Heart Failure: A Companion to Braunwald's Heart Disease

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 Myocardial Viability
Morphologic and Functional Evaluation
Imaging for Nonischemic Causes of Cardiac Dysfunction
Imaging to Determine Prognosis
Right-heart Catheterization
Endomyocardial Biopsy
Assessing Exercise Capacity
Key References
References
Chapter 32: Cardiac Imaging in Heart Failure
Definition of Heart Failure
Epidemiology of Heart Failure
Objectives of Cardiac Imaging in Heart Failure
Cost of Imaging Tests
Heart Failure with Reduced Ejection Fraction Versus Heart Failure with Preserved Ejection Fraction
Evaluation of Left Ventricular Diastolic Dysfunction
Multiple Modality Cardiac Imaging
Assessment of Left Ventricular Function by Echocardiography
Myocardial Strain and Strain Rate
Nuclear Cardiology: Radionuclide SPECT and PET
Assessment of Physiologic Ischemia
Assessment of Right and Left Ventricular Volumes and Function
Imaging Autonomic Dysfunction
Computed Tomography
Cardiac Magnetic Resonance Imaging
Valvular Heart Disease and Heart Failure
Mitral Valve Regurgitation
Aortic Valve Disease as a Cause of Heart Failure
Aortic Stenosis
Cardiovascular Magnetic Resonance Assessment of Valvular Heart Disease
Myocardial Viability
Stress Echocardiography
Radiotracer-Based Assessment of Myocardial Viability and Remodeling
Cardiovascular Magnetic Resonance Stress
Detection of Myocardial Ischemia with Cardiovascular Magnetic Resonance
Detection of Infarction with Cardiovascular Magnetic Resonance I
Transition From Myocardial Infarction to Heart Failure with Reduced Ejection Fraction
Cardiac Magnetic Resonance Infarction II
Cardiac Resynchronization Therapy
Nuclear Imaging for Cardiac Resynchronization Therapy
Cardiovascular Magnetic Resonance for Resynchronization Therapy
Idiopathic Dilated Cardiomyopathy
Miscellaneous Causes of Heart Failure
Assessment of Right Ventricular Function
Complications of Heart Failure
Future Directions in Cardiac Imaging
Nuclear Imaging
Injury and Inflammation
Apoptosis and Cell Death
Imaging Inflammation
Imaging Inflammatory Cell Activity
Ventricular Remodeling
Metabolism and Ischemic Memory
Cardiac Magnetic Resonance
Four-Dimensional Flow for Cardiac Resynchronization Therapy Optimization
Creatine Chemical Exchange Saturation Transfer Imaging
Cardiovascular Magnetic Resonance Assessment of Myocardial Fiber Orientation
Cardiovascular Magnetic Resonance Molecular Imaging of Apoptosis
Key References
References
Chapter 33: Biomarkers and Precision Medicine in Heart Failure
Biomarkers: Definition and Guidelines for Evaluation
Major Society Guidelines
Heart Failure Biomarkers
Myocardial Insult
Myocardial Stretch
Cardiac Necrosis
Oxidative Stress
Neurohormonal Activation
Sympathetic Nervous System
Renin-Angiotensin-Aldosterone System
Myocardial Remodeling
Inflammation
Hypertrophy/Fibrosis
Extracellular Matrix Remodeling
Apoptosis
Markers of Comorbidity
Renal Biomarkers
Hematologic Biomarkers
Liver Function Tests and Serum Albumin
Adipokines
Neprilysin
Future Directions: Proteomics, Metabolomics, and Multimarker Testing
Future Directions: Precision Medicine in Heart Failure
Acknowledgments
Key References
References
References for Table 33.6
Chapter 34: Hemodynamics in Heart Failure
Technical Issues
Hemodynamic Waveforms
Right Atrium and Ventricle
Pulmonary Capillary Wedge
Measuring Cardiac Output
Hemodynamics of Heart Failure with Reduced Ejection Fraction
Hemodynamics for Assessment and Management
Hemodynamics and Advanced Heart Failure
Heart Transplantation
Left Ventricular Assist Devices
The Hemodynamics of Heart Failure with Preserved Ejection Fraction
Hemodynamic Challenges: Exercise and Volume Loading
Technical Considerations
Specific Clinical Scenarios
Key References
References
Section V: Therapy for Heart Failure
Chapter 35: Disease Prevention in Heart Failure
Primordial Prevention of Cardiovascular Disease and Heart Failure
Smoking
Physical Activity
Healthy Dietary Pattern
Disease Prevention in Stage A Heart Failure
Hypertension and Heart Failure
Diabetes Mellitus and Heart Failure
Atherosclerotic Disease and Heart Failure
Metabolic Syndrome and Heart Failure
Obesity and Heart Failure
Disease Prevention in Stage B Heart Failure
Identifying Patients with Structural Cardiac Alterations for Preventive Therapy
Use of Risk Scores for Prediction of Incident Heart Failure
Use of Biomarkers for Screening and Prevention of Heart Failure
Use of Imaging for Evaluation of Newly Suspected or Potential Heart Failure
Future Directions
Key References
References
Chapter 36: Acute Heart Failure
Background and Epidemiology
Definition: What Is Acute Heart Failure? Why Does the Definition Matter?
