MicroRNAs as neuro-prognostic biomarkers after cardiac arrest: a systematic review

Cardiac arrest (CA) remains a leading cause of global mortality, largely due to hypoxic-ischaemic brain injury sustained during periods of absent cardiac output. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and have demonstrated diagnostic and prognostic potential in neurological and cardiovascular disease. This review assessed the value of miRNAs for predicting 6-month neurological outcomes following CA and return of spontaneous circulation (ROSC). Following PRISMA guidelines, PubMed and Cochrane Library searches identified ten clinical studies, comprising four biomarker studies and six post-hoc biomarker analyses from a large randomized controlled trial (RCT). Data on miRNA expression, patient characteristics, predictive accuracy (area under the receiver operating characteristic curve, AUC), and associations with outcome were extracted. Eleven miRNAs were differentially expressed within 72 h of ROSC; only miR-124-3p (up-regulated at 6 h) was replicated across studies. Eight studies contributed fifteen AUC values ranging from 0.62 to 0.89. Strong predictors included miR-6511b-5p (6 h, AUC = 0.85), miR-191-5p (48 h, AUC = 0.89), and miR-124 (48 h, AUC = 0.89). Four studies report associations between altered miRNA expression and unfavourable neurological outcomes, whilst one identified miR-122-5p as a positive prognostic biomarker. To conclude, miRNAs demonstrate distinct expression profiles following CA and ROSC, with several showing clinically useful prediction accuracy for 6-month neurological outcomes. Larger, unbiased studies using standardized methodologies are required to validate these findings and clarify confounding factors. Despite the current evidence limitations, this data supports further investigation of circulating miRNAs as neuro-prognostic biomarkers after cardiac arrest.