Has late rejection decreased in pediatric heart transplantation in the current era? A multi-institutional study

Background: Late (occurring >1 year) rejection (LR) has been shown to increase mortality and morbidity after pediatric heart transplantation (HTx). The incidence of rejection has decreased in the first year after pediatric HTx in the current era. We hypothesized a similar phenomenon has occurred with LR. Methods: The Pediatric Heart Transplant Study database was used to analyze the effects of era (1993 to 1998 vs 1999 to 2007) and other factors on the prevalence of LR and its relationship to mortality, moderate-severe coronary vasculopathy (CAV) and retransplantation. Results: Freedom from first LR (59% vs 69% 5-year post-HTx, p < 0.001) and recurrent LR (p < 0.001) was significantly lower in the current vs earlier era. LR was significantly (p < 0.001) associated with early rejection (ER; rejection <1 year post-HTx) in both eras. Independent risk factors for LR were: earlier era (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.25 to 1.73, p < 0.001); non-white race (HR 1.41; 95% CI 1.19 to 1.67, p < 0.001); older recipient age (HR 1.05, 95% CI 1.03 to 1.06, p < 0.001); recipient Status 2 at transplant (HR 1.21, 95% CI 1.01 to 1.45, p = 0.037); and male donor (HR 1.17; 95% CI 1.0 to 1.37, p = 0.055). Late rejectors had a similar higher risk of mortality (odds ratio [OR] 4.20, 95% CI 3.04 to 5.81, p < 0.001) and incidence of moderate-severe CAV or retransplantation (OR 2.63, 95% CI 1.78 to 3.90, p < 0.001) in both eras. Conclusions: LR has decreased in the recent era in pediatric HTx recipients. Its effect on mortality and the development of CAV has not changed over time, suggesting an ongoing need for improved primary prevention strategies.