Pathophysiology of Acute Heart Failure
Comorbid Conditions
Initial Management
Emergency Department Management
Diagnosis
Chest X-Ray and Lung Ultrasound
Focused Ultrasound
Natriuretic Peptides and Troponin (see also Chapter 33)
Initial Classification
Warm and Wet—Vascular Type
Warm and Wet—Cardiac Type
Cold and Wet
Emergency Department Risk Stratification
Inpatient Management (and Re-Risk Stratification)
Further Assessment: Possible Causes and Precipitating Factors
In-Hospital Monitoring
Assessment of Congestion and Volume Status
Echocardiography
Invasive Hemodynamic Monitoring
Pharmacologic Management
Diuretics
Doses and Modes of Administration
Diuretic Response and Diuretic Resistance
Nonloop Diuretics and Aquaretics
Ultrafiltration
Vasodilators
Nitrates
Nesiritide
Recent Agents Tested in Acute Heart Failure Clinical Trials
Inotropic Agents
Dobutamine
Dopamine
Epinephrine and Norepinephrine
Phosphodiesterase Inhibitors
Levosimendan
Other Treatments in the Acute Phase
Evidence-Based Treatment and Predischarge Assessment
Conclusion
Key References
References
Guidelines: the Hospitalized Patient
Chapter 37: Contemporary Medical Therapy for Heart Failure Patients with Reduced Ejection Fraction
Goals of Therapy in Heart Failure and Reduced Ejection Fractionthe
General Measures
Diet and Fluid Restriction
Activity
Therapies to Avoid
Diuretics and Management of Volume Status
Loop Diuretics
Thiazides and Thiazide-Like Diuretics
Mineralocorticoid Receptor Antagonists and Potassium-Sparing Diuretics
Vasopressin Antagonists
Practical Issues in the Use of Diuretics in Heart Failure
Risks of Diuretic Use
Diuretic Resistance and Management
Neurohormonal Antagonists in the Management of Heart Failure
Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers
Rationale/Pathophysiologic Basis for Use
Effects on Hemodynamics
Effects on Ventricular Structure
Effects on Functional Capacity and Symptoms
Effects on Morbidity and Mortality
Mechanisms Underlying These Effects
Side Effects, Complications, and Drug Interactions
Practical Tips
Angiotensin–Neprilysin Inhibition
Practical Tips
β-Blockers
Rationale/Pathophysiologic Basis for Use
Effects on Ventricular Structure
Effects on Functional Capacity/Symptoms
Effects on Morbidity and Mortality
Side Effects
Practical Tips
Mineralocorticoid Receptor Antagonists
Rationale/Pathophysiologic Basis for Use
Effects on Ventricular Structure/Hemodynamics
Effects on Morbidity and Mortality
Side Effects
Practical Tips
Hydralazine and Nitrates
Side Effects
Practical Tips
Ivabradine
Digoxin
Future Directions
Key References
References
Guidelines: Management of Heart Failure with a Reduced Ejection Fraction
Treatment of Patients at High Risk of Developing Heart Failure (Stage A)
Treatment of Patients with Left Ventricular Dysfunction Who Have Not Developed Symptoms (Stage B)
Treatment of Patients with Left Ventricular Dysfunction and Current or Prior Symptoms (Stage C)
Treatment of Patients with Refractory End-Stage Heart Failure (Stage D)
Comorbidities in Heart Failure Patients
Coordinating Care for Patients with Chronic Heart Failure
References
Chapter 38: Management of Arrhythmias and Device Therapy in Heart Failure
Atrial Fibrillation
Epidemiology
Pathophysiology
Clinical Presentation
Diagnosis
Management of Acute Episodes of Atrial Fibrillation
Chronic Management of Atrial Fibrillation
Rate Control Versus Rhythm Control
Rate Control
Pharmacologic Rhythm Control
Atrial Fibrillation Ablation in Heart Failure
Anticoagulation in Atrial Fibrillation and Atrial Flutter
Prognosis
Atrial Flutter
Epidemiology
Pathophysiology and Diagnosis
Management
Ventricular Arrhythmias
Acute Episodes of Sustained Monomorphic Ventricular Tachycardia
Nonsustained Ventricular Tachycardia
Sudden Cardiac Death in Patients with Heart Failure
Pharmacologic Therapy for Chronic Management of Ventricular Tachycardia
Catheter Ablation of Ventricular Tachycardia
Device Therapy
