Timing matters: Detection of clonal hematopoiesis and its association with adverse outcomes in heart transplant recipients.

Clonal hematopoiesis (CH) promotes inflammation and is associated with the development of cardiovascular disease. Previous studies assessing CH mutations in orthotopic heart transplant (OHT) recipients have revealed inconsistent findings, likely due to small sample size and differing sample collection time. In this study, we investigated the association between CH and post-transplant outcomes with a more consistent sample collection window. This retrospective study included 209 patients who underwent OHT between 2015 and 2022. Targeted sequencing detected CH mutations from samples obtained within a window of six months before or after transplantation. Clinical data were collected from the electronic medical record. Patients undergoing OHT had a median age of 53 years, and 27% were female. CH-associated mutations with a variant allele frequency (VAF) greater than 2% were detected in 29 patients (13.9%). The commonly mutated genes included DNMT3A, TET2, and ASXL1. CH mutations were associated with an increased risk of antibody-mediated rejection (AMR) (HR 2.42, 95% CI 1.07-5.47, p=0.033), but without detected differences in mortality or cardiac allograft vasculopathy (CAV). CH mutations detected at the time of transplant were associated with clinically significant AMR. Sample analysis at the time of transplant provides the clearest association between CH mutations and outcomes in OHT.