Heart failure: a hemodynamic disorder complicated by maladaptive proliferative responses

Abstract

Heart failure has traditionally been viewed as a hemodynamic syndrome characterized by fluid retention, high venous pressure, and low cardiac output. Over the past decade, however, it has become clear that because of deterioration and progressive dilatation (remodeling) of the diseased heart, this is also a rapidly fatal syndrome. The importance of prognosis came to be appreciated when clinical trials showed that therapy which initially improves such functional abnormalities, as high venous pressure and low cardiac output, often fail to improve survival, and that some drugs which improve hemodynamics worsen long‐term prognosis. The latter is true for most vasodilators which, in spite of alleviating the adverse short‐term consequences of high afterload, shorten survival. Notable exceptions are ACE inhibitors, whose vasodilator effects do not explain their ability to prolong survival; instead, these drugs slow both deterioration and remodeling of the failing heart. Inotropic agents, while providing immediate relief of symptoms, generally shorten long‐term survival, whereas β‐blockers slow deterioration and remodeling, and reduce mortality. Aldosterone antagonists exert beneficial effects on prognosis that are not easily explained by their diuretic effects, but instead can be explained by their ability to inhibit signaling pathways that stimulate maladaptive hypertrophy, remodeling, apoptosis and other deleterious responses that cause deterioration of the failing heart. These and other findings demonstrate that heart failure is more than a hemodynamic disorder; these patients suffer from maladaptive proliferative responses that cause cardiac cell death and progressive dilatation that play a key role in determining the poor progressive in this syndrome.