Biomarkers; Circular RNAs; Out-of-hospital cardiac arrest; Prognostication; Emergency Medicine; Critical Care and Intensive Care Medicine; Physiology (medical)
Abstract :
[en] [en] 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.
Disciplines :
Anesthesia & intensive care
Author, co-author :
Stefanizzi, Francesca M; Cardiovascular Research Unit, Department of Population Health, Luxembourg Institute of Health, 1A-B rue Edison, 1445, Strassen, Luxembourg
Zhang, Lu; Cardiovascular Research Unit, Department of Population Health, Luxembourg Institute of Health, 1A-B rue Edison, 1445, Strassen, Luxembourg
Salgado-Somoza, Antonio; Cardiovascular Research Unit, Department of Population Health, Luxembourg Institute of Health, 1A-B rue Edison, 1445, Strassen, Luxembourg
Dankiewicz, Josef; Department of Cardiology, Clinical Sciences, Lund University and Skane University Hospital, 221 85, Lund, Sweden
STAMMET, Pascal ; University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) > Medical Education ; Department of Intensive Care Medicine, Centre Hospitalier de Luxembourg, 1210, Luxembourg, Luxembourg
Hassager, Christian; Department of Cardiology B, The Heart Centre, Rigshospitalet University Hospital, 2100, Copenhagen, Denmark
Wise, Matthew P; Department of Intensive Care, University Hospital of Wales, Cardiff, CF14 4XW, UK
Friberg, Hans; Department of Anesthesia and Intensive Care, Clinical Sciences, Lund University and Skane University Hospital, 221 85, Malmö, Sweden
Cronberg, Tobias; Department of Neurology and Rehabilitation Medicine, Clinical Sciences, Lund University and Skane University Hospital, 221 85, Lund, Sweden
Hundt, Alexander; Integrated BioBank of Luxembourg, Luxembourg Institute of Health, Dudelange, Luxembourg
Kjaergaard, Jesper; Department of Cardiology B, The Heart Centre, Rigshospitalet University Hospital, 2100, Copenhagen, Denmark
Nielsen, Niklas; Department of Anesthesia and Intensive Care, Clinical Sciences, Lund University and Helsingborg Hospital, 25187, Lund, Sweden
DEVAUX, Yvan ; University of Luxembourg ; Cardiovascular Research Unit, Department of Population Health, Luxembourg Institute of Health, 1A-B rue Edison, 1445, Strassen, Luxembourg. yvan.devaux@lih.lu
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
Funding text :
This work is supported by independent research grants from nonprofit or governmental agencies (the Swedish Research Council [Vetenskapsrådet], Swedish Heart–Lung Foundation, Stig and Ragna Gorthon Foundation, Knutsson Foundation, Laerdal Foundation, Hans-Gabriel and Alice Trolle-Wachtmeister Foundation for Medical Research, and Regional Research Support in Region Skåne) and by governmental funding of clinical research within the Swedish National Health Service. YD is supported by the National Research Fund of Luxembourg (Grants # C14/BM/8225223 and C17/BM/11613033), the Ministry of Higher Education and Research of Luxembourg, and the Heart Foundation—Daniel Wagner. FMS is supported by the National Research Fund of Luxembourg (Grant # C17/BM/11613033).
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