Heart Failure: A Companion to Braunwald's Heart Disease E-Book

Up-to-date, authoritative and comprehensive, Heart Failure, 4th Edition, provides the clinically relevant information you need to effectively manage and treat patients with this complex cardiovascular problem. This fully revised companion to Braunwald’s Heart Disease helps you make the most of new drug therapies such as angiotensin receptor neprilysin inhibitors (ARNIs), recently improved implantable devices, and innovative patient management strategies. Led by internationally recognized heart failure experts Dr. G. Michael Felker and Dr. Douglas Mann, this outstanding reference gives health care providers the knowledge to improve clinical outcomes in heart failure patients. Focuses on a clinical approach to treating heart failure, resulting from a broad variety of cardiovascular problems. Covers the most recent guidelines and protocols, including significant new updates to ACC, AHA, and HFSA guidelines. Covers key topics such as biomarkers and precision medicine in heart failure and new data on angiotensin receptor neprilysin inhibitors (ARNIs). Contains four new chapters: Natriuretic Peptides in Heart Failure; Amyloidosis as a Cause of Heart Failure; HIV and Heart Failure; and Neuromodulation in Heart Failure. Covers the pathophysiological basis for the development and progression of heart failure. Serves as a definitive resource to prepare for the ABIM’s Heart Failure board exam. 2016 British Medical Association Award: First Prize, Cardiology (3rd Edition). Enhanced eBook version included with purchase. Your enhanced eBook allows you to access all of the text, figures, and references from the book on a variety of devices. Cover Copyright Contributors Foreword Preface Acknowledgments Braunwald's Heart Disease Family of Books Section I: Basic Mechanisms of Heart Failure Chapter 1: Molecular Basis of Heart Failure Types of Heart Failure HFrEF Versus HFpEF: Ramifications for Understanding the Underlying Biology Investigative Techniques and Molecular Modeling Molecular Determinants of Physiologic Cardiac Growth, Hypertrophy, and Atrophy Molecular Determinants of Pathologic Hypertrophy Is Load-Induced Hypertrophy Ever Compensatory? Transcriptional Regulation of Pathologic Cardiac Hypertrophy Cellular Mechanisms of Impaired Cardiomyocyte Viability Activation of Cell Death Pathways Cell Survival Pathways Mitochondria and Metabolic Remodeling in Pathologic Hypertrophy Neurohormonal Signaling and Cardiomyocyte Dysfunction Biased Agonism as a Novel Concept in Cardiac Therapeutics Cascades That Transduce Hypertrophic Signaling Biomechanical Sensors of Hypertrophic Stimuli Neurohormonal and Growth Factor Signaling α-Adrenergic Receptors Angiotensin Signaling Endothelin The Gαq/Phospholipase C/Protein Kinase C Signaling Axis Mitogen-Activated/Stress-Activated Protein Kinase Signaling Cascades Inositol 1,4,5-Trisphosphate-Induced Ca2+-Mediated Signaling, Calcineurin/NFAT Axis, and Ca2+/Calmodulin-Dependent Protein Kinase Signaling Epigenetic Regulation of Transcription in Cardiac Hypertrophy Cross Talk Between Gαq and PI3K/Akt/mTOR/GSK3 Hypertrophic Signaling Pathways Non–Insulin-Like Growth Factor Signaling in Hypertrophy Role of Small G Proteins Cardiac Fibrosis Cardiac Inflammation Summary and Future Directions Key References References Chapter 2: Cellular Basis for Heart Failure Contractile Dysfunction Normal Excitation-Contraction Coupling Impaired Ca2+ Handling in Failing Cardiac Myocytes Reduced SR Ca2+ Reuptake in Heart Failure Increased NCX Activity in the Failing Heart “Leaky” RyR2 Cause Diastolic SR Ca2+ Loss in Heart Failure Contribution of Impaired Ca2+ Handling to Arrhythmia Sarcomeric Dysfunction in Heart Failure Global Mechanisms Affecting Cardiomyocyte Function in Heart Failure Redox Homeostasis in the Heart Protein Synthesis, Turnover, Quality Control, and Stress Responses Endoplasmic Reticulum and the Unfolded Protein Response Autophagy Ubiquitin-Proteasome System Paracrine Effects of Endothelial Cells Paracrine Effects of Fibroblasts Cardiomyocyte Angiogenic Signaling Activation of Inflammatory Pathways