DK1160_half-series-title.qxd 12/9/04 11:13 AM Page A DK1160_half-series-title.qxd 12/9/04 11:13 AM Page B Fundamental and Clinical Cardiology Editor-in-Chief Samuel Z. Goldhaber, M.D. Harvard Medical School and Brigham and Women’s Hospital Boston, Massachusetts 1. Drug Treatment of Hyperlipidemia, edited by Basil M. Rifkind 2. Cardiotonic Drugs: A Clinical Review, Second Edition, Revised and Expanded, edited by Carl V. Leier 3. Complications of Coronary Angioplasty, edited by Alexander J. R. Black, H. Vernon Anderson, and Stephen G. Ellis 4. Unstable Angina, edited by John D. Rutherford 5. Beta-Blockers and Cardiac Arrhythmias, edited by Prakash C. Deedwania 6. Exercise and the Heart in Health and Disease, edited by Roy J. Shephard and Henry S. Miller, Jr. 7. Cardiopulmonary Physiology in Critical Care, edited by Steven M. Scharf 8. Atherosclerotic Cardiovascular Disease, Hemostasis, and Endothelial Function, edited by Robert Boyer Francis, Jr. 9. Coronary Heart Disease Prevention, edited by Frank G. Yanowitz 10. Thrombolysis and Adjunctive Therapy for Acute Myocardial Infarction, edited by Eric R. Bates 11. Stunned Myocardium: Properties, Mechanisms, and Clinical Manifestations, edited by Robert A. Kloner and Karin Przyklenk 12. Prevention of Venous Thromboembolism, edited by Samuel Z. Goldhaber 13. Silent Myocardial Ischemia and Infarction: Third Edition, Peter F. Cohn 14. Congestive Cardiac Failure: Pathophysiology and Treatment, edited by David B. Barnett, Hubert Pouleur and Gary S. Francis 15. Heart Failure: Basic Science and Clinical Aspects, edited by Judith K. Gwathmey, G. Maurice Briggs, and Paul D. Allen 16. Coronary Thrombolysis in Perspective: Principles Underlying Conjunctive and Adjunctive Therapy, edited by Burton E. Sobel and Desire Collen 17. Cardiovascular Disease in the Elderly Patient, edited by Donald D. Tresch and Wilbert S. Aronow 18. Systemic Cardiac Embolism, edited by Michael D. Ezekowitz 19. Low-Molecular-Weight Heparins in Prophylaxis and Therapy of Thromboembolic Diseases, edited by Henri Bounameaux 20. Valvular Heart Diseases, edited by Muayed Al Zaibag and Carlos M. G. Duran 21. Implantable Cardioverter-Defibrillators: A Comprehensive Textbook, edited by N. A. Mark Estes, Antonis S. Manolis, and Paul J. Wang 22. Individualized Therapy of Hypertension, edited by Norman M. Kaplan and C. Venkata S. Ram 23. Atlas of Coronary Balloon Angioplasty, Bernhard Meier and Vivek K. Mehan DK1160_half-series-title.qxd 12/9/04 11:13 AM Page C 24. Lowering Cholesterol in High-Risk Individuals and Populations, edited by Basil M. Rifkind 25. Interventional Cardiology: New Techniques and Strategies for Diagnosis and Treatment, edited by Christopher J. White and Stephen Ramee 26. Molecular Genetics and Gene Therapy of Cardiovascular Diseases, edited by Stephen C. Mockrin 27. The Pericardium: A Comprehensive Textbook, David H. Spodick 28. Coronary Restenosis: From Genetics to Therapeutics, edited by Giora Z. Feuerstein 29. The Endothelium in Clinical Practice: Source and Target of Novel Therapies, edited by Gabor M. Rubanyi and Victor J. Dzau 30. Molecular Biology of Cardiovascular Disease, edited by Andrew R. Marks and Mark B. Taubman 31. Practical Critical Care in Cardiology, edited by Zab Mohsenifar and P. K. Shah 32. Intravascular Ultrasound Imaging in Coronary Artery Disease, edited by Robert J. Siegel 33. Saphenous Vein Bypass Graft Disease, edited by Eric R. Bates and David R. Holmes, Jr. 34. Exercise and the Heart in Health and Disease: Second Edition, Revised and Expanded, edited by Roy J. Shephard and Henry S. Miller, Jr 35. Cardiovascular Drug Development: Protocol Design and Methodology, edited by Jeffrey S. Borer and John C. Somberg 36. Cardiovascular Disease in the Elderly Patient: Second Edition, Revised and Expanded, edited by Donald D. Tresch and Wilbert S. Aronow 37. Clinical Neurocardiology, Louis R. Caplan, J. Willis Hurst, and Mark Chimowitz 38. Cardiac Rehabilitation: A Guide to Practice in the 21st Century, edited by Nanette K. Wenger, L. Kent Smith, Erika Sivarajan Froelicher, and Patricia McCall Comoss 39. Heparin-Induced Thrombocytopenia, edited by Theodore E. Warkentin and Andreas Greinacher 40. Silent Myocardial Ischemia and Infarction: Fourth Edition,Peter F. Cohn 41. Foundations of Cardiac Arrhythmias: Basic Concepts and Clinical Approaches, edited by Peter M. Spooner and Michael R. Rosen 42. Interpreting Electrocardiograms: Using Basic Principles and Vector Concepts, J. Willis Hurst 43. Heparin-Induced Thrombocytopenia: Second Edition, edited by Theodore E. Warkentin and Andreas Greinacher 44. Thrombosis and Thromboembolism, edited by Samuel Z. Goldhaber and Paul