Pharmacological modulation of cardiovascular remodeling: a guide to heart failure therapy

Abstract

Cardiac remodeling is a complex process, which involves genetic, molecular and cellular changes in cardiomyocytes and the interstitium, leading to progressive structural and functional alterations, including cardiac dilatation, interstitial fibrosis, and a reduction in contractility and relaxation. As cardiac function worsens, ventricular dysfunction, heart failure and end-stage heart disease are the ultimate consequences. Underlying mechanisms include myocardial stretch and neurohormonal and cytokine activation. Consequently, therapies aiming counteracting these mechanisms have proven successful in attenuating or even preventing cardiac remodeling. In particular, ACE inhibition, beta-blockade and aldosterone antagonism have proven to be effective in modulating the process of remodeling and in reducing the occurrence of adverse events in heart failure. Of interest, although several other antagonists of neurohormonal, including endothelin, or of cytokine activation have been shown to effectively modulate remodeling, studies thus far have been negative in terms of event reduction in heart failure. Whereas insight in cardiovascular remodeling has already significantly contributed to existing management strategies in heart failure, further studies in different mechanisms may provide additional therapeutic measures.