MicroRNA and Long Noncoding RNA-Dependent Pathways Conclusions and Future Directions Acknowledgments Key References References Chapter 3: Cellular Basis for Myocardial Regeneration and Repair The Postnatal Heart Is Not a Postmitotic Organ Sources of Controversy in Postnatal Mammalian Cardiomyocyte Proliferation Evidence of Cardiomyocyte Turnover in the Adult Heart Molecular Basis of the Terminally Differentiated State of Cardiomyocytes Mechanisms of Cardiac Regeneration Endogenous Heart Regeneration in Lower Vertebrates and Mammals Induction of Cardiomyocyte Proliferation Cyclins and Cyclin-Dependent Kinases microRNAs Transcription Factors Nerves Hippo Signaling Ventricular Unloading Direct Reprogramming to Cardiomyocyte Fate Exogenous Cardiomyocytes for Cell Therapy Direct Reprogramming to Cardiomyocyte Fate Noncardiomyocyte Cell Therapy: Where We Stand Conclusions and Future Directions Key References References Chapter 4: Myocardial Basis for Heart Failure: Role of Cardiac Interstitium Myocardial Extracellular Matrix Structure and Composition The Myocardial Fibroblast Myocardial Extracellular Matrix Proteolytic Degradation: The Matrix Metalloproteinases Transcriptional Regulation of Extracellular Matrix Degradation; Matrix Metalloproteinase Polymorphisms Matrix Metalloproteinase Posttranscriptional Regulation Matrix Metalloproteinase Posttranslational Regulation Endogenous Matrix Metalloproteinase Inhibition Heart Failure with Reduced Ejection Fraction and Extracellular Matrix Remodeling-Dilated Cardiomyopathy Heart Failure With Reduced Ejection Fraction and Extracellular Matrix Remodeling—Hypertensive Heart Disease Myocardial Extracellular Matrix Remodeling in Heart Failure—Diagnostic Potential Imaging Summary and Future Directions The Extracellular Matrix and Diagnostics The Extracellular Matrix and Therapeutics Key References References Section II: Mechanisms of Disease Progression in Heart Failure Chapter 5: Molecular Signaling Mechanisms of the Renin-Angiotensin System in Heart Failure A Perspective on the Renin Angiotensin Aldosterone System The Biochemical Physiology of the Renin Angiotensin System Renin and Pro-Renin Other Nonrenin Enzymes Angiotensinogen Angiotensin I and II Forming Enzymes Angiotensin-Converting Enzyme Chymase Angiotensin-Converting Enzyme 2 Other Angiotensin-Forming Enzymes Main Angiotensin Products Angiotensin-(1-12) Angiotensin-(1-9) Angiotensin I and Angiotensin II Angiotensin III and Angiotensin IV Angiotensin-(1-7) Ala1-Angiotensin II and Almandine Angiotensin II Mediated Signaling Pathways Angiotensin II Receptors Ang II/AT1-R-Mediated G Protein-Coupled Pathways Ang II/AT1-R-Mediated Classic G Protein-Coupled Signaling Pathways Ang II/AT1-R-Mediated Transactivation of Receptor Tyrosine Kinases Ang II/AT1-R-Mediated Nonreceptor Tyrosine Kinases Activation Ang II/AT1-R-Mediated Mitogen-Activated Protein Kinases Activation Ang II/AT1-R-Mediated Reactive Oxygen Species Signaling G-Protein-Independent AT1-R Signaling Pathways Ang II/AT2-R-Mediated Signaling Pathways Summary and Conclusions Acknowledgments Key References Further Reading References Chapter 6: Adrenergic Receptor Signaling in Heart Failure Role of Increased Adrenergic Drive in the Natural History of Heart Failure Adrenergic Receptor Pharmacology Altered β-Adrenergic Receptor Signal Transduction in the Failing Heart Molecular Basis of β-Adrenergic Receptor Signaling Regulation of β-Adrenergic Receptors Gene Expression Myopathic Potential of Individual Components of Adrenergic Receptor Pathways β1- and β2-Adrenergic Receptors α1-Adrenergic Receptors G-Proteins and Adenylate Cyclases G-Protein Receptor Kinases Adrenergic Receptor Polymorphisms and Their Importance in Heart Failure Natural History or Therapeutics Noncatecholamine Ligands That Activate Myocardial β-Adrenergic Receptors, and Their Role in Producing Dilated Cardiomyopathies Summary and Future Directions Key References References Chapter 7: Role of Innate Immunity in Heart Failure Overview of Innate Immunity Expression and Regulation of Pattern Recognition Receptors in the Heart Toll Receptors Role of Toll-like Receptors