Early immune biomarkers and intermediate‐term outcomes after heart transplantation: Results of Clinical Trials in Organ Transplantation‐18

Clinical Trials in Organ Transplantation‐18 (CTOT‐18) is a follow‐up analysis of the 200‐subject multicenter heart transplant CTOT‐05 cohort. CTOT‐18 aimed to identify clinical, epidemiologic, and biologic markers associated with adverse clinical events past 1 year posttransplantation. We examined various candidate biomarkers including serum antibodies, angiogenic proteins, blood gene expression profiles, and T cell alloreactivity. The composite endpoint (CE) included death, retransplantation, coronary stent, myocardial infarction, and cardiac allograft vasculopathy. The mean follow‐up was 4.5 ± SD 1.1 years. Subjects with serum anti‐cardiac myosin (CM) antibody detected at transplantation and at 12 months had a higher risk of meeting the CE compared to those without anti‐CM antibody (hazard ratio [HR] = 2.9, P = .046). Plasma VEGF‐A and VEGF‐C levels pretransplant were associated with CE (odds ratio [OR] = 13.24, P = .029; and OR = 0.13, P = .037, respectively). Early intravascular ultrasound findings or other candidate biomarkers were not associated with the study outcomes. In conclusion, anti‐CM antibody and plasma levels of VEGF‐A and VEGF‐C were associated with an increased risk of adverse events. Although this multicenter report supports further evaluation of the mechanisms through which anti‐CM antibody and plasma angiogenesis proteins lead to allograft injury, we could not identify additional markers of adverse events or potential novel therapeutic targets.