THE CELLULAR BASIS OF DILATED CARDIOMYOPATHY IN HUMANS

The present investigation was designed to evaluate whether end-stage c ardiac failure in patients affected by dilated cardiomyopathy (DC) was dependent upon extensive myocyte cell death with reduction in muscle mass or was the consequence of collagen accumulation in the myocardium independently from myocyte cell loss, In addition, the mechanisms of ventricular dilation were analysed in order to determine whether the c hanges in cardiac anatomy were important variables in the development of intractable congestive heart failure. DC is characterized by chambe r dilation, myocardial scarring and myocyte hypertrophy in the absence of significant coronary atherosclerosis, However, the relative contri bution of each of these factors to the remodeling of the ventricle is currently unknown. Moreover, no information is available concerning th e potential etiology of collagen deposition in the myocardium and the changes in number and size of ventricular myocytes with this disease. Morphometric methodologies were applied to the analysis of 10 DC heart s obtained from patients undergoing cardiac transplantation. An identi cal number of control hearts was collected from individuals who died f rom causes other than cardiovascular diseases. DC produced a 2.2-fold and 4.2-fold increase in left ventricular weight and chamber volume re sulting in a 48% reduction in mass-to-volume ratio. In the right ventr icle, tissue weight and chamber size were both nearly doubled. Left ve ntricular dilation was the result of a 59% lengthening of myocytes and a 20% increase in the transverse circumference due to slippage of myo cytes within the wall. Myocardial scarring represented by segmental, r eplacement and interstitial fibrosis occupied approximately 20% of eac h ventricle, and was indicative of extensive myocyte cell loss. Howeve r, myocyte number was not reduced and average cell volume increased 2- fold in both ventricles. In conclusion, reactive growth processes in m yocytes and architectural rearrangement of the muscle compartment of t he myocardium appear to be the major determinants of ventricular remod eling and the occurrence of cardiac failure in DC.