in Myocardial Disease Toll-like Receptor Signaling in Ischemia Reperfusion Injury and Myocardial Infarction Functional Role of Toll-like Receptor Signaling in Human Heart Failure NOD Receptors Other Pattern Recognition Receptors Effectors of the Innate Immune Response in the Heart Proinflammatory Cytokines Tumor Necrosis Factor Superfamily Interleukin-1 Family Interleukin-6 Family Chemokines Leukocytes Conclusion and Future Directions Key References References Chapter 8: Oxidative Stress in Heart Failure Reactive Oxygen Species and Antioxidant Systems Reactive Oxygen Species Primary Antioxidant Systems Ancillary Antioxidant Mechanisms Markers of Oxidative Stress in Human Heart Failure Lipid Oxidation Products Glycoprotein and DNA Products Other Oxidative Stress Markers Mechanisms of Increased Oxidative Stress in Heart Failure Oxidases Mitochondria Nitric Oxide Synthase Decreased Antioxidant Activity Nonenzymatic Auto-Oxidation Oxidative Stress and Antioxidant Therapy in Animal Models of Heart Failure Hemodynamic Overload NAD(P)H Oxidase Transgenic Mice NOS3 Knockout and Tetrahydrobiopterin Thioredoxin and N-2-Mercaptopropionyl Glycine Peroxisomal Catalase Vitamins E and C, and Resveratrol Mitochondrial Antioxidants Heart Failure in Gαq-Transgenic Mice Anthracycline-Induced Cardiomyopathy Models of Diastolic Dysfunction Other Experimental Heart Failure Models Human Trials of Antioxidant Therapies Left Ventricular Remodeling Myocyte Hypertrophy Myocyte Death Interstitial Fibrosis Molecular and Cellular Mechanisms of Reactive Oxygen Species-Induced Heart Failure Mitogen-Activated Protein Kinases Mitochondrial Signaling and Energetics Endoplasmic Reticulum Stress Response Calcium Handling Impaired Energetics Summary and Future Directions Key References References Chapter 9: Natriuretic Peptides in Heart Failure: Pathophysiologic and Therapeutic Implications Natriuretic Peptides: Historical Background General Overview of Natriuretic Peptide System Natriuretic Peptide System in Heart Failure: Pathophysiology, Diagnostics, and Treatment Novel Designer Natriuretic Peptides in the Therapy of Heart Failure Role of Natriuretic Peptides in Cardiac Regeneration and Repair Conclusions and Future Directions Key References References Chapter 10: Systolic Dysfunction in Heart Failure Cellular and Molecular Determinants: a View From 30,000 Feet Measuring Systolic Function: A Primer on Pressure-volume Relations Beat-to-Beat Regulation of Systolic Function Acute Stretch—The Frank-Starling Effect Effect of Systolic Load—The Anrep Effect Effect of Heart Rate Integrative Measures of Systolic Function Impact of Pericardial Loading on Systolic Function Ventricular–arterial Interaction Pulmonary Hypertension and Systolic Function of the Right Ventricle Treating Systolic Dysfunction Systolic Effects of Dyssynchrony and Resynchronization Summary Key References References Chapter 11: Alterations in Ventricular Function: Diastolic Heart Failure Physiology of Diastolic Filling and Compliance Diastolic Dysfunction Invasive Measurement of Diastolic Function: Relaxation and Chamber Stiffness Noninvasive Measurement of Diastolic Function: Echocardiography Estimation of Left Ventricle Filling Pressures Left Ventricle Hypertrophy Left Atrial Dysfunction Natriuretic Peptides Diagnosis of Heart Failure with Preserved Ejection Fraction Heart Failure with Preserved Ejection Fraction: High Diastolic Left Ventricle Stiffness Regulation of Diastolic Stiffness by the Extracellular Matrix Regulation of Myocardial Stiffness by the Cardiomyocyte Comorbidities in Heart Failure with Preserved Ejection Fraction Increased Age Female Gender Chronic Obstructive Pulmonary Disease Anemia Renal Dysfunction Hypertension Metabolic Risk Factors Inflammation and Endothelial Dysfunction The New Paradigm for Heart Failure with Preserved Ejection Fraction Heart Failure with Preserved Ejection Fraction: a Systemic Disorder Heterogeneity in Heart Failure with Preserved Ejection Fraction Pathophysiologic Stratification in Heart Failure With Preserved Ejection Fraction Summary and Future Directions Acknowledgment Key References References