Cardiac Remodeling: From Concepts to Therapeutics

Abstract

Cardiac dysfunction in heart failure is widely recognized as a progressive process regardless of clinical signs and symptoms. It is now well accepted that the key to success in reducing the extremely high morbidity and mortality associated with heart failure is slowing or reversing the process of disease progression by favorably altering the course of cardiac remodeling. Thus, a paradigm shift from symptomatic control towards treating the pathophysiologic processes that underlie remodeling has emerged. The shift from traditional concepts that heart failure is merely a 'muscle dysfunction' problem, and hence intervention to support function as remedy to the problem has emanated from the sober recognition that strategies aimed to correct hemodynamic and cardiac contraction dysfunction neither prevent the progression of heart failure nor improve mortality. The only medical interventions that provided some remedy (in the form of reduced morbidity and mortality) are those that affect neurohormonal systems which either directly or indirectly modulate cardiac remodeling. Such systems include the renin-angiotensin-aldosterone and the sympathetic nervous system. This brief review of cardiac remodeling and heart failure provides definitions and concepts that underlie contemporary understanding of heart failure. We also summarize cellular and molecular mechanisms that underwrite the remodeling process and their impact on clinical outcome.