specialist should have the competence to treat all vascular territories including coronary angioplasty. References 1. Barnes RW, Ernst CB (1996) Vascular surgical training of general and vascular surgery residents. J Vasc Surg 24:1057–1063 2. Berguer R (2004) Problems facing vascular surgery in 2004. Vascular 12:39–41 3. Biasi GM, Piazzoni C (2004) Postgraduated training in endovascular surgery for vascular surgeons. Int Congr Ser 1272:109–115
4. Brevetti LS, Nackman GB, Shindelman LE, Ciocca RG, Gerard Crowley J, Graham AM (2003) Influence of endovascular training on fellowship and general surgery training. J Surg Res 115:100–105 5. Calligaro KD, Dougherty MJ, Sidawy AN, Cronenwett JL (2004) Choice of vascular surgery as a specialty: survey of vascular surgery residents, general surgery chief residents, and medical students at hospitals with vascular surgery training programs. J Vasc Surg 40:978–984 6. Choi ET, Wyble CW, Rubin BG, Sanchez LA, Thompson RW, Flye MW, Sicard GA (2001) Evolution of vascular fellowship training in the new era of endovascular techniques. J Vasc Surg 33:S106–S110 7. Cronenwett JL (2004) Vascular surgery training in the United States, 1994 to 2003. J Vasc Surg 40:660–669 8. Dayal R, Faries PL, Lin SC, Bernheim J, Hollenbeck S, DeRubertis B, Trocciola S, Rhee J, McKinsey J, Morrissey NJ, Kent KC (2004) Computer simulation as a component of catheter-based training. J Vasc Surg 40:1112–1117 9. Hsu JH, Younan D, Pandalai S, Gillespie BT, Jain RA, Schippert DW, Narins CR, Khanna A, Surowiec SM, Davies MG, Shortell CK, Rhodes JM, Waldman DL, Green RM, Illig KA (2004) Use of computer simulation for determining endovascular skill levels in a carotid stenting model. J Vasc Surg 40:1118–1125 10. Lin PH, Bush RL, Milas M, Terramani TT, Dodson TF, Chen C, Chaikof EL, Lumsden AB (2003) Impact of an endovascular program on the operative experience of abdominal aortic aneurysm in vascular fellowship and general surgery residency. Am J Surg 186:189–193 11. Maurer PC (1995) Vascular surgery in European Union: current state, developments and prospects for the future. Int Angiol 14:335–338
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1.11 Peripheral Arterial Disease and Emerging Biochemical Vascular Risk Factors Stella S. Daskalopoulou, Marios E. Daskalopoulos, Christos D. Liapis, Dimitri P. Mikhailidis
1.11.1 Introduction Peripheral arterial disease (PAD) affects more than 10 million people in the United States. The risk factors associated with PAD are similar to those for coronary heart disease (CHD) and cerebrovascular disease (CVD) [4, 7]. Medical therapy of PAD must include modification of vascular risk factors with application of strict secondary prevention guidelines [7]. Established risk factors such as smoking, diabetes, hypertension and dyslipidaemia are commonly found in patients with PAD [7]. Furthermore, several emerging risk factors such as homocysteine (Hcy), lipoprotein (a) [Lp(a)], C-reactive protein (CRP) and fibrinogen have also been documented in patients with PAD [1–3, 5–12, 15, 17, 19, 21–28]. This review briefly considers the role of these emerging risk factors in the pathogenesis and treatment of PAD.
1.11.2 Homocysteine (Hcy) Elevated Hcy levels have been reported in patients with PAD [2, 5, 15, 22–24, 27] Moreover, Hcy concentrations were found to be significantly lower in patients with isolated PAD than in patients who also had additional systemic atherosclerosis in PAD (10.1±4.4 versus 16.7±7.0 μmol/l, p<0.0001) [23]. Similarly, Hcy in type 2 diabetes was found to be associated with the angiographic severity of PAD. Even in young women, hyperhomocysteinaemia is a risk factor for PAD [27]. Furthermore, there is a strong synergistic effect between Hcy and traditional vascular risk factors, but this synergism may not be seen in CHD and CVD [27]. Thus, in a study of 6880 unselected primary care patients (aged ≥65 years) the association between atherothrombotic manifestations and Hcy diminished substantially after adjusting for age, gender, smok-
ing status, diabetes, hypertension, lipid disorders and estimated glomerular filtration rate [5]. The odds ratio (OR) for PAD decreased to 1.4; for CHD, to 1.0; and for CVD, to 1.1. Therefore, after adjusting for established risk factors, the association between Hcy and PAD is small but no longer present for CHD and CVD. There is also evidence of a relationship between Hcy and nonfatal atherothrombotic stroke in patients with symptomatic PAD [24]. This could be clinically relevant because of the high incidence of cerebrovascular complications in PAD patients. However, we need to consider that not all studies support a strong association between PAD and Hcy. The adverse effect of Hcy on the vasculature may include the accumulation of the endogenous nitric oxide (NO) synthase inhibitor, asymmetric dimethylarginine (ADMA) [24]. This may result in platelet activation. There are as yet no convincing intervention trials indicating whether lowering Hcy levels (e.g. by administering folic acid or vitamin B12) results in a decreased risk of vascular events. Nevertheless, it is unlikely that the administration of vitamin supplements is harmful in cases where there is no haematological abnormality.
1.11.3 C-reactive Protein (CRP) Circulating CRP levels are elevated in the presence of PAD [1, 2, 11, 15, 17, 21]. Moreover, symptomatic PAD patients were found to have higher CRP levels than asymptomatic PAD patients. CRP also correlated negatively with the ankle/brachial pressure index (ABPI) [1]. Higher CRP levels were associated with poorer walking performance. Among several atherothrombotic markers assessed at baseline, CRP and the total cholesterol:highdensity lipoprotein cholesterol (HDL-C) ratio were the strongest independent predictors for the development of PAD [15]. As with CHD, CRP provided additive prog-
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1.11 Peripheral Arterial Disease and Emerging Biochemical Vascular Risk Factors
nostic information over standard lipid measures. The relationship between PAD and CRP appears to be stronger than that between PAD and Hcy. PAD is commoner in type 2 diabetic patients [1]. Therefore, it is interesting that higher CRP levels are reported in those with diabetes and PAD as compared with diabetes alone. In fact, only the serum CRP level, the duration of diabetes and use of angiotensin converting enzyme inhibitors (ACEI) were independently associated with PAD in type 2 diabetes mellitus. Physical activity may lower serum CRP levels in patients with PAD [1]. Statins reduce the event rate in PAD.[7, 18]. However, there is evidence that this benefit is limited to, or at least more obvious in, the presence of high inflammatory activity. In this context, it is interesting that statins lower the circulating levels of CRP [1]. It is not clearly established if there is a dose–response relationship between the extent of LDL-C lowering (and possibly the statin dose used) and the fall in CRP levels. In this context, it is interesting that ezetimibe (a selective cholesterol transport inhibitor) lowers CRP levels further when added to a statin [7]. Some fibrates (e.g. ciprofibrate and fenofibrate) can also lower the circulating levels of CRP [7]. Preprocedural CRP levels predict a high incidence of myocardial infarction (MI) in patients with PAD, independently of previous CHD and established vascular risk factors [17]. CRP levels at baseline and 48 h after intervention may also be independent predictors of postangioplasty outcome (e.g. restenosis at 6 months [20]). Although serum CRP levels have been used as “markers” of vascular disease, it is important to consider that there is evidence that CRP may also participate in atherogenesis (e.g. by acting as a chemoattractant).
1.11.4 Lipoprotein (a) [Lp(a)] Lp(a) is an independent risk factor for PAD [15, 25]. This is even true for type 1 and 2 diabetic patients. The relationship between PAD and Lp(a) may be stronger than that between Lp(a) and CHD and stroke. A threshold of ≥30 mg/dl has been proposed as an independent risk factor for premature peripheral atherosclerosis in men. Lp(a) levels correlated with LDL-C, total cholesterol, fibrinogen and apolipoprotein B levels as well as disease severity. An elevated Lp(a) level may be associated with more severe forms of PAD [15].
Serum Lp(a) levels are elevated in patients with early impairment of renal function and are associated with a greater prevalence of vascular disease. An inverse correlation between serum Lp(a) level and creatinine clearance may account for this elevation. This relationship may be relevant since patients with PAD may have impaired renal function (e.g. due to co-existing atherosclerotic renal artery stenosis). In a multivariate regression analysis, Lp(a) and Hcy were the best predictors for acute MI, whereas Lp(a), Hcy and the total cholesterol:HDL-C ratio were the best predictors for PAD [15]. The circulating levels of Lp(a) are largely genetically determined; therefore, it is difficult to influence this variable. Nicotinic acid can lower Lp(a) levels but compliance may be a problem because of side-effects (e.g. flushing). Correcting hypothyroidism or administering hormone replacement therapy may also lower Lp(a) levels. Since the risk attributed to Lp(a) is influenced by the LDL-C level, it may be that the overall risk of a vascular event can be decreased by aggressively lowering the LDL-C levels (e.g. with a statin [7]). The structural homology between Lp(a) and plasminogen means that Lp(a) is considered as a “bridge” between dyslipidaemia and haemostasis.
1.11.5 Fibrinogen Patients with PAD have elevated plasma fibrinogen levels that also indicate an increased risk for poor outcome, particularly for fatal cardiovascular complications [9]. There is not only a correlation between plasma fibrinogen concentration and the severity of CHD but also a correlation with the incidence of additional PAD or CVD. In CHD, the fibrinogen level is associated with the number of stenosed coronary arteries. Fibrinogen probably exerts its adverse effects by several mechanisms. These include increasing blood viscosity, activating platelets, modulating endothelial function and promoting smooth muscle cell proliferation and migration as well as participating in the coagulation process [9]. Several factors influence plasma fibrinogen levels. Among these are smoking, diabetes/insulin resistance, obesity and the acute phase response [9]. There is an inverse association between physical activity and plasma fibrinogen levels. Patients receiving statin
1.11.7 PAD and Other Potentially Relevant Emerging Risk Factors
therapy had significantly less inflammation (hs-CRP p<0.001, fibrinogen p=0.007, albumin p<0.001 and neutrophils p=0.049) and better survival [adjusted hazard ratio (HR) 0.52, p=0.022] and event-free survival rates (adjusted HR 0.48, p=0.004) than patients not treated with statins [18]. However, the short-term effect of statins on plasma fibrinogen levels remains controversial. In contrast, fibrates (with the possible exception of gemfibrozil) consistently lower plasma fibrinogen levels [7]. High fibrinogen concentrations appear to be detrimental to early angioplasty success.
1.11.6 Endothelium The endothelium is not a passive lining of the arterial tree [3]. It is an active organ that plays a key role in regulating vascular reactivity and preventing thrombosis. Inflammation is implicated in the pathophysiology of endothelial dysfunction in PAD. For example, a multivariate analysis showed an association of CRP, fibrinogen and ABPI with brachial artery flow-mediated dilation (FMD) [3]. The adhesive protein von Willebrand factor (vWF), a marker of endothelial damage, contributes to platelet function by mediating the initiation and progression of thrombus formation at sites of vascular injury. vWF is significantly associated with the risk of developing PAD [3]. Increased levels of vWF are independently associated with cardiovascular and all-cause mortality in both diabetic patients and nondiabetic subjects. The ABPI correlates positively with FMD and negatively with CRP, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) [3]. Thus, in PAD, endothelial function and inflammatory status are related to the severity of the circulatory impairment. The associated thrombotic tendency may contribute to the increased risk of MI and stroke.
1.11.7 PAD and Other Potentially Relevant Emerging Risk Factors 1.11.7.1 Creatinine Renal impairment is associated with an increased risk of mortality in advanced PAD, irrespective of the presence of hypertension and diabetes mellitus [5, 12]. This sug-
gests that impaired renal function exerts an unfavourable effect on outcome, independently of these risk factors. After multivariable proportional-hazard adjustment for potential confounders and other known risk factors for PAD, women with a decreased creatinine clearance (<60 ml·min– 1 ·1.73 m– 2 ) had a significantly increased risk of PAD (and/or other vascular problems) compared with those with a creatinine clearance ≥60 ml·min– 1 ·1.73 m– 2 [14]. Clinicians should be aware of the high prevalence of PAD among patients with renal insufficiency [7]. Type 2 diabetic patients with PAD had longer diabetic duration, higher serum creatinine levels, a higher total cholesterol: HDL-C ratio, more hypertension and a history of cerebrovascular events and higher CRP and inteleukin-6 (IL6) levels [21, 28]. The renal haemodynamic profile in atherosclerotic patients might constitute functional evidence of the silent phase of ischaemic renal disease. The findings suggest that renal function should be carefully assessed in patients with extrarenal atherosclerosis, particularly in those with classic vascular risk factors. In other words, recent evidence strongly suggests that renal and vascular disease progress in parallel. In turn, the same treatment that improves vascular disease may also preserve/restore renal function [7]. It is important to consider that impaired renal function will adversely affect other variables; for example, by raising the circulating levels of Hcy, urate and Lp(a) [5]. Future studies should determine whether correcting or preventing impaired renal function will result in a decreased risk of vascular events. In this context, there is evidence that treatment with statins and antihypertensive drugs results in improved renal function or a delay in renal disease progression [6, 7].
1.11.7.2 Urate Elevated uric acid levels were found to be a significant and independent risk factor for PAD as well as a predictor of CHD [10]. However, the link between plasma urate levels and the risk of vascular events remains controversial [6]. Hyperuricaemia is more pronounced in hypertension complicated by PAD and is associated with worse functional status of the peripheral circulation [10]. Circulating urate levels are influenced by renal function and there is evidence that hyperuricaemia is associated with an increased risk of vascular events [7].
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Statins may lower plasma urate levels by improving renal function [6]. Fenofibrate exerts a uricosuric effect [6].
1.11.7.3 Microalbuminuria Microalbuminuria is associated with increased vascular and all-cause mortality, probably because it reflects generalized atherosclerosis [7, 26]. Albuminuria is associated with diabetes mellitus, PAD, hypertension, CHD, hyperlipidaemia and in some cases with elevated plasma fibrinogen levels. Microalbuminuria and PAD are mutually independent risk indicators. Aggressive blood pressure lowering (especially with ACEI or angiotensin II receptor blockers) or statins exert a favourable effect on microalbuminuria and renal function [7, 26].
1.11.7.4 Insulin Resistance and Metabolic Syndrome The incidence of PAD is greater in patients with diabetes or impaired glucose tolerance and insulin resistance [8]. The metabolic syndrome is also associated with a higher risk of vascular events [8]. The prevalence of the metabolic syndrome in a secondary prevention population has been reported as: 58% in PAD patients, 41% in CHD patients, 43% in CVD patients and 47% in abdominal aortic aneurysm patients. With the increasing prevalence of the metabolic syndrome we expect to see more PAD associated with insulin resistance. Patients with the metabolic syndrome may have raised levels of urate and fibrinogen as well as impaired fibrinolysis [8].
1.11.7.5 Platelets, Fibrinolysis and D-Dimers Patients with PAD have impaired fibrinolytic activity, manifested primarily as raised levels of the inhibitor of fibrinolysis, plasminogen activator inhibitor-1 (PAI-1). Six months of exercise training improved fibrinolysis. Physical activity lowers D-dimer levels, which may be a sensitive marker of the extent of atherosclerosis in lower extremity arteries [11]. High D-dimer levels are associated with poorer physical activity among individuals with and without PAD. Additional work is needed to determine whether D-dimers (and CRP) are involved in the
pathophysiology of functional impairment or whether they are simply markers of the extent of systemic atherosclerosis [11]. PAD is associated with platelet activation; this may be why antiplatelet drugs exert a beneficial effect in these patients [13, 16]. Unfortunately, it is difficult to evaluate platelet function because of the need for fresh samples. It is possible that in the future this limitation will be overcome by the measurement of the plasma levels of soluble P-selectin.
