A growing body of experimental and clinical evidence suggests that HF progresses as a result of the overexpression of biologically active molecules that are capable of exerting deleterious effects on the heart and circulation (Fig. 25-1B).^[1] The portfolio of compensatory mechanisms that have been described thus far includes activation of the adrenergic nervous system and renin-angiotensin system (RAS), which are responsible for maintaining cardiac output through increased retention of salt and water, peripheral arterial vasoconstriction, and increased contractility, and activation of inflammatory mediators, which are responsible for cardiac repair and remodeling. The term neurohormoneis largely a historical term, reflecting the original observation that many of the molecules elaborated in HF are produced by the neuroendocrine system and thus act on the heart in an endocrine manner. However, it has since become apparent that a …