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(BQ) Part 1 book “900 questions - An interventional cardiology board review” has contents: Vascular biology, inflammation and arterial injury, intravascular contrast agents, elective coronary intervention, chronic total occlusions, ostial and bifurcation lesions,… and other contents.
900 Questions: An Interventional Cardiology Board Review 900 Questions: An Interventional Cardiology Board Review EDITORS Debabrata Mukherjee, MD Associate Professor of Medicine Director, Cardiac Catheterization Laboratories Gill Foundation Professor of Interventional Cardiology Gill Heart Institute and Division of Cardiovascular Medicine University of Kentucky Lexington, Kentucky Leslie Cho, MD Director, Women’s Cardiovascular Center Medical Director, Preventive Cardiology and Rehabilitation Department of Cardiovascular Medicine Cleveland Clinic Foundation Cleveland, Ohio David J Moliterno, MD Professor and Vice-Chairman of Medicine Chief, Cardiovascular Medicine Jefferson Morris Gill Professor of Cardiology Gill Heart Institute and Division of Cardiovascular Medicine University of Kentucky Lexington, Kentucky Donna A Gilbreath Managing Editor Gill Heart Institute and Division of Cardiovascular Medicine University of Kentucky Lexington, Kentucky Acquisitions Editor: Frances R DeStefano Managing Editor: Nicole Dernoski Project Manager: Jennifer Harper Senior Manufacturing Manager: Benjamin Rivera Marketing Manager: Angela Panetta Art Director: Risa Clow Production Services: Laserwords Private Limited, Chennai, India Printer: Victor Graphics, Inc © 2007 by LIPPINCOTT WILLIAMS & WILKINS, a Wolters Kluwer business 530 Walnut Street Philadelphia, PA 19106 USA LWW.com All rights reserved This book is protected by copyright No part of this book may be reproduced in any form or by any means, including photocopying, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotations embodied in critical articles and reviews Materials appearing in this book prepared by individuals as part of their official duties as U.S government employees are not covered by the above-mentioned copyright We appreciate that even with the best of efforts from the authors, editors, and publishers that some of the questions or answers in this textbook may need refinement So, too, while the object was to carefully design each question with a single best answer, some questions may be more controversial than intended or may have more than one reasonable response With these points in mind and with our hopes to continually improve this book with future editions, comments regarding this first edition are welcomed and can be sent to Dr Debabrata Mukherjee (Mukherjee@uky.edu) or Dr David Moliterno (Moliterno@uky.edu) Printed in the USA Library of Congress Cataloging-in-Publication Data 900 questions : an interventional cardiology board review / editors, Debabrata Mukherjee [et al.] p ; cm ISBN-13: 978-0-7817-7349-2 ISBN-10: 0-7817-7349-0 Heart—Diseases—Treatment—Examinations, questions, etc Cardiovascular system—Diseases—Treatment—Examinations, questions, etc I Mukherjee, Debabrata II Title: Nine hundred questions [DNLM: Cardiovascular Diseases—Examination Questions Cardiovascular Diseases—therapy—Examination Questions WG 18.2 Z9991 2007] RC683.8.N564 2007 616.1 20076—dc22 2006027893 Care has been taken to confirm the accuracy of the information presented and to describe generally accepted practices However, the authors, editors, and publisher are not responsible for errors or omissions or for any consequences from application of the information in this book and make no warranty, expressed or implied, with respect to the currency, completeness, or accuracy of the contents of the publication Application of this information in a particular situation remains the professional responsibility of the practitioner The authors, editors, and publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accordance with current recommendations and practice at the time of publication However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions This is particularly important when the recommended agent is a new or infrequently employed drug Some drugs and medical devices presented in this publication have Food and Drug Administration (FDA) clearance for limited use in restricted research settings It is the responsibility of the health care provider to ascertain the FDA status of each drug or device planned for use in their clinical practice To purchase additional copies of this book, call our customer service department at (800) 638-3030 or fax orders to (301) 