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Heart Failure as a Consequence of Viral and Nonviral Myocarditis

In the attempt to diagnose heart disease more accurately, the term myocarditis is wisely being abandoned in large part; we must remember, nevertheless, that there does exist such a condition as myocarditis . . . . Paul Dudley White Dr. White’s concerns about the “abandonment” of the term myocarditis were unfounded, and over half a century after his initial observations, myocarditis remains an important pathologic term…

Heart Failure as a Consequence of Congenital Heart Disease

Adults with congenital heart disease (CHD) have multiple mechanisms placing them at risk for heart failure, leading one author to refer to CHD as “the original heart failure syndrome.” These mechanisms include chronic pressure and/or volume loading, inadequate myocardial preservation during prior surgeries, myocardial fibrosis, surgical injury to a coronary artery, and neurohormonal activation. The number of heart failure–related admissions for adult congenital heart disease (ACHD)…

Heart Failure as a Consequence of Valvular Heart Disease

Valvular heart disease (VHD) is not simply a disease of the valve. 1,2 Cardiac valves are the major determinants of the direction of blood flow in the circulation that consists of a system of vessels that distribute and collect blood, and cardiac chambers that create the propelling force for blood movement. VHD causes a disruption of the entire circulatory system. In addition, there is a complex…

Heart Failure as a Consequence of Hypertension

Introduction: Definition and Impact Hypertension (HTN) affects over 1 billion people worldwide and is the most prevalent risk factor for the development of heart failure. Despite some improvements in the treatment and control of HTN, the societal burden of hypertensive heart disease in an aging population has increased and heart failure—one major manifestation of hypertensive heart disease—continues to be the most frequent hospital admission diagnosis in…

Heart Failure as a Consequence of Genetic Cardiomyopathy

The genetic contributions to heart failure are numerous and remarkably heterogeneous, extending from the monogenic forms of cardiomyopathy to more common polygenic diseases, such as hypertension, coronary atherosclerosis, and myocardial infarction. For monogenic diseases, the responsible mutations are rare but carry a very high pathogenic burden. Polygenic conditions typically include DNA variants that are common in healthy populations, imparting only a small pathogenic effect. For all…

Heart Failure as a Consequence of Hypertrophic Cardiomyopathy

Overview Henri Liouville, a French pathologist, described the first case of hypertrophic cardiomyopathy (HCM) in 1869. The patient was an elderly woman with symptoms of heart failure, a ventricular wall thickness of 3.5 to 4 cm and left ventricular outflow tract (LVOT) obstruction. Dr. Liouville described the LVOT obstruction as “Rétrécissement cardiaque sous aortique,” which literally translates to subaortic cardiac. Since this initial description, there has…

Cardiac Amyloidosis

Amyloidosis is a deposition disease in which proteins with unstable structures misfold and aggregate into amyloid fibrils, which deposit in the heart, kidneys, liver, peripheral nerves, gastrointestinal tract, lungs, and soft tissues. Amyloid fibrils are insoluble nonbranching structures 7 nm to 10 nm wide and of variable length that are resistant to proteolysis. Under normal light microscopy when stained with Congo red, amyloid deposits display a…

Restrictive and Infiltrative Cardiomyopathies and Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

Restrictive cardiomyopathy is the least prevalent of cardiomyopathies relative to dilated ( see Chapter 20 ) and hypertrophic forms ( see Chapter 23 ) of heart muscle diseases. All forms of cardiomyopathy are diseases of heart muscle that result from a myriad of insults, such as genetic defects ( see Chapter 24 ), cardiac myocyte injury, or infiltration of myocardial tissues. Thus cardiomyopathies result from insults…

Heart Failure as a Consequence of Dilated Cardiomyopathy

Definition The term dilated cardiomyopathy (DCM) refers to a spectrum of heterogeneous myocardial disorders ( Table 20.1 ) that are characterized by ventricular dilation and depressed myocardial contractility in the absence of abnormal loading conditions (such as hypertension or valvular disease) or ischemic heart disease sufficient to cause global systolic impairment. Such a definition with emphasis on anatomic description has been challenging, as there could be…

Heart Failure as a Consequence of Ischemic Heart Disease

Despite significant progress in the prevention and treatment of cardiovascular disease over the past 30 years, national statistics indicate that the incidence and prevalence of heart failure (HF) continue to rise. This has occurred during a time period in which death rates from coronary artery disease (CAD) and stroke have declined. HF and CAD are both age-related conditions (the prevalence of HF is 1% between the…

