Cell-free DNA as a potential biomarker for acute myocardial infarction: A systematic review and meta-analysis

BACKGROUND: Tissue necrosis releases cell-free deoxyribonucleic acid (cfDNA), leading to rapid increases in plasma concentration with clearance independent of kidney function. AIM: To explore the diagnostic role of cfDNA in acute myocardial infarction (AMI). METHODS: This systematic review and meta-analysis included studies of cfDNA in patients with AMI and a comparator group without AMI. The quality assessment of diagnostic accuracy studies-2 (QUADAS-2) tool was used, with AMI determined from the criteria of the original study. Standardised mean differences (SMD) were obtained using a random-effects inverse variance model. Heterogeneity was reported as I(2). Pooled sensitivity and specificity were computed using a bivariate model. The area under the curve (AUC) was estimated from a hierarchical summary receiver operating characteristics curve. RESULTS: Seventeen studies were identified involving 1804 patients (n = 819 in the AMI group, n = 985 in the comparator group). Circulating cfDNA concentrations were greater in the AMI group (SMD 3.47 (95%CI: 2.54–4.41, p < 0.001)). The studies were of variable methodological quality with substantial heterogeneity (I(2) = 98%, p < 0.001), possibly due to the differences in cfDNA quantification methodologies (Chi(2) 25.16, p < 0.001, I(2) = 92%). Diagnostic accuracy was determined using six studies (n = 804), which yielded a sensitivity of 87% (95%CI: 72%-95%) and specificity of 96% (95%CI: 92%-98%). The AUC was 0.96 (95%CI: 0.93–0.98). Two studies reported a relationship between peak cfDNA and peak troponin. No studies reported data for patients with pre-existing kidney impairment. CONCLUSION: Plasma cfDNA appears to be a reliable biomarker of myocardial injury. Inferences from existing results are limited owing to methodology heterogeneity.