223-2320 International customers should call (301) 223-2300 Visit Lippincott Williams & Wilkins on the Internet: at LWW.com Lippincott Williams & Wilkins customer service representatives are available from 8:30 am to pm, EST 10 ‘‘To my parents, for their infinite patience, love, and understanding, who continue to be my source of inspiration, and to my wonderful wife, Suchandra, for her love and support’’ Debabrata Mukherjee ‘‘To Nathaniel and Benjamin, my sons and suppliers of life’s important questions, and to Judith, my wife and partner in finding the answers’’ David J Moliterno Preface Insightful questions have been used through the ages as a metric to assess one’s knowledge, but when coupled with carefully delivered answers they can become a powerful teaching tool This book of questions and annotated answers covering the field of interventional cardiology is meant to serve as a helpful resource for individuals preparing for the interventional cardiovascular medicine board examination as well as for clinicians who wish to perform an in-depth self-assessment on individual topics or the full spectrum The book has many key features, which we believe will make the reader successful in passing the boards and improving clinical practice Of foremost importance, the areas covered are relevant not only to the day-to-day practice of interventional cardiology, but have also been patterned in scope and content to the actual board examination The book begins with several chapters dedicated to the anatomy and physiology associated with interventional cardiology and the pathobiology of atherosclerosis and inflammation This corresponds to the 15% of the board examination targeting material in basic science The subsequent chapters focus on the essential interventional pharmacotherapy of antiplatelets, anticoagulants, and other commonly used medications in the catheterization laboratory and outpatient setting for patients with atherosclerosis These chapters correspond to the next 15% of the boards centering on pharmacology A similar-sized 15% of the board examination is directed toward imaging, and the book includes specific chapters on radiation safety, catheterization laboratory equipment and technique, contrast agents, and intravascular ultrasound The two largest areas of the examination, each covering 25% of the content, include case selection–management and procedural techniques The review book dedicates 25 chapters to comprehensively cover these areas Finally, we have included chapters for the miscellaneous remaining areas covered by the board examination, including peripheral vascular disease, ethics, statistics, and epidemiology, as well as a chapter directed at improving test-taking skills Also essential to the quality and appropriateness of the questions and annotated answers is the expertise of the chapter authors We are fortunate to have assembled the ‘‘who’s who of academic interventional cardiology’’ The 59 contributing authors from leading medical centers around the world have over 4,600 articles cited in PubMed We are greatly indebted to these authors who are recognized both for their interventional expertise and for their teaching skills In the end, the true value of this textbook is not only the relevance of the questions, the outstanding quality of the authors, but also the value of the annotated answers The text includes 910 questions and 254 figures and tables The corresponding answers have been appropriately detailed to provide relevant facts and information as well as up-to-date journal citations The practice of interventional cardiology is exciting, rewarding, and a privilege each of us enjoys Likewise, it has been our privilege to work with the superb contributors, our colleagues in interventional cardiology, as well as the editorial team at the University of Kentucky and Lippincott Williams and Wilkins It is our personal hope that you will enjoy this book and that it will be a valuable resource to you in passing the board examination and providing the highest quality care possible to your patients DEBABRATA MUKHERJEE, MD LESLIE CHO, MD DAVID J MOLITERNO, MD vii Contributors Robert J Applegate, MD Director, Cardiovascular Training Program Wake Forest University School of Medicine Winston-Salem, North Carolina Joseph Babb, MD Professor of Medicine Department of Internal Medicine, Cardiology Division Brody School of Medicine East Carolina University; Director, Cardiac Catheterization Laboratories Pitt County Memorial Hospital Greenville, North Carolina Thomas M Bashore, MD Professor of Medicine Division of Cardiovascular