Chapter 12: Alterations in Ventricular Structure: Role of Left Ventricular Remodeling and Reverse Remodeling in Heart Failure Left Ventricular Remodeling Alterations in the Biology of the Cardiac Myocyte Alterations in the Myocardium Changes in Left Ventricular Geometry Clinical Studies Linking Left Ventricular Remodeling With Untoward Patient Outcomes Reverse Left Ventricular Remodeling Reversal of Alterations in the Biology of the Cardiac Myocyte Reversal of Alterations in the Myocardium Reversal of Changes in Left Ventricular Geometry Myocardial Remission and Myocardial Recovery Summary and Future Directions Key References References Chapter 13: Alterations in the Sympathetic and Parasympathetic Nervous Systems in Heart Failure Assessment of Human Sympathetic and Parasympathetic Nervous System Activity Catecholamines Microneurography Arterial Baroreflex Sensitivity Heart Rate Variability Cross-Spectral Analysis Tracer Imaging With Catecholamine Analogues Sympathetic Activation and Parasympathetic Withdrawal in Human Heart Failure Heart Failure With Reduced Systolic Function Sympathetic Activation Parasympathetic Withdrawal Heart Failure With Preserved Ejection Fraction Clinical Consequences of Autonomic Imbalance Cardiac Peripheral Exercise Mortality Mechanisms Disturbing Autonomic Equilibrium Afferent Influences Arterial Baroreceptor Reflexes Cardiopulmonary Reflexes Nonbaroreflex Mechanisms Central Integration and Interactions Experimental Heart Failure Models Clinical Studies Efferent Mechanisms Ganglionic Neurotransmission Prejunctional Mechanisms and Efferent Sympathovagal Interactions Therapeutic Implications Pharmacological Interventions Nonpharmacological Interventions Cardiac Resynchronization Therapy Cardiac Sympathetic Denervation Carotid Baroreceptor Stimulation Carotid Body Denervation Diet Exercise Training Positive Airway Pressure Renal Denervation Spinal Cord Stimulation Vagal Nerve Stimulation Summary and Future Directions Key References References Chapter 14: Alterations in the Peripheral Circulation in Heart Failure Pathophysiologic Insights Endothelial Dysfunction in Clinical Heart Failure Endothelial Dysfunction of the Coronary Circulation in Heart Failure Systemic Nature of Endothelial Dysfunction in Heart Failure Endothelial Dysfunction and Clinical Outcomes in Heart Failure Circulating Markers of Endothelial Dysfunction in Heart Failure Prothrombotic Transformation of the Endothelium in Heart Failure Treatment of Endothelial Dysfunction in Heart Failure Pharmaceutical Agents and Endothelial Function Nutritional Supplements and Endothelial Function in Heart Failure Exercise and Endothelial Function in Heart Failure Genetic Predisposition to Endothelial Dysfunction in Heart Failure Endothelial Progenitors and Angiogenic Factors in Heart Failure Conclusions and Future Directions Key References References Chapter 15: Alterations in Kidney Function Associated With Heart Failure Epidemiology of Chronic Kidney Disease and the Impact on Heart Failure Worsening Kidney Function and Prognosis Pathophysiology of Chronic Kidney Disease in Heart Failure Peripheral Volume Sensors Baroreceptors and Mechanoreceptors The Juxtaglomerular Apparatus Renal Sympathetic Nerves Central Venous Pressure as a Determinant of Kidney Function Neurohormonal Regulation of Kidney Function The Renin-Angiotensin-Aldosterone System Catecholamines Natriuretic Peptides Arginine Vasopressin Prostaglandins Biomarkers of Kidney Dysfunction Summary and Future Directions Key References References Chapter 16: Alterations in Skeletal Muscle in Heart Failure Skeletal Muscle Adaptations in Heart Failure Skeletal Muscle Atrophy Skeletal Muscle Protein Synthesis and Reduced Anabolic Hormones/Effectors Skeletal Muscle Protein Breakdown and Increased Catabolic Hormones/Effectors Skeletal Muscle Contractile Dysfunction Myofilament Contractile Adaptations Myofilament Protein Expression Myofilament Protein Function Excitation-Contraction Coupling Adaptations Decreased Oxidative Capacity and Metabolism Mitochondrial Adaptations Fiber Type Adaptations Vascular Adaptations Effectors of Skeletal Muscle