Abstract 4147327: Race and Ethnic Differences in Donor-Derived Cell-Free DNA and Gene Expression Profiling in Heart Transplant Recipients in a Negative Biopsy Cohort

Introduction: The Donor-Derived Cell-Free DNA-Outcomes AlloMap Registry (D-OAR) study has highlighted the significant capability of dd-cfDNA, showcasing a 97% negative predictive value (NPV) for identifying both acute cellular rejection (ACR) and antibody-mediated rejection (AMR) at a dd-cfDNA threshold of 0.20%. This development has greatly enhanced the range of biomarkers available to clinicians, confirming dd-cfDNA as a reliable clinical biomarker for monitoring heart transplant (HT) recipients. Short and long-term outcomes for African American HT recipients are worse. Given these findings, our study aims to investigate baseline differences in the levels and positivity rates of dd-cfDNA stratified by race in a negative biopsy cohort. Methods: We conducted a single-center retrospective review of all HT recipients from 2019 to 2023 with at least one valid combined dd-cfDNA sample drawn between April 2019 and July 2023. Multiorgan transplant recipients and those without a paired biopsy result were excluded. A positive biopsy result was defined as >= ISHLT grade 1R/1B or pAMR>0. Dd-cfDNA (AlloSure, AS) result was considered positive if ≥0.12%, and as a sub-analysis using a threshold ≥0.20%. A positive peripheral GEP (pGEP, AlloMap, AM) test was defined as >30 in the first five months post-transplant and >34 afterward. Samples associated with a positive biopsy result were excluded. We further stratified our cohort based on race. Results: Of 643 paired dd-cfDNA/GEP samples from 227 patients, the median age was 55 years, and 27% were female. The cohort was stratified into four categories: 53% were white, 18.8% were AA, 20.4% were Hispanic/Latino, and 7.8% were of other races. We observed no baseline differences in the positive dd-cfDNA levels (p=0.39) and positivity rates of dd-cfDNA at a threshold of 0.12% and 0.20% (p=0.08, p=0.06) or GEP positivity rates (p=0.52) between the 4 race categories in our surveillance cohort (Figure 1). Further comparison of patients treated for rejection based on non-invasive monitoring did not reveal a difference. Conclusions: In our surveillance cohort, dd-cfDNA levels and positivity rates were not different between AA and white HT recipients. Further prospective randomized trials are needed to elucidate potential race-related differences in dd-cfDNA levels.