Medicine; Director, Fellowship Training Program and Adult Congenital and Valvular Disease Program Duke University Medical Center Durham, North Carolina Matthew C Becker, MD Fellow in Cardiovascular Disease Department of Cardiovascular Medicine Cleveland Clinic Foundation Cleveland, Ohio Deepak L Bhatt, MD Associate Professor of Medicine Staff, Cardiac, Peripheral, and Carotid Intervention Department of Cardiovascular Medicine Cleveland Clinic Foundation Cleveland, Ohio David C Booth, MD Endowed Professor Medicine Gill Heart Institute and Division of Cardiovascular Medicine University of Kentucky; Chief of Cardiology Lexington VA Medical Center Lexington, Kentucky Sorin J Brener, MD Associate Professor of Medicine Department of Medicine Case Western Reserve University; Staff Physician Department of Cardiovascular Medicine Cleveland Clinic Foundation Cleveland, Ohio Ivan P Casserly, MD Assistant Professor of Medicine Cardiology Division University of Colorado; Director of Interventional Cardiology Denver VA Medical Center Denver, Colorado Leslie Cho, MD Director, Women’s Cardiovascular Center Medical Director, Preventive Cardiology and Rehabilitation Department of Cardiovascular Medicine Cleveland Clinic Foundation Cleveland, Ohio Antonio Colombo, MD Chief of Invasive Cardiology Universit`a Vita-Salute and San Raffaele Scientific Institute and Columbus Hospitals Milan, Italy Harold L Dauerman, MD Professor of Medicine University of Vermont; Director, Cardiovascular Catheterization Laboratories Fletcher Allen Health Care Burlington, Vermont Steven R Daugherty, PhD Assistant Professor of Psychology Assistant Professor of Preventive Medicine Rush Medical College Chicago, Illinois ix x Contributors Stephen G Ellis, MD Professor of Medicine Department of Cardiovascular Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University; Director, Cardiac Catheterization Laboratories Cleveland Clinic Foundation Cleveland, Ohio Nezar Falluji, MD, MPH Clinical Instructor Gill Heart Institute Division of Cardiovascular Medicine University of Kentucky Lexington, Kentucky Hussam Hamdalla, MD Assistant Professor of Medicine Gill Heart Institute and Division of Cardiovascular Medicine University of Kentucky Lexington, Kentucky Robert A Harrington, MD Professor of Medicine Director, Cardiovascular Clinical Trials Co-Director, Cardiovascular Research Duke Clinical Research Institute Department of Medicine, Division of Cardiology Duke University Medical Center Durham, North Carolina Howard C Herrmann, MD David P Faxon, MD Director of Strategic Planning Department of Medicine Brigham and Women’s Hospital; Professor of Medicine Department of Medicine Harvard Medical School Boston, Massachusetts Joel A Garcia, MD Interventional Cardiology and Research Fellow Department of Cardiology University of Colorado Denver, Colorado Thomas Gehrig, MD Cardiology Fellow Division of Cardiovascular Medicine Duke University Medical Center Durham, North Carolina Professor of Medicine Cardiovascular Division University of Pennsylvania School of Medicine; Director, Interventional Cardiology and Cardiac Catheterization Laboratories Hospital of the University of Pennsylvania Philadelphia, Pennsylvania L David Hillis, MD Professor and Vice Chair Department of Internal Medicine University of Texas Southwestern Medical Center Dallas, Texas Alice K Jacobs, MD Professor of Medicine Department of Medicine, Section of Cardiology Boston University School of Medicine; Director, Cardiac Catheterization Laboratories and Interventional Cardiology Boston Medical Center Boston, Massachusetts John Lynn Jefferies, MD, MPH Bernard Gersh, MB, ChB, DPhil Professor of Medicine Cardiology Diseases Mayo Clinic College of Medicine Rochester, Minnesota John C Gurley, MD, MBA Professor of Medicine Director, Interventional Cardiology Fellowship Gill Heart Institute Division of Cardiovascular Medicine University of Kentucky Lexington, Kentucky Assistant Professor Adult and Pediatric Cardiology Baylor College of Medicine Divisions of Adult Cardiovascular Diseases and Pediatric Cardiology Texas Children’s Hospital Texas Heart Institute at St Luke’s Episcopal Hospital Houston, Texas Hani Jneid, MD Division of Cardiology Massachusetts General Hospital and Harvard Medical School Boston, Massachusetts Restenosis and Percutaneous Options 11 Rapamycin, used for the prevention of in-stent restenosis, is associated with which of the following biological characteristics? (A) Inhibition of vascular smooth muscle cell migration (B) Inhibition of vascular smooth muscle cell proliferation (C) Immunosuppression (D) Anti-inflammatory (E) All of the above 12 Which of the following statements best describes the biological mechanism of action of paclitaxel? (A) Stabilizes microtubule assembly (B) Enhances microtubule breakdown (C) Blocks cell cycle progression at the G1 to S phase transition in vascular smooth muscle cells (D) Functions as a macrolide antibiotic (E) All of the above 13 Various polymers can be used to affix pharmaceutical agents to stents Some polymers themselves have been shown to increase the likelihood of restenosis (A) True (B) False 14 The following figure shows a frequency distribution curve from a hypothetical trial comparing two stents, ‘‘Stent A’’ and ‘‘Stent B’’ On the basis of the figure, which one of the following statements is true? Stent A Stent B 6-month follow-up 100 Post stent Cumulative frequency (%) 80 60 40 Prestent 20 –30 –20 –10 10 20 30 40 50 60 70 80 90 100 Percent diameter stenosis (A) The incidence of angiographic restenosis, defined as a stenosis severity of ≥50% at 6-month follow-up, is greater for Stent A than for Stent B (B) The differences in 6-month restenosis rates between the two stents can be attributed to better acute gain with Stent A 127 (C) Late loss is more pronounced for Stent B than for Stent A (D) Angiographic restenosis is approximately 40% for Stent A (E) All of the above 15 Which of the following pharmacologic agents has been associated with a significant reduction in subsequent restenosis compared with placebo when tested in the setting of a randomized controlled clinical trial? (A) Pravastatin (B) Valsartan (C) Prednisone (D) Troglitazone (E) None of the above (F) All of the above 16 Which one of the following statements regarding drug-eluting stent (DES) use in patients with diabetes mellitus is true? (A) DESs have been shown to reduce the risk of angiographic restenosis and the need for repeat target lesion revascularization relative to BMSs among patients with diabetes (B) Paclitaxel-coated stents are associated with significantly less late loss than Rapamycincoated stents among patients with diabetes (C) Patients with diabetes are at a greater risk of late stent thrombosis than patients without diabetes following DES placement (D) When performing multivessel stenting in patients with diabetes, the use of DESs is associated with reduced late mortality compared with the use of BMSs 17 A 52-year-old man presented with low-threshold angina During an exercise stress echocardiogram he developed typical angina at a moderate cardiac workload associated with 1.5 mm horizontal STsegment depression in the inferolateral leads and transient hypokinesis of the inferior wall Subsequent angiography demonstrated a lengthy 90% stenosis of the proximal-to-mid RCA, which was treated successfully with slightly overlapping 3.5 × 33 and 3.0 × 18 mm sirolimus-eluting stents His angina resolved after the intervention, and he returns to your office for follow-up year later He continues to lead an active lifestyle and is free of angina Which one of the following would constitute the most appropriate means to screen for stent patency at this time? (A) Exercise stress echocardiogram (B) Exercise treadmill test without adjunctive imaging 128 900 Questions: An Interventional Cardiology Board Review (C) Multislice computer tomography (CT) angiogram (D) Coronary angiography (E) No testing is indicated 18 Which one of the following features has not been identified as an independent predictor of angiographic in-stent restenosis following DES implantation? (A) Longer stent length (B) Diabetes mellitus (C) Type B2 or C American College of Cardiology (ACC)/American Heart Association (AHA) lesion classification (D) Smaller vessel reference diameter (E) Ostial lesion location 19 A 74-year-old woman who underwent placement of a 2.5 × 15 mm BMS in her mid-left anterior descending (LAD) returned 12 months later with unstable angina and is found to have severe instent restenosis Regarding the use of DESs for the treatment of in-stent restenosis in this patient, which one of the following statements is true? (A) For the treatment of in-stent restenosis, DESs are more effective than balloon angioplasty in reducing recurrent angiographic but not clinical restenosis (B) For the treatment of in-stent restenosis, DESs are more effective than balloon angioplasty in reducing both recurrent angiographic and clinical restenosis (C) When used in the setting of in-stent restenosis, paclitaxel-eluting stents are associated with less subsequent late lumen loss than rapamycineluting stents (D) DESs are associated with lower restenosis rates when used for