MircoRNA-9-3p: a novel predictor of neurological outcome after cardiac arrest

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Background Resuscitated out-of-hospital cardiac arrest (OHCA) patients who remain comatose after hospital arrival are at high risk of mortality due to anoxic brain injury. Markers of neurological outcome and consequently, neuroprotective targets are of great interest, and novel approaches are warranted. MicroRNA are small non-coding RNA molecules, ultimately involved in gene-silencing. They show promise as biomarkers, as they are stable in body fluids. The microRNA 9-3p (miR-9-3p) is associated to neurological injury in trauma and subarachnoid hemorrhage. Hypothesis: MiR-9-3p changes following OHCA and is associated with neurological outcome. Methods This post hoc analysis included 171 comatose patients included at a single center in the target temperature management (TTM) trial. Patients were randomized to TTM at either 33◦C or 36◦C for 24 h. MicroRNA-9-3p (miR-9-3p) was measured in plasma sampled at admission and at 28, 48 and 72 h. Results miR-9-3p levels changed markedly following OHCA with a peak at 48h. There were no significant differences in median miR-9-3p levels between TTM 33◦C vs. 36◦C at any of the four time points. Elevated miR-9-3p levels were strongly associated with a poor neurological outcome (see figure, p<0.0001). There were no significant differences in age, gender, comorbidities, and pre-hospital data, including lactate level at admission, between miR-9-3p level quartiles. Creatinine and C-reactive protein were not correlated with miR-9-3p levels at 48 h. Conclusion MiR-9-3p is strongly associated with the neurological outcome following OHCA, and the levels are highest 48 hours following cardiac arrest. MicroRNAs, including miR-9-3p, may be involved in upstream regulatory processes and its potential as a therapeutic target should be investigated