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Pathologic changes in the long-term transplanted heart: a morphometric study of myocardial hypertrophy, vascularity,
1Department of Pathology, Stanford University School of Medicine, CA 94305.
Insights
Cardiac transplant recipients commonly develop myocyte hypertrophy, but distant donor procurement and cyclosporine do not significantly worsen this or cause fibrosis. Reduced myofibril content may impact long-term function.
Area of Science:
- Cardiology
- Transplantation Immunology
- Pathology
Background:
- Myocyte hypertrophy and myocardial fibrosis are observed in transplanted hearts, potentially affecting long-term function.
- Concerns exist regarding distant donor procurement and cyclosporine immunosuppression increasing these risks.
- Quantitative data on the incidence and severity of these changes are limited.
Purpose of the Study:
- To quantitatively assess myocardial collagen volume fraction, myocyte width, vascularity, and myofibril content in cardiac transplant recipients.
- To compare these parameters between recipients with locally versus distantly procured donor hearts.
- To evaluate the impact of cyclosporine versus non-cyclosporine immunosuppression on these cardiac changes.
Main Methods:
- Light microscopic morphometric methods for collagen volume fraction and myocyte width estimation.
- Electron microscopic stereology for myocardial vascularity and myocyte myofibril content assessment.
- Analysis of right ventricular endomyocardial biopsies from 95 recipients at 3 years post-transplantation.
Main Results:
- No significant differences in myocardial collagen volume fractions were found.
- Myocyte hypertrophy was typical in all transplant biopsies (mean width 20.2 microns vs. 11.8 microns in controls).
- Distant procurement and cyclosporine did not significantly affect hypertrophy or fibrosis; reduced myofibril volume fraction was observed in transplants.
Conclusions:
- Distant donor heart procurement (average ischemic time <3 hours) and cyclosporine treatment are not primary causes of significant hypertrophy or fibrosis in most heart transplants.
- Hypertrophy is a common characteristic of transplanted hearts.
- Reduced myofibril content may suggest potential for gradual decompensation in some long-term survivors.
Abstract:
Myocyte hypertrophy and myocardial fibrosis have been observed in transplanted human hearts, and both could potentially have an adverse effect on long-term cardiac function. There has been some concern that distant donor heart procurement and cyclosporine treatment increase the risk of these changes, but their incidence and severity have not been documented quantitatively in large numbers of cardiac transplant recipients. We used light microscopic morphometric methods to estimate myocardial collagen volume fraction and myocyte width in right ventricular endomyocardial biopsies from 95 recipients at 3 years posttransplantation, and electron microscopic stereology to estimate myocardial vascularity and myocyte myofibril content in 40 recipients, also at 3 years posttransplantation. We compared those with locally and distantly procured donor hearts (mean ischemic time 160 minutes) and cyclosporine versus noncyclosporine immunosuppression. Controls were pretransplant right ventricular biopsies from 20 donor hearts which were free of heart disease. We found no significant differences in myocardial collagen volume fractions. Myocyte hypertrophy was typical of all the transplant biopsies (mean myocyte width 20.2 microns, SD 3.0 in all transplants versus 11.8 microns, SD 2.2 in controls, P less than 0.001), but distant donor procurement and cyclosporine had no significant effect. There were significant reductions of myofibril volume fraction in the transplants, which raises the possibility of gradual decompensation in some patients. There were no significant differences in myocardial vascularity, although a few patients were well below the control range. We conclude that distant donor heart procurement, with ischemic times averaging less than 3 hours, and cyclosporine treatment are not responsible for significant hypertrophy or fibrosis in most transplants. Hypertrophy is typical of the transplanted heart, and it is possible that associated abnormalities might have an effect on cardiac function in some long-term survivors.