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Heart failure is a complex clinical syndrome in which the typical symptoms of shortness of breath and fatigue are associated with functional or structural damage to the heart. The diagnosis usually portends an early death preceded by unpleasant symptoms limiting the quality of life. Heart failure is common and becoming more common as the population ages and as patients survive myocardial infarction (MI) with consequent persistent damage to the muscle of the heart. The entity of heart failure is easily recognized by experienced physicians and can be detected in the community, and treatment reduces both morbidity and mortality. Although the molecular biology and integrated physiology of heart failure remain incompletely understood, several concepts and principles have evolved over the past decades. A key feature of heart failure is the impaired ability of the heart to act as a pump. But many body responses, which are secondary adaptive responses maintaining short-term circulatory function, eventually become maladaptive and contribute substantially to the long-term progression of heart failure. These numerous adaptations in response to the onset of heart failure occur in the peripheral circulation, the kidney, skeletal muscle, and almost all organs of the body. The changes contribute to the overall clinical syndrome and phenotype of heart failure. An understanding of how these changes occur provides insight into the pathophysiology of the syndrome and explains why some are therapeutic targets.


A widely known definition of heart failure is “a pathophysiological state in which an abnormality of cardiac function is responsible for the failure of the heart to pump blood at a rate commensurate with the requirements of the metabolizing tissues.“1 This definition places the emphasis on the physiology of the circulation. More recent definitions have taken a more pragmatic and clinically useful approach. One American definition is “a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. The cardinal manifestations of heart failure are dyspnea and fatigue, which may limit exercise tolerance, and fluid retention, which may lead to pulmonary congestion and peripheral edema.“2 A recent European definition is similar: “Heart failure is a complex syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the heart to function as a pump to support a physiological circulation. The syndrome of heart failure is characterized by symptoms such as breathlessness and fatigue, and signs such as fluid retention.“3 The definition of heart failure remains a point of controversy to this day.


Congestive heart failure denotes the clinical syndrome with the features of dyspnea, increased fatigue, and fluid accumulation (jugular venous distension, dependent edema, enlarged liver, and pulmonary edema). Congestive heart failure should be distinguished from cardiac dysfunction, which is a structural definition based on imaging techniques and characterized by abnormal contractility (systolic) or relaxation (diastolic), often accompanied by compensatory ventricular hypertrophy, dilatation (so-called cardiac remodeling), or both. The ...

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