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Zangwill SD, Deshpande SR, Simpson PM, et al. Increase in nuclear cell-free DNA is associated with major adverse events in adult and pediatric heart transplant recipients. Clin Transplant. 2021;36(1):e14509doi: 10.1111/ctr.14509.
Zangwill, S. D., Deshpande, S. R., Simpson, P. M., Liang, H. L., Zhang, L., Dasgupta, M., Richmond, M. E., Kindel, S. J., Bichell, D. P., Mahle, W. T., Wigger, M. A., Schroder, J. N., Knecht, K. R., Pahl, E., Gaglianello, N. A., North, P. E., Tomita-Mitchell, A., & Mitchell, M. E. (2022). Increase in nuclear cell-free DNA is associated with major adverse events in adult and pediatric heart transplant recipients. Clinical transplantation, 36(1), e14509. https://doi.org/10.1111/ctr.14509
Zangwill, Steven D, et al. "Increase in nuclear cell-free DNA is associated with major adverse events in adult and pediatric heart transplant recipients." Clinical transplantation vol. 36,1 (2022): e14509. doi: https://doi.org/10.1111/ctr.14509
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 ME. 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. doi: 10.1111/ctr.14509. Epub 2021 Nov 24. PMID: 34649304.
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Clin Transplant. 2022 Jan;36(1):e14509. doi: 10.1111/ctr.14509. Epub 2021 Nov 24.

Increase in nuclear cell-free DNA is associated with major adverse events in adult and pediatric heart transplant recipients.

Clinical transplantation

Steven D Zangwill, Shriprasad R Deshpande, Pippa M Simpson, Huan Ling Liang, Liyun Zhang, Mahua Dasgupta, Marc E Richmond, Steven J Kindel, David P Bichell, William T Mahle, Mark A Wigger, Jacob N Schroder, Kenneth R Knecht, Elfriede Pahl, Nunzio A Gaglianello, Paula E North, Aoy Tomita-Mitchell, Michael E Mitchell

Affiliations

  1. Division of Cardiology, Phoenix Children's Hospital, Phoenix, Arizona, USA.
  2. Division of Cardiology and Division of Cardiac Intensive Care, Children's National Hospital, Washington, District of Columbia, USA.
  3. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
  4. Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
  5. Department of Pediatrics, Division of Pediatric Cardiology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
  6. Division of Pediatric Cardiology, Department of Pediatrics, Medical College of Wisconsin, Herma Heart Institute, Children's Wisconsin, Milwaukee, Wisconsin, USA.
  7. Division of Pediatric Cardiac Surgery, Department of Surgery, Vanderbilt University, Nashville, Tennessee, USA.
  8. Division of Cardiology, Department of Pediatrics, Emory University, Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
  9. Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
  10. Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University, Durham, North Carolina, USA.
  11. Department of Pediatrics, Arkansas Children's Hospital, Little Rock, Arkansas, USA.
  12. Professor Emeritus Pediatrics, Cardiology, Lurie Children's Hospital, Chicago, Illinois, USA.
  13. Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
  14. Department of Pathology, Medical College of Wisconsin, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, USA.
  15. Division of Pediatric Cardiothoracic Surgery, Department of Surgery, Medical College of Wisconsin, Herma Heart Institute, Milwaukee, Wisconsin, USA.
  16. Division of Pediatric Cardiothoracic Surgery, Department of Surgery, Medical College of Wisconsin, Herma Heart Institute, Children's Wisconsin, Milwaukee, Wisconsin, USA.

PMID: 34649304 DOI: 10.1111/ctr.14509

Abstract

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.

© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Keywords: biomarkers; cell-free DNA; heart transplantation; non-invasive surveillance; rejection

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