AUTHOR=Jiménez-Blanco Bravo Marta , Pérez-Gómez Laura , Hernández-Pérez Francisco J. , Arellano-Serrano Carlos , Torres-Sanabria Mario , Gómez-Bueno Manuel , Oteo-Domínguez Juan F. , Mingo-Santos Susana , Segovia-Cubero Javier 

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

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.856600

DOI=10.3389/fcvm.2022.856600

ISSN=2297-055X

ABSTRACT=<sec><title>Background</title><p>Cardiac 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.</p></sec><sec><title>Methods</title><p>We prospectively measured dd-cfDNA levels in all patients undergoing routine coronary angiography &gt;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.</p></sec><sec><title>Results</title><p>We included 94 heart transplant recipients, a median of 10.9 years after transplant. Coronary angiogram revealed CAV<sub>0</sub>, CAV<sub>1</sub>, CAV<sub>2</sub>, and CAV<sub>3</sub> in 61, 19, 14, and 6% of patients, respectively. Comparison of dd-cfDNA levels in patients with CAV<sub>0</sub> and CAV<sub>1–2–3</sub> (primary end-point) did not show significant differences (0.92%, IQR 0.46–2.0 vs. 0.46%, IQR 0.075–1.5, <italic>p</italic> = 0.059), nor did the comparison between patients with stable CAV (no new coronary lesions since previous angiogram, <italic>n</italic> = 77) and progressive CAV (<italic>n</italic> = 17); dd-cfDNA values 0.735% (IQR 0.195–2.0) vs. 0.9% (IQR 0.12–1.8), <italic>p</italic> = 0.76. However, we found an association between NTproBNP levels and CAV degree (<italic>p</italic> = 0.017). Dd-cfDNA levels did not correlate with NTproBNP (ρ = −0.095).</p></sec><sec><title>Conclusion</title><p>In this study, dd-cfDNA did not perform as a useful biomarker to avoid surveillance coronary angiograms for CAV diagnosis.</p></sec><sec><title>Clinical Trial Notation</title><p>Potential Role of Donor-derived Cell Free DNA as a Biomarker in Cardiac Allograft Vasculopathy, NCT 04791852.</p></sec>