Adaptations Hypoperfusion Inflammation Oxidative Stress Muscle Disuse Contribution of Skeletal Muscle Adaptations to Symptomology Summary and Future Directions Key References References Chapter 17: Alterations in Cardiac Metabolism in Heart Failure Overview of Cardiac Metabolism Hallmarks and Regulation of Cardiac Energy Metabolism Crosstalk Between Cardiac Metabolism and Signaling Significance of Cardiac Energetics for Heart Disease Metabolic Dysfunction in the Failing Heart Energy Depletion in the Failing Heart Substrate Utilization and Mitochondrial Metabolism in the Failing Heart Novel Concepts Linking Metabolic Changes and Epigenetic Changes and Posttranslational Modifications Downstream of Metabolic Intermediates Crosstalk Between Cardiac Metabolism and Systemic Metabolism Metabolic Remodeling and Risk for Heart Failure Development Cardiac Hypertrophy Obesity Diabetes Mellitus Methods to Evaluate Defects in Cardiac Energetics Therapeutic Approaches to Modulate Cardiac Energetics Modulation of Substrate Oxidation Patterns Modulation of ROS Detoxification and Oxidative Phosphorylation Exercise and Cardiac Metabolism Summary and Future Directions Key References References Section III: Etiologic Basis for Heart Disease Chapter 18: Epidemiology of Heart Failure Patient Characteristics Demographic Distribution Comorbidities Prevalence and Incidence Estimates and Trend Impact of Demographics and Socioeconomic Status Age Sex Race Socioeconomic Status Lifetime Risk of Heart Failure Prevalence of Preclinical (Stage A and B) Heart Failure Major Contributors to Heart Failure Heart Failure After Acute Coronary Syndromes Hypertension Diabetes Obesity Atrial Fibrillation Renal Disease Hospitalized Heart Failure Trends in Hospitalization Rates Length of Stay Effect of Heart Failure Hospitalization on Outcomes Heart Failure with Reduced, Midrange, and Preserved Ejection Fraction Distribution of Ejection Fraction in HF Registries and Cohorts Patient Characteristics According to Ejection Fraction Outcomes Outcomes in Outpatients Mortality Hospitalization and Composite Outcomes Progression to Stage D Heart Failure Long-Term Outcomes Outcomes in Outpatients With Improved or Recovered Ejection Fraction Prognosis of Hospitalized Heart Failure Short-Term Outcomes Long-Term Outcomes Outcomes After Post-AMI Heart Failure Key References References Chapter 19: Heart Failure as a Consequence of Ischemic Heart Disease Prevalence of Coronary Artery Disease in Heart Failure Prognostic Significance of Coronary Artery Disease in Heart Failure Pathophysiology of Acute Heart Failure in Patients with Coronary Artery Disease Underlying Coronary Artery Disease Acute Coronary Syndromes Pathophysiology of Chronic Heart Failure in Patients with Coronary Artery Disease and Reduced Ejection Fraction Left Ventricular Remodeling Myocardial Ischemia Hibernation/Stunning Diagnosis Clinical Implications Endothelial Dysfunction Endothelial Vasodilators Endothelial Vasoconstrictors Clinical Manifestations Coronary Artery Disease and Diastolic Heart Failure Diabetes, Heart Failure, and Coronary Artery Disease Therapeutic Options Immediate Management of the Hospitalized Patient Long-Term Therapies for the Heart Failure Patient With Coronary Artery Disease Conclusions Key References References Chapter 20: Heart Failure as a Consequence of Dilated Cardiomyopathy Definition Epidemiology of Dilated Cardiomyopathy Natural History of Dilated Cardiomyopathy Pathophysiology Diagnostic Strategies in Dilatedcardiomyopathy General Management Strategies of Dilated Cardiomyopathy Myocardial Diseases Presenting as Dilated Cardiomyopathy Idiopathic Dilated Cardiomyopathy Familial/Genetic Cardiomyopathies Cardiomyopathy Due to Cardiotoxins Alcoholic Cardiomyopathy Cocaine Cardiomyopathy Cardiomyopathy Related to Other Stimulant Drugs Chemotherapy Other Myocardial Toxins Inflammation-Induced Cardiomyopathy Infectious Causes Acquired Immunodeficiency Syndrome Noninfectious Causes Hypersensitivity Myocarditis Systemic Lupus Erythematosus Scleroderma Rheumatoid Arthritis Sarcoidosis Peripartum Cardiomyopathy Autoimmune Mechanisms Endocrine