ABO Blood Group Mismatch in Heart Transplantation Is Not Associated With Elevated Donor-Derived Cell-Free DNA

Donor-derived cell-free DNA (dd-cfDNA) is a reliable, noninvasive marker for detecting allograft rejection after heart transplantation (HT). We evaluated whether dd-cfDNA levels differ in recipients of ABO-compatible, nonidentical (mismatched) grafts. We performed a retrospective single-center cohort study of 219 adult HT recipients transplanted between January 2019 and May 2023, each with at least one dd-cfDNA sample collected between November 2019 and April 2024. ABO mismatch was defined as a donor blood type A, B, or AB that was compatible with but nonidentical to the recipient's type; only ABO-compatible transplants were included. dd-cfDNA was measured using a commercially available assay (AlloSure, CareDx, Brisbane, CA), and a level ≥0.20% was defined as positive. A total of 1,783 dd-cfDNA tests were analyzed, with a 16.0% overall positivity rate. Positivity was 20.1% in the mismatched group and 15.5% in the matched group, with no statistically significant difference whether dd-cfDNA was treated as a binary (p = 0.95) or continuous (p = 0.26) variable. No statistically significant differences were observed between groups in gene expression profiling, donor-specific antibodies, rejection, or survival. In this adult cohort, ABO-compatible nonidentical HT was not associated with higher dd-cfDNA levels, although the small mismatched subgroup limits statistical power.