Donor-derived cell-free DNA, gene expression profile, and acute rejection in donation after circulatory death (DCD) heart transplant recipients

Abstract

BackgroundAcute rejection (AR) is a leading cause of early morbidity and mortality in heart transplant (HTx) recipients. There is limited data in donor after circulatory death (DCD) HTx recipients where ischemia reperfusion injury may contribute to development of AR and may be detected early with non-invasive biomarkers such as donor-derived cell-free DNA (dd-cfDNA) and gene expression profile (GEP). The goal of this study is to compare dd-cfDNA, GEP and rejection outcomes in DCD and donor after brain death (DBD) HTx recipients. MethodsThis single-center, retrospective study included DCD and DBD HTx recipients from January 2020 to September 2022. Patients were excluded from the study if dd-cfDNA and GEP were not available. The CareDx HeartCare platform was used to obtain dd-cfDNA (AlloSure-Heart) and GEP (AlloMap) with the highest values for each patient recorded at 6 and 12 months. The mean values for these non-invasive markers were compared between DCD and DBD groups. Patients were followed for clinical outcomes, including treated AR, coronary allograft vasculopathy (CAV) and death, through September 2023. ResultsA total of 156 HTx patients were included with 50 DCD and 106 DBD recipients. Baseline characteristics were similar between DCD and DBD recipients including mean age (58.5 years vs 56.9 years, p = 0.48), male sex (82% vs 76%, p = 0.56) and Caucasian race (46% vs 43%, p = 0.78). There were no significant differences in mean AlloSure-Heart at 6 and 12 months between DCD and DBD recipients. AlloMap was significantly lower at 6 months (p = 0.04), but not at 12 months between DCD and DBD recipients. With respect to clinical outcomes at 1 year, there were no significant differences in treated AR (22% vs 14%, p = 0.32), ISHLT grade ≥ 2 CAV (0 vs 4%, p = 0.44) or mortality (2% vs 0%, p = 0.69) between DCD and DBD recipients. ConclusionsIn this single center study, there were no significant differences in mean dd-cfDNA and treated AR at 1 year between DCD and DBD HTx recipients. There was a significant increase in mean GEP at 6 months, but not at 12 months in the DBD cohort. Overall, there does not appear to be clinically significant cardiac allograft injury related to DCD as measured by non-invasive markers. Further work is needed to confirm these findings.