Implantable Cardioverter-Defibrillator
Cardiac Resynchronization Therapy
Arrhythmias Associated with Left Ventricular Assist Device Therapy
Arrhythmia Management After Heart Transplantation
Key References
References
Guidelines: Cardiac Resynchronization Therapy and Implantable Cardioverter-defibrillators for Heart Failure with a Reduced Ejection Fraction
References
Chapter 39: Treatment of Heart Failure with Preserved Ejection Fraction
Development of Treatment Strategies Based on the Pathophysiology of Heart Failure with Preserved Ejection Fraction
Treatment of Volume Overload and Congestion
Nitrates and Nitrites
Treatment of Hypertension
Renin-Angiotensin-Aldosterone Blockade
Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers
Aldosterone Receptor Antagonists
Angiotensin Receptor/Neprilysin Inhibitors
Beta-Blockade
If Channel Blocker: Ivabradine
Selective Phosphodiesterase Type 5 Inhibition
Other Targets for Medical Therapy
Endothelin Antagonists
Advanced Glycation End Products Cross-Link Breakers
Novel Hypoglycemic Agents
Metabolic Modulators
Antiinflammatory Agents
Lusitropic Agents
Device-Based Therapies
Treatment of Obstructive Sleep Apnea
Pacemakers
Mechanical Targeting of Left Atrial Pressure Reduction
Pressure Monitoring Devices in Heart Failure with Preserved Ejection Fraction
Exercise Training in Heart Failure with Preserved Ejection Fraction
Current Recommendations for the Management of Patients with Heart Failure with Preserved Ejection Fraction (Guideline Recommendations)
Summary and Future Directions
Key References
References
Guidelines: Treatment of Heart Failure with a Preserved Ejection Fraction
REFERENCE
Chapter 40: Management of Heart Failure in Special Populations: Older Patients, Women, and Racial/Ethnic Minority Groups
Heart Failure in Older Adults
Epidemiology
Prognosis
Pathophysiology
Diagnosis and Clinical Features
Frailty and Cognitive Dysfunction
Treatment
Biomarker Guided Therapy
Pharmacologic Interventions for HFrEF
Device Therapy for HFrEF
Pharmacologic Interventions for HFpEF
Nonpharmacologic Interventions for HFpEF
Heart Failure in Women
Epidemiology
Clinical Features
Ischemic Heart Failure in Women
Therapy in Women
Angiotensin Converting Enzyme Inhibitors
Angiotensin Receptor Blockers
Beta-Blockers
Aldosterone Antagonists
Hydralazine/Isosorbide Dinitrate
Digoxin
Valsartan–Sacubitril and Ivabradine
Cardiac Resynchronization Therapy
Implantable Cardioverter Defibrillator
Left Ventricular Assist Devices
Heart Transplantation
Heart Failure in Racial/Ethnic Minority Groups
Prevalence
Clinical Features
Pathophysiology
Racial Differences in Response to Drug Treatment
ACE Inhibitors
β-Blockers
Hydralazine/Isosorbide Dinitrate
Angiotensin Receptor Blockers, Aldosterone Antagonists, Digoxin
Valsartan–Sacubitril and Ivabradine
Implantable Cardioverter Defibrillators and Cardiac Resynchronization Therapy
Heart Transplantation
Summary
Key References
References
Chapter 41: Stem Cell-Based and Gene Therapies in Heart Failure
Cardiac Cell Therapy
Mechanisms of Action for Cardiac Cell Therapy
Clinical Trials of Cardiac Cell Therapy
Bone Marrow–Derived Mononuclear Cells
Bone Marrow–Derived Mesenchymal Stem Cells
Cardiac Stem/Progenitor Cells
Cardiosphere-Derived Cells
Open Questions in Optimizing Cardiac Cell Therapy
Cell Source
Cell Dose
Timing of Therapy
Route of Administration
Gene Therapies in Heart Failure
Gene Therapy Enhancing Contractility
Gene Therapy Enhancing Stem Cell Homing
Gene Therapy for Cardiac Regeneration
Summary and Future Directions
Key References
References
Chapter 42: Neuromodulation in Heart Failure
Anatomy of the Autonomic Nervous System
Cardiac Reflexes
Measurement of Autonomic Nervous System Activity
Pharmacological Targeting of Autonomic Nervous System Dysfunction in Heart Failure
Device-Based Modulation of Autonomic Nervous System Dysfunction in Heart Failure
Vagus Nerve Stimulation
