Non-invasive detection of human cardiomyocyte death using methylation patterns of circulating DNA

Nat Commun. 2018 Apr 24;9(1):1443. doi: 10.1038/s41467-018-03961-y.


Detection of cardiomyocyte death is crucial for the diagnosis and treatment of heart disease. Here we use comparative methylome analysis to identify genomic loci that are unmethylated specifically in cardiomyocytes, and develop these as biomarkers to quantify cardiomyocyte DNA in circulating cell-free DNA (cfDNA) derived from dying cells. Plasma of healthy individuals contains essentially no cardiomyocyte cfDNA, consistent with minimal cardiac turnover. Patients with acute ST-elevation myocardial infarction show a robust cardiac cfDNA signal that correlates with levels of troponin and creatine phosphokinase (CPK), including the expected elevation-decay dynamics following coronary angioplasty. Patients with sepsis have high cardiac cfDNA concentrations that strongly predict mortality, suggesting a major role of cardiomyocyte death in mortality from sepsis. A cfDNA biomarker for cardiomyocyte death may find utility in diagnosis and monitoring of cardiac pathologies and in the study of normal human cardiac physiology and development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Case-Control Studies
  • Cell Death / physiology
  • Cell-Free Nucleic Acids / blood*
  • Cell-Free Nucleic Acids / chemistry
  • Creatine Kinase / blood
  • DNA Methylation*
  • Heart Diseases / blood
  • Heart Diseases / diagnosis
  • Heart Diseases / pathology
  • Humans
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology*
  • Polymerase Chain Reaction / methods
  • Reference Values
  • ST Elevation Myocardial Infarction / blood
  • ST Elevation Myocardial Infarction / diagnosis
  • ST Elevation Myocardial Infarction / pathology
  • Troponin / blood


  • Biomarkers
  • Cell-Free Nucleic Acids
  • Troponin
  • Creatine Kinase