Circular RNAs to predict clinical outcome after cardiac arrest

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 prognosticatio...

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Main Authors: Francesca M. Stefanizzi, Lu Zhang, Antonio Salgado-Somoza, Josef Dankiewicz, Pascal Stammet, Christian Hassager, Matthew P. Wise, Hans Friberg, Tobias Cronberg, Alexander Hundt, Jesper Kjaergaard, Niklas Nielsen, Yvan Devaux
Format: Article
Language:English
Published: SpringerOpen 2022-10-01
Series:Intensive Care Medicine Experimental
Subjects:
Online Access:https://doi.org/10.1186/s40635-022-00470-7
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author Francesca M. Stefanizzi
Lu Zhang
Antonio Salgado-Somoza
Josef Dankiewicz
Pascal Stammet
Christian Hassager
Matthew P. Wise
Hans Friberg
Tobias Cronberg
Alexander Hundt
Jesper Kjaergaard
Niklas Nielsen
Yvan Devaux
author_facet Francesca M. Stefanizzi
Lu Zhang
Antonio Salgado-Somoza
Josef Dankiewicz
Pascal Stammet
Christian Hassager
Matthew P. Wise
Hans Friberg
Tobias Cronberg
Alexander Hundt
Jesper Kjaergaard
Niklas Nielsen
Yvan Devaux
author_sort Francesca M. Stefanizzi
collection DOAJ
description 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.
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spelling doaj.art-fafdce2fe5a9417bbd724aee143cda2a2022-12-22T03:22:25ZengSpringerOpenIntensive Care Medicine Experimental2197-425X2022-10-0110111510.1186/s40635-022-00470-7Circular RNAs to predict clinical outcome after cardiac arrestFrancesca M. Stefanizzi0Lu Zhang1Antonio Salgado-Somoza2Josef Dankiewicz3Pascal Stammet4Christian Hassager5Matthew P. Wise6Hans Friberg7Tobias Cronberg8Alexander Hundt9Jesper Kjaergaard10Niklas Nielsen11Yvan Devaux12Cardiovascular Research Unit, Department of Population Health, Luxembourg Institute of HealthCardiovascular Research Unit, Department of Population Health, Luxembourg Institute of HealthCardiovascular Research Unit, Department of Population Health, Luxembourg Institute of HealthDepartment of Cardiology, Clinical Sciences, Lund University and Skane University HospitalDepartment of Intensive Care Medicine, Centre Hospitalier de LuxembourgDepartment of Cardiology B, The Heart Centre, Rigshospitalet University HospitalDepartment of Intensive Care, University Hospital of WalesDepartment of Anesthesia and Intensive Care, Clinical Sciences, Lund University and Skane University HospitalDepartment of Neurology and Rehabilitation Medicine, Clinical Sciences, Lund University and Skane University HospitalIntegrated BioBank of Luxembourg, Luxembourg Institute of HealthDepartment of Cardiology B, The Heart Centre, Rigshospitalet University HospitalDepartment of Anesthesia and Intensive Care, Clinical Sciences, Lund University and Helsingborg HospitalCardiovascular Research Unit, Department of Population Health, Luxembourg Institute of HealthAbstract 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.https://doi.org/10.1186/s40635-022-00470-7Out-of-hospital cardiac arrestBiomarkersPrognosticationCircular RNAs
spellingShingle Francesca M. Stefanizzi
Lu Zhang
Antonio Salgado-Somoza
Josef Dankiewicz
Pascal Stammet
Christian Hassager
Matthew P. Wise
Hans Friberg
Tobias Cronberg
Alexander Hundt
Jesper Kjaergaard
Niklas Nielsen
Yvan Devaux
Circular RNAs to predict clinical outcome after cardiac arrest
Intensive Care Medicine Experimental
Out-of-hospital cardiac arrest
Biomarkers
Prognostication
Circular RNAs
title Circular RNAs to predict clinical outcome after cardiac arrest
title_full Circular RNAs to predict clinical outcome after cardiac arrest
title_fullStr Circular RNAs to predict clinical outcome after cardiac arrest
title_full_unstemmed Circular RNAs to predict clinical outcome after cardiac arrest
title_short Circular RNAs to predict clinical outcome after cardiac arrest
title_sort circular rnas to predict clinical outcome after cardiac arrest
topic Out-of-hospital cardiac arrest
Biomarkers
Prognostication
Circular RNAs
url https://doi.org/10.1186/s40635-022-00470-7
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