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The cellular basis of dilated cardiomyopathy in humans
C A Beltrami1, N Finato, M Rocco
1Department of Pathology, University of Udine, Italy.
Insights
Dilated cardiomyopathy (DC) causes heart failure not from cell death, but from myocyte growth and rearrangement. This study clarifies the mechanisms behind ventricular remodeling in DC patients.
Area of Science:
- Cardiology
- Pathology
- Biomedical Engineering
Background:
- Dilated cardiomyopathy (DC) is characterized by ventricular dilation, myocardial scarring, and myocyte hypertrophy.
- The precise mechanisms driving ventricular remodeling and heart failure in DC remain unclear.
- The roles of myocyte cell loss, collagen accumulation, and architectural changes are not well-defined.
Purpose of the Study:
- To determine if end-stage cardiac failure in DC is due to myocyte cell death or collagen accumulation.
- To analyze the mechanisms of ventricular dilation and their contribution to heart failure.
- To investigate the etiology of collagen deposition and changes in myocyte size and number in DC.
Main Methods:
- Morphometric analysis of 10 dilated cardiomyopathy hearts from transplant patients.
- Comparison with 10 control hearts from non-cardiovascular disease deaths.
- Quantification of myocyte size, number, collagen content, and ventricular dimensions.
Main Results:
- DC increased left ventricular weight (2.2-fold) and chamber volume (4.2-fold), reducing mass-to-volume ratio by 48%.
- Left ventricular dilation resulted from myocyte lengthening (59%) and slippage, not cell loss.
- Myocardial scarring (fibrosis) was extensive (~20%), yet myocyte number was unchanged; average cell volume doubled.
Conclusions:
- Ventricular remodeling in DC is primarily driven by myocyte hypertrophy and architectural rearrangement, not myocyte loss.
- Reactive myocyte growth and altered myocardial structure are key determinants of heart failure in dilated cardiomyopathy.
- Collagen accumulation and myocyte slippage contribute to ventricular dilation and dysfunction in DC.
Abstract:
The present investigation was designed to evaluate whether end-stage cardiac 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 changes in cardiac anatomy were important variables in the development of intractable congestive heart failure. DC is characterized by chamber dilation, myocardial scarring and myocyte hypertrophy in the absence of significant coronary atherosclerosis. However, the relative contribution of each of these factors to the remodeling of the ventricle is currently unknown. Moreover, no information is available concerning the 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 hearts obtained from patients undergoing cardiac transplantation. An identical number of control hearts was collected from individuals who died from causes other than cardiovascular diseases. DC produced a 2.2-fold and 4.2-fold increase in left ventricular weight and chamber volume resulting in a 48% reduction in mass-to-volume ratio. In the right ventricle, tissue weight and chamber size were both nearly doubled. Left ventricular dilation was the result of a 59% lengthening of myocytes and a 20% increase in the transverse circumference due to slippage of myocytes within the wall. Myocardial scarring represented by segmental, replacement and interstitial fibrosis occupied approximately 20% of each ventricle, and was indicative of extensive myocyte cell loss. However, myocyte number was not reduced and average cell volume increased 2-fold in both ventricles. In conclusion, reactive growth processes in myocytes and architectural rearrangement of the muscle compartment of the myocardium appear to be the major determinants of ventricular remodeling and the occurrence of cardiac failure in DC.