1.11.7.6 Other Markers of Inflammation Low serum albumin levels are associated with a greater incidence of major adverse cardiac events (MACE: MI, percutaneous coronary interventions, coronary artery by-pass graft and death) in patients with advanced atherosclerosis [19]. Serum amyloid A, another marker of inflammation, can mirror the results seen with CRP (see above) [11, 18]. Patients with PAD also have higher levels of IL-6. Platelet activation may play a significant role through the expression of CD40 ligand as a source of activation signals to endothelial cells. This, in turn, may modulate the inflammatory response. In this context, it is relevant that both statins and the antiplatelet agent clopidogrel may influence the CD40 activation process [13, 16].
1.11.8 Conclusions Several emerging biochemical markers have shown promise in terms of predicting the probability of developing PAD, the risk of vascular events or further progression of lower limb arterial disease. Among these are Hcy, Lp(a), CRP and fibrinogen. There is a need to confirm their role as predictors of vascular risk and as targets for pharmacologic or lifestyle intervention. These factors may also prove useful for patient surveillance. The currently available medical treatment for PAD (antiplatelet, lipid-lowering, hypoglycaemic and antihypertensive drugs) may influence these emerging risk factors. It is also relevant to mention that noninvasive diagnostic imaging techniques are being developed. These techniques, when used in conjunction with biochemical markers, will help detect early vascular disease as well as evaluate the effectiveness of any treatment.
References
References 1. Bassuk SS, Rifai N, Ridker PM (2004) High-sensitivity Creactive protein: clinical importance. Curr Probl Cardiol 29:439–493 2. Bloemenkamp DG, van den Bosch MA, Mali WP, Tanis BC, Rosendaal FR, Kemmeren JM, Algra A, Visseren FL, van der Graaf Y (2002) Novel risk factors for peripheral arterial disease in young women. Am J Med 113:462–467 3. Brevetti G, Silvestro A, Di Giacomo S, Bucur R, Di Donato A, Schiano V, Scopacasa F (2003) Endothelial dysfunction in peripheral arterial disease is related to increase in plasma markers of inflammation and severity of peripheral circulatory impairment but not to classic risk factors and atherosclerotic burden. J Vasc Surg 38:374–379 4. Criqui MH, Denenberg JO, Langer RD, Fronek A (1997) The epidemiology of peripheral arterial disease: importance of identifying the population at risk. Vasc Med 2:221–226 5. Darius H, Pittrow D, Haberl R, Trampisch HJ, Schuster A, Lange S, Tepohl HG, Allenberg JR, Diehm C (2003) Are elevated homocysteine plasma levels related to peripheral arterial disease? Results from a cross-sectional study of 6880 primary care patients. Eur J Clin Invest 33:751–757 6. Daskalopoulou SS, Athyros VG, Elisaf M, Mikhailidis DP (2004) Uric acid levels and vascular disease. Curr Med Res Opin 20:951–954 7. Daskalopoulou SS, Daskalopoulos ME, Liapis CD, Mikhailidis DP (2005) Peripheral arterial disease: a missed opportunity to administer statins so as to reduce cardiac morbidity and mortality. Curr Medicinal Chem 12:763–771 8. Daskalopoulou SS, Mikhailidis DP, Elisaf M (2004) Prevention and treatment of the metabolic syndrome. Angiology 55:589–612 9. Koenig W (2003) Fibrinogen in cardiovascular disease: an update. Thromb Haemost 89:601–609 10. Langlois M, De Bacquer D, Duprez D, De Buyzere M, Delanghe J, Blaton V (2003) Serum uric acid in hypertensive patients with and without peripheral arterial disease. Atherosclerosis 168:163–168 11. McDermott MM, Greenland P, Green D, Guralnik JM, Criqui MH, Liu K, Chan C, Pearce WH, Taylor L, Ridker PM, Schneider JR, Martin G, Rifai N, Quann M, Fornage M (2003) D-dimer, inflammatory markers, and lower extremity functioning in patients with and without peripheral arterial disease. Circulation 107:3191–3198 12. Mlekusch W, Exner M, Sabeti S, Amighi J, Schlager O, Wagner O, Minar E, Schillinger M (2004) Serum creatinine predicts mortality in patients with peripheral artery disease: influence of diabetes and hypertension. Atherosclerosis 175:361–367
13. Peripheral Arterial Diseases Antiplatelet Consensus Group (2003) Antiplatelet therapy in peripheral arterial disease. Consensus statement. Eur J Vasc Endovasc Surg 26:1–16 14. Reddan DN, O’Shea JC, Sarembock IJ, Williams KA, Pieper KS, Santoian E, Owen WF, Kitt MM, Tcheng JE (2003) Treatment effects of eptifibatide in planned coronary stent implantation in patients with chronic kidney disease (ESPRIT Trial). Am J Cardiol 91:17–21 15. Ridker PM, Stampfer MJ, Rifai N (2001) Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease. J Am Med Assoc 285:2481–2485 16. Robless P, Mikhailidis DP, Stansby G (2001) Systematic review of antiplatelet therapy for the prevention of myocardial infarction, stroke or vascular death in patients with peripheral vascular disease. Br J Surg 88:787–800 17. Rossi E, Biasucci LM, Citterio F, Pelliccioni S, Monaco C, Ginnetti F, Angiolillo DJ, Grieco G, Liuzzo G, Maseri A (2002) Risk of myocardial infarction and angina in patients with severe peripheral vascular disease: predictive role of Creactive protein. Circulation 105:800–803 18. Schillinger M, Exner M, Mlekusch W, Amighi J, Sabeti S, Muellner M, Rumpold H, Wagner O, Minar E (2004) Statin therapy improves cardiovascular outcome of patients with peripheral artery disease. Eur Heart J 25:742–748 19. Schillinger M, Exner M, Mlekusch W, Amighi J, Sabeti S, Schlager O, Wagner O, Minar E (2004) Serum albumin predicts cardiac adverse events in patients with advanced atherosclerosis – interrelation with traditional cardiovascular risk factors. Thromb Haemost 91:610–618 20. Schillinger M, Exner M, Mlekusch W, Rumpold H, Ahmadi R, Sabeti S, Haumer M, Wagner O, Minar E (2002) Vascular inflammation and percutaneous transluminal angioplasty of the femoropopliteal artery: association with restenosis. Radiology 225:21–26 21. Silvestro A, Scopacasa F, Ruocco A, Oliva G, Schiano V, Zincarelli C, Brevetti G (2003) Inflammatory status and endothelial function in asymptomatic and symptomatic peripheral arterial disease. Vasc Med 8:225–232 22. Spark JI, Laws P, Fitridge R (2003) The incidence of hyperhomocysteinaemia in vascular patients. Eur J Vasc Endovasc Surg 26:558–561 23. Taute BM, Taute R, Heins S, Behrmann C, Podhaisky H (2004) Hyperhomocysteinemia: marker of systemic atherosclerosis in peripheral arterial disease. Int Angiol 23:35–40 24. Taylor LM Jr (2003) Elevated plasma homocysteine as risk factor for peripheral arterial disease – what is the evidence? Semin Vasc Surg 16:215–222
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25. Tseng CH (2004) Lipoprotein(a) is an independent risk factor for peripheral arterial disease in Chinese type 2 diabetic patients in Taiwan. Diabetes Care 27:517–521 26. Tseng CH, Tseng CP, Tai TY, Chong CK (2005) Effect of angiotensin blockade on the association between albuminuria and peripheral arterial disease in elderly Taiwanese patients with type 2 diabetes mellitus. Circ J 69:965–970
27. van den Bosch MA, Bloemenkamp DG, Mali WP, Kemmeren JM, Tanis BC, Algra A, Rosendaal FR, van der Graaf Y (2003) Hyperhomocysteinemia and risk for peripheral arterial occlusive disease in young women. J Vasc Surg 38:772–778 28. Yu HI, Sheu WH, Song YM, Liu HC, Lee WJ, Chen YT (2004) C-reactive protein and risk factors for peripheral vascular disease in subjects with Type 2 diabetes mellitus. Diabet Med 21:336–341
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1.12 Quality Control in Vascular Surgery P. G. Settembrini, M. Carmo, R. Dallatana, G. Mercandalli, G. A. T. De Angelis
1.12.1 Introduction Intraoperative assessment of technical adequacy is a necessary part of all arterial reconstructions. Detection of any technical imperfection in the operating room allows the surgeon to provide immediate correction of the abnormalities that may lead to early thrombosis. Technical imperfection accounts for about 2.4–26% of all failures according to different studies [6]. In the past most surgeons used to check the reconstruction through the palpation of a pulse in the vessel distal to the anastomosis; only later was continuous wave (CW) Doppler adopted, providing data on the physiology of the reconstruction (flow velocity). Intraoperative angiography was introduced in the 1970s, thus providing information on the morphology of the by-pass. In recent years duplex scan and colour duplex scan have been widely used, thus permitting us to check the reconstruction for its physiological and morphological parameters (vessel wall and lumen).
1.12.1.2 Angiography Angiography is still considered the gold standard for the assessment of vessel patency. Introduced in the intraoperative setting, this technique was able to accurately depict the anatomy of reconstruction and the outflow. However, it remains an invasive procedure, which requires direct injection of contrast dye into the vessel. Angiography requires two projections to obtain an appropriate vision of the vessel. Complications related to needle insertion (dissection and thrombosis) or the contrast dye (nephrotoxicity or allergic reaction) have been described. Their incidence is probably less frequent than commonly thought [7], and the introduction of digital subtraction (available also on portable machinery) has further lowered this rate. Its disadvantages are the same as those encountered for preoperative diagnosis: besides the cost of the machinery and the necessity for specifically trained personnel, its accuracy has been questioned. The presence of air inside the lumen, and an excessive or poor concentration of the contrast dye can easily cause over- or underestimation of the defects.
1.12.1.1 Physical Examination This is frequently forgotten in an era of advanced technology. Pulsatility of distal arteries, pink colour of the skin and warm temperature of the limbs often indicate that a normal blood supply has been restored. These findings alone cannot ensure the technical adequacy of the reconstructions, however their absence is not always indicative of the presence of a defect: spasm and calcification of the peripheral arteries can prevent a pulsation from being palpable. A thrill on the anastomosis can indicate the presence of a stenosis, but at the same time the turbulence associated with a high flow can produce the same “sound”.
1.12.1.3 Continuous Wave (CW) Doppler In the earliest era of vascular surgery, CW Doppler was the first method used to test construction. It remains valid due to its simplicity and cost-effectiveness: the probes are cheap, easy to use and always available, and can be directly sterilized or covered by a sterile sheath. They detect the velocity inside the vessel by direct contact with the external wall, providing indirect measurement of the relative decrease in the diameter of the lumen. The older CW Doppler machines were only able to transform the velocity into sound. Interpretation relied only on the experience of the operator. More recent machines have a screen showing the flow wave, allowing precise measurement of the peak systolic velocity (PSV) and the end-
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diastolic velocity (EDV), expressed in cm/s. The absolute maximum PSV and the ratio between the maximum PSV and the value measured in the vessel before the increase are the two parameters commonly used to characterize the stenosis. The simplicity of the method represents its major limit. In fact it does not enable one to see inside the vessel in order to choose the point where to detect the velocity. This would allow one to precisely correlate the morphologic defect with the increased velocity. Its measurement is prone to large variation due to the angle of the probe with the vessel: 45° is the required angle. Experienced operators are therefore required to correctly perform and interpret the examination. Moreover any minor defect not producing a significant change in flow velocity is difficult to detect with this method.
1.12.1.4 Duplex and Colour Duplex Scan The colour duplex scan machine associates a B-mode ultrasound with a pulsed wave (PW) Doppler. The colour is the visual translation of the PW Doppler to help the operator test the exact point where the defect is visible (area of stenosis, turbulence, etc.). Initially used in the preoperative setting, it has recently been introduced for intraoperative use. The implementation of the technology has produced smaller probes (now measuring about 2 cm), with longer wavelength, thus providing better two-dimensional resolution. The major advantage of this technique is the possibility of obtaining both anatomic and functional information about the vessel. Direct vision of the lumen and wall allows one to visualize the presence of stenosis, thrombus, dissection or intimal flap. Measurement of flow velocity can confirm findings from a B-mode examination and provide more reliable parameters in order to grade the lesion (as discussed in Section 1.12.1.3). This technique is applicable to any vessel and does not require the use of nephrotoxic contrast dye. The major limitation in this case is its dependence on the operator. Polytetrafluoroethylene (PTFE) grafts and patches cannot be appropriately scanned due to the presence of air inside the wall of the graft, which masks the lumen. Moreover the outflow vessel can be scanned only within the limit of the surgical wound, where the probe can be appropriately placed directly on the artery.
1.12.1.5 Intravascular Ultrasonography (IVUS) This application was introduced in the 1980s but has become more popular recently, and has been widely used during endovascular procedures. Moreover, over the years catheters have reduced in diameter from 2.5–3 mm to less than 1 mm. The wavelength of the ultrasound reaches 40 MHz, allowing a high resolution for the view of the surrounding tissues. The probe is placed on the tip of a flexible catheter introduced inside the artery. The image is a 360° transverse scan of the vessel, obtained through either a single rotating transducer or a phased array. The major advantage is the accuracy of its measurements. For this reason it is being used in some centres during endovascular aneurysm repair (EVAR), enabling the operator to take measurements of neck diameter and length, to check the exact position of the graft and to verify the patency of the renal arteries at the end of the procedure. It accuracy is applicable to all different kinds of arterial and venous lesions, such as restenosis and flaps.
1.12.1.6 Angioscopy This technique allows direct vision of the inner wall of any artery, vein or by-pass by using optic fibres. The blood represents the major obstacle. For this reason blood flow needs to be interrupted and the vessel to be filled with saline. Catheter diameters range from 0.5 to 3.5 mm depending on the presence of a coaxial channel used for irrigation with water. Blood flow is usually interrupted through an inflatable balloon. The optic fibres have a high resolution and are very flexible. When the fibre is connected to a camera, the images obtained are visible on a monitor and the inner wall can thus be directly visualized, distinguishing between different plaque characteristics (ulcers or heavy calcifications). The presence of the light at the end of the fibre helps one to correlate the lesion found to the skin surface, thus allowing one to make small incisions in exactly the right area when open surgery is required. For in situ or non-reversed vein by-pass surgery, this method is helpful when checking for the presence of residual valves inside the vein graft. Gloviczki has described another particular application [12] for valvuloplasty of the femoral vein without venotomy: the stitches are placed under direct vision of the inner surface by introducing the angioscopic fibre through the great saphenous vein.
1.12.2 Arteries of the Abdomen
The limitations are mainly the cost and the fact that the procedure remains invasive: lesion on the wall, with flaps or dissection, and trauma due to water pressure or fluid overload secondary to excessive irrigation are the most common complications.
1.12.1.7 Flowmetry This method has been used particularly in the USA. The method uses an electromagnetic or ultrasonographic flow meter: a small cuff (an appropriate diameter needs to be chosen) is placed around the vessel (graft or native artery) and the transducer measures the flow inside the conduit. Usually papaverine is injected in the distal outflow vessel to maximize the sensitivity of the test. The technique is very simple and precise. The cost is related to the machinery, as the probes can be re-sterilized. This method has a high specificity but a low sensitivity, as minor defects or even major ones are not detectable if they do not decrease the flow. Moreover, PTFE isolates the flow from the transducer both for the ultrasound flow meter (because of the air inside the wall of the graft) and the electromagnetic one (PTFE is a good electric isolator). For these reasons this method is usually associated with another technique as quality control.
