Association of Donor Age and Plasma Donor-Derived Cell-Free DNA Levels with CAV Development after Heart Transplant: SHORE Preliminary Data

Abstract

<h3>Purpose</h3> Cardiac Allograft Vasculopathy (CAV) is a leading cause of long-term graft dysfunction and loss after HT. Elevated plasma donor-derived cell-free DNA (dd-cfDNA) levels may predict <i>de novo</i> HLA Class I &/or II elaboration after HT. We queried whether dd-cfDNA levels may reflect new or progressive CAV development in the observational <i>Surveillance HeartCare Outcomes Registry</i> (SHORE). <h3>Methods</h3> Over 1200 unique patients at 60 HT Centers across the United States were enrolled into surveillance by gene expression profiling (GEP; AlloMap®) and dd-cfDNA (AlloSure®) in concert with clinical, catheterization and pathologic data capture. Coronary assessments per angiography were classified as either "New" or "Progressive" while "Stable" or "None" comprised the comparison cohorts. We performed analysis by Cox Proportional Hazards Modeling and type III statistical testing with donor age and dd-cfDNA as covariates for development of CAV (p<0.05) <h3>Results</h3> We identified 195 unique HT recipients with dd-cfDNA data within the preceding 30-days of CAV assessment. There were 15 CAV events classified as either "New" or "Progressive" [TABLE]. Mean time from the last dd-cfDNA monitoring and CAV development was 6.07 days (9.95). Both dd-cfDNA (p=0.04) and donor-age (p=0.017) were significant covariates for CAV development. An association of donor-age (p=0.018) and a trend for dd-cfDNA plasma levels (p=0.079) with new onset / progressive CAV was demonstrated. <h3>Conclusion</h3> Preliminary data from SHORE demonstrated the correlation of donor-age and CAV, while elevated dd-cfDNA plasma levels trended towards the development of new onset or progressive CAV after HT. Further data development that encompasses longer-term follow-up and standard CAV methods of assessment, should provide value in refining the impact of CAV on dd-cfDNA.