Donor-derived cell-free DNA is associated with cardiac allograft vasculopathy

Background: The role of donor-derived cell-free DNA (dd-cfDNA) in screening for cardiac allograft vasculopathy (CAV) is unknown. We hypothesized that dd-cfDNA correlates with CAV, markers of inflammation, and angiogenesis in stable heart transplant (HT) recipients. Methods: Sixty-five HT recipients ≥2 years post-transplant, without recent rejection, were stratified by high (≥0.12%) versus low levels (<0.12%) of dd-cfDNA. A targeted amplification, next-generation sequencing assay (AlloSure^®; CareDx, Inc.) was used to detect dd-cfDNA. Peripheral blood inflammatory and angiogenesis markers were assessed using a multiplex immunoassay system (Bioplex^®). Results: Of 65 patients, 58 patients had a known CAV status and were included. Thirty had high levels of dd-cfDNA (≥0.12%), and 28 had low levels (<0.12%). CAV was present in 63% of patients with high dd-cfDNA vs. 35% with low dd-cfDNA (p =.047). Donor-specific antibodies were present in 25% of patients with high dd-cfDNA vs. 3.8% in those with low dd-cfDNA (p =.03). There were no differences in rejection episodes, inflammatory, or angiogenesis markers. Importantly, dd-cfDNA levels were not different when stratified by time post-transplant. Conclusions: Higher dd-cfDNA levels were associated with CAV in stable chronic HT recipients. Further studies are warranted to investigate a possible association between dd-cfDNA levels and CAV severity and whether dd-cfDNA can predict CAV progression.