cfDNA methylation detection as potential liquid biopsy of multiple organ injury in myocarditis patients

Myocarditis is inflammatory injury of the myocardium and causes approximately 30,000 deaths globally each year. Fulminant myocarditis is an extremely severe form of myocarditis. Currently, the clinical evaluation of myocarditis and fulminant myocarditis is primarily based on symptoms, ECG findings, and biochemical markers. Cardiac magnetic resonance and endomyocardial biopsy can provide further support for the diagnosis, but both have limitations in routine practice. Recent studies have shown that cell-free DNA (cfDNA) has distinct methylation patterns depending on the organ of origin, suggesting new possibilities for tracking specific types of organ damage. The core mechanism of fulminant myocarditis is a cytokine storm, leading to multiorgan damage, differing from clinically suspected myocarditis. We performed Genome-wide cfDNA methylation detection on plasma from 20 healthy donors and 22 patients (fulminant myocarditis: clinically suspected myocarditis = 9:13, COVID-19 positive: COVID-19 negative = 14:8) and found that cfDNA can be used to specifically identify early multiorgan damage caused by fulminant myocarditis, and its AUC is superior to traditional biochemical indicators such as troponin, high-sensitivity troponin, and lactate dehydrogenase. This is critically important for the timely clinical recognition and treatment of this condition. Furthermore, our study findings suggest that SARS-CoV-2 infection may exacerbate the severity of myocarditis and multiorgan damage. In summary, cfDNA shows great potential as a noninvasive, early, and sensitive biomarker for reflecting disease severity and systemic injury in fulminant myocarditis, which may help guide earlier risk stratification and intervention.