Heart-specific DNA methylation analysis in plasma for the investigation of myocardial damage

BACKGROUND: Circulating cell-free DNA (cfDNA) can be released when myocardial damage occurs. METHODS: Here, we used the methylated CpG tandem amplification and sequencing (MCTA-seq) method for analyzing dynamic changes in heart-derived DNA in plasma samples from myocardial infarction (MI) patients. RESULTS: We identified six CGCGCGG loci showing heart-specific hypermethylation patterns. MCTA-seq deconvolution analysis combining these loci detected heart-released cfDNA in MI patients at hospital admission, and showed that the prominently elevated total cfDNA level after percutaneous coronary intervention (PCI) was derived from both the heart and white blood cells. Furthermore, for the top marker CORO6, we developed a digital droplet PCR (ddPCR) assay that clearly detected heart damage signals in cfDNA of MI patients at hospital admission. CONCLUSIONS: Our study provides insights into MI pathologies and developed a new ddPCR assay for detecting myocardial damage in clinical applications. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-022-03234-9.