CYTOMEGALOVIRUS-INFECTION AND ACCELERATED CARDIAC ALLOGRAFT VASCULOPATHY IN HUMAN CARDIAC ALLOGRAFTS

Cardiac allograft vasculopathy is a major limiting factor of the long-term survival of heart transplant patients. An association of cytomegalovirus infection and cardiac allograft vasculopathy has been described. We analyzed 104 endomyocardial biopsy specimens obtained from 53 heart transplant recipients and correlated the histologic findings with 115 angiograms obtained from the same patients during 4 postoperative years. The frequency of vascular changes in endomyocardial biopsy specimens was significantly higher than in angiograms during the first 3 posttransplantation years (P < 0.001, P < 0.005, P < 0.03, respectively). Also, in patients with angiographically documented cardiac allograft vasculopathy, significantly higher scores of capillary and arteriolar endothelial cell accumulation and arteriolar intimal thickness were recorded when compared with the recipients with normal angiograms (P < 0.02, P < 0.05, P < 0.005, respectively). Altogether, 29 of 53 recipients underwent cytomegalovirus infection during the first posttransplant year. Cytomegalovirus infection was associated with arteriolar endothelial cell accumulation and with increased intimal thickness of intramyocardial vessels of 1-year endomyocardial biopsy specimens when compared with cytomegalovirus-free recipients (P < 0.02 and P < 0.005, respectively). After the second year, the cytomegalovirus-associated endothelial cell response subsided, but the thickness of intima had increased when compared with cytomegalovirus-free patients (P < 0.05). Thereafter, the cytomegalovirus-associated histologic changes reached a plateau. In coronary angiography, the cardiac allograft vasculopathy changes were detected in a slower pace. Thus only after 2 posttransplantation years, cytomegalovirus-associated acceleration of cardiac allograft vasculopathy was observed, compared with cytomegalovirus-free patients (P < 0.05). Early diagnosis and active treatment of cytomegalovirus infection may be important steps in avoiding cardiac allograft vasculopathy.