1.12.2 Arteries of the Abdomen 1.12.2.1 Abdominal Aorta Due to the large calibre of the abdominal aorta and iliac arteries, the issue of possible technical defects during the reconstruction is less important. In any case (and in particular for the iliac arteries), any time an unsatisfactory pulse is present at the end of the procedure some kind of quality control is required. Flow meters, CW Doppler and duplex are all used in this setting. Endovascular techniques are obviously different: in this case the angiography is part of the procedure itself. However, even in the presence of increased creatinine, long procedures or other relative contraindications, a completion angiography should always be performed at the end of the procedure to test for patency of the renal and iliac arteries and the presence of endoleaks [24]. The use of angioscopy in this setting has already been discussed.
1.12.2.2 Visceral Arteries Papers on visceral artery revascularization rarely report on intraoperative controls used after surgery. A recent article from the Mayo Clinic reviewed their experience with intraoperative duplex scan. Oderich et al. [21] described 68 patients who received arterial revascularization on 120 visceral arteries [coeliac artery in 52 cases, superior mesenteric artery (SMA) in 60, inferior mesenteric artery (IMA) in 8] between 1992 and 2001 [21]. Intraoperative duplex ultrasound was performed at the end of the procedure in all of them. Table 1.12..1 describes the parameters used to classify the defects for the coeliac artery and SMA. One hundred and two had normal findings (85%); 13 of them had nonfocal increased velocity due to vessel–graft mismatch. Eight arteries (6.6%) had minor defects, while ten (8.4%) presented major alterations: four had a residual stenosis, two had a thrombus, another two a kink, and bidirectional flow and dissection were present in one artery each. All arteries with a major defect were immediately revised. In all cases the abnormality was confirmed during re-intervention. Only one case had a persistent major defect (bidirectional flow) after revision, while another two had a reduction of the residual stenosis to a minor defect. Perioperative mortality was 4.4% (3 cases): in two of them it was correlated to graft occlusion and in one there was a minor unrepaired defect in the vessel. Patients with abnormal intraoperative findings had a higher incidence of early thrombosis (14.2% versus 1%; p=0.04), late restenosis (18.2% versus 3.2%; p=0.08) and visceral re-intervention (21.4% versus 3.2%; p=0.03). Univariate analysis identified a positive association between graft-related complication/death and both abnormal intraoperative findings (55.5% versus 7.8%, Table 1.12.1 Classification of intraoperative duplex findings for visceral artery revascularization. Presence of abnormal velocities in the absence of any kind of visible defect was classified as calibre mismatch between graft and native vessel PSV (cm/s)
Ratio
B-mode
Coeliac artery
Superior mesenteric artery
-
Normal
< 2.0
< 2.75
<2
Normal
Minor defect
< 2.0
< 2.75
<2
Abnormal
Major defect
> 2.0
> 2.75
>2
Abnormal
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p=0.04) and single vessel revascularization (35.7% versus 10.8%, p=0.4). Multiple regression analysis confirmed the presence of abnormal intraoperative findings as the only independent risk factor for graft-related complication/ death (OR 7.08; 95% CI 1.65–30.4; p=0.08).
1.12.2.3 Renal Arteries For renal revascularization ultrasound has always been the first choice. In fact angiography has its major limitation in the poor renal function of the patients undergoing this type of surgery. Moreover, due to its anterior location, the proximal anastomosis of an aorto-renal by-pass is not easily shown with the distal one in a single projection. For this reason a second shot is usually required, thus increasing the use of contrast dye. Four different studies aimed to report on intraoperative ultrasound for renal revascularization. In the first experience, Okuhn et al. [22] reported on 96 arterial reconstructions: out of these only 83 were renal. B-mode scans (narrowing, flap or thrombus), spectral broadening and flow velocities determined the classification of the examination as normal or abnormal. Sixtyfive arteries had normal findings (68%) and 31 abnormal (32%). A postoperative confirmatory examination was available for 73 of 96 arteries (76%). Assuming these examinations to be truthful, this means that intraoperative duplex findings among renal arteries have 85% sensitivity and 75% specificity. The Winston–Salem group published in 1991 their experience with intraoperative ultrasound [13]. In a 25month period they performed 41 renal reconstructions followed by intraoperative ultrasound. Only 35 patients with 57 arteries had follow-up, but in one case the examination was not satisfactory, leaving 56 arteries for analysis. Table 1.12.2 shows the classification of the defects used for this study. There were 13 defects. Seven minor
defects were not revised. Six major were revised: at revision the abnormality was confirmed to be present in all cases. Follow-up was obtained on all living patients (two deaths). Normal intraoperative findings resulted in a 98% patency at follow-up. Minor defects had a 100% patency (one case at autopsy). Among six major defects four arteries were patent, one had an early restenosis and one occluded. These results lead to 86% sensitivity and 100% specificity for intraoperative ultrasound. The Mayo Clinic experience was reported by Dougherty et al. [10]. In all, 35 patients had 64 arteries reconstructed. Intraoperative classification was similar to that used by Winston–Salem; only severely dampened systolic/diastolic flow was added as a major defect. Seven arteries were revised because of major defects (11%); in all cases ultrasound findings were confirmed at revision and in all but one the defect was correctable. Postoperative studies were obtained in 43 of 64 arteries. If we consider only a major defect as the primary end-point, intraoperative ultrasound had 100% sensitivity and 98% specificity. A more recent paper from van Weel et al. [34] reports on 73 renal revascularization procedures where both intraoperative duplex was performed and follow-up studies were available. Sixty-seven arteries (91.8%) were found to be normal at intraoperative duplex, while only six (8.2%) required revision. In only two cases was the presence of the defect confirmed at re-intervention. However, despite the absence of surgical correction, the subsequent duplex showed improvement of the parameters in all cases. The authors conclude that, assuming those four cases as true positive, duplex had 66.7% sensitivity and 100% specificity. In conclusion the available literature indicates that intraoperative duplex is an accurate mean of obtaining quality control during renal artery revascularization. This seems to be mandatory, especially if we consider that early occlusion has a prohibitive rate of kidney loss [14].
1.12.3 Lower Extremity By-pass Table 1.12.2 Classification of intraoperative duplex findings for renal artery revascularization. Presence of abnormal velocities in the absence of any kind of visible defect was classified as calibre mismatch between graft and native vessel PSV
B-mode
Normal
< 2.0 m/s
Normal
Minor defect
< 2.0 m/s
Abnormal
Major defect
> 2.0 m/s and turbulence
Abnormal
Five factors contribute substantially to maintaining the patency of lower extremity by-passes. They are: • appropriate inflow • appropriate outflow • low thrombogenicity of the conduit • absence of technical defects • individual factors such as the patient’s coagulation function.
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ography was performed. Among by-passes in the lower extremities, angiography showed technical problems in 2.2% of the grafts. Papers published later confirmed the role of completion angiography in the improvement of the patency of the reconstructions and its superiority to physical examination and CW Doppler. Mills et al. [20] performed a completion angiography at the end of the procedure on all but one of the 214 reversed vein by-passes. In 18 cases a technical error was shown (8%); femoropopliteal grafts had fewer defects (6%) than femorodistal ones (12%). In only three cases was the presence of a defect suspected on the basis of the physical examination or CW Doppler measurement. Early occlusion occurred in seven cases, but only in two of them was a technical defect found, leading to 90% sensitivity and 98% specificity for angiography. Marin et al. [19] evaluated 78 infrapopliteal by-passes to grade the lesions found at angiography into four classes. Six class I lesions did not require revision. Eighteen by-passes in classes I and II received minimal treatment, such as urokinase or papaverine infusion. Surgical revision was performed on 15 grade III lesions (total cut-off of the graft or outflow artery, opacification or irregular intraluminal filling defects of distal by-pass or outflow artery). When compared to 39 by-passes with no visible defect (class 0) classes I and II together showed no difference in their patency rates at 30 days and 1 year (87% and 82% versus 87% and 79%). Grade III lesions had poorer results (33% and 27%) despite surgical revision. The authors concluded that angiography might not always be able to define appropriately the extent of the problem associated with the defect. Later, angiography was further improved with the introduction of digital subtraction. However, this technique requires expensive equipment, trained personnel and a longer time to be performed. The advantage of angiography is the ability to provide information on both the reconstruction and distal run-off. This fact is particularly important in the emergent procedures: in these cases the surgeon often faces an unknown vascular tree, where the poor status due to the underlying disease can compromise any successful attempt to solve the acute problem (Fig. 1.12.1).
1.12.3.2 Ultrasound (CW Doppler, PW Doppler, Duplex, Colour Duplex) In the 1980s some authors explored the possibility of testing the reconstruction with CW Doppler and pulsed Doppler, in an effort to avoid using angiography. The re-
sults were encouraging, but the technology was still poor, not allowing different defects to be distinguished, such as valve cusps or the presence of a fistula [32]. With the introduction of duplex scanners and colour duplex scanners, the accuracy of this method increased. MacKenzie, of the McGill University in Montreal, reported on 78 infra-inguinal by-passes where duplex was used as an intraoperative control [18]. The cut-off used to determine the need for re-intervention was: PSV > 200 cm/s and < 45 cm/s and a velocity ratio >2. Thirty bypasses met the criteria for revision, but only 12 were reopened. In the latter group, surgeons felt the defects were reversible or not correctable. When they analysed the 6-months primary and secondary patency for the three groups, they found a significant difference between the first two groups (93% and 97% for the normal and 91% and 100% for the revised) when compared to the group that was not revised (53% and 71%); this result was confirmed by the log-rank test on the Kaplan–Meier curves (p<0.001). Doppler and later duplex have been extensively studied by the group of Bandyk. The landmark paper reported in 2000 on 626 infra-inguinal procedures receiving intraoperative duplex at the end of the procedure [16]. The protocol required a 30-mg papaverine injection inside the by-pass to be performed before scanning to obtain maximum vasodilatation of the run-off, thus enhancing the sensitivity of the test. Table 1.12.4 shows the classifica-
Fig. 1.12.2 Intraoperative duplex showed an end-diastolic velocity (EDV) of 0 cm/s and an increase in the peripheral vascular resistance (PVR) on the tibioperoneal trunk. The by-pass occluded a few days later despite aggressive antithrombotic and anticoagulant therapy
1.12.3 Lower Extremity By-pass
Table 1.12.4 Classification of intraoperative duplex findings for infra-inguinal by-passes. (Vr Velocity ratio) Stenosis category
PSV (cm/s)
Normal
Vr
Interpretation
<125
1–2
Moderate
125–180
2–2.5
Severe
180–300
2.5–5
>300
>5
High-grade
Normal Residual abnormality: rescan after a second papaverine dose. Consider angiography Significant abnormality. Revise or perform angiography Critical lesion: revise
Modified from [16]
Table 1.12.5 Algorithm for management of low-flow infra-inguinal by-passes. (LMWH Low molecular weight heparin, PVR peripheral vascular resistance) Category
Graft flow velocity
PVR
Interpretation and management
Normal
> 45 cm/s
Low
Normal graft flow: dextran and aspirin
Low flow, low PVR
< 45 cm/s
Low
Heparin or LMWH, dextran, aspirin
Low flow, high PVR
< 45 cm/s
High
Consider adjunctive procedure to increase flow; if not possible, treat as low flow graft
Low
Repair stenosis; heparin or LMWH, dextran, aspirin
Low flow, graft stenosis
> 200 cm/s at anastomosis
Modified from [16]
tion of the stenosis according to the parameters recorded. Ninety-six by-passes (15%) had major defects at duplex scan and 53 (8%) had minor defects, which were left unrepaired. All major defects were revised and only one was not confirmed at redo surgery. If 67 of them normalized after revision, 29 had a residual moderate stenosis, leaving a total of 82 arteries with moderate stenosis and 531 normal arteries for follow-up. Among the abnormal group the 90-days thrombosis/stenosis rate was 40%, which was significantly higher than the 2.5% rate for normal arteries. The aforementioned classification was used to grade only normal flow conduits. For this reason Bandyk considered another two factors for judging low-flow conduits: a PSV less than 45 cm/s and peripheral vascular resistance (PVR). Table 1.12.5 shows the algorithm used according to different patterns. It is remarkable to note that among 13 low-flow conduits, 38% developed a thrombosis within 3 months. Clearly the classification adopted from Bandyk applies only to normal-flow conduits. For this reason the group of Walsh and Cronenwett of New Hampshire [28] studied 45 infrapopliteal by-passes at high risk of failure: 20% had poor outflow (defined as small, <1 mm, arteries, need for endarterectomy at the anastomotic site or
no direct line to the foot); and 31% had “disadvantaged” conduits (composite grafts, sclerotic segments in the vein and spliced veins). At 12 months 25 were patent and 20 occluded. Two of them were found to have retained valve leaflets, while in 18 cases the reason was attributed to the poor outflow or disadvantaged conduit. Among failed by-passes PSV <45 cm/s failed to predict occlusion (35% sensitivity and 36% specificity). With regression analysis only EDV <8 cm/s was able to predict thrombosis at 12 months (p<0.05), with 76% sensitivity and 75% specificity (Fig. 1.12.2). It is important to note that all by-passes with EDV = 0 cm/s failed within 6 months. A recent paper compared, in a small series, duplex with angiography in a community hospital, resulting in a 100% correlation between the two methods [29]. However, angiography was more expensive (650 $) when compared to duplex (350 $) and took longer.
1.12.3.3 Angioscopy Angioscopy was introduced in the late 1960s, when Vollmar first used a rigid angioscope to evaluate an endar-
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terectomy performed with rings. Since then the improvement of technology and the introduction of optic fibres has led to smaller, flexible instruments. Its use is mainly limited to in situ vein grafts, where it allows direct visualization of the whole vein, allowing complete lyses of the valves and ligation of collateral branches. Gilbertson et al. [11] published the first series that compared angioscopy to angiography and duplex on this particular type of graft. Twenty patients underwent the three tests. Angioscopy had the best sensitivity for side branches (66% versus angiography 44% and duplex 11%; p<0.01) and cusps (100% versus 22% and 11%; p<0.01). Since none of the stenoses found were confirmed at revision, comparison needs to be performed using the false-positive rate: again angioscopy had the best results, with 0% compared to 20% for angiography and 10% for duplex. One of the advantages of this method is the possibility of immediately correcting the defects, by introducing operating instruments through the angioscope inside the vessel or allowing small skin incisions through the exact location of a side branch. The limit is mainly the cost and the difficulty of examining the distal anastomosis. The latter is particularly important, as this is the site where most of the defects are usually located.
1.12.3.4 Flowmetry Lepäntalo and coworkers in Finland have extensively studied this technique. Two recent papers from this group showed the benefits of flowmetry in predicting poor patency and stenosis development. In the first one [2], they recorded rest flow and maximum flow capacity, the latter by injecting 40 mg of papaverine before measurement. There was a significant difference (p<0.001) in the primary assisted patency for infrapopliteal by-passes with a maximum flow >90 ml/min and those with a flow <90 ml/min. In a logistic regression model aimed at finding predictors of 1-year failure, maximum flow capacity had a 0.53 relative risk for every 30 ml/min increase in blood flow (protective effect); this was highly significant (p<0.001). A later study divided the by-passes according to flow quartiles [15]. Using Kaplan–Meier survival analysis, the authors were able to correlate poor flow to the development of stenosis (10% at 2 years for the highflow group, compared to 39%, 38% and 36% for the other three groups; p=0.027). This was confirmed also at multiple regression analysis, where low flow and female sex were the only independent predictors.
1.12.3.5 Conclusions All the methods described above were able, when appropriately used, to provide accurate evaluation of the technical adequacy of lower extremity arterial reconstructions. It is our opinion that, due to its accuracy and lack of potential harm, duplex scan should be the first choice. Angiography is certainly preferred whenever outflow status knowledge is missing, such as during emergency procedures, and if a combined endovascular procedure is planned or potentially required. Angioscopy is undoubtedly best used for in situ vein grafts, but needs to be associated with another method able to provide information on the distal anastomosis. Flowmetry has the advantage of being the fastest and cheapest method, but its sensitivity is still poor and it seems to be a better predictor of mid-term results rather than technical adequacy.