M. Ridker 45. Cardiovascular Plaque Rupture, edited by David L. Brown 46. New Therapeutic Agents in Thrombosis and Thrombolysis: Second Edition, Revised and Expanded, edited by Arthur A. Sasahara and Joseph Loscalzo 47. Heparin-Induced Thrombocytopenia: Third Edition, edited by Theodore E. Warkentin and Andreas Greinacher 48. Cardiovascular Disease in the Elderly, Third Edition,edited by Wilbert Aronow and Jerome Fleg 49. Atrial Fibrillation,edited by Peter Kowey and Gerald Naccarelli 50. Heart Failure: A Comprehensive Guide to Diagnosis and Treatment, edited by G. William Dec DK1160_half-series-title.qxd 12/9/04 11:13 AM Page D ADDITIONAL VOLUMES IN PREPARATION Phamacoinvasive Therapy in Acute Myocardial Infarction, edited by Harold L. Dauerman and Burton E. Sobel Clinical, Interventional, and Investigational Thrombocardiology, edited by Richard Becker and Robert A. Harrington DK1160_half-series-title.qxd 12/9/04 11:13 AM Page i Editor G. William Dec Massachusetts General Hospital Boston, Massachusetts, U.S.A. Harvard Medical School Cambridge, Massachusetts, U.S.A. Associate Editors Thomas DiSalvo, Roger J. Hajjar, and Marc J. Semigran Harvard Medical School Cambridge, Massachusetts, U.S.A. MarcelDekker NewYork MD-0427—5827-7—DEC—FM—R3—11-18-04 14:25:57— Althoughgreatcarehasbeentakentoprovideaccurateandcurrentinformation,neithertheauthor(s) nor the publisher, nor anyone else associated with this publication, shall be liable for any loss, damage,orliabilitydirectlyorindirectlycausedorallegedtobecausedbythisbook.Thematerial contained herein is not intended to provide specific advice or recommendations for any specific situation. Trademarknotice:Productorcorporatenamesmaybetrademarksorregisteredtrademarksandare usedonlyforidentificationandexplanationwithoutintenttoinfringe. LibraryofCongressCataloging-in-PublicationData AcatalogrecordforthisbookisavailablefromtheLibraryofCongress. ISBN:0-8247-5827-7 Thisbookisprintedonacid-freepaper. 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Currentprinting(lastdigit): 10 9 8 7 6 5 4 3 2 1 PRINTEDINTHEUNITEDSTATESOFAMERICA This book is dedicated to Donna, Sarah, and Jonathan Preface Heartfailureisagrowingworld-wideepidemicwithaprevalenceofmorethan5million casesintheUnitedStatesand6.5millioncasesinEurope.Epidemiologicdatademonstrate arapidincreaseinitsincidenceduringthepasttwodecades.Thistrendislikelytocontinue as the population ages. It is currently the most common hospital discharge diagnosis for patientsovertheageof65yearsandaccountsforsubstantialmorbidityandhighmortality. Fortunately, major advances have occurred in our understanding of the cellular mecha- nisms,pathophysiologicalabnormalities,nonpharmacologictherapyandsurgicaltherapeu- ticoptionsforthissyndromeduringthepastdecade.Thistextbookfocusesthemostrecent developments in the pathogenesis, etiologic considerations, diagnosis, and treatment of heartfailure andhas beenwritten byinternationally recognizedphysicians andscientists involved on a daily basis in heart failure research and clinical care. Theauthors’aimistoprovideanup-to-dateandcomprehensivereviewofthediagno- sis and treatment of heart failure. The text is divided into five sections that concisely summarizefundamentalcellularandmolecularbasesforheartfailure,itspathophysiology, currentinvasiveandnoninvasivediagnostictechniques,pharmacologicadvancesandde- vice-based therapy, surgical options, and evolving molecular therapies. The first section focusesonthetremendousadvancesthathaveoccurredoverthelastdecadeinourunder- standing of the basic mechanisms of heart failure. These discoveries have reshaped our understanding of the basic causes of "the heart failure phenotype" and will allow us to redesigntherapeuticstrategiesforthetreatmentofthisdisease.Thesechaptersspecifically focusonthegeneticsofdilatedandhypertrophiccardiomyopathy,theroleofhypertrophy andapoptosis,beta-adrenergicreceptorsignaling,andexcitation-contractioncouplingab- normalities that contribute to ventricular dysfunction. In each of these chapters, the role ofnewtools,suchasmicroarrayanalysis,proteomics,andmolecularimagingaredetailed. Thesecondsectionsummarizesrecentinsightsintotheactivationofvasoconstrictor and vasodilator pathways, including a host of crucial neurohormones and cytokines. Is- chemic left ventricular remodeling, cardiomyopathies of the adult, and diagnostic and etiologic considerations in diastolic heart failure complete this section. The third section summarizes current diagnostic methodologies and nonsurgical treatmentoptions.Prognosticmarkersincludingbrainnatriureticpeptides(BNP)arehigh- lighted.Recent pivotalmulticenterclinicaltrials thathaveevaluated thetherapeuticeffi- v