and Metabolic Causes of Cardiomyopathy Obesity Diabetic Cardiomyopathy Hyperthyroidism Hypothyroidism Acromegaly and Growth Hormone Deficiency Nutritional Causes of Cardiomyopathy Thiamine Deficiency Carnitine Deficiency Selenium Deficiency Hematologic Causes of Cardiomyopathy Cardiomyopathy Due to Iron Overload: Hemochromatosis and Thalassemia Hemodynamic and Stress-Induced Cardiomyopathy Tachycardia-Induced Dilated Cardiomyopathy Premature Ventricular Contractions and Cardiomyopathy Stress-Induced Cardiomyopathy Summary and Future Directions Key References References Chapter 21: Restrictive and Infiltrative Cardiomyopathies and Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Restrictive and Infiltrative Cardiomyopathy Clinical Evaluation Cardiac Catheterization and Endomyocardial Biopsy Prognosis Clinical Manifestations Laboratory Studies Inherited and Acquired Infiltrative Disorders Causing Restrictive Cardiomyopathy Fabry Disease Cardiac Findings Gaucher Disease Hemochromatosis Pathology Clinical Manifestations Glycogen Storage Disease Inflammatory Causes of Infiltrative Cardiomyopathy Sarcoidosis Endomyocardial Disease Definition and Pathogenesis Differences Between Löffler Endocarditis and Endomyocardial Fibrosis Role of Eosinophils Löffler Endocarditis: The Hypereosinophilic Syndrome Endomyocardial Fibrosis Pathology Histologic Findings Clinical Manifestations Right Ventricular Endomyocardial Fibrosis Left Ventricular Endomyocardial Fibrosis Biventricular Endomyocardial Fibrosis Endocardial Fibroelastosis Neoplastic Infiltrative Cardiomyopathy — Carcinoid Heart Disease Pathology Clinical Manifestations Management Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Presenting Symptoms and Natural History Pathology Genetics Diagnosis Management Summary and Future Perspectives Key References References Chapter 22: Cardiac Amyloidosis Epidemiology Natural History Clinical Features Misdiagnosis and Obstacles to Early Diagnosis Raising Clinical Suspicion for Cardiac Amyloidosis Diagnosis Electrocardiography Laboratory Testing Cardiac Imaging Tissue Biopsy and Confirmation of the Causative Precursor Protein Genetic Analysis Clinical Management Biomarker Staging Systems Prognostication from Advanced Cardiac Imaging Supportive Nondisease-Modifying Therapies Diuretics Drug Intolerances in Advanced CA Calcium Channel Blockers and Digoxin Atrial Fibrillation, Thromboembolic Complications, and Anticoagulation Permanent Pacemaker Implantation Implantable Cardioverter Defibrillators Organ Transplantation Disease-Targeted Therapies for AL-CA Chemotherapy and Stem Cell Transplantation Disease-Modifying Therapeutic Opportunities forATTR-CA Silencers of TTR Gene Expression TTR Stabilization Fibril Degradation and Reabsorption Future Perspectives Key References References Chapter 23: Heart Failure as a Consequence of Hypertrophic Cardiomyopathy Overview Definition Epidemiology Molecular Genetic Basis of Hypertrophic Cardiomyopathy Pathogenesis Effects of the Mutations on Transcription and Translation Effects of Mutations on Sarcomere Assembly and Function Molecular Pathways Liking the Initial Defects to the Phenotype Determinants of the Clinical Phenotype of Hypertrophic Cardiomyopathy Phenotypic Features of Hypertrophic Cardiomyopathy Clinical Manifestations Chest Pain Heart Failure Ventricular Arrhythmias and Sudden Cardiac Death Supraventricular Arrhythmias Prognosis Management of Patients with Hypertrophic Cardiomyopathy Genetic Testing Management of Risk of Sudden Cardiac Death in Hypertrophic Cardiomyopathy Management of Patients with Left Ventricular Outflow Tract Obstruction Management of Cardiac Arrhythmias Experimental Therapies Summary and Future Directions Key References References Chapter 24: Heart Failure as a Consequence of Genetic Cardiomyopathy Clinical Presentations Findings That Indicate a Genetic Form of Cardiomyopathy Fabry Disease Danon Disease Familial Cardiac Amyloidosis Arrhythmogenic Right Ventricular Cardiomyopathy Left Ventricular Noncompaction Cardiomyopathy Genetic Causes of Cardiomyopathy Sarcomere Mutations Clinical Implications Cytoskeletal Mutations