1.12.4 Carotid Arteries The role for carotid endarterectomy in the prevention of stroke is well established. Randomized trials have confirmed its effectiveness when compared to best medical treatment. However, surgery needs to maintain high-level standards; in fact morbidity and mortality should be under 7% for symptomatic, and under 3% for asymptomatic, disease. To be able to obtain these results technical perfection is mandatory. Angiography was the first method tested as quality control. In 1978 Anderson et al. [3] reported on 131 angiographies. Seven patients (5.3%) had major defects, which were revised. Only three with complications related to angiography were observed: all of them required surgical correction (for carotid occlusion), and one of them resulted in a stroke. None of the patients revised for the presence of defects had complications. Coubier et al. [8] published a comparison between two consecutive series before and after the introduction of intraoperative angiography. Out of 100 patients in the second series, only 5 were revised due to major defect, while another 37 had minor defects (3 were spasms) and 58 had normal results. Among patients with normal angiography only 3.5% were found to have a restenosis at a mean follow-up of 19 months. When comparing clinical outcome in the two series, patients undergoing intraoperative angiography had 2% stroke rate; patients without angiography, 8.2%. However, there is a substantial differ-
1.12.4 Carotid Arteries
ence in the preoperative characteristics: only 38% were asymptomatic in the old series compared to 58% in the new one. When ultrasounds were first introduced, they did not obtain the expected results: Seifert and Blackshear [31] used CW Doppler on 229 carotid endarterectomies and found 30 abnormal cases: in 10 of them the internal carotid artery was involved. Two underwent immediate revision, while in 8 an angiography was performed. Five defects were confirmed, thus leading to 70% sensitivity only when compared to angiography. Dilley used B-mode echotomography to detect anomalies after endarterectomy and compared it to angiography [9]. Twelve defects were found in 158 patients (8.3%); four were found by both techniques, three by B-mode only and five by angiography only. These results confirmed angiography as the gold standard. In 1988 Bandyk compared angiography and duplex in 235 patients undergoing 250 CEA [5]. Duplex found 20 severe defects, but only 10 were confirmed by angiography. These patients were promptly revised and surgery confirmed the diagnosis. In another 10 carotids duplex indicated the presence of a severe flow disturbance, while no defect was visible at angiography. For this reason none was revised. Two of them experienced major neurological deficit in the recovery room and were revised. Both had a complete thrombosis and experienced a stroke; one patient died. Eight patients were asymptomatic, but developed restenosis of >50% in three cases and of <50% in the remaining five. This study showed that the more the ultrasound technology improved, the more this was able to overcome angiography. The problem encountered with duplex was that a lot of minor defects were visible and physicians were not sure about the behaviour of these lesions. Sawchuck studied the fate of 21 unrepaired minor defects found at duplex [30]. Only one flap of the external carotid artery occluded. Among nine defects on the internal, seven resolved and two developed a stenosis of <30%. An elegant paper from University of California, San Francisco (UCSF) reported in 1990 on 131 carotids where a completion duplex was performed at the end of the procedure [25]. They divided the carotid bifurcation into operated and nonoperated segments. They recorded if any segment was not visible or poorly visualized. They also classified the defects detected according to their size. Any defect in a nonoperated segment was defined as residual disease, while defects in the operated ones were flaps. Excluding the external carotid artery, only 10% of the com-
mon-internal segments were not visualized. This rate further reduced down to 5% if the proximal common carotid was not taken into consideration. The percentage of narrowing and length of the flap relative to segment diameter classified the defects. Fifteen arteries were found to have at least one defect at intraoperative control and were therefore revised. In seven cases the internal carotid was involved; the common carotid artery in three. Follow-up studies were performed at 1, 3 and 6 months. Restenosis was classified according to the percentage of narrowing from 0 (no restenosis) to 6 (100%). The authors built an ordinal logistic regression model using several local and systemic factors to predict the severity of restenosis. Among technical factors only intraoperative size defect predicted severity of restenosis (p=0.0175). Among systemic factors hypertension, smoking and cholesterol were positively associated with restenosis. Similar results were found by Kinney a few years later [17]. Among 461 carotids operated in 430 patients, 410 (89%) received an intraoperative duplex scan. An angiography was added in 268 of them, while the remaining 51 patients received physical examination and clinical inspection only. Twenty-six carotids were revised based on the classification in Table 1.12.6 (Figs. 1.12.3, 1.12.4). Three of them had moderate flow disturbance at redo duplex scan. After all revisions 337 arteries had normal flow, 73 moderate disturbance and 51 were unknown, not having had any test. At 1 month no strokes were recorded in the group not receiving any test. Seven strokes occurred in the 337 patients in the normal-flow group, compared to 3/73 (4.1%) among the moderate abnormal flow one (p=NS). This difference increased at 5 years (3.9% versus 9.3%) but still it was not statistically significant. Estimated survival analysis for freedom from restenosis showed a significant difference between normal duplex arteries when compared to either the untested group or the abnormal one. Multiple regressions indicated that female gender had 2.8 relative risk of developing carotid restenosis (95% CI 1.21–6.723; p=0.024), while normal completion duplex had a protective effect (RR 0.276; 95% CI 0.126–0.604; p=0.0015). Only normal duplex was significantly inversely related to long-term ipsilateral stroke (RR 0.173; 95% CI 0.031–0.965; p=0.037). Baker et al. [4] reviewed 316 carotids operated in 283 patients. They patched 153 vessels (48.4%), the remaining being primary closure. A 3-mm cut-off was used to distinguish between major and minor defects at intraoperative duplex (Fig. 1.12.5). This was positive in 254 arteries (80.4%) and abnormal in 62 (19.6%). Nine of
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Fig 1.12.3 Normal intraoperative duplex scan of a carotid artery. PSV reaches 60 cm/s
Fig. 1.12.5 Small flaps inside an operated internal carotid artery
Table 1.12.6 Classification of intraoperative duplex findings for carotid endarterectomy. (SB Spectral broadening) Grade Normal
Diameter reduction (%) 0–15
PSV (cm/s)
Spectral analysis
< 100 No or minimal SB
Mild
16–49
100–125 SB only in diastole
Moderate
50–75
126–150 SB in systole and diastole
> 75
> 150 SB in systole and diastole
Severe
Modified from [17]
Fig. 1.12.4 Abnormal velocities recorded during intraoperative duplex following carotid endarterectomy. A platelet aggregate is clearly visible. The PSV right after the defect is about 300 cm/s
them were major defects (14.5%); all of them were revised and the abnormality was confirmed at surgery in all but one (only turbulent flow). None of the 53 minor defects (85.5%) was reopened. Early stroke rate was 1.6%; duplex follow-up was done at 1 day, 6 months and then every 12 months. Among normal carotids four patients experienced a stroke (1.3%); this was not significantly different from the percentage for the group with unrepaired defects (1 stroke – 1.9%). Recurrent stenosis occurred in eight patients with normal intraoperative findings (3.1%),
four of them on the first postoperative day and four at late controls. Nine restenoses occurred among those 52 patients who had unrepaired defects (17.5%). The difference was highly significant (p=0.002). No neurological complications were recorded among patients revised and only one restenosis was seen at 6 months. A significant difference in restenosis rate was noted when patched arteries were compared to primary closure technique (2.6% versus 9.2%, p=0.025). Another recent study confirmed the correlation between unrepaired minor defects and restenosis. Padayachee studied 244 arteries [23]; in 76 cases a shunt was used and only 37 cases were patched. Intraoperative duplex found 52 stenoses: according to flow velocity 18 were severe stenosis of the internal carotid, but they re-
References
vised only 9 of them where a flap was associated with the increased PSV. This left 41 arteries with an untreated defect for follow-up and 172 with normal findings. In the latter group restenosis rate was 23%, significantly lower (p<0.0001) than the 51% observed in the normal one. It is interesting to note that all the nine arteries with severely increased flow velocity that were left untreated showed some kind of stenosis regression at follow-up. No correlation was shown between the presence of defects at intraoperative control and postoperative stroke or occlusion. A comparison between intraoperative duplex and angiography was the aim of a study by Valenti et al. [33]. They reported on 141 CEA on 138 patients. All arteries received an intraoperative duplex and angiography at the end of the procedure. The operating surgeon read the results. Thirty-six defects were detected, but only four were major defects, which required revision. Among 32 minor defects, duplex was able to pick up 28 of them, while only 19 were visible at angiography. These results led to 100% sensitivity and specificity for both techniques, but 87% specificity for duplex compared to 59% of angiography for minor defects. To conclude, the reported studies underline the importance of coupling morphology and physiological parameters. Flaps alone are often benign lesions, which improve with time and usually disappear during the remodelling that occurs after endarterectomy. At the same time increased flow velocity without visible defects might be caused by spasm or calibre change and rarely threaten the operated artery. Duplex scan can provide both kinds of information. It is relatively cheap, safe and accurate. The major flaw is that the operator needs adequate training and experience to be able to discriminate between small benign lesions and the others that can really jeopardize the short- and long-term results of the operation. References 1. Albäck A, Lepäntalo M (1998) Immediate occlusion of in situ saphenous vein bypass grafts: a survey of 329 reconstructions. Eur J Surg 164:745–750 2. Albäck A, Roth WD, Ihlberg L, Biancari F, Lepäntalo M (2000) Preoperative angiographic score and intraoperative flow as predictors of the mid-term patency of infrapopliteal bypass grafts. Eur J Vasc Endovasc Surg 20:447–453 3. Andersen CA, Collins GJ, Rich NM (1978) Routine operative arteriography during carotid endarterectomy: a reassessment. Surgery 83:67–71 4. Baker WH, Koustas G, Burke K, Littoy FN, Greisler HP (1994) Intraoperative duplex scanning and late carotid artery stenosis. J Vasc Surg 19:829–833
5. Bandyk DF, Kacbnick HK, Adams MB, Towne JB (1988) Turbulence after carotid bifurcation endarterectomy: a harbinger of residual and recurrent carotid stenosis. J Vasc Surg 7:261–274 6. Carmo M, De Angelis GAT, Tassinari L, Roveri S, Mercandalli G, Merlini D, Settembrini PG (2002) Controllo di qualità intraoperatorio con ecocolor doppler in chirurgia carotidea. In: Pratesi C, Pulli R (eds) Chirurgia della carotide extracranica. Minerva Medica, Turin, pp 292–298 7. Courbier R, Jausseran JM, Reggi M (1977) Detecting complications of direct arterial surgery. The role of intraoperative arteriography. Arch Surg 112:1115–1118 8. Courbier R, Jausseran JM, Reggi M, Bergeron P, Formichi M, Ferdani M (1986) Routine intraoperative carotid angiography: its impact on operative morbidity and carotid restenosis. J Vasc Surg 3:343–350 9. Dilley RB, Bernestein EF (1986) A comparison of B-mode real-time imaging and arteriography in the intraoperative assessment of carotid endarterectomy. J Vasc Surg 4:256–262 10. Dougherty MJ, Hallett JW, Naessens JM, Bower TC, Cherry KJ, Gloviczki P, James EM (1997) Optimizing technical success of renal revascularization: the impact of intraoperative color-flow duplex ultrasonography. J Vasc Surg 17:849–857 11. Gilbertson JJ, Walsh DB, Zwolak RM, Waters MA, Musson A, Magnant JG, Schneider JR, Cronenwett JL (1992) A blinded comparison of angiography, angioscopy and duplex scanning in the intraoperative evaluation of in situ saphenous vein bypass grafts. J Vasc Surg 15:121–129 12. Gloviczki P, Merrell SW, Bower TC (1991) Femoral vein valve repair under direct vision without venotomy: a modified technique with use of angioscopy. J Vasc Surg 14:276–279 13. Hansen KJ, O’Neil EA, Reavis SW, Craven TE, Plonk GW, Dean RH (1991) Intraoperative duplex sonography during renal artery reconstruction. J Vasc Surg 14:364–374 14. Hansen KJ, Deitch JS, Oskin TC, Ligush J, Craven TE, Dean RH (1998) Renal artery repair: consequence of operative failures. Ann Surg 227:678–689 15. Ihlberg LHM, Albäck NA, Lassila R, Lepäntalo M (2001) Intraoperative flow predicts the development of stenosis in infrainguinal vein grafts. J Vasc Surg 34:269–276 16. Johnson BL, Bandyk DF, Back MR, Avino AJ, Roth SM (2000) Intraoperative duplex monitoring of infrainguinal vein bypass procedures. J Vasc Surg 31:678–690 17. Kinney EV, Seabrook GR, Kinney LY, Bandyk DF, Towne JB (1993) The importance of intraoperative detection of residual flow abnormalities after carotid artery endarterectomy J Vasc Surg 17:912–923
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18. MacKenzie KS, Hill AB, Steimetz OK (1999) The predictive value of intraoperative duplex for early vein graft patency in lower extremity revascularization. Ann Vasc Surg 13:275–283 19. Marin ML, Veith FJ, Panetta TF, Suggs WD, Wengerter KR, Bakal C, Cynamon J (1993) A new look at intraoperative completion arteriography: classification and management strategies for intraluminal defects. Am J Surg 166:136–139 20. Mills JL, Fujitani RM, Taylor SM (1992) Contribution of routine intraoperative completion arteriography to early infrainguinal bypass patency. Am J Surg 164:506–511 21. Oderich GS, Panneton JM, Macedo TA, Noel AA, Bower TC, Lee RA, Cha SS, Gloviczcki P, Cherry KJ (2003) Intraoperative duplex ultrasound of visceral revascularizations: optimizing technical success and outcome. J Vasc Surg 38:684–691 22. Okuhn SP, Reilly LM, Bennett JB, Hughes L, Goldstone J, Ehrenfeld WK, Stoney RJ (1987) Intraoperative assessment of renal and visceral artery reconstruction: the role of duplex scanning and spectral analysis. J Vasc Surg 5:137–147 23. Padayachee TS, Arnold JA, Thomas N, Aukett M, Colchester ACF, Taylor PR (2002) Correlation of intra-operative duplex findings during carotid endarterectomy with neurological events and recurrent stenosis at one year. Eur J Vasc Endovasc Surg 24:435–439 24. Reed A, Mozes G, Carmo M, Andrews JC, Macedo TA, Gloviczki P (2004) Renal artery coverage during endovascular aortic aneurysm repair: proximal migration or misplacement of the graft. Persp Vasc Endovasc Surg 16:135–140 25. Reilly LM, Okhun SP, Rapp JH, Bennett JB, Ehrenfeld WK, Goldstone J, Stoney RJ (1990) Recurrent carotid stenosis: a consequence of local or systemic factors ? The influence of unrepaired technical defects J Vasc Surg 11:448–460 26. Renwick S, Royle JP, Martin P (1968) Operative angiography after femoropopliteal arterial reconstruction: its influence on early graft failure rate. Br J Surg 55:134–136
27. Robinson KD, Sato DT, Gregory RT, Gayle RG, DeMasi RJ, Parent FN, Wheeler JR (1997) Long term outcome after early infrainguinal graft failure. J Vasc Surg 26:425–437 28. Rzucidlo EM, Walsh DB, Powell RJ, Zwolak RM, Fillinger MF, Schermerhorn ML, Cronenwett JL (2002) Prediction of early graft failure with intraoperative completion duplex ultrasound scan. J Vasc Surg 36:975–981 29. Sawaqed RS, Podbielski FJ, Rodriguez HE, Wiesman IM, Connolly MM, Clark ET (2001) Prospective comparison of intraoperative angiography with duplex scanning in evaluating lower extremity bypass grafts in a community hospital. Am Surg 67:601–604 30. Sawchuck AP, Flanigan DP, Machi J, Schuler JJ, Sifel B (1989) The fate of unrepaired minor technical defects detected by intraoperative ultrasonography during carotid endarterectomy. J Vasc Surg 9:671–676 31. Seifert KB, Blackshear WM (1985) Continuous-wave doppler in the intraoperative assessment of carotid endarterectomy. J Vasc Surg 2:817–820 32. Spencer TD, Goldman MH, Hyslop JW, Lee HM, Barnes RW (1984) Intraoperative assessment of in situ saphenous vein bypass grafts with continuous-wave Doppler probe. Surgery 96:874–877 33. Valenti D, Gaggiano A, Berardi G, Ferri M, Mazzei R, Roda G, Palombo D (2003) Intra-operative assessment of technical defects after carotid endarterectomy: a comparison between angiography and colour duplex scan Cardiovasc Surg 11:26–29 34. van Weel V, van Bockel JH, van Wissen R, van Baalen JM (2000) Intraoperative renal duplex sonography: a valuable method for evaluating renal artery reconstructions. Eur J Vasc Endovasc 20(3):268–272 35. Walsh DB (2000) Technical adequacy and graft thrombosis. In: Rutherford RB (ed) Vascular surgery. Saunders, Philadelphia, p 720
Cerebrovascular Arteries
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2.1 Haemodynamic Changes and Other Risk Factors for Complications During Carotid Procedures Hakan N. Parsson
2.1.1 Cerebral Blood Flow
Table 2.1.1 Cerebral blood flow pathology Loss of autoregulation
The brain’s ability to keep cerebral blood flow (CBF) relatively constant despite changes in systemic blood pressure (BP) is due to cerebrovascular autoregulation. The actual cerebral perfusion pressure (CPP) depends on the BP and the intracranial pressure (ICP). The aim with cerebral autoregulation is to keep CBF independent of systemic changes in BP. In clinical practice, transcranial Doppler (TCD) is commonly used for both dynamic and static measurements of intra-cerebral flow velocity as an indicator of cerebral perfusion [10]. Other methods less frequently used to measure cerebral perfusion include: • Arterio-jugular oxygen content difference, • Transit time flowmetry, • Cerebral oximetry, • Positron emission tomography (PET) [14]. Loss of autoregulation in areas of previous cerebral infarction and those compromised by recent embolization is well recognized [23] (Table 2.1.1). This makes the brain more vulnerable to changes in BP. The association of severe carotid artery stenosis with cerebral haemodynamic dysfunction has also been documented. Insufficient cerebral collateral flow during occlusion of the internal carotid artery (ICA), such as by cross-clamping or balloon occlusion, may also result in inadequate perfusion. It is also important to recognize the possibility of adequate ipsilateral flow (>100 ml/min) even in the presence of a severely stenosed ICA (>90%) [14].
