Circulating microRNAs after cardiac arrest

Objective: Prediction of clinical outcome after cardiac arrest is clinically important. While the potential of circulating microRNAs as biomarkers of acute coronary syndromes is an active field of investigation, it is unknown whether microRNAs are associated with outcome in cardiac arrest patients. Design: Prospective, single-center proof-of-concept study. Setting: Eighteen-bed adult general intensive care unit of an academic tertiary care hospital in Luxembourg. Patients: Twenty-eight patients with cardiac arrest treated by therapeutic hypothermia after cardiac resuscitation were enrolled. Measurements and Main Results: Blood samples were obtained at 48 hrs after cardiac arrest for the determination of microRNA levels and neuron-specific enolase. Neurological outcome was determined by the cerebral performance category at discharge from the intensive care unit and at 6-month follow-up. Analysis of microRNA arrays and quantitative assessment by polymerase chain reaction identified two microRNAs, miR-122 and miR-21, overexpressed in patients with poor neurological outcome (cerebral performance category 3-5, n = 14) compared to patients with favorable neurological outcome (cerebral performance category 1-2, n = 14) (48-fold and three-fold, respectively). In vitro experiments showed that both miR-122 and miR-21 are produced by neuronal cells, indicating that the elevation of circulating levels of these microRNAs after cardiac arrest may reflect brain damage. miR-122 and miR-21 predicted neurological outcome with areas under the receiver operating characteristic curve of 0.73 and 0.77, respectively. Patients within the highest third of miR-122 or miR-21 values had elevated mortality rate (p = .02). Neuron-specific enolase was an accurate predictor of neurological outcome (areas under the receiver operating characteristic curve = 0.98) and mortality (p < .001). MicroRNA levels were not associated with myocardial damage or activation of inflammation. Conclusions: As compared to neuron-specific enolase, circulating microRNAs are modest but significant predictors of neurological outcome and mortality in this small group of patients with cardiac arrest. This motivates assessing the prognostic value of microRNAs in larger cohorts of cardiac arrest patients. (Crit Care Med 2012; 40:3209-3214)