Clinical Implications Mutations Altering Calcium Handling Clinical Implications Nuclear Envelope Mutations Clinical Implications Ion Channel Mutations Clinical Implications Transcription and Splicing Factor Mutations Clinical Implications Desmosome Mutations Clinical Implications Mitochondrial Mutations Clinical Implications Genetic Testing Key References References Chapter 25: Heart Failure as a Consequence of Hypertension Introduction: Definition and Impact Left Ventricular Hypertrophy Epidemiology Pathophysiologic Mechanisms Molecular Mechanisms Genetic Determinants of Left Ventricular Hypertrophy Classification and Diagnosis of Hypertensive Heart Disease Clinical Presentation/Functional Classes Anatomic Classification of Left Ventricular Hypertrophy Diagnostic Criteria for Left Ventricular Hypertrophy Electrocardiogram Echocardiography Computed Tomography Cardiac Magnetic Resonance Imaging Complications of Hypertensive Heart Disease Heart Failure With Preserved Ejection Fraction Systolic Heart Failure Myocardial Ischemia Atrial Fibrillation Sudden Cardiac Death All-Cause Mortality Treatment General Considerations and Regression of Left Ventricular Hypertrophy Treatment Targets and the J-Curve Debate Key References References Chapter 26: Heart Failure as a Consequence of Valvular Heart Disease Valvular Heart Disease as a Treatable Cause of Heart Failure Etiologies, Epidemiology, and Demographics of Valvular Heart Disease Pathophysiology of Valvular Heart Disease Mechanisms Involved in Producing Stenotic and Regurgitant Heart Valves Genetics Aspects of Valvular Heart Disease Quantification of Valve Lesion Severity Impact on Chamber Size, Function, and Myocardial Hypertrophy Systemic and Pulmonary Arterial Systems in Valvular Heart Disease Reverse Remodeling After Correction of Valvular Heart Disease Clinical Manifesations of Valvular Heart Disease Specific Valve Lesions Aortic Stenosis Aortic Regurgitation Mitral Regurgitation Mitral Stenosis Tricuspid Regurgitation Changing Manifestations of Valvular Heart Disease Related to Comorbid Conditions and Aging Isolated Valve Lesions Versus Multivalvular Heart Disease Clinical Evaluation of Patients with Valvular Heart Disease Diagnostic Modalities Laboratory Testing Functional Testing Stages of Valvular Heart Disease and Stages of Heart Failure Treatment of Valvular Heart Disease Timing of Interventions Current State of Transcatheter Therapies for Valvular Heart Disease Current State of Surgical Therapies for Valvular Heart Disease Treatment of Valvular Heart Disease the Heart Team and Shared Decision Making Treatment of Valvular Heart Disease Patients After Interventions Key References References Chapter 27: Heart Failure as a Consequence of Congenital Heart Disease Epidemiology Diagnosis Imaging Echocardiography Cardiac Magnetic Resonance Imaging Cardiopulmonary Exercise Testing Biomarkers Treatment Cardiac Resynchronization Therapy and Implantable Defibrillators in Adult Congenital Heart Disease Cardiac Resynchronization Therapy in Specific Populations Tetralogy of Fallot Systemic Right Ventricle Single Ventricle Transplantation and Mechanical Support Exercise Training in CHD Specific Conditions Tetralogy of Fallot Systemic Right Ventricle Single Ventricle Summary Key References References Chapter 28: Heart Failure as a Consequence of Viral and Nonviral Myocarditis History Viral Etiologies Autoimmune (Nonviral) Etiologies Pathogenesis in Murine Models Clinical Presentation Cardiac Imaging Endomyocardial Biopsy Myocarditis Mimicking Acute Coronary Syndrome Medical Therapy Immunosuppressive Therapy Acute Versus Chronic Inflammatory Cardiomyopathy Viral Diagnostics and Targeted Therapeutics Mechanical Support and Recovery Pediatric Myocarditis Peripartum Cardiomyopathy Genomics of Myocarditis and Inflammatory Cardiomyopathy Summary and Future Therapeutic Directions Key References References Chapter 29: Heart Failure in the Developing World Heart Failure: A Global Perspective Global Burden of Heart Failure in the Developing World What Do We Know About the Variation of Risk Factor Prevalence? What Do We Not Know? Specific