2.1.2 General Complications During carotid endarterectomy (CEA) as well as carotid angioplasty and stent placement (CAS), a significant in-
Insufficient collateral flow Hypoperfusion Hyperperfusion (HPS) Intracerebral haemorrhage (ICH)
stability of BP is frequently noted and can result in both hypertension and hypotension [18, 21]. The mechanism behind systemic hypertension during and after carotid artery manipulation seems to be transient dysfunction of adventitial baroreceptors in the endarterectomized area [6]. Infiltration of local anaesthetic into the periadventitial tissue around the carotid sinus might abolish this response [3]. Release of metabolic factors such as renin, vasopressin and cranial norepinephrine has also been described [2]. Sudden increases in CBF due to removal of a significant stenosis may also contribute to the hypertension. Postprocedural hypertension is a critical finding associated with hyperperfusion syndrome (HPS) or intracranial haemorrhage (ICH). This has been well described following CEA and is associated with significant morbidity and mortality. The incidence of HPS after CEA is <3%, with symptoms such as irritability, seizure and confusion, and rarely progresses to ICH if treated in time. The incidence of HPS and ICH after CAS seems to be about equal to that after CEA [1, 7]. The mechanisms involved include a chronic low-flow CBF due to significant carotid artery disease in combination with impaired autoregulation. Following reperfusion, loss of ability to change resistance in response to BP changes results in increased CBF. Patients with severe (>90%) carotid stenoses may be predisposed to ICH, particularly with concurrent hypertension and contralateral carotid occlusion. A more intense haemodynamic monitoring and aggressive treatment of hypertension such as β-blockers, nitroprusside
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2.1 Haemodynamic Changes and Other Risk Factors for Complications During Carotid Procedures
Table 2.1.2 General haemodynamic complications and treatment options Systemic hypertension
Nitroprusside, calcium antagonists, β-blockers
Systemic hypotension
Vasopressors, dopamine, phenylephrine
Bradycardia
Atropine
Table 2.1.3 Cerebral monitoring and protection General versus local anaesthesia Transcranial Doppler (TCD) Transit time flowmetry Arterio-jugular oxygen content difference Cerebral oximetry Positron emission tomography (PET)
and calcium antagonists are recommended (Table 2.1.2). A CT scan in patients with symptoms is recommended to exclude secondary haemorrhage and visualize cerebral oedema. Bradycardia sometimes in combination with hypotension is also frequently seen intraoperatively as well as in the immediate postoperative period. This has been attributed to increased activity from the carotid baroreceptors related to increased stretch and compliance in the arterial wall after removal of the atherosclerotic plaque. History of myocardial infarction (MI) also predisposes to postprocedural hypotension probably due to increased sensitivity of baroreceptors in patients with coronary artery disease. This is important during CAS too, which also involves manipulation of baroreceptors and the carotid sinus and contributes to haemodynamic instability. Bradycardia during CAS can be severe and result in asystole unless treated. Hypotension in the post dilatation period is common and adequate postprocedural monitoring of BP and electrocardiographic changes is important. Sameday discharge for patients after CAS may not be adequate with such a risk of instability [26]. Treatments include early administration of atropine and vasopressors. The need for significant pressor therapy may, however, contribute to postoperative myocardial ischaemia and infarction. In selected patients, prophylactic placement of a transvenous pacemaker can be used to treat periprocedural haemodynamic changes [6, 13].
2.1.3 Cerebral Monitoring and Protection During CEA Indications as well as methodology for cerebral monitoring and protection during surgical interventions are controversial issues. Several methods have been used to estimate adequate cerebral perfusion during ICA clamping (Table 2.1.3). Most patients have sufficient collateral flow
to allow for clamping without using a shunt, as demonstrated in CEA performed under local anaesthesia (LA). Shunting for ischaemia was necessary in 4.5% of all cases and in 19% of patients with contralateral occlusion using LA as the sole method for monitoring [15]. Four different approaches can be used to perform CEA with regard to cerebral monitoring and/or protection [12]: 1 Regional anaesthesia and shunting for patients who have changes in neurological status. 2 Deep general anaesthesia with no shunt. 3 General anaesthesia and use of cerebral monitoring such as TCD, EEG, stump pressure or oximetry. Patients with threshold values or changes are selectively shunted. 4 General anaesthesia with routine shunting. Regional anaesthesia is advocated by some clinicians because of the possibility of continuous neurological assessment and less haemodynamic instability. Disadvantages may include restlessness, anxiety and discomfort. It is well recognized that general anaesthetics have the ability to protect the brain during ischaemic conditions, mainly by decreasing oxygen demand (cerebral metabolic rate). Hypotension and tachycardia are frequent during general anaesthesia and often the administration of α1-adrenergic agonists such as phenylephrine is required, which in turn can lead to myocardial ischaemia. Controversy still exists over the optimal means for cerebral monitoring and anaesthesia, and no consensus has been agreed upon. An ongoing randomized clinical trial such as the GALA trial (General Anaesthesia vs Local Anaesthesia) might clarify these matters.
2.1.5 Adjuvant Medical Therapy
2.1.4 Cerebral Embolization during CEA and CAS Perioperative cerebral embolization during CEA or CAS is a potentially devastating complication and is probably correlated with the embolic potential of the plaque (Table 2.1.4). Echolucent plaques as measured by grey-scale median (GSM), obtained from standardized preoperative ultrasonography Duplex, seem to have increased plaque cellularity and a larger embolic potential [4, 11]. Some plaques also show thrombus associated with plaque rupture, indicating a possible vulnerable state [25]. This has been associated with an increased risk of stroke in both the preoperative and intraoperative period. Using ex vivo flow models, the highest embolic potential seems to be in the most severe stenoses. The use of preoperative statin treatment may reduce the amount of embolization, possibly by a stabilizing and anti-inflammatory effect [5]. Embolization during dissection and in particular during CA seems to be associated with the presence of an ulcerated plaque and associated thrombus. Intraoperative TCD monitoring can detect potentially harmful embolization during this stage, enabling the surgical technique to be modified appropriately [16]. The use of cerebral emboli protection devices during CAS, such as filters, can reduce the amount of embolization as measured by TCD [24] but currently no consensus has been agreed upon. Diffusion-weighted MRI (DWI) offers the possibility of visualizing even small and asymptomatic cerebral lesions shortly after their emergence. Recent studies have demonstrated more frequent ischaemic lesions after CAS as compared with CEA but the detected lesions did not cause neurological deficits [9, 20]. Following CEA or CAS the optimal flow surface should not be flow-limiting, and all embolic sources should be removed and minimally thrombogenic. Residual disease and technical defects are associated with perioperative strokes and restenosis. The aetiology includes:
Table 2.1.4 Cerebral embolization during carotid endarterectomy (CEA) and carotid angioplasty and stent placement (CAS) Embolic potential of the plaque During surgical dissection During CAS Postoperative embolization; technical problems
• • • •
Kinking of the vessel, Dissection, Flaps, Residual atheroma with embolic potential.
2.1.5 Adjuvant Medical Therapy Adjuvant medical therapy helps in decreasing the initial complication rate and includes pre- and postoperative antiplatelet agents [8] and perioperative anticoagulation (Table 2.1.5). Antiplatelet therapy should not be discontinued during the operative period. Agents include aspirin and clopidogrel. In a recent study preoperative clopidogrel in combination with aspirin significantly reduced the number of cerebral emboli as compared with heparin alone, however with some concerns of increased bleeding and an increased amount of ICH [19]. Intraoperative anticoagulation includes heparin, which promotes inactivation of thrombin and inhibits the activation of prothrombin. Ideally a target activated clotting time (ACT) should be used for heparin monitoring. However, heparin may, in combination with antiplatelet agents, predispose to postoperative bleeding. A recent study demonstrated increased platelet aggregation in response to arachidonic acid after heparin administration, despite adequate inhibition by aspirin administered preoperatively. This apparent reversal in antiplatelet activity persisted into the immediate early postoperative period, and could explain why a small proportion of patients are at increased risk for acute cerebrovascular and cardiovascular events despite aspirin therapy [27]. Heparin reversal by means of protamine carries an increased risk of postoperative complications. Several studies have demonstrated sustained micro-embolization in the immediate perioperative period following CEA as measured by TCD [17]. Intravenous administration of dextran seems to be beneficial in these situations. Abciximab, a nonselective glycoprotein IIb/IIIa inhibitor, has also been used during CAS with a
Aspirin Clopidogrel Heparin Dextran Abciximab Statins
Table 2.1.5 Adjuvant medical therapy
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reduced frequency of ischaemic stroke in high-risk patients. However, the benefit was lost because of an increased rate of ICH [22].