the treatment of in-stent restenosis than when used for the treatment of de novo lesions 20 Which of the following patterns of in-stent restenosis is associated with the highest likelihood of recurrent restenosis following percutaneous intervention? (A) aa (B) aa (C) aa (D) aa 21 A 78-year-old otherwise healthy man underwent implantation of a 3.0 × 15 mm BMS at the ostium of his LAD coronary artery months earlier for low threshold exertional angina He is now referred for repeat angiography after experiencing two episodes of angina at rest The angiogram demonstrates a concentric 70% stenosis involving the proximal portion of the ostial LAD stent and also involving the distal aspect of the left main trunk The origin of the left circumflex (LCx) artery is widely patent How is revascularization best approached? (A) Place a single guidewire into the LAD and deploy a DES within the previous stent and distal left main The LCx should be treated provisionally if there is significant plaque shift into the vessel origin (B) Place guidewires in both the LAD and LCx and deploy ‘‘kissing’’ DESs in the LAD and LCx, allowing the proximal ends of the stents to cover the narrowing in the distal left main (C) Place a guidewire in the LAD and perform cutting balloon angioplasty, with provisional stenting of the LAD and LCx only if the angioplasty result is inadequate (D) Refer the patient for coronary artery bypass surgery, with placement of grafts to the LAD and LCx coronary arteries Restenosis and Percutaneous Options 22 Which one of the following statements regarding the use of intracoronary brachytherapy for the treatment of in-stent restenosis is true? (A) The incidence of late aneurysm formation following brachytherapy is 6% to 8% (B) γ -Emitting sources are associated with a lower incidence of recurrent restenosis than β-emitting sources (C) Late recurrent restenosis, occurring from months to years following PCI for in-stent restenosis, is more common among patients treated with brachytherapy than placebo (D) Among individuals who develop recurrent instent restenosis following brachytherapy, a repeat attempt at brachytherapy is contraindicated because of an unacceptably high risk of subsequent stent thrombosis 23 A 54-year-old man underwent placement of a 3.0 × 23 mm BMS in the mid-RCA Eight months later he presented to the emergency room with chest pain The electrocardiogram (EKG) showed no interval changes, and his serum troponin T concentration was within normal limits Coronary angiography demonstrated diffuse restenosis within and proximal to the previously placed stent, and he underwent placement of a 3.0 × 32 mm paclitaxel eluting stent within and proximal to the original stent Ten months later he again noted recurrent angina, and coronary angiography was repeated Below is an image of the RCA in the right anterior oblique projection Which one of the following statements is true regarding the use of DESs for the treatment of in-stent restenosis within a BMS? 129 (A) Underexpansion of the DES used to treat in-stent restenosis is an important cause of recurrent restenosis (B) The likelihood of restenosis is equivalent when DESs are used for the treatment of in-stent restenosis as with de novo lesions (C) The immediate post-procedural minimal lumen diameter at the treatment site is typically greater following balloon angioplasty than following DES placement (D) Negative vascular remodeling is a common contributor to recurrent restenosis following DES placement 24 Compared with the use of standard balloon angioplasty for the treatment of in-stent restenosis, which one of the following potential benefits is not associated with the use of cutting balloon angioplasty? (A) Less recoil of the angioplasty site within the first 24 hours (B) Lower likelihood of balloon slippage during inflation (C) Less late luminal loss (D) Lower number of balloons required during the intervention 25 Which of the following anticoagulant or antiplatelet agents, when used as an adjunct to balloon angioplasty during the treatment of in-stent restenosis, is associated with a lower rate of subsequent recurrent restenosis? (A) Abciximab (B) Clopidogrel (C) Bivalirudin (D) Aspirin (E) None of the above Answers and Explanations Answer C Two randomized studies have demonstrated that the use of stents with thinner struts is associated with a significant reduction of angiographic and clinical restenosis (Circulation 2001;103: 2816–2821, J Am Coll Cardiol 2003;41:1283–1288) Heparin coating has not been shown to affect the likelihood of subsequent in-stent restenosis, and likewise