STRUCTURAL BASIS OF END-STAGE FAILURE IN ISCHEMIC CARDIOMYOPATHY IN HUMANS

Background Ischemic cardiomyopathy is characterized by myocyte loss, r eactive cellular hypertrophy, and ventricular scarring. However, the r elative contribution of these tissue and cellular processes to late fa ilure remains to be determined. Methods and Results Ten hearts were ob tained from individuals undergoing cardiac transplantation as a result of chronic coronary artery disease in its terminal stage. An identica l number of control hearts were collected at autopsy from patients who died from causes other than cardiovascular disease, and morphometric methodologies were applied to the analysis of the left and right ventr icular myocardium. Left ventricular hypertrophy evaluated as a change in organ weight, aggregate myocyte mass, and myocyte cell volume per n ucleus showed increases of 85%, 47%, and 103%, respectively. Correspon ding increases in the right ventricle were 75%, 74%, and 112%. Myocyte loss, which accounted for 28% and 30% in the left and right ventricle s, was responsible for the difference in the assessment of myocyte hyp ertrophy at the ventricular, tissue, and cellular levels. Left ventric ular muscle cell hypertrophy was accomplished through a 16% and 51% in crease in myocyte diameter and length, whereas right ventricular myocy te hypertrophy was the consequence of a 13% and 67% increase in these linear dimensions, respectively. Moreover, a 36% reduction in the numb er of myocytes included in the thickness of the left ventricular wall was found. Collagen accumulation in the form of segmental, replacement , and interstitial fibrosis comprised an average 28% and 13% of the le ft and right ventricular myocardia, respectively. The combination of c ell loss and myocardial fibrosis, myocyte lengthening, and mural slipp age of cells resulted in 4.6-fold expansion of left ventricular cavita ry volume and a 56% reduction in the ventricular mass-to-chamber volum e ratio. Conclusions These results are consistent with the contention that both myocyte and collagen compartments participate in the develop ment of decompensated eccentric ventricular hypertrophy in the cardiom yopathic heart of ischemic origin.