Lack of Usefulness of Donor-Derived Cell-Free DNA as a Biomarker for Cardiac Allograft Vasculopathy: A Prospective Study

BackgroundCardiac allograft vasculopathy (CAV) remains a major cause of morbidity and mortality among long-term heart transplant recipients. There is an unmet need for a non-invasive biomarker of CAV that could obviate the need to perform surveillance coronary angiograms in these patients. Our aim was to evaluate the performance of Donor-derived Cell Free DNA (dd-cfDNA) as a biomarker of CAV. MethodsWe prospectively measured dd-cfDNA levels in all patients undergoing routine coronary angiography >1 year after heart transplant at a single center. Endpoints included the association between dd-cfDNA levels and the presence CAV, according to several prespecified criteria. ResultsWe included 94 heart transplant recipients, a median of 10.9 years after transplant. Coronary angiogram revealed CAV(0), CAV(1), CAV(2), and CAV(3) in 61, 19, 14, and 6% of patients, respectively. Comparison of dd-cfDNA levels in patients with CAV(0) and CAV(1-2-3) (primary end-point) did not show significant differences (0.92%, IQR 0.46-2.0 vs. 0.46%, IQR 0.075-1.5, p = 0.059), nor did the comparison between patients with stable CAV (no new coronary lesions since previous angiogram, n = 77) and progressive CAV (n = 17); dd-cfDNA values 0.735% (IQR 0.195-2.0) vs. 0.9% (IQR 0.12-1.8), p = 0.76. However, we found an association between NTproBNP levels and CAV degree (p = 0.017). Dd-cfDNA levels did not correlate with NTproBNP (rho = -0.095). ConclusionIn this study, dd-cfDNA did not perform as a useful biomarker to avoid surveillance coronary angiograms for CAV diagnosis.