Pathways of myocyte death: implications for development of clinical laboratory biomarkers

The recognition that cardiac myocytes die by multiple mechanisms and thus substantially affect ventricular remodeling in diseased human hearts supports the concept of ongoing myocyte death in the progression of heart failure and constitutes the basis of this review. In addition, based on the pathophysiology of myocardial cell deaths, the present study emphasizes that currently methodologies, although with some inherent limitations, are available to recognize and measure quantitatively the contribution of myocyte cell death to the progression of the pathologic state of the heart. Our own studies show that application of such methodologies including modern microscopy techniques and the use of different molecular and immunohistochemical markers may generate the consensus that myocyte cell death is a quantifiable parameter in the normal and pathological human heart. The present study also demonstrates that myocyte cell death, apoptotic, oncotic or autophagic in nature, has to be regarded as an additional critical variable of the multifactorial events implicated in the alterations of cardiac anatomy and myocardial structure of the diseased human heart.