CLINICAL STUDIES
Quantitative investigation of cardiomyocyte hypertrophy and myocardial fibrosis over 6 years after cardiac transplantation
Arthur T. Armstrong, PhD*,
Philip F. Binkley, MD, FACC*,
Peter B. Baker, MD ,
P. David Myerowitz, MD, FACC and
Carl V. Leier, MD, FACC*
* Division of Cardiology, The Ohio State University College of Medicine, Columbus, Ohio, USA
Department of Pathology, The Ohio State University College of Medicine, Columbus, Ohio, USA
Division of Cardiac Surgery, The Ohio State University College of Medicine, Columbus, Ohio, USA
Manuscript received October 31, 1997;
revised manuscript received May 4, 1998,
accepted May 15, 1998.
Address for correspondence: Dr. Carl V. Leier, Division of Cardiology, The Ohio State University Hospitals, 669 Means Hall, 1654 Upham Drive, Columbus, Ohio 43210
Objectives. This study was performed to determine the degree and time course over 6 years of cardiomyocyte hypertrophy and myocardial fibrosis of the cardiac allograft in transplanted patients.
Background. Diastolic dysfunction and to a certain extent systolic dysfunction are common cardiac findings after heart transplantation. The development of posttransplant cardiomyocyte hypertrophy and myocardial fibrosis likely contributes to these derangements.
Methods. Cardiomyocyte diameter and percent fibrosis were determined in serial endomyocardial biopsy specimens obtained from 1 month up to 6 years following heart transplantation in 50 patients. Endomyocardial biopsy specimens from 40 patients with primary dilated cardiomyopathy and 11 normal subjects were similarly analyzed for control data. Analyses were performed in a blinded format using a validated computerized image analysis system (Optimas 5.2).
Results. Early (1 month) cardiomyocyte enlargement decreased to the smallest diameter 6 months posttransplant, but thereafter progressively increased by 10% to 20% over the subsequent 5- to 6-year period. Although not statistically established, principal stimuli may include a discrepancy in body size (recipient > donor), coronary allograft vasculopathy and posttransplant systemic hypertension. Percent myocardial fibrosis rose early (1 to 2 months) posttransplant and thereafter remained at the same modest level of severity.
Conclusions. Cardiomyocyte diameter of the transplanted heart gradually increases over time, while percent myocardial fibrosis rises early and remains in a modestly elevated plateau after 2 months posttransplant. These histostructural changes likely contribute to the hemodynamic and cardiac functional alterations commonly observed posttransplant.
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