Abstract 14759: Combining High-Sensitivity Cardiac Troponin and Donor-Derived Cell-Free Dna to Diagnose Acute Heart Transplant Rejection, on Behalf of the Graft Investigators

Introduction: Donor-derived cell-free DNA (%ddcfDNA) is a reliable non-invasive biomarker of acute rejection (AR). High-sensitivity cardiac troponin T (hs-cTnT) has been shown to be an easy to perform, low-cost, biomarker of myocyte injury. Hypothesis: We hypothesized that hs-cTnT correlates with %ddcfDNA in heart transplant patients and complements %ddcfDNA to improve the non-invasive diagnosis of AR. Methods: The Genomic Research Alliance for Transplantation (GRAfT) is a multicenter, prospective, longitudinal cohort study of heart transplant patients transplanted between 2015 and 2021. The %ddcfDNA was quantitated with shotgun sequencing; hs-cTnT was measured on the Roche instrument. AR was ISHLT grade ≥2R acute cellular rejection (ACR) or pAMR ≥1 antibody-mediated rejection (AMR). Results: This analysis included 171 patients from the GRAfT cohort (mean age 52.3±12.4 yrs; 41% Black; 31% Female). Of the 1,030 simultaneous measurements of hs-cTnT and %ddcfDNA, 662 were paired with an endomyocardial biopsy. Median hs-cTnT was 1451 ng/L (IQR: 865-1931) on post-operative day 1 and decayed to 26 ng/L (IQR: 18-56) at approximately 90-days. The Spearman correlation between %ddcfDNA and hs-cTnT was ρ=0.52 (p<0.001). After 28 days, AR occurred in in 22% of patients (26 ACR and 17 AMR episodes). From day 28 on, %ddcfDNA and hs-cTnT detected AR with an area under the curve (AUC) of 0.88 (95%CI:0.84-0.92) and 0.74 (95%CI:0.63-0.84), respectively. When both biomarkers were combined, the AUC improved to 0.91 (95% CI:0.86-0.96, Figure). Conclusions: %ddcfDNA and hs-cTnT correlate moderately after heart transplant. Performance of hs-cTnT at diagnosing AR was inferior to %dd-cfDNA. When both biomarkers were combined, the overall diagnostic performance improved beyond that provided by %ddcfDNA alone.