2.1.6 Conclusion The overall benefit of prophylactic CEA or CAS is dependent on the perioperative results regarding the combined risks of stroke and death. Major risk factors involve perioperative embolization and haemodynamic instability. Restoration of cerebral perfusion without neurological damage is the final endpoint. Meticulous techniques in respect to both the actual carotid lesion and cardiovascular care are extremely important in order to achieve a good outcome. References 1. Abou-Chebl A, Yadav JS, Reginelli JP, Bajzer C, Bhatt D, Krieger DW (2004) Intracranial hemorrhage and hyperperfusion syndrome following carotid artery stenting: risk factors, prevention, and treatment. J Am Coll Cardiol 43:1596–1601 2. Ahn SS, Marcus DR, Moore WS (1989) Post-carotid endarterectomy hypertension: association with elevated cranial norepinephrine. J Vasc Surg 9:351–360 3. Al-Rawi PG, Sigaudo-Roussel D, Gaunt ME (2004) Effect of lignocaine injection in carotid sinus on baroreceptor sensitivity during carotid endarterectomy. J Vasc Surg 39:1288–1294 4. Biasi GM, Froio A, Diethrich EB, Deleo G, Galimberti S, Mingazzini P, Nicolaides AN, Griffin M, Raithel D, Reid DB, Valsecchi MG (2004) Carotid plaque echolucency increases the risk of stroke in carotid stenting: the Imaging in Carotid Angioplasty and Risk of Stroke (ICAROS) study. Circulation 110:756–762 5. Bicknell CD, Cowling MG, Clark MW, Delis KT, Jenkins MP, Hughes AD, Thom SA, Wolfe JH, Cheshire NJ (2003) Carotid angioplasty in a pulsatile flow model: factors affecting embolic potential. Eur J Vasc Endovasc Surg 26:22–31 6. Bush RL, Lin PH, Bianco CC, Hurt JE, Lawhorn TI, Lumsden AB (2004) Reevaluation of temporary transvenous cardiac pacemaker usage during carotid angioplasty and stenting: a safe and valuable adjunct. Vasc Endovascular Surg 38:229–235 7. Coutts SB, Hill MD, Hu WY (2003) Hyperperfusion syndrome: toward a stricter definition. Neurosurgery 53:1053–1058
8. Engelter S, Lyrer P (2003) Antiplatelet therapy for preventing stroke and other vascular events after carotid endarterectomy. Cochrane Database Syst Rev CD001458 9. Flach HZ, Ouhlous M, Hendriks JM, Van Sambeek MR, Veenland JF, Koudstaal PJ, Van Dijk LC, Van Der Lugt A (2004) Cerebral ischemia after carotid intervention. J Endovasc Ther 11(3):251–257 10. Gaunt ME, Brown L, Hartshorne T, Bell PR, Naylor AR (1996) Unstable carotid plaques: preoperative identification and association with intraoperative embolisation detected by transcranial Doppler. Eur J Vasc Endovasc Surg 11:78–82 11. Goncalves I, Moses J, Pedro LM, Dias N, Fernandes e Fernandes J, Nilsson J, Ares MP (2003) Echolucency of carotid plaques correlates with plaque cellularity. Eur J Vasc Endovasc Surg 26:32–38 12. Hamdan AD, LoGerfo FW (2000) Should all patients be shunted? If not, how can I predict which patients will require a shunt? In: Naylor RA, Mackay WC (eds) Carotid artery surgery. Harcourt, London, pp 249–254 13. Harrop JS, Sharan AD, Benitez RP, Armonda R, Thomas J, Rosenwasser RH (2001) Prevention of carotid angioplastyinduced bradycardia and hypotension with temporary venous pacemakers. Neurosurgery 49:814–820 14. Kragsterman B, Parsson H, Bergqvist D (2004) Local haemodynamic changes during carotid endarterectomy – the influence on cerebral oxygenation. Eur J Vasc Endovasc Surg 27:398–402 15. Lawrence PF, Alves JC, Jicha D, Bhirangi K, Dobrin PB (1998) Incidence, timing, and causes of cerebral ischemia during carotid endarterectomy with regional anesthesia. J Vasc Surg 27:329–334 16. Lennard N, Smith J, Dumville J, Abbott R, Evans DH, London NJ, Bell PR, Naylor AR (1997) Prevention of postoperative thrombotic stroke after carotid endarterectomy: the role of transcranial Doppler ultrasound. J Vasc Surg 26:579–584 17. Mauney MC, Buchanan SA, Lawrence WA, Bishop A, Sinclair K, Daniel TM, Tribble CG, Kron IL (1995) Stroke rate is markedly reduced after carotid endarterectomy by avoidance of protamine. J Vasc Surg 22:264–269 18. Mendelsohn FO, Weissman NJ, Lederman RJ, Crowley JJ, Gray JL, Phillips HR, Alberts MJ, McCann RL, Smith TP, Stack RS (1998) Acute hemodynamic changes during carotid artery stenting. Am J Cardiol 82:1077–1081 19. Payne DA, Jones CI, Hayes PD, Thompson MM, London NJ, Bell PR, Goodall AH, Naylor AR (2004) Beneficial effects of clopidogrel combined with aspirin in reducing cerebral emboli in patients undergoing carotid endarterectomy. Circulation 109:1476–1481
References
20. Poppert H, Wolf O, Resch M, Theiss W, Schmidt-Thieme T, Graefin von Einsiedel H, Heider P, Martinoff S, Sander D (2004) Differences in number, size and location of intracranial microembolic lesions after surgical versus endovascular treatment without protection device of carotid artery stenosis. J Neurol 251:1198–1203 21. Qureshi AI, Luft AR, Sharma M, Janardhan V, Lopes DK, Khan J, Guterman LR, Hopkins LN (1999) Frequency and determinants of postprocedural hemodynamic instability after carotid angioplasty and stenting. Stroke 30:2086–2093 22. Qureshi AI, Suri MF, Ali Z, Kim SH, Lanzino G, Fessler RD, Ringer AJ, Guterman LR, Hopkins LN (2002) Carotid angioplasty and stent placement: a prospective analysis of perioperative complications and impact of intravenously administered abciximab. Neurosurgery 50:466–473 23. Reinhard M, Muller T, Roth M, Guschlbauer B, Timmer J, Hetzel A (2003) Bilateral severe carotid artery stenosis or occlusion - cerebral autoregulation dynamics and collateral flow patterns. Acta Neurochir 145:1053–1059
24. Schmidt A, Diederich KW, Scheinert S, Braunlich S, Olenburger T, Biamino G, Schuler G, Scheinert D (2004) Effect of two different neuroprotection systems on microembolization during carotid artery stenting. J Am Coll Cardiol 44:1966–1969 25. Spagnoli LG, Mauriello A, Sangiorgi G, Fratoni S, Bonanno E, Schwartz RS, Piepgras DG, Pistolese R, Ippoliti A, Holmes DR (2004) Extracranial thrombotically active carotid plaque as a risk factor for ischemic stroke. J Am Med Assoc 292:1845–1852 26. Tan KT, Cleveland TJ, Berczi V, McKevitt FM, Venables GS, Gaines PA (2003) Timing and frequency of complications after carotid artery stenting: what is the optimal period of observation? J Vasc Surg 38:236–243 27. Webster SE, Payne DA, Jones CI, Hayes PD, Bell PR, Goodall AH, Naylor AR (2004) Anti-platelet effect of aspirin is substantially reduced after administration of heparin during carotid endarterectomy. J Vasc Surg 40:463–468
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2.2 Extracranial Carotid Artery Disease José Fernandes e Fernandes, Luís Mendes Pedro
2.2.1 Introduction Ischaemic stroke represents a major health problem and an important cause of morbidity and mortality in several western countries [12]. Mortality from stroke ranges between 10% and 30% [61] and its survivors remain at a high annual risk of recurrent ischaemic events and mortality both from myocardial infarct and repeated stroke [76]. Atherosclerosis from supra-aortic vessels, especially from the common carotid bifurcation, is the major single aetiology of ischaemic stroke in developed countries as opposed to intracranial occlusive disease and cardioembolization. The association between internal carotid artery occlusion and severe ischaemic stroke was first credited to Savory [82], obtained from the autopsy of a woman
Fig. 2.2.1 First cerebral arteriogram performed by Egas Moniz
with a history of monocular blindness and contralateral hemiplegia and occlusion of the left carotid artery associated with bilateral subclavian occlusions. Subsequent descriptions were reported [33, 87] and in 1914 Ramsey Hunt published an important paper, which correlated the presence of diminished cervical carotid pulsations with intermittent neurological symptoms and drew attention to the need for “careful examination of the neck vessels” in such patients [49]. With the introduction of angiography, Egas Moniz [62] provided the first demonstration in vivo of occlusion of the internal carotid and stroke (Fig. 2.2.1) and also described the correlation between transient strokes and carotid bifurcation stenosis [63]. His observations were confirmed in subsequent studies using angiography [18, 51], although the established arteriographic technique routinely practised often failed to visualize the extracranial vessels [13, 42]. Embolization from carotid bifurcation lesions was suggested by Miller Fisher [35, 36] to be the pathogenic mechanism of ischaemic brain symptoms associated with extracranial carotid disease and led to the possibility of preventing stroke by eventual surgical correction of the diseased arteries. The most frequent lesion is stenosis at the common carotid bifurcation and origin of the internal carotid artery; however, atheroma of the aortic arch protruding into the ostia of the innominate and left common carotid arteries may cause severe flow-reducing stenosis and act as a source of cerebral embolization. Reconstructive surgery for chronic arterial occlusive disease started in Lisbon in 1947, with the introduction of endarterectomy by João Cid dos Santos [19], a technique conceived to be used for the obliteration of limb occlusive disease ideally in short segmental obstructions. The first carotid intervention was performed in Buenos Aires in 1951 by Carrea, Mollins and Murphy [17], consisting of resection of the proximal internal carotid segment and re-establishment of flow by anastomosing the external carotid to the distal internal carotid.
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DeBakey [24] described the first carotid disobliteration in 1953, in a patient with a complete occlusion, which succeeded in restoring flow. Eastcott, in 1954 [27], performed the first successful elective carotid operation on a patient with internal carotid stenosis and multiple transient ischaemic attacks (TIAs) in order to prevent stroke, resulting in the patient remaining asymptomatic for more than 30 years. Successful endarterectomy of the innominate artery with a 2-year follow-up was described in 1956 [21], followed by several reports of correction of proximal and/or ostial lesions at the aortic arch through by-pass procedures. The development of arterial catheterization for arteriography [83] and its widespread use provided easier diagnosis of extracranial disease as a major cause of brain ischaemia and set the stage for the generalized use of carotid surgery, aiming to restore arterial perfusion to the brain and avoid distal atheroembolization to prevent severe ischaemic syndromes. The 80 multicentre cooperative studies, in both Europe and the USA [29, 70], provided level 1 evidence for the benefit of carotid endarterectomy (CEA) in patients with transient neurological symptoms (TIAs) and reversible stroke; for carotid stenosis it was greater than 70%, contributing to a more appropriate and rational use of CEA. Reduction of surgical risk and the need for specific accreditation of surgeons and institutions for the treatment of extracranial carotid disease were recognized [64] in order to ensure greater benefit from CEA. The selection of patients for surgical treatment, and the need to reduce overall morbidity and mortality in patient management, both for symptomatic and asymptomatic patients, must be considered; the impact of the new endovascular surgical procedures requires careful re-evaluation of established concepts, to offer the best available treatment for each patient, and to provide guidelines for institutions and individual practitioners dealing with extracranial carotid disease.
2.2.2 Pathogenesis of Brain Ischaemia The mechanisms of neurological dysfunction in extracranial carotid disease are: • Atheroembolization – from local thrombosis associated with unstable plaques [53, 88]
• Haemodynamic – with reduction of cerebral blood flow, associated with sudden occlusion of a carotid artery, severe bilateral disease and ostial stenosis in the aortic arch Local thrombosis in ulcerated plaques results from disruption of its endothelial surface and fibrous cap causing: • Ulceration or subintimal haemorrhage • Platelet and erythrocyte aggregation to the subendothelial layer • Distal embolization of the thrombus and debris from the plaque contents These events are associated with clinical symptoms and progression of the atheromatous plaque [5, 7, 37, 54]. High-definition ultrasonography [9, 72, 79] and magnetic resonance imaging [90, 91] allow in vivo visualization of carotid bifurcation lesions in patients with symptoms of brain ischaemia. It is possible to identify markers of plaque activity, such as: • Echolucency • Presence of heterogeneity in its echostructure • Presence of echolucent areas near the arterial lumen • Surface disruption and/or ulceration (Fig. 2.2.2), which correlates with the presence of ipsilateral appropriate neurological symptoms [72] • Increased levels of elastin degradation products, cellularity and DNA contents of the plaque [39–41] Stroke occurs when there is brain infarct due to local reduction of cerebral blood flow (CBF), which is maintained around 45–50 ml/100 g of tissue per min by the mechanisms of autoregulation, for systolic blood pressures between 60 and 130 mmHg [4, 23, 31, 38, 56, 60]. With flow reduction (CBF <16 ml/100 g tissue per min) there is cessation of electrical brain activity, flattening of the EEG and failure to synthesize biochemical neurotransmitters, but the neuron may still be viable. When CBF is <10 ml/100 g tissue per min, disruption of aerobic metabolism, reduction of depolarization of the cell membrane and cell necrosis occur, leading to infarct [38]. There is a central area of necrosis, surrounded by an area of impaired function but viable tissue known as the ischaemic penumbra, its extent depending upon the functional capability of the collateral circulation. The severity of the stroke is correlated with the location and extent of the brain infarct, and also with the dysfunction of the penumbra area, which may be recovered by re-establishment
2.2.2 Pathogenesis of Brain Ischaemia
Fig. 2.2.2 High-definition ultrasonographic markers of risk in carotid plaques
of arterial flow. Haemorrhagic transformation may occur in 20% to 40% of brain infarcts during the first week after onset of symptoms [32], which limits the scope of arterial intervention in acute stroke with established infarct [89]. The onset, severity and duration of the neurological symptoms associated with carotid disease depend upon several factors: • Progression of the atheromatous plaque and presence of structural alterations predisposing to local thrombotic events. • Location of the atheroembolic material and the extent of the brain tissue area with flow impairment. • Compensation by the collateral circulation, with functional integrity of the circle of Willis and patency of the remaining extracranial arteries. The presence of transient or reversible neurological symptoms carries a higher risk of stroke at 1 year, repre-
senting a 16-fold increase when compared to the age- and sex-matched normal population. The European Carotid Surgery Trial (ECST) and North American Symptomatic Carotid Endarterectomy Trial (NASCET) confirmed a significant risk of stroke in patients with stenosis ≥70%, despite adequate antiplatelet treatment with aspirin [29, 70]. The stroke risk with severe incapacitating deficit increases to 60% and 70% in patients with progressing stroke. Asymptomatic carotid stenosis has an annual risk of ipsilateral stroke of between 1% and 2% [45, 59], but recent observations from multicentre randomized studies suggest that a significant risk reduction of stroke may be achieved by CEA in the presence of stenosis greater than 70% [30, 66]. Also, this benefit may be enhanced by the identification of high-risk lesions [68], that is those with higher potential for instability and embolization where a 5.3% annual risk of ipsilateral stroke was demonstrated.
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2.2.3 Clinical Manifestations 2.2.3.1 Amaurosis fugax • Monocular sudden loss of vision lasting for seconds or minutes, followed by full recovery of the normal vision. • Often related to atheroembolization from the carotid plaque, consisting mainly of cholesterol crystals, into the retinal vessels (Fig. 2.2.3). • Recent studies seem to suggest reduced risk of ipsilateral stroke in patients with amaurosis fugax when compared with hemispheric transient ischaemic attacks (TIAs) [86].
2.2.3.2 Transient/Reversible Cerebral Ischaemia Its clinical manifestations result from neurological dysfunction in the territory of the internal carotid artery and its main branches, the anterior and middle cerebral arteries. They can be: • Transient (TIAs), when lasting less than 24 h with full recovery. • Reversible, when the symptoms disappear after 24 h without neurological deficit. Symptoms depend upon the involved area, giving rise to contralateral motor and/or sensory deficit. Dysphasia/aphasia may also arise following dominant hemisphere lesions. • Crescendo TIAs, characterized by a succession of TIAs in a short period of time which could correspond to multiple embolization from active carotid plaques carrying an increased risk of permanent neurological deficit.
2.2.3.3 Established Stroke • A major neurological deficit lasting for more than 24 h with/without partial recovery, which may determine physical incapacity.
Fig. 2.2.3 Histologic examination of a carotid plaque removed by endarterectomy with cholesterol crystals surrounded by inflammatory infiltrate
2.2.3.5 Global Cerebral Ischaemia 2.2.3.4 Stroke in Evolution (“Waving and Waning”) • Persistent neurological dysfunction, with repeated exacerbations, corresponding to dysfunction of the ischaemic penumbra area.
• Progressive deterioration of the intellectual capacities. • Related to reduced cerebral perfusion associated with multiple occlusive lesions in the supra-aortic vessels.
2.2.4 Diagnosis
2.2.3.6 Asymptomatic Carotid Disease • Often associated with cervical bruits. • More prevalent in patients with atherosclerotic occlusive lesions in other territories (coronary and lower limbs). • May represent an increased risk of stroke without warning. • The specificity of cervical bruit as an indicator of carotid disease is only 50%, its absence being recognized in complete carotid occlusions or pre-occlusive stenosis with a residual luminal diameter <2 mm, where turbulence may be insufficient to produce an audible bruit.
2.2.4 Diagnosis 2.2.4.1 Arteriography • Arteriography has been the gold standard technique to demonstrate extracranial carotid occlusive disease. • It outlines the inner surface of the arterial wall by providing direct visualization of blood flow inside the artery acting as a mould of the lesions from the arterial wall. • It was first obtained by direct puncture of the common carotid. • Following the development of arterial catheterization, it became standard practice to do it through selective retrograde catheterization, from the femoral or brachial/axillary arteries, providing full visualization of the extracranial vessels (Fig. 2.2.4) and also of the intracranial circulation. • It provides no direct visualization of the arterial wall and its morphologic alterations, thus limiting its ability to reveal the underlying changes leading to stenosis or occlusion. • Its use as a diagnostic tool in extracranial carotid disease was limited by local complications from arterial access (haematomas, false aneurysms) requiring treatment, allergic reactions to the contrast and deterioration of renal function. • Digital subtraction techniques and the introduction of safer nonionic contrast media reduced its complications and improved the outcome of carotid arteriography, although recent published results [30] documented a stroke risk of 1.2%.
Fig. 2.2.4 Angiography of the carotid bifurcation showing a complex stenotic lesion involving the first portion of the internal carotid artery
2.2.4.2 Colour Flow Duplex Scan • Colour flow Duplex scan was introduced by Strandness et al. [85]. • It was a major turning point in vascular diagnosis, by providing safe, noninvasive and reliable technology to evaluate both the morphological changes within the arterial wall and their repercussions on blood flow. • It combines real-time B-mode ultrasound imaging technology with a pulsed Doppler flow detector and spectral analyser. • The effect of arterial stenosis on flow is recognized by acceleration with a significant increase in peak systolic and diastolic velocities in association with increased disorganization of the velocity spectra (Fig. 2.2.5c).
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Fig. 2.2.5a–c Quantification of the degree of stenosis by colour flow Duplex scan. a Diameter measurement of longitudinal section. b Area measurement on cross-section. c Haemodynamic assessment with peak systolic and end diastolic velocities calculation
Fig. 2.2.6 Computer-assisted carotid plaque analysis and determination of echogenicity using the GSM and P40 parameters
Several limitations of colour flow Duplex scan are recognized: • Difficult insonation at the base of the neck with failure to identify proximal stenotic lesions (innominate artery, left common carotid) that may require treatment, suspected by abnormal velocity tracings in the proximal common carotid artery. • Impossibility to visualize the distal segments of the internal carotid artery, which may be diseased (distal and/or siphon stenosis).
• Distinction between high-grade stenosis and complete occlusion, which could be overcome by new technological advances for recording low velocities and the use of acoustic contrast [57]. • Absence of information on the intracranial circulation and detection of stenosis and arterial aneurysms. • The clinical relevance of concomitant intracranial occlusive disease for the management of extracranial carotid disease has been controversial; siphon stenosis is rare – <6% – and its significance as a risk factor af-
2.2.4 Diagnosis
fecting the outcome of carotid endarterectomy or as a cause of recurrence of symptoms has not been confirmed [77]. • Cerebral aneurysms are also a rare event (<2%) [2] and can be suspected on the basis of clinical symptomatology, or by modern brain imaging techniques.
