Abstract
BackgroundExtending graft survival after heart transplant (HT) is of paramount importance to achieve survival well into adulthood for childhood recipients. Acute rejection is a significant adverse event, and biopsy remains the most specific means for diagnosing acute cellular rejection (ACR) versus antibody-mediated rejection (AMR). MethodsAll children in the Pediatric Heart Transplant Society (PHTS) Registry who underwent HT between 1/2015 and 6/2022 and had ≥1 episode of treated rejection were included. Survival after rejection was compared between those with AMR and those with ACR-only. Secondary outcomes of infection, malignancy, and cardiac allograft vasculopathy (CAV) were assessed. Risk factors for graft loss after AMR were identified using Cox proportional hazard modeling. ResultsAmong 906 children treated for rejection during follow-up through 12/2022, 697 (77%) with complete biopsy information were included. AMR was present on biopsy in 261 (37%) patients; ACR-only was present in 436 (63%) patients. Time to treated rejection was earlier in those with AMR, median time from HT to rejection 0.11 versus 0.29 years, p=0.0006. When rejection occurred within the 1st year, survival after AMR was lower than survival after ACR-only. Predictors of graft loss after AMR were younger age at HT, diagnosis of congenital heart disease, and rejection with hemodynamic compromise. There was no difference in time to CAV, infection, or malignancy after treated rejection between groups. ConclusionsThe largest analysis of pediatric HT recipients treated for rejection with biopsy data to identify AMR underscores the continued importance of AMR on survival. AMR is associated with higher graft loss versus ACR when occurring in the first-year post HT. Predictors of graft loss after AMR identify patients who may benefit from increased surveillance, more aggressive rejection treatment, or augmented maintenance immunosuppression.
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