Aspects of Heart Failure in Key Regions in the Developing World Sub-Saharan Africa Heart Failure Overall Heart Failure Due to Hypertensive Heart Disease Heart Failure Due to Cardiomyopathies South America Asia and the Pacific Region East Asia Regional Comparisons Indigenous Peoples Key Considerations for the Prevention and Management of Heart Failure in the Developing World What Is Needed for a Global Heart Failure Prevention Strategy? Key References References Chapter 30: Heart Failure and Human Immunodeficiency Virus What Is Human Immunodeficiencyvirus-Associated Heart Failure? Historical Perspective Contemporary Shifts in Epidemiology Pathophysiology of Heart Failure in Human Immunodeficiency Virus Poor Human Immunodeficiency Viral Control, Opportunistic Infections, and Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome Cardiomyopathy The Role of Atherosclerosis, Thrombosis, and Myocardial Infarction Inflammation, Immune Dysfunction, and Diastolic Dysfunction in Human Immunodeficiency Virus Pulmonary Arterial Hypertension Cardiac Effects of Antiretroviral Therapy Nucleoside Reverse Transcriptase Inhibitors Protease Inhibitors Cardiac Effects of Antiretroviral Therapy in Children Comorbidities and Behavioral Factors Hypertension Diabetes Hepatitis C Kidney Disease Substance Abuse Manifestations of Heart Failure Low Left Ventricular Ejection Fraction Myocardial Strain and Fibrosis Poor Inotropic Contractile Reserve Diastolic Dysfunction Clinical Management of Patients with Human Immunodeficiency Virus and Heart Failure Human Immunodeficiency Virus-specific Management Coronary Artery Bypass Surgery Devices and Advanced Heart Failure Therapies Summary and Future Directions Key References References Section IV: Clinical Assessment of Heart Failure Chapter 31: Clinical Evaluation of Heart Failure Introduction and Goals of Clinical Evaluation History and Physical Examination: The Core of the Evaluation Medical History Symptoms Information About Past Medical History and Comorbidities Social and Family History Familial Cardiomyopathy and Genetic Testing Physical Examination Cardiovascular System Laboratory Essential Selective Biomarkers The Electrocardiogram Chest X-ray Echocardiography Cardiac Structure and Systolic Function Left Ventricular Volumes and Systolic Function Right Ventricular Systolic Function Cardiac Volumes Diastolic Function and Hemodynamics Determination of Pressures Valvular Disease Structural Abnormalities Pericardial Disease Dyssynchrony Assessment Detection of Cardiac Thrombi Performing Repeat Echocardiograms Other Imaging Modalities Ischemic Evaluation: Coronary Anatomy and Myocardi

Up-to-date, authoritative and comprehensive, Heart Failure, 4th Edition, provides the clinically relevant information you need to effectively manage and treat patients with this complex cardiovascular problem. This fully revised companion to Braunwald’s Heart Disease helps you make the most of new drug therapies such as angiotensin receptor neprilysin inhibitors (ARNIs), recently improved implantable devices, and innovative patient management strategies. Led by internationally recognized heart failure experts Dr. G. Michael Felker and Dr. Douglas Mann, this outstanding reference gives health care providers the knowledge to improve clinical outcomes in heart failure patients.

• Focuses on a clinical approach to treating heart failure, resulting from a broad variety of cardiovascular problems.
• Covers the most recent guidelines and protocols, including significant new updates to ACC, AHA, and HFSA guidelines.
• Covers key topics such as biomarkers and precision medicine in heart failure and new data on angiotensin receptor neprilysin inhibitors (ARNIs).
• Contains four new chapters: Natriuretic Peptides in Heart Failure; Amyloidosis as a Cause of Heart Failure; HIV and Heart Failure; and Neuromodulation in Heart Failure.
• Covers the pathophysiological basis for the development and progression of heart failure.
• Serves as a definitive resource to prepare for the ABIM’s Heart Failure board exam.
• 2016 British Medical Association Award: First Prize, Cardiology (3rd Edition).