AbstractBackgroundCardiogenic shock (CS) is a severe myocardial dysfunction secondary to various cardiac conditions including ST‐segment elevation acute myocardial infarction (STEMI) and associated with a high risk of death. Little is known on epigenetic determinants in CS. Here, we investigated plasma miRNAs in relation to CS stratification in STEMI‐patients.MethodsSTEMI‐patients (n = 49), with (CS, n = 25) and without CS (non‐CS, n = 24) fulfilling inclusion criteria were included from HSCSP‐cohort (Derivation‐cohort). CS‐miRNAs were analysed by Affymetrix‐microarray and RT‐PCR. Results were validated in a second cohort of CS‐patients (CardShock: n = 35) with similar inclusion/exclusion criteria as the derivation cohort. In silico analysis were performed to identify potential miRNA target genes.ResultsOf the 5‐miRNA signature obtained from microarray analysis, miR‐619‐5p showed higher levels in CS than in Non‐CS patients (p = .003) and discriminating power for CS by ROC (AUC: .752, p = .003). miR‐619‐5p directly associated with risk scores [GRACE, p = .001; CardShock, p < .001]. Furthermore, miR‐619‐5p showed discrimination power for death in CS. Thus, miRNA levels were significantly higher in patients with mortality outcome both in the Derivation HSCSP‐cohort (p = .02; AUC: .78 ± .095) and the Validation CardShock‐cohort (p = .017; AUC: .737 ± .086) By in silico analysis, miR‐619‐5p target genes and TNF‐alpha were involved in the regulation of inflammation. miR‐619‐5p and TNF‐alpha levels discriminated mortality outcome in CS‐patients during 30‐day follow‐up (Validation‐Cohort: ROC: .812, p = .002; HR: 9.99, p = .003).ConclusionsUp‐regulation of miR‐619‐5p is found in the plasma of STEMI‐patients with CS and mortality outcome. These findings highlight the specificity of epigenetic regulation of inflammation on the disease severity of MI.