Carotid Baroreceptor Stimulation
Spinal Cord Stimulation
Renal Sympathetic Denervation
Summary and Future Directions
Key References
References
Chapter 43: Pulmonary Hypertension
Pulmonary Hypertension: Definition and Classification
Clinical Features Raising the Suspicion of Pulmonary Hypertension
Diagnostic Evaluation of Pulmonary Hypertension
Echocardiographic Evaluation of Known or Suspected Pulmonary Hypertension
Laboratory Testing
Pulmonary Function Testing
Right Heart Catheterization
Group 1: Pulmonary Arterial Hypertension
Epidemiology and Clinical Features
Idiopathic Pulmonary Arterial Hypertension
Heritable Pulmonary Arterial Hypertension
Pulmonary Arterial Hypertension Associated Conditions
Connective Tissue Disease
Congenital Heart Disease
Drugs and Toxins
Chronic Liver Disease
Pulmonary Venoocclusive Disease and Pulmonary Capillary Hemangiomatosis
Prognosis in Group I Pulmonary Arterial Hypertension
Clinical Assessment
Biomarkers
Hemodynamics
Management of Group I Pulmonary Hypertension
General Treatment Recommendations for Patients with Pulmonary Hypertension
Drug Therapy for Group I PAH-PAH Targeted Therapy
Drug Therapy for Group I Pulmonary Arterial Hypertension- Adjuvant Therapy
Group 2: Pulmonary Hypertension with Left Heart Disease
Pulmonary Hypertension Due to Left-Sided Valvular Heart Disease
Pulmonary Hypertension in Heart Failure With Preserved or Reduced Ejection Fraction
Pulmonary Hypertension Due to Left Atrial Disease
Treatment
Group 3: Pulmonary Hypertension Associated with Lung Diseases and/or Hypoxia
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Pulmonary Hypertension Associated With Interstitial Lung Disease
Pulmonary Hypertension and Sleep-Disordered Breathing
Group 4: Pulmonary Hypertension Due to Pulmonary Artery Obstructions
Epidemiology, Clinical Features, and Diagnostic Evaluation
Treatment
Group 5: Pulmonary Hypertension Associated with Unclear Multifactorial Mechanisms
Key References
References
Chapter 44: Heart Transplantation
Evaluation and Management of Heart Transplant Candidates
Indications for Transplant
Evaluation of the Heart Transplant Candidate
The Heart Transplant Procedure
Donor Heart Evaluation and Management
Donor Heart Allocation
Surgical Procedure
Postoperative Care
Immune Management of the Heart Transplant Recipient
Overview
Clinical and Pathologic Subtypes of Cardiac Allograft Rejection
Noninvasive Monitoring for Allograft Rejection
Treatment of Allograft Rejection
Immunosuppression in Heart Transplantation
Historical Perspective
The Pharmacology of Immunosuppression
Clinical Trials of Immunosuppressive Agents
Complications in the Heart Transplant Recipient
Overview of Outcomes After Heart Transplant
Cardiac Allograft Vasculopathy
Infection
Cancer
Future Innovations
Novel Strategies to Enlarge the Donor Heart Pool
Improving Access and Outcomes for Allosensitized Patients
Novel Approaches to the Detection of Rejection
Key References
References
Chapter 45: Circulatory Assist Devices in Heart Failure
Acute Cardiogenic Shock
Devices
Intra-Aortic Balloon Pump
TandemHeart
Impella
Extracorporeal Membrane Oxygenation
Indications for Implantable Mechanical Circulatory Support Devices
Patient Selection for Mechanical Circulatory Support
Mechanical Circulatory Support Devices
Temporary Continuous Flow Ventricular Assist Devices
CentriMag
Rotaflow
Durable Continuous Flow Pumps
HeartMate II
HeartWare HVAD
HeartMate 3
Jarvik 2000
Management Issues of a Continuous Flow Pump
Adverse Events
Right Heart Failure
Neurologic Events
Infection
Bleeding
Valvular Heart Disease
Hemolysis/Pump Thrombosis
Support for Biventricular Heart Failure
Mechanical Circulatory Support in Children
Future Directions
Partial Support Devices
Totally Implantable Systems
Novel Patient Populations
Myocardial Recovery
Key References
References
Chapter 46: Cardio-Oncology and Heart Failure
Epidemiology of Heart Failure in Patients with Cancer