Epidemiology of Heart Failure

Improved outcomes of acute cardiac conditions, population aging, increasing prevalence of lifestyle risk factors, and advances in heart failure (HF) therapeutics all have led to an increasing prevalence of HF. Because of these trends, HF has become a public health priority in developed countries and a major noncommunicable syndrome in developing regions. In the United States, the population prevalence of HF among adults, currently estimated at…

Alterations in Cardiac Metabolism in Heart Failure

Overview of Cardiac Metabolism Hallmarks and Regulation of Cardiac Energy Metabolism Cardiac energy metabolism is essential to maintain cardiac pump function. To enable the heart to beat 100,000 times a day for a lifetime, the heart exhibits a highly regulated and efficient system for adenosine triphosphate (ATP) regeneration, generating up to 6 kg of ATP every day, which is 15- to 20-fold its own weight. Thus…

Alterations in Skeletal Muscle in Heart Failure

The syndrome of heart failure (HF) is characterized by adaptations in numerous physiologic systems that contribute to disease symptomology and progression. The cardinal symptom of HF, exercise intolerance, which manifests as dyspnea and skeletal muscle fatigue, has long been attributed to cardiac insufficiency. However, research over the past three decades has conclusively demonstrated a role for adaptations in the skeletal musculature in these symptoms. The overall…

Alterations in Kidney Function Associated With Heart Failure

Control of circulating blood volume is a tightly regulated physiological process and is critical for maintaining cardiovascular homeostasis. Under normal homeostatic conditions, there is extensive cross-talk between the kidney and the heart (the “cardiorenal axis”) that is essential for regulation of salt and water homeostasis. However, as will be discussed here, in the setting of heart failure (HF), the normal mechanisms that control sodium and water…

Alterations in the Peripheral Circulation in Heart Failure

The complex pathology of heart failure (HF) can be attributed, at least in part, to important changes that occur in the peripheral circulation. As cardiac output declines, systemic perfusion pressure is maintained predominantly by peripheral vasoconstriction and sodium retention, both of which can be attributed to complex interactions among the autonomic nervous system (see also Chapter 13 ), neurohormonal mechanisms, and the kidney (see also Chapter…

Alterations in the Sympathetic and Parasympathetic Nervous Systems in Heart Failure

Despite substantive advances in medical and device therapy of heart failure, symptom burden and rates of hospitalization and death remain high. Increased plasma norepinephrine (NE) concentration, its rate of appearance in coronary sinus efflux, and diminished tonic and reflex heart rate modulation were among the first characteristics of heart failure with reduced ejection fraction (HFrEF) that were shown to identify individuals at particular risk of premature…

Alterations in Ventricular Structure: Role of Left Ventricular Remodeling and Reverse Remodeling in Heart Failure

One of the major conceptual advances in the field of heart failure (HF) has been the recognition that HF progresses because of the structural changes that occur in the heart in response to hemodynamic, neurohormonal, epigenetic and genetic factors. Although the complex changes that occur in the heart during left ventricular (LV) remodeling have traditionally been described in anatomic terms, the process of LV remodeling arises…

Alterations in Ventricular Function: Diastolic Heart Failure

Acknowledgment Supported by grants from CVON (Cardioavasculair Onderzoek Nederland), Dutch Heart Foundation, The Hague (RECONNECT, EARLY HFPEF). Heart failure (HF) with preserved ejection fraction (EF; HFpEF) currently accounts for greater than 50% of all HF cases, and its prevalence relative to HF with reduced EF (HFrEF) continues to rise at a rate of 1% per year ( see also Chapter 39 ). By 2020, the prevalence…

Systolic Dysfunction in Heart Failure

Depressed systolic function is a core manifestation in nearly half of all patients with heart failure (HF). The underlying mechanisms are many and include defects in sarcomere function (see Chapter 2 ), abnormal excitation-contraction coupling and calcium homeostasis, ion channel dysfunction (see Chapter 1 ), mitochondrial and metabolic abnormalities, depressed cell survival signaling, enhanced autophagy and mitophagy, abnormal proteostasis, redox pathobiology (see Chapter 8 ), inflammation…

Natriuretic Peptides in Heart Failure: Pathophysiologic and Therapeutic Implications

Natriuretic Peptides: Historical Background The discovery of natriuretic peptides (NPs) changed the classical paradigm of the heart as solely a pump and developed the novel concept of the heart as an endocrine organ. The current and potential applications of NPs in clinical practice and medical research are endless. Currently, NPs remain the “gold standard” for the diagnosis and prognosis of heart failure (HF) and the evaluation…