there is no evidence to suggest that the use of cobalt chromium stent platforms is related to higher rates of restenosis than stainless steel (Am J Cardiol 2003;92:463–466) In fact, because the composition of cobalt chromium allows for thinner strut thickness, these stents may be associated with less risk of restenosis Stents with a coil design, such as the Gianturco-Roubin stent, are associated with restenosis rates that are significantly greater than slotted tubular stents (Am J Cardiol 2001;87:34–39, Circulation 2000;102:1364–1368) Randomized studies have shown that gold coating is associated with higher rates of restenosis than implantation of identically designed stents that are not gold-coated (Circulation 2000;101:2478–2483, Am J Cardiol 2002;89:872–875, Catheter Cardiovasc Interv 2004;62:18–25) Answer A Late loss is the key parameter used to quantitate the degree of intimal hyperplasia that has developed at the site of PCI between the time of the procedure and subsequent angiographic follow-up Late loss within a stent is defined as the in-stent minimum lumen diameter immediately following stent placement minus the in-stent minimum lumen diameter on late follow-up angiography (Circulation 1992;86:1827–1835, J Am Coll Cardiol 1992;19:1493–1499) Answer D Diabetes, length of the initial stent, and smaller final minimum luminal diameter following the repeat intervention have all been associated with a higher likelihood of recurrent in-stent restenosis (Textbook of Interventional Cardiology 2003;455– 473) Long-term success is also less likely when instent restenosis presents in a diffuse or occlusive pattern rather than as a focal narrowing within the stent (J Am Coll Cardiol 1998;32:980–984, Circulation 1999;100:1872–1878) Answer B Although thienopyridine therapy is effective in reducing the incidence of stent thrombosis following implantation of BMSs or DESs and 130 following intracoronary brachytherapy, no prospective data have demonstrated the necessity of this therapy when stand-alone balloon angioplasty is used as a treatment for in-stent restenosis Answer A In-stent restenosis typically occurs within the first months of BMS implantation After months, serial angiographic followup studies have demonstrated a gradual spontaneous improvement in the degree of luminal narrowing within the stent (spontaneous regression) (Am J Cardiol 1996;77:247–251, N Engl J Med 1996;334:561–566) Late stent recoil, although occasionally noted, is an uncommon occurrence (Am J Cardiol 1999;84:1247–1250, Am J Cardiol 1998;81:9) Patients presenting with restenosis early (within the first months of stent implantation) have an increased risk of recurrent restenosis following repeat PCI compared with patients who present later (Am J Cardiol 2000;85:1427–1431) Answer B β-Emitters generate radiation in the form of electrons, whereas γ sources emit radiation in the form of photons β-emitters demonstrate a rapid falloff in dose as distance from the source increases, which limits tissue penetration Because of the rapid dose falloff, centering of the β-energy delivery source may be necessary in larger vessels to ensure adequate circumferential delivery of radiation to the vessel wall The rapid dose falloff, however, reduces radiation exposure to cath lab personnel Because β-emitters are associated with higher energy levels, shorter dwell times are required to achieve adequate tissue doses (Internat J Cardiol 2004;93:1–5, Cardiovasc Res 2004;63:22–30) Answer F Before the advent of vascular brachytherapy and, more recently, DESs to treat in-stent restenosis, several methods of tissue debulking were studied for the treatment of in-stent restenosis Although data evaluating these techniques is limited, none appear to reduce the incidence of recurrent instent restenosis compared with stand-alone balloon angioplasty (J Am Coll Cardiol 2004;43:936–942, Eur Heart J 2003;24:266–273) In the randomized controlled angioplasty versus rotational atherectomy for the treatment of diffuse restenosis trial (ARTIST) study, rotational atherectomy used in the setting of in-stent restenosis was associated with an increased Restenosis and Percutaneous Options likelihood of recurrent clinical and angiographic restenosis compared with balloon angioplasty alone (Circulation 2002;105:583–588) Anecdotal reports have described mixed results with the use of directional atherectomy and the excimer laser for the treatment of in-stent restenosis The restenosis intrastent balloon versus stent trial (RIBS) trial, a randomized study of repeat BMS implantation versus balloon angioplasty for the