2.2.4.3 High-resolution Ultrasonography • High-resolution ultrasonography (HDU) with computerized analysis of the plaque structure provides a more precise and detailed study of the arterial wall and also objective measurement of plaque echogenicity, expressed as gray scale median (GSM) and P40 (percentage of pixels of echolucency) (Fig. 2.2.6) [73]. • Markers of plaque instability, such as disruption of its cap, ulceration, juxta-luminal location of echolucent areas and plaque heterogeneity, as described previously [73], can be identified. • These markers are powerful new tools for diagnosing vulnerable carotid plaques, monitoring their progression and assessing the potential effect of new pharmacological agents. • These wall changes identified by HDU may have clinical relevance, particularly in asymptomatic patients; in fact, plaque ulcerations identified by angiography represent an independent risk factor for cerebral events, with a cumulative effect, in association with the degree of stenosis [78].
2.2.4.4 Measuring the Degree of Stenosis • Appropriate measurement of degree of stenosis is essential for treatment selection [29, 30, 66, 70]. • Different methods have been suggested based on arteriography (Fig. 2.2.7) and discrepancies between these methods have been reported [69]. • Discrepancies can be overcome by B-mode ultrasonography and colour flow Doppler assessment, which provides accurate measurements of diameter and area reduction in complex and eccentric lesions (Fig. 2.2.5b). • Transcervical measurements have an excellent correlation with intraoperative evaluation of cross-sectional area reduction, obtained previously to endarterectomy.
Fig. 2.2.7 Most common methods for quantification of carotid stenosis by angiography
• Transcervical measurements combined with flow velocity changes provide higher specificity for the identification of severe carotid stenosis [71].
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2.2.4.5 Transcranial Doppler Examination • Transcranial Doppler examination (TCD) was first described by R. Aaslid [1] for the diagnosis of intracranial severe stenosis, and to assess the patency and function of the circle of Willis. • It can be obtained with colour flow Duplex imaging, allowing more precise evaluation of the intracranial arteries and it should be included in the overall evaluation of the patient suspected of having carotid artery disease. • Colour flow Duplex scan and TCD provide information equivalent to the classic four-vessel arteriography, without its risks, and are used routinely in our practice.
2.2.4.6 Other Flow-imaging Techniques • Other flow-imaging techniques such as MR angiography and rapid sequence CT scans of the neck may provide useful information; their accuracy and reproducibility are not superior to those of the colour flow Duplex scan when performed by an experienced operator, and their evaluation tends to overestimate the degree of stenosis [74].
2.2.4.7 Indications for Arteriography The present indications for arteriography in our practice today are limited to: • Failure to meet the requirements for adequate colour flow Duplex scan. • Patients with nonhemispheric symptoms and evidence of multi-vessel occlusive disease on the Duplex scan examination. • Suspicion of proximal/ostial stenosis amenable to treatment by endovascular procedures. • Patients with stroke-in-evolution considered for carotid surgery, where it may be useful to exclude significant occlusions of the intracranial vessels. • Suspicion of severe siphon stenosis which could be treated by endovascular interventions.
2.2.4.8 Computerized Tomography and Magnetic Resonance Imaging • It is mandatory that all patients for whom carotid intervention is proposed undergo a preoperative brain imaging study, with either computerized tomography (CT) or magnetic resonance imaging (MRI). • CT and MRI provide direct visualization of the brain and are important for the investigation of patients with cerebrovascular disease. • Using these techniques enables distinction between ischaemic infarct and haemorrhage [8, 81], essential information for the proper management of acute strokes. • The precise location and type of ischaemic infarct may bear clinical relevance: cortical and subcortical lesions may correspond to atheroembolic phenomena, watershed infarcts are more common in the presence of haemodynamic impairment of cerebral blood flow and deep lacunae small infarcts are usually associated with small-vessel disease [25]. • Routine use of CT scan investigations in patients with TIAs confirmed the presence of unsuspected, silent infarcts [22, 48], which may increase the risk of carotid surgery. • Cerebral atrophy – leuko-ariosis – may be associated with carotid disease and reduced survival following carotid surgery (NASCET). • There is a clear advantage on the use of MRI over CT scan, despite its higher costs, particularly in acutely symptomatic patients. • The new weighted-diffusion techniques may detect early unsuspected infarcts, provide assessment of the status of the blood–brain barrier and are essential for identifying a subgroup of patients with acute stroke that could benefit from early carotid intervention without a significant increase in haemorrhagic transformation of an ischaemic infarct [3, 67].
2.2.4.9 Examination of the Retina • Overlooked in more recent practice. • The classical description of the Hollenhorst plaque [45] with bright cholesterol crystals impacted in the retinal vessels with associated localized infarct has been confirmed by several observations in patients with amaurosis fugax.
2.2.5 Selection, Treatment and Results
• There are some specific retinal alterations in giant-cell arteritis [47] and it is important to recognize occlusion of the central retinal artery, a condition rarely associated with atheroembolization, from a carotid lesion and a potential cause of severe and persistent unilateral blindness.
2.2.5 Selection, Treatment and Results 2.2.5.1 Medical Treatment • Medical treatment is based on the use of antiplatelet medication with aspirin [26], ticlopidine and clopidogrel [15].
Aspirin • Several trials have shown the advantage of aspirin over placebo in the prevention of stroke [14, 34]. • Data from both ECST and NASCET confirmed the advantage of aspirin over surgical treatment in patients with minimal carotid disease and stenosis <30%. • The exact dose of aspirin remains controversial; in both multicentre trials it was 300 mg daily, but there is a trend to reduce its dosage to 150 mg daily.
• Floating thrombus in the carotid bifurcation • Patients with pre-occlusive stenosis before surgery Long-term anticoagulation is not recommended except for patients with atrial fibrillation because of the risk of haemorrhagic complications.
Correction of Metabolic Risk Factors for Atherosclerosis Correction of metabolic risk factors for atherosclerosis should be carried out thoroughly and are integral parts of adequate management of atherosclerosis: • Cessation of smoking • Correction of dyslipidaemias • Diabetes mellitus • Control of hypertension • Appropriate correction of hyperhomocysteinemia with folic acid Statins have been shown to reduce the incidence of stroke [44] and to have a stabilizing effect on the atheromatous plaque [20] beyond its effect on lowering cholesterol. Its routine use in diabetic patients with arterial disease has been recommended recently [84] to reduce cardiovascular events, but as yet there is no definitive evidence that it should be used in all patients despite a normal cholesterol level.
Antiplatelet Treatment 2.2.5.2 Surgical Treatment • Antiplatelet treatment is also indicated because of concomitant coronary artery disease and during the peri-operative period following endarterectomy, to reduce platelet aggregation and thrombus formation in the operated segment [55]. • Long-term antiplatelet therapy should be maintained to reduce the incidence of cardiovascular events, particularly in those patients with evidence of systemic atherosclerosis.
Surgical treatment is dominated by carotid bifurcation endarterectomy, proven to be effective in the prevention of stroke for symptomatic patients with transient or reversible ocular and hemispheric dysfunction associated with stenosis >70% and also in asymptomatic patients [29, 30, 70] with severe stenosis.
Moderate Stenosis Anticoagulation Anticoagulation with unfractionated heparin, warfarin or low-molecular weight heparins may be indicated in: • “Crescendo” TIAs • Waning and waving neurological deficits
For moderate stenosis (50–70%) the benefit of endarterectomy in patients with (1) TIAs (single or multiple) or crescendo with or without plaque ulceration, or (2) mild or moderate stroke irrespective of antiplatelet therapy was evident, if neurological morbidity and mortality of the procedure was kept under 5% [6].
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Asymptomatic Patients In asymptomatic patients several factors, other than the severity of stenosis, should be considered: • Presence of contralateral carotid occlusion • Ipsilateral brain infarcts and leuko-ariosis detected in pre-operative CT/MR scans [50] • The structure of the atheromatous plaque In fact, there is some criticism of the data from both the Asymptomatic Carotid Atherosclerosis Study (ACAS) and ACST, prompted by the following observations: • The need to perform a substantial number of operations to prevent a single stroke. • Operation with a risk <3%, probably not achievable outside centres of excellence. • Heterogeneity of asymptomatic carotid disease, with different stroke risks, and the need to identify a subgroup of patients with a higher risk of stroke [68]. Surgical decision requires careful evaluation of the overall risk for the individual patient, the presence of concomitant cardiac and respiratory disease and also the individual surgeon’s experience and institutional capabilities.
Patients with Severe Coronary Disease • Patients with severe coronary disease require careful evaluation and should be appropriately treated, either by surgery or pharmacotherapy. • Routine use of β-blockers has been recommended to reduce peri-operative myocardial infarct in patients with arterial disease [75]. • Prophylactic carotid endarterectomy, particularly in the presence of severe bilateral stenosis or associated contralateral occlusion, may be required before coronary revascularization to reduce the incidence of postoperative stroke [80].
Stroke • Established stroke with partial recovery carries a higher risk of repeated neurological events and mortality [65]; there is indication for endarterectomy, despite its higher risk than for TIAs or reversible stroke. • For acute stroke there is evidence that prompt intervention in adequately selected noncomatose patients,
and in whom there is evidence of a viable area of ischaemic penumbra confirmed by functional imaging techniques (diffusion-weighted NMR and/or positron-emission tomography), may benefit the patient by reducing the severity of the stroke. However, this should only be carried out within strict experimental protocols [11] because of the high risk of intracerebral haemorrhage. Appropriate selection of patients and reduced surgical risk are essential factors to support the efficacy of carotid artery surgery in the prevention of stroke; reduction of its associated morbidity and mortality is a major requirement to be pursued in all centres dealing with these patients.
2.2.5.3 Technique of Carotid Endarterectomy Carotid endarterectomy (CEA) can be performed under general or regional anaesthesia and requires full cardiac and blood pressure monitoring. Transcranial Doppler is a major adjuvant for: • Identifying embolic events (microembolic signals, MES) that may occur during surgical dissection. • Deciding whether to use shunt when the operation is performed under general anaesthesia. • Assessing function and cerebral flow post-operatively. Persistent MES after carotid declamping and/or in the recovery room may represent an increased risk of thrombus formation at the operated carotid and subsequent stroke. Longitudinal or oblique (skin crease) cervical incision is performed and exposure of the carotid bifurcation obtained by division of the facial vein. Careful dissection is mandatory to avoid iatrogenic lesions of the hypoglossal, vagus and recurrent laryngeal nerve, causing dysphonia and hoarseness; unnecessary manipulation of the arteries should be avoided to prevent cerebral embolization. Heparin (2500–5000 U) is routinely administered before clamping and a longitudinal arteriotomy is performed from the distal common carotid to the internal carotid as far as the end of the plaque. Subsequent steps of the operation are shown in Fig. 2.2.8. Insertion of a shunt to preserve flow depends upon the appearance of appropriate neurological symptoms when the operation is performed with the patient awake, or based upon indirect evidence of insufficient collateral flow assessed by:
2.2.5 Selection, Treatment and Results
Fig. 2.2.8 Carotid endarterectomy: plaque removal and final aspect before artery closing
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• A carotid stump pressure <50 mmHg • A 50% reduction in flow velocity detected in the middle cerebral artery by TCD if the operation is performed under general anaesthesia. To remove the plaque, dissection is initiated in a sub-adventitial plane using the Watson–Cheyne dissector and it is carried out meticulously, separating the lesion from the arterial wall. Complete removal of the lesion should always be attempted; when the dissection is in the correct plane the plaque “feathers out” distally, so tacking sutures of the distal intima are very seldom required. Clearing of the external carotid artery ostium and of its initial segment is performed routinely, and proximally, in the common carotid, the lesion is cut with scissors to avoid fragmentation and irregularities. Extreme care is taken to remove all remaining fragments of plaque and intimal flaps, which may be a source of secondary embolization or lead to secondary thrombosis. The arteriotomy is routinely closed with a Dacron patch, aiming to enlarge the artery and to prevent early recurrent restenosis secondary to proliferative fibrosis [71], to correct kinking of the artery immediately distal to the endarterectomized segment and to reduce post-operative neurological morbidity [28]. Clamps are released sequentially in order to allow an initial flush through the external carotid and to prevent cerebral embolization. Vein can also be used, but there is no convincing evidence of its additional advantage over the Dacron patch. Peri-operative completion assessment is routinely performed with colour flow Duplex scan to identify technical defects such as thrombus, floating flaps >2 mm or residual stenosis, which, if present, require prompt correction. Monitoring with transcranial Doppler is continued in the recovery room to detect brain embolization; if there is evidence of repeated high-intensity transient signals (HITS), this could correspond to thrombus formation at the endarterectomized segment. Administration of 250 ml Dextran 40 is performed intravenously, and usually this is sufficient to ensure its disappearance. However, if there is persistence of HITS despite Dextran administration, immediate cervical re-exploration is carried out, the arteriotomy opened and thrombectomy of the carotid artery performed to prevent a major stroke [43]. Drainage is always applied and routine closure of subcutaneous tissues and skin performed after careful inspection and perfect haemostasis. Other techniques have been described, such as eversion endarterectomy. Details of this technique can be
Table 2.2.1. Early results of carotid endarterectomy. (TIA Transient ischaemic attack) Morbidity and mortality < 30 days Asymptomatic disease
0.7 % (1/129)
TIAs/reversible stroke
1.5 % (6/376)
Stroke with partial deficit
4.8 % (2/41)
Acute stroke
10 % (1/10)
found in this volume in Chapter 2.3, Reversed Carotid Endarterectomy, by D. Kiskinis. Our preference is for conventional endarterectomy and our personal experience is based upon 556 patients and 610 procedures, two-thirds symptomatic patients, either TIAs or reversible strokes, and the overall morbidity and mortality was 1.7%. Its stratification according to clinical presentation is as in Table 2.2.1. Complications of CEA in our patients were acute thrombosis in three patients, leading to major stroke and death in two; two patients had haemorrhagic stroke, with full recovery after several weeks and two patients died during the first 30 days postoperatively, one from pulmonary embolus and the second from acute myocardial infarct. Peripheral nerve injuries have been described in association with CEA; in our patients its incidence was 2.5%, mainly dysphonia due to vocal cord paralysis and reversible in all patients except one, who required transient tracheotomy followed by laser segmental cord resection, because of contralateral cord paralysis following previous stroke. Neck and submandibular paraesthesia are common and transient. The impact of completion assessment in our practice was analysed in a consecutive group of 114 patients; 4 required immediate re-operation to correct minor defects such as free-floating flaps, thrombi at the endarterectomy area and/or significant residual stenosis. There was no mortality or neurological morbidity in this group of patients. Long-term results were analysed during a follow-up period, mean 48 months, ranging from 6 to 120 months; restenosis was identified by colour flow Duplex scan and its overall incidence was 7.5%, but for >70% it was only 3.3%, and the majority were asymptomatic. The annual stroke incidence in the operated patients was 0.9% and the major cause of death in this group was myocardial infarct.
2.2.6 Endovascular Treatment
2.2.6 Endovascular Treatment Kerber et al. [52] reported the first dilatation of the proximal common carotid during conventional endarterectomy of a bifurcation lesion, and it was followed by several anecdotal reports of cases where the procedure was attempted with several degrees of success. Mathias [58] performed the first successful transluminal angioplasty (PTA) of a carotid bifurcation stenosis and a surge of enthusiasm followed several reports confirming the feasibility, safety and patency of the carotid arteries following PTA. The advantages of endovascular treatment are obvious: • Absence of surgical incision • Ability to perform the procedure under local anaesthesia • Monitoring of the neurological status of the patient during the procedure • Avoidance of peripheral nerve injuries. Disadvantages have also been recognized: • Embolism during manipulation (crossing the lesion with guidewires and balloons, balloon inflation and deflation during PTA) • Acute thrombosis • Spasm and failure to treat some calcified lesions. Carotid tortuosity and the specific anatomy at the aortic arch and origin of the supra-aortic vessels may cause additional difficulties for selective carotid catheterization, and increase the risk of peri-procedural cerebral embolization.
