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

Tissue necrosis releases cell-free deoxyribonucleic acid (cfDNA), leading to rapid increases in plasma concentration with clearance independent of kidney function. To explore the diagnostic role of cfDNA in acute myocardial infarction (AMI). 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 I2. 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. 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 (I2 = 98%, p < 0.001), possibly due to the differences in cfDNA quantification methodologies (Chi2 25.16, p < 0.001, I2 = 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. Plasma cfDNA appears to be a reliable biomarker of myocardial injury. Inferences from existing results are limited owing to methodology heterogeneity.