Specific Cancer Therapies, Their Mechanisms of Cardiotoxicity, and Implications for Clinical Practice
Anthracyclines
Radiation Therapy
Cyclophosphamide
Targeted Therapies
ErbB2 Targeted Therapies: Trastuzumab, Lapatinib, and Pertuzumab
Angiogenesis Inhibitors
Bcr-Abl Inhibitors
Proteasome Inhibitors
Immune Checkpoint Inhibitors
Emerging Cancer Therapies
Risk Assessment, Screening, and Monitoring
Prevention of Heart Failure During Cancer Treatment
Modification of Chemotherapeutic Regimens
Dexrazoxane
Beta-Blockers
Renin-Angiotensin-Aldosterone Axis Inhibition
Statins
Managing Heart Failure During Cancer Treatment
Advanced Therapies in the Cancer Patient with Heart Failure
Key References
References
Chapter 47: Disease Management and Telemedicine in Heart Failure
Defining Disease Management
The Self-Care Paradigm
Heart Failure Disease Management Classification Schemes
Heart Failure Disease Management in the Inpatient Setting
Heart Failure Disease Management in the Outpatient Setting
Cardiac Rehabilitation for Heart Failure
Clinic-Based Follow-Up
Home Nursing Visits
Telephone Interventions and Telemonitoring
Cardiac Telerehabilitation
Invasive Telemonitoring
Wearables and mHealth in Heart Failure
Why Have We Not Seen Clear Benefit with Heart Failure Disease Management Programs?
Are We Targeting the Correct Patient Population?
Do We Have the Correct Health Care Providers on the Team?
Are We Measuring the Right Parameters?
Key References
References
Chapter 48: Management of Comorbidities in Heart Failure
Anemia and Iron Deficiency
Definitions, Prevalence, and Outcomes
Diagnosis of Anemia
Treatment
Summary/Conclusions
Chronic Obstructive Pulmonary Disease
Definitions, Prevalence, and Outcomes
Pulmonary Function Tests and Heart Failure
Treatment
Heart Failure–Related Treatment in Patients With COPD
Chronic Obstructive Pulmonary Disease Treatment in Patients With Heart Failure
Summary/Conclusions
Sleep-Disordered Breathing
Definitions, Prevalence, and Outcomes
Treatment
Summary/Conclusions
Diabetes
Definitions, Prevalence, and Outcomes
Treatment
Treatment of Heart Failure for Patients With Diabetes
Treatment of Diabetes for Patients With Heart Failure
Summary/Conclusions
Overall Summary
Key References
References
Chapter 49: Quality and Outcomes in Heart Failure
General Principles of Quality Measurement
Defining Quality
Institute of Medicine Principles
Framework
Structure
Process
Outcomes
Key Components for Quality: Integrative Model for Quality
Health Care System
Health Information Technology
Status of Heart Failure Quality Measures and Programs
Public Reporting
Process Measures
Outcome Measures
Pay-for-Performance
Effectiveness
Patient-Centeredness
Equity
Improving Quality of Care (Implementation)
Quality Improvement Registries
Health Care Delivery Models
Future Directions for Quality of Care
Key References
References
Chapter 50: Decision Making and Palliative Care in Advanced Heart Failure
Medical Decision Making
Risk Assessment and Expectations for the Future
Categories of Major Treatment Decisions
Low-Intensity Interventions That May Improve Quantity and Quality of Life
High-Intensity Interventions That May Improve Quantity and Quality of Life
High-Intensity Interventions That May Improve Quantity But Not Quality of Life
Temporary Therapies with Potential Dependence
Noncardiac Procedures in Patients with Advanced Heart Failure
Palliative Care
Types of Palliative Care
Primary Palliative Care
Secondary (Specialty) Palliative Care
Indications for a Palliative Care Consultation
Hospice
Symptom Palliation
Dyspnea
Pain
Depression
Fatigue
End-of-Life Care and Device Deactivation
Decision-Making Approaches and Communication Skills
Timing of Discussions
Optimal Communication Techniques
Overcoming Barriers to Optimal Communication
Decision Support to Assist With Particularly Difficult Conversations
Unmet Needs and Directions for the Future
Conclusions
Key References
References