PROGRAMMED CELL-DEATH IN THE PROGRESSION OF HEART-FAILURE

A characteristic feature of heart failure is the progressive deteriora tion of left ventricular function that occurs in the absence of clinic ally apparent intercurrent adverse events. The mechanism or mechanisms responsible for this haemodynamic deterioration are not known but may be related to progressive intrinsic contractile dysfunction of cardio myocytes and/or to ongoing degeneration and loss of viable cardiomyocy tes. In this review we examine the concept of ongoing cardiac myocyte loss as a potential factor responsible for the progression of left ven tricular dysfunction in heart failure. The discussion focuses on apopt osis or 'programmed cell death' as a potential mediator of cardiomyocy te loss. While available data support the existence of myocyte apoptos is in the failing heart, studies addressing possible physiological and molecular triggers of this process of cell death in the failing heart are lacking. As a part of the discussion, we construct a case in supp ort of the concept that the failing myocardium is subject to regional hypoxia, an abnormality that can potentially trigger cardiomyocyte apo ptosis. If loss of cardiomyocytes through apoptosis can be shown to be an important contributor to the progression of heart failure, and if the trigger of cardiomyocyte apoptosis in the failing heart can be ide ntified, the foundation would be strengthened for the development of n ovel, target-specific therapeutic modalities aimed at preventing, or a t the very least retarding, the process of progressive ventricular dys function and the transition toward intractable heart failure.