Increase in nuclear cell-free DNA is associated with major adverse events in adult and pediatric heart transplant recipients. Clin Transplant 2022 Jan;36(1):e14509
Date
10/15/2021Pubmed ID
34649304DOI
10.1111/ctr.14509Scopus ID
2-s2.0-85120575732 (requires institutional sign-in at Scopus site) 2 CitationsAbstract
BACKGROUND: Cell-free DNA is an emerging biomarker. While donor fraction may detect graft events in heart transplant recipients, the prognostic value of total nuclear cell-free DNA (ncfDNA) itself is largely unexplored.
OBJECTIVE: Explore the relationship between ncfDNA and clinical events in heart transplant recipients.
METHODS: We conducted a multi-center prospective study to investigate the value of cell-free DNA in non-invasive monitoring following heart transplantation. Over 4000 blood samples were collected from 388 heart transplant patients. Total ncfDNA and donor fraction were quantified. Generalized linear models with maximum likelihood estimation for repeated measures with subjects as clusters were used to explore the relationship of ncfDNA and major adverse events. Receiver operating characteristic curves were used to help choose cutpoints.
RESULTS: A ncfDNA threshold (50 ng/ml) was identified that was associated with increased risk of major adverse events. NcfDNA was elevated in patients who suffered cardiac arrest, required mechanical circulatory support or died post heart transplantation as well as in patients undergoing treatment for infection.
CONCLUSIONS: Elevated ncfDNA correlates with risk for major adverse events in adult and pediatric heart transplant recipients and may indicate a need for enhanced surveillance after transplant.
Author List
Zangwill SD, Deshpande SR, Simpson PM, Liang HL, Zhang L, Dasgupta M, Richmond ME, Kindel SJ, Bichell DP, Mahle WT, Wigger MA, Schroder JN, Knecht KR, Pahl E, Gaglianello NA, North PE, Tomita-Mitchell A, Mitchell MEAuthors
Nunzio A. Gaglianello MD Associate Professor in the Medicine department at Medical College of WisconsinSteven J. Kindel MD Associate Professor 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
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
AdultCell-Free Nucleic Acids
Child
Graft Rejection
Heart Transplantation
Humans
Prospective Studies
Tissue Donors
Transplant Recipients