Fig. 2.2.9 PTA/stenting of the innominate artery
Details on endovascular treatment can be found in Chapter 2.6, Endovascular Treatment of Carotid Stenosis, by T. Gerasimidis. The durability of endovascular treatment needs to be determined with accuracy; results vary from 10% to 25%; early restenoses have been reported, although recent series suggest a restenosis rate of between 5% and 10%. Refinement of endovascular procedures, with the development of new and more suitable stents, increased experience and adequate selection of the lesions [10] will yield better results in the future. Prospective randomized studies comparing carotid angioplasty and stent placement (CAS) and CAE will be required to provide definitive evidence of the relative merits and indications of CAS compared to the established procedure of CAE. For ostial lesions of the innominate and of the left common carotid arteries PTA/STENT has been reported as a durable and safe procedure as shown in Fig. 2.2.9, reducing the indication for conventional open surgery with median sternotomy or extra-anatomic by-pass reconstructions.
2.2.6.1 What are the Established Indications for Endovascular Procedures in Extracranial Carotid Disease? Published evidence [16] suggests that PTA/STENT may yield comparable or better results than conventional surgery for: • Early restenosis following carotid bifurcation endarterectomy, a fibrous lesion which seems to be associat-
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ed with a smaller embolic risk than the atheromatous lesion, and wherever conventional surgery may cause higher incidence of peripheral nerve injury. • Radiation arteritis and “hostile neck” situations. • Distal lesions of the internal carotid artery inaccessible to conventional surgery. • Ostial disease of the innominate and common carotid arteries. References 1. Aaslid R, Markwalder TM, Nornes H (1982) Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries. J Neurosurg 57:769–774 2. Akers DL, Bell WH 3rd, Kerstein MD (1988) Does intracranial dye study contribute to evaluation of carotid artery disease? Am J Surg 156:87–90 3. Albers G, Lansberg M, Norbash A et al (2000) Yield of diffusion-weighted MRI for detection of potentially relevant findings in stroke patients. Neurology 54:1562–1567 4. Astrup J, Siesjo BK, Symon L (1981) Thresholds in cerebral ischaemia. The ischaemic penumbra [editorial]. Stroke 12:723–725 5. Badimon JJ, Gallo R, Badimon L et al (1998) The role of atherosclerotic plaque disruption and thrombosis in acute coronary heart disease. In: Mercuri M, McPherson DD, Bassiouny H, Glagov S (eds) Non-invasive diagnosis of atherosclerosis. Kluwer, Boston 6. Barnett HJ, Taylor DW, Eliasziw M, Fox AJ, Ferguson GG, Haynes RB, Rankin RN, Clagett GP, Hachinski VC, Sackett DL, Thorpe KE, Meldrum HE (1998) Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 339:1415–1425 7. Bassiouny HS, Sakaguchi Y, Mikucki SA, McKinsey JF, Piano G, Gewertz BL, Glagov S (1997) Juxtalumenal location of plaque necrosis and neoformation in symptomatic carotid stenosis. J Vasc Surg 26:585–594 8. Bentsson JR (1996) Computed tomography in stroke. In: Moore WS (ed) Surgery for cerebrovascular disease. Churchill Livingstone, New York, pp 201–216 9. Biasi GM, Sampaolo A, Mingazzini P, De Amicis P, El Barghouty N, Nicolaides NA (1999) Computer analysis of ultrasonic plaque echolucency in identifying high risk carotid bifurcation lesions. Eur J Vasc Endovasc Surg 17:476–479 10. Biasi GM, Frio A, Diethrich EB et al (2004) Carotid plaque echolucency increases the risk of stroke in carotid stenting. Circulation 110:756–762
11. Biller J, Feinberg WM, Castaldo JE, Whittemore AD, Harbaugh RE, Dempsey RJ, Caplan LR, Kresowik TF, Matchar DB, Toole J, Easton JD, Adams HP Jr, Brass LM, Hobson RW 2nd, Brott TG, Sternau L (1998) Guidelines for carotid endarterectomy: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 29:554–562 12. Bonita R, Stewart A, Beaglehole R (1990) International trends in stroke mortality: 1970–1985. Stroke 21:989–992 13. Cadwater WB (1912) Unilateral optic atrophy and contralateral hemiplegia consequent on occlusion of the cerebral vessels. J Am Med Assoc 59:2248 14. Canadian Cooperative Study Group (1978) A randomized trial of aspirin and sulfinpyrazone in threatened stroke. N Engl J Med 299:53–59 15. CAPRIE Steering Committee (1996) Lancet 348:1329–1339 16. Caps MT (2004) Summary of results of carotid bifurcation angioplasty and stenting. In: Schneider PA, Bohannon W, Sila MB (eds) Carotid interventions. Dekker, New York, Chapter 16 17. Carrea R, Mollins M, Murphy G (1955) Surgical treatment of spontaneous thrombosis of the internal carotid artery in the neck: carotid carotideal anastomosis. Acta Neurol Latinoamer 1:71–78 18. Chao WH, Kwan ST, Lyman RS et al (1938) Thrombosis of the left internal carotid artery. Arch Surg 37:100–111 19. Cid dos Santos J (1947) Sur la desobliteration des thromboses arterièlles anciènnes. Mem Acad Chir (Paris) 73:409 20. Crisby M, Nordin-Fredriksson G, Shah PK, Yano J, Zhu J, Nilsson J (2001) Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: implications for plaque stabilization. Circulation 103:926–933 21. Davies JB, Grove WJ, Julian OC (1956) Thrombotic occlusion of the branches of the aortic arch, Martorell’s syndrome: report of a case treated surgically. Ann Surg 144:124–126 22. Davies PH, Clarke WR, Bendixen BH et al (1996) Silent cerebral infarction in patients enrolled in the TOAST study. Neurology 46:942–948 23. Dearden NM (1985) Ischaemic brain. Lancet 2:255–259 24. DeBakey ME (1975) Successful carotid endarterectomy for cerebrovascular insufficiency: nineteen year follow-up. J Am Med Assoc 233:1083–1085 25. DeWitt LD, Buonanno FS, Kistler JP et al (1984) Nuclear magnetic resonance imaging in evaluation of clinical stroke syndromes. Ann Neurol 16:535–545 26. Dyken ML (1979) Assessment of the role of antiplatelet aggregating agents in transient ischemic attacks, stroke and death. Stroke 10:602
References
27. Eastcott HHG, Pickering GW, Robb CG (1954) Reconstruction of the internal carotid artery in a patient with intermittent attacks of hemiplegia. Lancet 2:994–999 28. Eikelboom BC, Ackerstaff RG, Hoeneveld H, Ludwig JW, Teeuwen C, Vermeulen FE, Welten RJ (1988) Benefits of carotid patching: a randomized study. J Vasc Surg 7:240–247 29. European Carotid Surgery Trialists‘ Collaborative Group (1991) MRC European Carotid Surgery Trial. Interim results for symptomatic patients with severe (70-99%) and with mild (0-29%) stenosis. Lancet 337:1235–1243 30. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study (1995) Endarterectomy for asymptomatic carotid artery stenosis. J Am Med Assoc 273:1421–1428 31. Fernandes e Fernandes J (2003) Extracranial carotid disease. University of Lisbon, Lisbon, 1985 32. Ferro JM (2003) Cardioembolic stroke: an update. Lancet Neurol 2:177–188 33. Fields WS, Lemak NA (1989) A history of stroke. Oxford University Press, Oxford 34. Fields WS, Lemak NA, Frankowski RH, Hardy RJ (1977) Controlled trial of aspirin in cerebral ischemia. Stroke 8:301–314 35. Fisher CM (1951) Occlusion of the internal carotid artery. Arch Neurol Psychiatry 65:346–377 36. Fisher CM (1952) Transient monocular blindness associated with hemiplegia. Arch Ophthalmol 47:167–203 37. Fuster V, Badimon JJ, Chesebro JH (1998) Atherothrombosis: mechanisms and clinical therapeutic approaches. Vasc Med 3:231–239 38. Garcia J, Ye Z, Liu K (1999) Mechanisms of neuronal cell death after ischemic injury to the brain. In: Fisher M, Bogousslavsky J (eds) Cerebrovascular disease, 3rd edn. Current Medicine, Philadelphia, Chapter 2 39. Gonçalves I, Moses J, Dias N, Pedro L, Fernandes e Fernandes J, Nilsson J, Ares M (2003) Changes related to age and cerebrovascular symptoms in the extracellular matrix of human carotid plaques. Stroke 34:616–622 40. Gonçalves I, Moses J, Pedro L, Dias N, Fernandes e Fernandes J, Nilsson J, Ares M (2003) Echolucency of carotid plaques correlates with plaque cellularity. Eur J Vasc Endovasc Surg 26:32–38 41. Gonçalves I, Lindholm M, Pedro L, Dias N, Fernandes e Fernandes J, Fredrikson G, Nilsson J, Moses J, Ares M (2004) Elastin and calcium rather than collagen or lipid content determine the echogenicity of human carotid plaques. Stroke 35:2795–2800 42. Guthrie LH, Mayou S (1908) Right hemiplegia and atrophy of left optic nerve. Proc R Soc Med 1:180
43. Hayes PD, Lloyd AJ, Lennard N et al (2000) Transcranial Doppler-directed Dextran-40 therapy is a cost-effective method of preventing carotid thrombosis after carotid endarterectomy. Eur J Vasc Endovasc Surg 19:56–61 44. Heart Protection Study Collaborative Group (2002) MRC/ BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360:7–22 45. Hobson R, Weiss D, Fields W et al (for Veterans Affairs Cooperative Study Group) (1993) Efficacy of carotid endarterectomy for asymptomatic carotid stenosis. N Engl J Med 328:221–227 46. Hollenhorst RW (1961) The significance of bright plaques in the retinal arteries. J Am Med Assoc 178:123–129 47. Hollenhorst RW, Brown JR, Wagener HP (1967) Neurologic aspects of temporal arteritis. Neurology 10:490–498 48. Hougaku H, Matsumoto M, Hashikawa K, Hori M (2000) The role of brain imaging in the preoperative evaluation of carotid surgical patients. In: Loftus CM, Kresowik TF (eds) Carotid artery surgery. Thieme, New York, pp 81–96 49. Hunt JR (1914) The role of the carotid arteries in the causation of vascular lesions of the brain, with remarks on certain special features of the symptomatology. Am J Med Soc 147:704–713 50. Inzitari D, Eliasziw M, Gates P (2000) The causes and risk of stroke in patients with asymptomatic internal-carotid-artery stenosis. N Engl J Med 342:1693–1701 51. Johnson HC, Walker AE (1951) The angiographic diagnosis of spontaneous thrombosis of the internal and common carotid arteries. J Neurosurg 8:631–659 52. Kerber CW, Cromwell LD, Loehden OL (1980) Catheter dilatation of proximal carotid stenosis during distal bifurcation endarterectomy. AJNR Am J Neuroradiol 1:348–349 53. Lammie GA, Path MR, Sandercock PA, Dennis MS (1999) Recently occluded intracranial and extracranial carotid arteries. Relevance of the unstable atherosclerotic plaque. Stroke 30:1319–1325 54. Libby P (1998) The interface of atherosclerosis and thrombosis: basic mechanisms. Vasc Med 3:225–229 55. Lindblad B, Persson N, Takolander R, Bergqvist D (1993) Does low-dose acetylsalicylic acid prevent stroke after carotid surgery? A double-blind, placebo-controlled randomized trial. Stroke 24:1125–1128 56. Lobo Antunes J, Fernandes e Fernandes J (1992) Cerebral ischemia. Surgical aspects. In: Ribeiro C, Carvalho LS, Braz Nogueira J (eds) Ischemia. University of Lisbon, Lisbon, pp 189–209 57. Martin RP, Lerakis S (2004) Contrast for vascular imaging. Cardiol Clin 22:313–320
151
152
2.2 Extracranial Carotid Artery Disease
58. Mathias K (1977) Ein neuartiges Kathetersystem zur percutanen transluminalen Angioplastie von Karotisstenosen. Fortschr 95:1007–1011 59. Mayo Asymptomatic Carotid Endarterectomy Study Group (1992) Results of a randomized controlled trial of carotid endarterectomy for asymptomatic carotid stenosis. Mayo Clin Proc 67:513–518 60. Millikan CH (1965) The pathogenesis of transient focal cerebral ischaemia. Circulation 32:438 61. Mohr JP, Caplan LR, Melski JW, Goldstein RJ, Duncan GW, Kistler JP, Pessin MS, Bleich HL (1978) The Harvard Cooperative Stroke Registry: a prospective registry. Neurology 28:754–762 62. Moniz E (1927) L’éncephalographie artérielle: son importance dans la localization des tumeurs cérébrales. Rev Neurol 2:172 63. Moniz E, Lima A, Lacerda R (1937) Hemiplegies par thrombose de la carotide interne. Presse Med 45:977 64. Moore WS, Barnett HJ, Beebe HG et al (1995) Guidelines for carotid endarterectomy. A multidisciplinary consensus statement from the ad hoc committee. AHA Stroke 26:188–201 65. Moore WS, Barnett HJ, Beebe HG et al (1995) Guidelines for carotid endarterectomy. A multidisciplinary consensus statement from the ad hoc committee. AHA Circulation 91:566–579 66. MRC Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group (2004) Prevention of disabling and fatal strokes by successful endarterectomy in patients without recent neurological symptoms: randomized controlled trial. Lancet 363:1491–1502 67. Neumann-Haefelin T, Moseley ME, Albers G et al (2000) New magnetic resonance imaging methods for cerebrovascular disease: emerging clinical applications. Ann Neurol 31:559–570 68. Nicolaides AN (2004) Carotid endarterectomy: coming of age and the future. Presentation at the Coronaries, Carotids, Peripherals, Renals Endovascular Therapy Meeting (CCPR 2004), Greece 69. Nicolaides AN, Shifrin EG, Bradbury A, Dhanjil S, Griffin M, Belcaro G, Williams M (1996) Angiographic and duplex grading of internal carotid stenosis: can we overcome the confusion? J Endovasc Surg 3:158–165 70. North American Symptomatic Carotid Endarterectomy Trial Collaborators (1991) Beneficial effect of carotid endarterectomy in symptomatic patients with high grade carotid stenosis. N Engl J Med 325:445–463
71. Pedro LM (2003) A window to atherosclerosis: high definition ultrasonography in the study of the arterial wall. University of Lisbon, Lisbon 72. Pedro LM, Pedro MM, Goncalves I, Carneiro TF, Balsinha C, Fernandes e Fernandes R, Fernandes e Fernandes J (2000) Computer-assisted carotid plaque analysis: characteristics of plaques associated with cerebrovascular symptoms and cerebral infarction. Eur J Vasc Endovasc Surg 19:118–123 73. Pedro LM, Fernandes e Fernandes J, Pedro MM, Gonçalves I, Dias NV, Fernandes e Fernandes R, Carneiro TF, Balsinha C (2002) Ultrasonographic risk score of carotid plaques. Eur J Vasc Endovasc Surg 24:492–498 74. Phan T, Huston J III, Bernstein MA, Riederer SJ, Brown RD Jr (2001) Contrast-enhanced magnetic resonance angiography of the cervical vessels: experience with 422 patients. Stroke 32:2282–2286 75. Poldermans D, Boersma E, Jeroen D et al (1999) The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. N Engl J Med 341:1789–1794 76. Robinson RE et al (1968) Natural history of cerebral thrombosis: 9–19 year
