A modern heart transplant rejection surveillance protocol utilizing cell-free DNA: A single-center experience

Abstract

INTRODUCTIONEndomyocardial biopsy (EMBx) is considered the gold standard for rejection monitoring after heart transplantation; however, it is invasive and histologic interpretation has limitations. Sensitive blood biomarkers including donor-derived cell-free DNA (dd-cfDNA) have emerged to decrease EMBx frequency. METHODSWe retrospectively reviewed data on 237 patients who underwent heart transplantation at our institution. Of these, 125 patients underwent monitoring using dd-cfDNA, combined with a fewer number of EMBx, and 112 patients underwent monitoring using EMBx only. We compared rates of rejection, graft dysfunction, and survival at 1 year. RESULTSMedian age at time of transplant was 59.8 years, and 77.6% were men. In the dd-cfDNA group, there were significantly fewer episodes of EMBx defined ACR (2.5% vs. 18.8%, P<0.001) and treated ACR (4.2% vs. 19.6%, P=0.001). Comparatively, there were more EMBx defined AMR (5% vs. 0.9%) and treated AMR (5% vs. 2.7%) in the dd-cfDNA group. No significant differences were observed in graft dysfunction, presence of donor-specific antibodies, or survival at 1 year. CONCLUSIONSIn conclusion, a modern rejection surveillance protocol utilizing non-invasive testing is safe, led to significantly fewer EMBx, fewer treated rejection episodes, and no difference in survival at 1 year. More AMR episodes identified via dd-cfDNA could lead the way for more accurate diagnostic and treatment decisions.