Vascular abnormalities and cardiomyocyte lipofuscin deposits in endomyocardial biopsy specimens of heart transplant recipients: are they related to the development of cardiac allograft vasculopathy?

Objective: The aim of this study was to assess the predictive value of microvascular abnormalities and lipofuscin observed in endomyocardial biopsy samples for the development of cardiac allograft vasculopathy.
Methods: The study group consisted of 68 cardiac allograft recipients (63 men and 5 women, 43 +/- 12 years old). We performed a re-evaluation of 1071 endomyocardial biopsy specimens to search for microvascular diseases and lipofuscin in cardiocytes. Endomyocardial biopsy specimens with an International Society for Heart and Lung Transplantation rejection grade of 2 or more and those without arterioles were excluded. Abnormalities found in the remaining 517 specimens were correlated with the grade of rejection. Biopsy specimens obtained 2 weeks, 12 months, and 36 months after transplantation were compared with coronary angiography results, clinical events of cardiac allograft vasculopathies, and survivals. Kaplan-Meier curves were constructed to compare the time to the development of cardiac allograft vasculopathy or death.
Results: Enlarged endothelial cells, lymphocytes inside the arteriolar wall, occluded arteriolar lumen, endothelial vacuolization, and hypertrophy of the vascular muscle were significantly correlated with rejection grade. Although none of the vascular abnormalities predicted cardiac allograft vasculopathy, patients with lipofuscin deposits at the 12-month biopsy specimens were characterized by the rapid development of angiography-confirmed cardiac allograft vasculopathy (P < .08) and events related to cardiac allograft vasculopathy (P < .03, log-rank test).
Conclusion: Microvascular abnormalities correlate with mild cellular rejection, but they do not seem to be predictive for development of cardiac allograft vasculopathy detected by angiography. The presence of lipofuscin in 12-month endomyocardial biopsy specimens may be predictive of development of angiographically confirmed cardiac allograft vasculopathy.