treatment of in-stent restenosis, demonstrated no significant differences in angiographic or clinical outcomes between the two strategies (J Am Coll Cardiol 2003;42:796–805) After encouraging registry studies examining the efficacy of cutting balloon angioplasty for treating in-stent restenosis, a more recent randomized trial failed to show a reduction in recurrent restenosis or major adverse cardiac events with the cutting balloon compared with conventional balloon angioplasty (J Am Coll Cardiol 2004;43:943–949) Answer D Intravascular brachytherapy has been associated with a reduction in the likelihood of recurrent in-stent restenosis in all of the settings listed (Catheter Cardiovasc Interv 2004;62:318–322, N Engl J Med 2002;346:1194–1199, Circulation 2000;101:1895–1898); however, brachytherapy has failed to reduce the likelihood of restenosis when used following stent implantation for a de novo lesion (Am Heart J 2003;146:775–786) Answer B Because of delayed endothelialization of the stent following brachytherapy, which is associated with a propensity toward late stent thrombosis, clopidogrel therapy is advised for at least 12 months following brachytherapy (Circulation 1999;100:789–792, Circulation 2002;106:776–778) The presence of thrombus within a stent has been considered to represent a contraindication to brachytherapy (Circulation 2003;107:1744–1749) The placement of additional stents during the brachytherapy procedure has been shown to increase the likelihood of subsequent recurrent restenosis, and may also increase the risk of stent thrombosis (Am Heart J 2003;146:142–145) Although multiple randomized controlled trials of brachytherapy for in-stent restenosis using both β and γ -emitting isotopes have demonstrated significant reductions in recurrent restenosis compared with placebo, the incidence of recurrent angiographic restenosis following brachytherapy has remained >20% in nearly all of these trials (ACC/AHA 2005 Guideline Update 2006) The ‘‘edge effect’’ is as defined in the question (J Am Coll Cardiol 2001;37:1026–1030, JAMA 2005;293:437–446) 131 10 Answer B Compared with stand-alone balloon angioplasty, stent implantation is associated with an exaggerated vascular smooth muscle cell proliferative response and consequently, an increased degree of neointima formation (Circulation 1999;99:44–52) Stent placement, however, essentially eliminates long-term negative remodeling of the vessel wall, which typically more than compensates for the exaggerated proliferative response and results in the reduced frequency of restenosis observed with stenting compared with balloon angioplasty (Circulation 1997;95:363–370) Restenotic tissue obtained following balloon angioplasty demonstrates fewer smooth muscle cells and greater collagen deposition than tissue recovered from stents that have developed restenosis (J Am Coll Cardiol 2000;35:157–163) 11 Answer E Rapamycin (sirolimus) possesses all of the listed biological characteristics, which likely contribute to its antirestenosis effects (Trends Cardiovasc Med 2003;13:142–148) 12 Answer A Microtubules are a fundamental component of the mitotic spindle apparatus, and play essential roles in other cellular functions including migration and growth factor signaling The assembly and disassembly of microtubules within a cell is maintained in a well-regulated equilibrium Paclitaxel (Taxol) produces its antiproliferative effects by stabilizing microtubules, thus shifting the dynamic balance toward assembly, which consequently interrupts cellular division Rapamycin (sirolimus) is a macrolide antibiotic that produces its cellular effects by blocking cell cycle progression at the G1 to S phase transition in vascular smooth muscle cells (Ann Rev Med 2004;55:169–178) 13 Answer A Polymer coatings are required for affixing most pharmaceutical agents to a stent platform for delivery The coatings act as a reservoir for the drug, and can serve to regulate the rate of drug elution into surrounding tissues A wide variety of potential coatings have been described, and the various polymers differ in terms of structure and biocompatibility (Ann Pharmaco 2004;38:661–669) Some coatings, when affixed to a BMS, have been shown in animal models to elicit a more aggressive inflammatory and hyperplastic response than seen with nonpolymercoated BMSs (Circulation 1996;94:1690–1697) 14 Answer C A great deal of information can be obtained from frequency distribution curves, which are typically used to display the immediate and late angiographic results of competing therapies in clinical 132 900 Questions: An Interventional