Abstract 13079: An Increase in Circulating Cardiomyocyte-specific Cell-free DNA in Heart Failure

Abstract

Introduction: Cardiomyocyte cell death is closely linked with the pathophysiology of heart failure. Cell-free DNA (cfDNA) is found in circulating blood as fragmented double-strand DNA, which is released from dying cells. However, the clinical significance of cfDNA in heart failure has not been elucidated. Methods and Results: The present study enrolled 32 heart failure patients and 28 control subjects. Circulating cfDNA was isolated from plasma samples in peripheral blood. The levels of total cfDNA assessed by quantitative PCR using LINE1-specific primers were not different between the two groups (P=0.343). Next, cfDNA was subjected to bisulfite conversion to identify cardiomyocyte-derived cfDNA, based on that FAM101A locus is unmethylated in a cardiac-specific manner. Digital PCR targeting the unmethylated FAM101A locus demonstrated that the copy numbers of cardiomyocyte-specific cfDNA were significantly elevated in heart failure patients compared to controls (0.99 [0.77 - 1.98] vs 0 [0 - 0.91] copies/mL, P=0.003, Figure A ). The receiver operating characteristic curve revealed that cardiomyocyte-specific cfDNA significantly discriminated heart failure patients from control subjects (AUC, 0.716, P=0.003). Correlation analysis showed that the levels of cardiomyocyte-specific cfDNA were significantly correlated with serum levels of high-sensitivity cardiac troponin I (r = 0.438, P = 0.012, Figure B ), but not with BNP (r = 0.275, P = 0.058), suggesting that the elevated cardiomyocyte-specific cfDNA might be associated with enhanced cardiomyocyte death but not with high ventricular filling pressure. Conclusions: A newly developed bisulfite-digital PCR system identified an increase in cardiomyocyte-specific cfDNA in heart failure patients. cfDNA may be a novel biomarker to measure the actual numbers of cardiomyocyte death in heart failure.