Related Experiment Videos
Structural basis of end-stage failure in ischemic cardiomyopathy in humans
C A Beltrami1, N Finato, M Rocco
1Department of Pathology, University of Udine, Italy.
Insights
Ischemic cardiomyopathy involves myocyte loss and hypertrophy, leading to significant ventricular enlargement and reduced mass-to-volume ratio. Both cell loss and fibrosis contribute to heart failure in this condition.
Area of Science:
- Cardiovascular Research
- Pathology
- Cardiac Physiology
Background:
- Ischemic cardiomyopathy is defined by myocyte loss, hypertrophy, and scarring.
- The precise roles of these cellular and tissue changes in late-stage heart failure require further elucidation.
Purpose of the Study:
- To quantify the contributions of myocyte loss, hypertrophy, and fibrosis to ventricular remodeling in end-stage ischemic cardiomyopathy.
Main Methods:
- Morphometric analysis of left and right ventricular myocardium from explanted hearts of transplant recipients with chronic ischemic heart disease.
- Comparison with age-matched autopsy-obtained control hearts.
Main Results:
- Significant increases in ventricular weight, myocyte mass, and cell volume were observed in both ventricles.
- Myocyte loss accounted for substantial differences in hypertrophy assessment.
- Extensive collagen accumulation (fibrosis) was present, averaging 28% in the left ventricle and 13% in the right ventricle.
- Combined effects led to a 4.6-fold expansion of left ventricular cavitary volume and a 56% reduction in the mass-to-chamber volume ratio.
Conclusions:
- Both myocyte alterations and collagen deposition are critical components in the development of decompensated eccentric hypertrophy in ischemic cardiomyopathy.
- These findings support a multifactorial model of cardiac remodeling in this condition.
Background:
Ischemic cardiomyopathy is characterized by myocyte loss, reactive cellular hypertrophy, and ventricular scarring. However, the relative contribution of these tissue and cellular processes to late failure remains to be determined.
Methods And Results:
Ten hearts were obtained from individuals undergoing cardiac transplantation as a result of chronic coronary artery disease in its terminal stage. An identical 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 ventricular myocardium. Left ventricular hypertrophy evaluated as a change in organ weight, aggregate myocyte mass, and myocyte cell volume per nucleus showed increases of 85%, 47%, and 103%, respectively. Corresponding increases in the right ventricle were 75%, 74%, and 112%. Myocyte loss, which accounted for 28% and 30% in the left and right ventricles, was responsible for the difference in the assessment of myocyte hypertrophy at the ventricular, tissue, and cellular levels. Left ventricular muscle cell hypertrophy was accomplished through a 16% and 51% increase in myocyte diameter and length, whereas right ventricular myocyte hypertrophy was the consequence of a 13% and 67% increase in these linear dimensions, respectively. Moreover, a 36% reduction in the number 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 left and right ventricular myocardia, respectively. The combination of cell loss and myocardial fibrosis, myocyte lengthening, and mural slippage of cells resulted in 4.6-fold expansion of left ventricular cavitary volume and a 56% reduction in the ventricular mass-to-chamber volume ratio.
Conclusions:
These results are consistent with the contention that both myocyte and collagen compartments participate in the development of decompensated eccentric ventricular hypertrophy in the cardiomyopathic heart of ischemic origin.