Cardiology Board Review trials of restenosis The median acute luminal gain for each therapy can be determined by measuring the distance between the prestent and poststent curve for each stent on a horizontal line drawn at the 50% mark on the y(cumulative frequency)-axis In the example, this distance is similar for Stents A and B Late lumen loss can be determined by comparing the distance between the poststent and the 6-month follow-up curve for each stent, which in the example is greater for Stent B The angiographic restenosis rate for each therapy can be determined by drawing a vertical line upward from the 50% diameter stenosis point on the xaxis (percent diameter stenosis) The point on the y-axis that corresponds to where this vertical line intersects the 6-month follow-up curve for each stent reveals the percentage of individuals who had a ≤50% stenosis at 6-month follow-up The frequency of angiographic restenosis for that particular stent is determined by subtracting this number from 100 (it is easier than it sounds!) In the example, the frequency of angiographic restenosis is approximately 10% for Stent A and 40% for Stent B 15 Answer F Small randomized trials have demonstrated significant reductions in angiographic restenosis for each of these agents Oral prednisone therapy was examined in a study that included 83 patients with elevated serum C-reactive protein concentrations 72 hours following stenting (J Am Coll Cardiol 2002;40:1935–1942) Patients were randomized to prednisone versus placebo for 45 days, and 6-month angiographic restenosis was significantly lower among patients treated with prednisone In the 250-patient Valsartan for Prevention of Restenosis after Stenting (VAL-PREST) study, valsartan therapy was associated with a 50% reduction in angiographic restenosis compared with placebo (J Invasive Cardiol 2001;13:93–97) Although 3-hydroxy-3 methylglutaryl (HMG)-CoA reductase inhibitor therapy has generally yielded disappointing results for restenosis prevention following PCI, pravastatin therapy was associated with a significant reduction in restenosis in the Regression Growth Evaluation Study (REGRESS) (Eur Heart J 2001;22:1642–1681) A small trial examining the antidiabetic agent troglitazone also demonstrated a restenosis benefit (J Am Coll Cardiol 2000;36:1529–1535) Although interesting, confirmation of these results in larger trials is necessary 16 Answer A Rapamycin and paclitaxel stents are both associated with a reduction in angiographic and clinical parameters of restenosis in patients with and without diabetes mellitus (J Am Coll Cardiol 2005; 45:1172–1179, Circulation 2004;109:2273–2278) In the intracoronary stenting and antithrombotic regimen (ISAR)-diabetes study, which randomized 250 patients with diabetes to implantation of rapamycin versus paclitaxel stents, the rapamycin-coated stent was associated with a significant reduction in late luminal loss at late angiographic follow-up (New Engl J Med 2005;353:663–670) Diabetes has not heretofore been identified as a predictor of subacute or late stent thrombosis following DES placement Although drug-coated stents significantly reduce the need for repeat revascularization compared with BMSs, they have not been shown to provide any relative mortality benefit 17 Answer E Routine stress testing (with or without adjunctive imaging) or other imaging studies to screen for stent patency have not been associated with improved prognosis, and in the absence of clinical symptoms are typically not indicated for screening purposes following successful PCI As discussed in the ACC/AHA Practice Guidelines for Exercise Testing, routine periodic monitoring of asymptomatic patients after PCI or coronary artery bypass graft (CABG) without specific indications is considered not useful (Class III indication) The guidelines suggest, however, that screening may be useful in patients considered to be at particularly high risk, for example, those with depressed left ventricular function, multivessel coronary disease, proximal LAD disease, multivessel disease, diabetes, hazardous occupations, or suboptimal PCI results (J Am Coll Cardiol 2002;40:1531–1540) Routine follow-up coronary angiography is typically advised in patients who undergo stenting of an unprotected left main coronary artery 18 Answer C In a large registry of patients treated with a sirolimus-eluting stent, the following clinical, angiographic, and procedural variables were found to be independent predictors of subsequent in-stent restenosis: Treatment of in-stent restenosis odds ratio (OR) 4.16, 95% CI, 1.63 to 11.01; p