MicroRNAs After Cardiac Arrest; Acute Expression and Predictive Ability for Neurological Outcomes

Background: Cardiac arrest (CA) results in significant mortality worldwide, largely due to the hypoxic-ischaemic brain injury sustained. MicroRNAs (miRNAs/miR), non-coding RNAs that regulate gene expression, have shown diagnostic potential in stroke and other neurological diseases. This work presents the expression and predictive value of blood miRNAs for 6-month neurological outcomes post-CA. Methods A comprehensive literature search of PubMed and the Cochrane Library identified clinical studies reporting blood miRNA expression post-CA and its association with 6-month neurological outcomes. MicroRNA expression, patient characteristics, and receiver operator characteristic Area Under Curve (ROC-AUC) values were extracted. MicroRNA expression was examined against neurological outcomes using the Cerebral Performance Score Category (favourable: CPC 1–2; unfavourable: CPC 3–5). Results Ten clinical studies (n = 2,414 patients) met inclusion criteria. Eleven miRNAs were differentially expressed within 72 hours of a return of spontaneous circulation (ROSC). ROC-AUC values for blood miRNAs ranged from 0.62–0.89 at various time points. Notably, an up-regulated miR-124-3p at 6hrs post-ROSC could predict unfavourable neurological outcomes with high accuracy (AUC = 0.84), while miR-191-5p was the most accurate predictor of neurological outcomes when taken at 48hrs post-ROSC (AUC = 0.89). Odds ratios and Hazard ratios were collated to establish the clinical value of changes in miRNA expression levels at various time points. 5 studies provided odds ratios and 1 study provided a hazard ratio. Discussion and Conclusion miRNAs have distinct and prognostically useful expression changes post-CA and ROSC. MiR-124-3p and miR-191-5p can relatively accurately predict 6-month neurological recovery within 72 hours of ROSC. Although blood miRNAs demonstrate potential as early molecular biomarkers of ischaemic brain damage, further work is required to account for existing pathologies that may also impact circulating miRNA expression. This work additionally emphasises the need for large scale pragmatic trials to establish the role of miRNAs in guiding clinical decision making within this group of patients.