Does acute cellular rejection correlate with cardiac allograft vasculopathy?

BACKGROUND: Previous studies of the association between acute cellular rejection and cardiac allograft vasculopathy (CAV) have yielded conflicting conclusions. We explored a possible association between acute cellular rejection and the extent of CAV, and we found a potential confounding variable that may obscure such an association.
METHODS: We investigated 140 patients (mean age, 51 +/- 11 years) who underwent serial intravascular ultrasound examinations at baseline and at 1 year after heart transplantation to assess CAV as change in maximal intimal thickness (CMIT). Patients were classified according to the presence or absence of biopsy-proven myocardial fibrosis. We used a standard biopsy-scoring system and a novel biopsy-scoring system, developed in our institution, to assess acute cellular rejection. Using univariate analysis, we found that CMIT was not associated with acute cellular rejection in the overall patient population (n = 140). However, we observed a correlation between CMIT and acute cellular rejection (standard method, r = 0.30, p = 0.01; novel method, r = 0.51, p < 0.0001) in patients who had no evidence of ischemic injury or fibrosis in their biopsy specimens (n = 57). Step-wise multiple regression showed that the rejection score derived from our novel method was associated more closely with the CMIT than was that derived from the traditional method.
CONCLUSIONS: This data indicate that the presence of myocardial fibrosis masks an actuarial association between acute cellular rejection and the development of de novo allograft vasculopathy. As previously suspected, myocardial fibrosis is a marker for non-immune-mediated graft injury independently associated with an increased incidence of CAV.