Apoptosis: a pivotal event or an epiphenomenon in the pathophysiology of heart failure?

Apoptosis: a pivotal event or an epiphenomenon in the pathophysiology of heart failure?Apoptosis, or programmed cell death, is an evolutionary conserved genetically programmed process by which multicellular organisms regulate cell numbers.It is critical in development and in tissue homeostasis.Unlike necrosis, the process is active, energy requiring and precisely regulated. Apoptosis in cardiac development and diseaseCardiac myocytes are by and large terminally diVerentiated and have a limited capacity for self renewal.It would therefore seem that loss of a significant number of cardiomyocytes would have lasting adverse consequences.Apoptosis is, however, integral to normal cardiac development and is also important in the morphogenesis of the conducting system.This can be illustrated by accessory pathway mediated arrhythmias caused by inadequate removal of loop short circuit cells by apoptosis.Apoptotic cardiomyocytes have also been identified in subjects with ischaemic heart disease and myocarditis.Moreover, evidence exists to show that apoptosis occurs in "end stage" heart failure.The relevance of this process in the overall pathophysiology and progression of heart failure is, however, still controversial.We hope to convey the current understanding of apoptosis with respect to its prevalence and its putative impact on chronic stable cardiomyopathy.We will also discuss the theoretical implications of blocking the apoptotic programme in the management of heart failure.