Idiopathic Dilated Cardiomyopathy: Cellular and Molecular Mechanisms, Clinical Consequences

ISBN-13: 9783642778933 / Angielski / Miękka / 2011 / 405 str.

Hans-Reiner Figulla; Reinhard Kandolf; Bruce McManus

Opis

Idiopathic cardiomyopathy has been categorized for over 10 years by the World Health Organization as dilated, hypertrophic, or restrictive. These categories have somewhat vague boundaries; however, idiopathic dilated cardiomyopathy (IDC) finds its general definition from unexplained four-chamber dilatation, prominent systolic dysfunction with depressed ejection fraction, a marked increase in total myocardial mass without wall thickening, myocyte hypertrophy and nuclear polyploidy, rarity of frank myocardial scars, but increased interstitial connective tissue and myocyte atrophy, all in the setting of anatomically normal heart valves and coronary arteries. Mural thrombi within cardiac chambers and atrioventricular valve regurgitation are common secondary con comitants. Myocardial inflammation is rare, but immunological abnormalities have been suggested. Ultrastructural features in clude increased mitochondrial numbers, lipid deposits, and myo fibrillar loss. Progressive pump failure with or without rhythm disturbances typically leads to ever-intensified medical therapies, and ultimately to transplantation or early death. The need for better understanding of IDC is represented by incidence rates varying from 5 to 8/100000 population across several populations, 10 000-20000 IDC deaths annually in the United States, and the generally increasing prevalence of the disease. More than 50% of heart transplant recipients have IDC as their primary myocardial disease. The half-life of patient sur vival without transplantation is generally less than 5 years. Treat ment with antiarrhythmics, calcium channel blockers, -adrenergic blockers, and angiotensin-converting enzyme inhibitors is being evaluated in clinical trials, but the role of such treatments in the pathobiology of progressive disease is unclear."

Spis treści

I. Introductory Perspectives.- Idiopathic Dilated Cardiomyopathy: Current Concepts in Clinical Research.- II. Epidemiology and Natural Course of IDC.- Epidemiology of Idiopathic Dilated Cardiomyopathy.- Natural History of Idiopathic Dilated Cardiomyopathy.- III. Basic Molecular Concepts Toward Understanding of IDC.- Molecular Analysis of Cardiac Growth and Development in Transgenic Mouse Model Systems.- The Promoter of the Human Cardiac ?-Myosin Heavy-Chain Gene Is Controlled by an Upstream Enhancer.- Growth Factor Expression in the Cardiac Myocyte.- IV. Structural Abnormalities in IDC.- The Cytoskeleton and Extracellular Matrix in Human Hearts with Dilated Cardiomyopathy.- Macro- and Micropathology of Dilated Cardiomyopathy.- Detection of Disruption of Sarcolemmal Membrane by Indium-111 Labeled Antimyosin Antibody Scan.- Extracellular Matrix Expression, Organization, and Interaction with Heart Myocytes During Development and Disease.- V. Contraction and Relaxation.- Ventricular Remodeling in Idiopathic Dilated Cardiomyopathies.- Mechanisms of Deficient cAMP Generation in Heart Failure.- Abnormal Calcium Metabolism in Heart Muscle Dysfunction.- Energy Requirements of Contraction and Relaxation of the Heart.- VI. Microcirculation and Oxygen Supply in Cardiac Hypertrophy and IDC.- Capillary Density, Distribution, and Length Parameters Related to Oxygen Supply in Myocardial Hypertrophy and Atrophy.- Microcirculation in the Cardiomyopathic Syrian Hamster and in Human Congestive Cardiomyopathy.- The Microcirculation in Cardiac Hypertrophy.- Myocardial Oxygen Consumption in Patients with Idiopathic Dilated Cardiomyopathy: Effects of Vasodilating and Inotropic Agents.- Regression of Cardiac Hypertrophy with Pharmacotherapeutic Regimen.- VII. Ionic Channels and Signal Gating.- ?-Adrenergic Receptor Dysfunction in the Pathogenesis of Idiopathic Dilated Cardiomyopathy.- Na+ Channels as Molecular Substrate of Cardiac Excitability: Elementary Properties and Responsiveness to Drugs.- The Involvement of Gs in Regulation of the L-Type Voltage-Gated Ca2+ Channel.- Inositol Phosphates in Cardiac Regulation.- VIII. Virus and Cardiomyopathy.- Enterovirus-Induced Cardiomyopathy: Molecular Analysis of Acute and Persistent Myocardial Infections.- Direct Damage of Myocardium by Enterovirus.- Natural History of Enterovirus Persistence in the Murine Model of Coxsackievirus-Induced Myocarditis: A Quantitative In Situ Hybridization and Immunohistochemistry Study.- Detection and Typing of Enteroviruses.- Specific and Nonspecific Heart Defenses in Enteroviral Infections.- IX. Immunological Factors in Cardiomyopathy.- Heart Autoantibodies in Human Myocarditis and Cardiomyopathy: Virus and Skeletal Muscle Cross-reactivity.- Are Anti-cardiac Antibodies in Dilated Cardiomyopathy “Natural” Antibodies?.- X. Therapeutic Options in IDC and Myocarditis.- Animal Models for Therapeutic Trials of Viral Myocarditis.- Immunosuppressive Therapy in Human Myocarditis.- Interferon Therapy in Enterovirus-Associated Idiopathic Dilated Cardiomyopathy.- The Role of ?-Blockers in Idiopathic Dilated Cardiomyopathy: Clinical Effect and Molecular Mechanism.- The Role of Calcium Channel Blockers in Idiopathic Dilated Cardiomyopathy.- Gene Therapy for Cardiovascular Disease: Realistic Possibilities for the Future.