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Heart failure (HF) is a complex clinical syndrome associated with increased mortality and morbidity.1 It is also common and becoming more prevalent with the aging population and improvement in survival of patients with cardiovascular diseases such as coronary artery disease. Although coronary artery disease is the most common cause of HF, patients can develop HF from any number of different cardiovascular diseases (Table 68–1); HF appears to be the final common pathway of ventricular dysfunction that share some important clinical characteristics and pathophysiology. Although the molecular biology and integrated physiology behind HF remain incompletely understood, several fundamental concepts and principles have evolved and are described here. In addition, many of the same proteins found in key HF pathophysiologic pathways have been evaluated as potential biomarkers in HF (some are well established in their clinical utility for diagnostic and prognostic purposes) and are important targets of therapeutic applications and exploration. An important caveat is that many of the proven concepts in HF were derived from HF models with reduced ejection fraction (HFrEF), and relatively little is known about the mechanisms involved in the development of HF with preserved ejection fraction (HFpEF). A special section on the pathophysiology of HFpEF is presented near the end of this chapter. Again, some of the concepts are shared between HFrEF and HFpEF.

TABLE 68–1.Disease Processes That Can Lead to Heart Failure

A key feature of HF is the impaired ability of the heart to move blood forward to meet the needs of the body, whether it is a result of a dysfunction in its ability to fill, contract, or coordinate with the rest of the body. However, many of the body's responses to cardiovascular abnormalities, which are initially adaptive and maintain short-term circulatory function, eventually become maladaptive; these changes ultimately result in further cardiovascular injury and contribute to the progression of HF. Adaptations, in ...

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