Total Cell-Free DNA Predicts Death and Infection Following Pediatric and Adult Heart Transplantation.

BACKGROUND Elevated total cell-free DNA (TCF) has been associated with critical illness in adults while elevated donor fraction (DF), the ratio of donor specific cell-free DNA to TCF present in the recipient's plasma, is associated with rejection following cardiac transplantation. This study investigates relationships between TCF and clinical outcomes following heart transplantation. METHODS A prospective, blinded, observational study of 87 heart transplantation recipients was performed. Samples were collected at transplantation, prior to endomyocardial biopsy, during treatment for rejection, and hospital readmissions. Longitudinal clinical data was collected and entered into a RedCAP Database. TCF and DF levels were correlated with endomyocardial biopsy and angiography results, as well as clinical outcomes. Logistic regression for modeling and repeated measures analysis using generalized linear modeling was used. The standard receiver operating characteristic curve, hazard and odds ratios were calculated. RESULTS There were 257 samples from 87 recipients analyzed. TCF levels greater than 50 ng/ml were associated with increased mortality (p = 0.01, AUC of 0.93, sensitivity of 0.44, specificity of 0.97) and treatment for infection (p < 0.005, AUC of 0.68, sensitivity of 0.45, specificity of 0.96). Increased DF was not correlated with treatment for infection. DF was associated with rejection and cardiac allograft vasculopathy (p < 0.0001), but TCF was not. CONCLUSIONS TCF elevation predicted death and treatment for infection. DF elevation predicted histopathologic acute rejection and cardiac allograft vasculopathy. Surveillance of TCF and DF levels may inform treatment following heart transplantation.