Novel cfDNA Methylation Biomarkers Reveal Delayed Cardiac Cell Death after Open-heart Surgery

Uri Pollak; Hai Zemmour; Elior Shaked; Judith Magenheim; Ori Fridlich; Amit Korach; Alain E. Serraf; David Mishaly; Benjamin Glaser; Ruth Shemer; Yuval Dor

doi:10.1007/s12265-022-10295-0

Novel cfDNA Methylation Biomarkers Reveal Delayed Cardiac Cell Death after Open-heart Surgery

Uri Pollak, Hai Zemmour, Elior Shaked, Judith Magenheim, Ori Fridlich, Amit Korach, Alain E. Serraf, David Mishaly, Benjamin Glaser, Ruth Shemer^*, Yuval Dor^*

^*Corresponding author for this work

Department of Developmental Biology and Cancer Research

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

The use of cardiopulmonary bypass (CPB) is thought to cause delayed cardiac damage. DNA methylation-based liquid biopsies are novel biomarkers for monitoring acute cardiac cell death. We assessed cell-free DNA molecules as markers for cardiac damage after open-heart surgery. Novel cardiomyocyte-specific DNA methylation markers were applied to measure cardiac cfDNA in the plasma of 42 infants who underwent open-heart surgery. Cardiac cfDNA was elevated following surgery, reflecting direct surgery-related tissue damage, and declined thereafter in most patients. The concentration of cardiac cfDNA post-surgery correlated with the duration of CPB and aortic cross clamping. Strikingly, cardiac cfDNA at 6 h predicted duration of mechanical ventilation and maximal vasoactive-inotropic score better than did maximal troponin levels. Cardiac cfDNA reveals heart damage associated with CPB, and can be used to monitor cardiac cell death, to predict clinical outcome of surgery and to assess performance of cardioprotective interventions. Graphical abstract: [Figure not available: see fulltext.]

Original language	American English
Pages (from-to)	199-208
Number of pages	10
Journal	Journal of Cardiovascular Translational Research
Volume	16
Issue number	1
DOIs	https://doi.org/10.1007/s12265-022-10295-0
State	Published - Feb 2023

Bibliographical note

Funding Information:
This work was supported by grants from the Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine, The Israel Science Foundation, the Waldholtz/Pakula family, the Robert M. and Marilyn Sternberg Family Charitable Foundation and the Helmsley Charitable Trust (to Y.D).

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Keywords

Cardiopulmonary bypass
Pediatric open-heart surgery
cell-free DNA
myocardial damage

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title = "Novel cfDNA Methylation Biomarkers Reveal Delayed Cardiac Cell Death after Open-heart Surgery",

abstract = "The use of cardiopulmonary bypass (CPB) is thought to cause delayed cardiac damage. DNA methylation-based liquid biopsies are novel biomarkers for monitoring acute cardiac cell death. We assessed cell-free DNA molecules as markers for cardiac damage after open-heart surgery. Novel cardiomyocyte-specific DNA methylation markers were applied to measure cardiac cfDNA in the plasma of 42 infants who underwent open-heart surgery. Cardiac cfDNA was elevated following surgery, reflecting direct surgery-related tissue damage, and declined thereafter in most patients. The concentration of cardiac cfDNA post-surgery correlated with the duration of CPB and aortic cross clamping. Strikingly, cardiac cfDNA at 6 h predicted duration of mechanical ventilation and maximal vasoactive-inotropic score better than did maximal troponin levels. Cardiac cfDNA reveals heart damage associated with CPB, and can be used to monitor cardiac cell death, to predict clinical outcome of surgery and to assess performance of cardioprotective interventions. Graphical abstract: [Figure not available: see fulltext.]",

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N2 - The use of cardiopulmonary bypass (CPB) is thought to cause delayed cardiac damage. DNA methylation-based liquid biopsies are novel biomarkers for monitoring acute cardiac cell death. We assessed cell-free DNA molecules as markers for cardiac damage after open-heart surgery. Novel cardiomyocyte-specific DNA methylation markers were applied to measure cardiac cfDNA in the plasma of 42 infants who underwent open-heart surgery. Cardiac cfDNA was elevated following surgery, reflecting direct surgery-related tissue damage, and declined thereafter in most patients. The concentration of cardiac cfDNA post-surgery correlated with the duration of CPB and aortic cross clamping. Strikingly, cardiac cfDNA at 6 h predicted duration of mechanical ventilation and maximal vasoactive-inotropic score better than did maximal troponin levels. Cardiac cfDNA reveals heart damage associated with CPB, and can be used to monitor cardiac cell death, to predict clinical outcome of surgery and to assess performance of cardioprotective interventions. Graphical abstract: [Figure not available: see fulltext.]

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Novel cfDNA Methylation Biomarkers Reveal Delayed Cardiac Cell Death after Open-heart Surgery

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