Abstract 9800: Racial Differences in Donor-Derived and Mitochondrial Cell-Free Dna Could Explain Inferior Outcomes in Black Heart Transplant Patients, on Behalf of the Graft Investigators

Abstract

Introduction: Black heart transplant patients are at higher risk of acute rejection (AR) and death than White patients. Our group has shown that %donor-derived cell-free DNA (%ddcfDNA) is a sensitive and specific marker of AR in heart transplantation. Cell-free mitochondrial DNA (cfmtDNA) has been linked to allograft dysfunction and may mechanistically implicated in inferior outcomes for Black heart transplant recipients. Hypothesis: Higher levels of allograft injury when quantitated using %ddcfDNA and total cfmtDNA will be seen in Black heart transplant patients as compared to White patients. Methods: The Genomic Research Alliance for Transplantation (GRAfT) is a multicenter, prospective, longitudinal cohort study of heart transplant patients transplanted between 2015 and 2021. We included Black and White patients and shotgun sequencing was used to quantitate %ddcfDNA and polymerase chain reaction (PCR) to quantitate total cfmtDNA levels. AR was defined as grade ≥2R cellular rejection or pAMR ≥1 antibody-mediated rejection (AMR). Results: We included 151 patients (73 Blacks and 78 Whites), the median age was 56y (29% Female sex). Patients of both racial groups had comparable baseline characteristics. There were a ~1100 ddcfDNA and cfmtDNA measures included in the analysis. At 18-months, the incidence of AR was 2.8% in White patients and 9.2% in Black patients (p<0.01). The diagnostic accuracy of %ddcfDNA to detect AR was comparable between Black and White patients (0.90 vs. 0.83, p=0.19). The %ddcfDNA and cfmtDNA was higher at serial time points after transplant in Black compared to White patients (Figure). CfmtDNA levels were also elevated with AMR which occurred almost exclusively in Black patients (No rejection: 146,345 copies/ul, AMR: 242,238 copies/ul; p=0.004). Conclusions: Elevated levels of %ddcfDNA and cfmtDNA after heart transplant may explain the higher incidence of AR, AMR, and inferior outcomes in Black heart transplant recipients.