MicroRNA-9-3p: a novel predictor of neurological outcome after cardiac arrest
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Updated: Sep 8, 2025

Author Spotlight: A Unique Mouse Model of Asphyxia-Induced Cardiac Arrest
Published on: April 14, 2023
Rasmus Paulin Beske1, Søren Bache2,3, Martin Abild Stengaard Meyer1
1Department of Cardiology, The Heart Centre, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Aims:
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. 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 with neurological injury in trauma and subarachnoid haemorrhage.
Methods And Results:
This post hoc analysis considered all 171 comatose OHCA patients from a single centre 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. There were no significant differences in age, gender, and pre-hospital data, including lactate level at admission, between miR-9-3p level quartiles. miR-9-3p levels changed markedly following OHCA with a peak at 48 h. Median miR-9-3p levels between TTM 33°C vs. 36°C were not different at any of the four time points. Elevated miR-9-3p levels at 48 h were strongly associated with an unfavourable neurological outcome [OR: 2.21, 95% confidence interval (CI): 1.64-3.15, P < 0.0001). MiR-9-3p was inferior to neuron-specific enolase in predicting functional neurological outcome [area under the curve: 0.79 (95% CI: 0.71-0.87) vs. 0.91 (95% CI: 0.85-0.97)].
Conclusion:
MiR-9-3p is strongly associated with neurological outcome following OHCA, and the levels of miR-9-3p are peaking 48 hours following cardiac arrest.
Insights
MicroRNA-9-3p (miR-9-3p) shows promise as a biomarker for neurological injury in out-of-hospital cardiac arrest (OHCA) survivors. Elevated miR-9-3p levels at 48 hours post-arrest strongly correlate with poor neurological outcomes.
Area of Science:
- Biochemistry
- Neuroscience
- Cardiology
Background:
- Comatose out-of-hospital cardiac arrest (OHCA) survivors face high mortality risks from anoxic brain injury.
- MicroRNAs (miRNAs) are small, non-coding RNA molecules involved in gene silencing and show potential as stable biomarkers in bodily fluids.
- MicroRNA-9-3p (miR-9-3p) has been linked to neurological injury in trauma and subarachnoid hemorrhage.
Purpose of the Study:
- To investigate the association between miR-9-3p levels and neurological outcomes in comatose OHCA patients.
- To determine the temporal profile of miR-9-3p levels following OHCA.
- To compare the predictive value of miR-9-3p with neuron-specific enolase for neurological outcomes.
Main Methods:
- A post hoc analysis of 171 comatose OHCA patients from the target temperature management (TTM) trial.
- Patients were randomized to TTM at 33°C or 36°C.
- Plasma miR-9-3p levels were measured at admission, 28, 48, and 72 hours post-arrest.
Main Results:
- miR-9-3p levels peaked at 48 hours post-OHCA.
- No significant differences in miR-9-3p levels were observed between the 33°C and 36°C TTM groups.
- Elevated miR-9-3p levels at 48 hours were strongly associated with unfavorable neurological outcomes (OR: 2.21, P < 0.0001).
- miR-9-3p demonstrated a lower predictive accuracy for neurological outcome compared to neuron-specific enolase (AUC: 0.79 vs. 0.91).
Conclusions:
- miR-9-3p is significantly associated with neurological outcomes in OHCA survivors.
- miR-9-3p levels peak 48 hours after cardiac arrest.
- While miR-9-3p shows prognostic value, neuron-specific enolase appears to be a superior biomarker for predicting functional neurological outcome.
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