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Total Cell-Free DNA Predicts Death and Infection Following Pediatric and Adult Heart Transplantation. Ann Thorac Surg 2021 Oct;112(4):1282-1289



Pubmed ID




Scopus ID

2-s2.0-85103701202 (requires institutional sign-in at Scopus site)   8 Citations


BACKGROUND: Elevated total cell-free DNA (TCF) concentration has been associated with critical illness in adults and elevated donor fraction (DF), the ratio of donor specific cell-free DNA to total cell-free DNA present in the recipient's plasma, is associated with rejection following cardiac transplantation. This study investigates relationships between TCF and clinical outcomes after 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 at hospital readmissions. Longitudinal clinical data were collected and entered into a RedCAP (Vanderbilt University) 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 ratios, and odds ratios were calculated.

RESULTS: There were 257 samples from 87 recipients analyzed. TCF greater than 50 ng/mL were associated with increased mortality (P = .01, area under the curve 0.93, sensitivity 0.44, specificity 0.97) and treatment for infection (P < .005, area under the curve 0.68, sensitivity 0.45, specificity 0.96). Increased DF was not correlated with treatment for infection. DF was associated with rejection and cardiac allograft vasculopathy (P < .001), 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 after heart transplantation.

Author List

Scott JP, Ragalie WS, Stamm KD, Mahnke DK, Liang HL, Simpson PM, Dasgupta M, Katz R, North PE, Tomita-Mitchell A, Zangwill SD, Kindel SJ, Mitchell ME


Steven J. Kindel MD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Donna K. Mahnke Research Scientist I in the Pediatrics department at Medical College of Wisconsin
Michael Edward Mitchell MD Chief, Professor in the Surgery department at Medical College of Wisconsin
Aoy Tomita Mitchell PhD Professor in the Surgery department at Medical College of Wisconsin
Paula E. North MD, PhD Professor in the Pathology department at Medical College of Wisconsin
John P. Scott MD Professor in the Anesthesiology department at Medical College of Wisconsin
Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cell-Free Nucleic Acids
Child, Preschool
Heart Transplantation
Postoperative Complications
Predictive Value of Tests
Prospective Studies
Single-Blind Method
Young Adult