The Levels of Circulating MicroRNAs at 6-Hour Cardiac Arrest Can Predict 6-Month Poor Neurological Outcome

Abstract

Early prognostication in cardiac arrest survivors is challenging for physicians. Unlike other prognostic modalities, biomarkers are easily accessible and provide an objective assessment method. We hypothesized that in cardiac arrest patients with targeted temperature management (TTM), early circulating microRNA (miRNA) levels are associated with the 6-month neurological outcome. In the discovery phase, we identified candidate miRNAs associated with cardiac arrest patients who underwent TTM by comparing circulating expression levels in patients and healthy controls. Next, using a larger cohort, we validated the prognostic values of the identified early miRNAs by measuring the serum levels of miRNAs, neuron-specific enolase (NSE), and S100 calcium-binding protein B (S100B) 6 h after cardiac arrest. The validation cohort consisted of 54 patients with TTM. The areas under the curve (AUCs) for poor outcome were 0.85 (95% CI (confidence interval), 0.72–0.93), 0.82 (95% CI, 0.70–0.91), 0.78 (95% CI, 0.64–0.88), and 0.77 (95% CI, 0.63–0.87) for miR-6511b-5p, -125b-1-3p, -122-5p, and -124-3p, respectively. When the cut-off was based on miRNA levels predicting poor outcome with 100% specificity, sensitivities were 67.7% (95% CI, 49.5–82.6), 50.0% (95% CI, 32.4–67.7), 35.3% (95% CI, 19.7–53.5), and 26.5% (95% CI, 12.9–44.4) for the above miRNAs, respectively. The models combining early miRNAs with protein biomarkers demonstrated superior prognostic performance to those of protein biomarkers.

Keywords

• heart arrest
• induced hypothermia
• prognostication
• biomarker
• microRNA