Blood N1-methyladenosine (m1A) RNA modification and outcome after cardiac arrest

Cardiac arrest (CA) is a leading cause of mortality and neurological disability. Prediction of post-CA outcomes is challenging. Epitranscriptomic (RNA) modifications are emerging as potential biomarkers due to their regulatory roles in RNA metabolism and disease progression. However, their relevance in CA remains unexplored. This study aimed to investigate the association between N1-methyladenosine (m¹A) RNA modification and outcome after CA. Total RNA was extracted from whole blood samples of 211 patients collected 48 h after return of spontaneous circulation (ROSC). M¹A and adenosine (A) blood levels were quantified using liquid chromatography coupled to mass spectrometry (LC-MS), and the ratio m¹A/A was calculated. Neurological outcome assessed using the cerebral performance category (CPC) score and survival at 6 months were used as end-points. Patients with moderate to severe neurological outcome or death within 6 months after CA (CPC 2–5) exhibited elevated m¹A/A ratio compared to survivors without neurological sequelae (CPC 1) (p = 0.03). In multivariable logistic regression, higher m1A/A levels were associated with an increased risk of moderate to severe neurological outcome or death at 6 months compared to survivors without neurological sequelae (odds ratio [95% confidence interval] 1.50 [1.04–2.19]), after adjustment for age, time between CA and return of spontaneous circulation, lactate and neuron-specific enolase levels. In Kaplan-Meier survival analysis, patients with elevated m¹A/A levels showed a lower probability of survival at 6 months (p = 0.003). This study provides the first evidence that m1A RNA methylation, reflected by the m1A/A ratio, is associated with neurological outcome and death at 6 months after CA. Although these findings require validation, they raise the possibility that m¹A RNA methylation could help to improve prognostication after CA.