Circular RNAs to predict clinical outcome after cardiac arrest

Author:

Stefanizzi Francesca M.,Zhang Lu,Salgado-Somoza Antonio,Dankiewicz Josef,Stammet Pascal,Hassager Christian,Wise Matthew P.,Friberg Hans,Cronberg Tobias,Hundt Alexander,Kjaergaard Jesper,Nielsen Niklas,Devaux YvanORCID

Abstract

Abstract Background Cardiac arrest (CA) represents the third leading cause of death worldwide. Among patients resuscitated and admitted to hospital, death and severe neurological sequelae are frequent but difficult to predict. Blood biomarkers offer clinicians the potential to improve prognostication. Previous studies suggest that circulating non-coding RNAs constitute a reservoir of novel biomarkers. Therefore, this study aims to identify circulating circular RNAs (circRNAs) associated with clinical outcome after CA. Results Whole blood samples obtained 48 h after return of spontaneous circulation in 588 survivors from CA enrolled in the Target Temperature Management trial (TTM) were used in this study. Whole transcriptome RNA sequencing in 2 groups of 23 sex-matched patients identified 28 circRNAs associated with neurological outcome and survival. The circRNA circNFAT5 was selected for further analysis using quantitative PCR. In the TTM-trial (n = 542), circNFAT5 was upregulated in patients with poor outcome as compared to patients with good neurological outcome (p < 0.001). This increase was independent of TTM regimen and sex. The adjusted odds ratio of circNFAT5 to predict neurological outcome was 1.39 [1.07–1.83] (OR [95% confidence interval]). CircNFAT5 predicted 6-month survival with an adjusted hazard ratio of 1.31 [1.13–1.52]. Conclusion We identified circulating circRNAs associated with clinical outcome after CA, among which circNFAT5 may have potential to aid in predicting neurological outcome and survival when used in combination with established biomarkers of CA.

Funder

Vetenskapsrådet

Hjärt-Lungfonden

Stig and Ragna Gorthon Foundation

Knutsson Foundation

Laerdal Foundation for Acute Medicine

Hans-Gabriel och Alice Trolle-Wachtmeisters stiftelse för medicinsk forskning

Regional Research Support in Region Skane

Governmental funding of clinical research within the Swedish National Health Service

Fonds National de la Recherche Luxembourg

Ministère de l'Enseignement Supérieur et de la Recherche

Heart Foundation Daniel Wagner

Publisher

Springer Science and Business Media LLC

Subject

Critical Care and Intensive Care Medicine

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