Cardiac arrest; Neurological outcome; Prognostic biomarker; Emergency Medicine; Critical Care and Intensive Care Medicine; Physiology (medical)
Abstract :
[en] [en] BACKGROUND: Cardiac arrest (CA) is a major cause of mortality and morbidity. Accurate prediction of neurological outcome and survival remains challenging. In this context, our study aimed to explore novel molecular biomarkers that could provide additional insights into the pathophysiology of brain injury after CA and potentially distinguish patients with no brain injury (CPC 1) from those with any degree of neurological damage from moderate injury up to death (CPC 2-5), and complement existing prognostic tools.
METHODS: Whole blood samples collected 48 h after return of spontaneous circulation were analyzed by RNA sequencing in a subgroup of 50 CA patients from the monocenter North Pole cohort, and by quantitative PCR in 233 patients from the same cohort as well as in 511 patients from the multicenter TTM trial. The association of gene expression changes with 6-month neurological outcome (assessed by the Cerebral Performance Category (CPC) score) and survival was studied.
RESULTS: In a discovery phase with a subset of 50 patients from the North Pole cohort (25 CPC 1 and 25 CPC 5), direct RNA sequencing identified the solute carrier family 2 member 1 (SLC2A1), a gene encoding a major glucose transporter at the blood-brain barrier (GLUT1), as significantly upregulated in CPC 5 patients (dead with severe neurological impairment) compared to survivors without neurological sequelae (CPC 1). This upregulation was confirmed by quantitative PCR and extended to the entire North Pole cohort (p < 0.001). SLC2A1 was an independent predictor of neurological sequelae or death in this cohort. In the TTM trial, SLC2A1 was also upregulated in patients with neurological sequelae or death (p < 0.001) and was an independent predictor of neurological sequelae or death, providing an incremental predictive value to a baseline clinical model (odds ratio = 2.06, 95% confidence interval 1.31-3.4, p = 2.82E-03, and likelihood ratio test p < 0.001).
CONCLUSION: Blood level of SLC2A1 is a tentative blood biomarker that may aid in neurological outcome prediction after CA and also provide new insights into post-CA injury mechanisms.
Disciplines :
Anesthesia & intensive care
Author, co-author :
Stopa, Victoria; Cardiovascular Research Unit, Department of Precision Health, Luxembourg Institute of Health, Strassen, Luxembourg
Sopic, Miron; Cardiovascular Research Unit, Department of Precision Health, Luxembourg Institute of Health, Strassen, Luxembourg ; Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
Zhang, Lu; Bioinformatics and AI Unit, Department of Medical Informatics, Luxembourg Institute of Health, Strassen, Luxembourg
Lumley, Andrew; Cardiovascular Research Unit, Department of Precision Health, Luxembourg Institute of Health, Strassen, Luxembourg
STAMMET, Pascal ; University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Health, Medicine and Life Sciences (DHML) > Medical Education ; Department of Anesthesia and Intensive Care Medicine, Centre Hospitalier de Luxembourg, Strassen, Luxembourg
Schrag, Claudia; Medizinische Intensivstation, Kantonsspital St. Gallen, St. Gallen, Switzerland
Smid, Ondrej; 2nd Department of Medicine, Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, U Nemocnice 2, 128 00, Prague 2, Czech Republic
Hassager, Christian; Department of Cardiology, Rigshospitalet and Dept of Clinical, Medicine, University of Copenhagen, Copenhagen, Denmark
Kjaergaard, Jesper; Department of Cardiology, Rigshospitalet and Dept of Clinical, Medicine, University of Copenhagen, Copenhagen, Denmark
Pellis, Tommaso; Departement of Emergency and Intensive Care, Azienda Sanitaria Friuli Occidentale, Via Montereale, 33170, Pordenone, Italy
Horn, Janneke; Dept of Intensive Care, Amsterdam UMC, Amsterdam, The Netherlands ; Amsterdam Neuroscience, University of Amsterdam, Amsterdam, The Netherlands
Kuiper, Michael; Department of Intensive Care, Frisius Medical Center, Leeuwarden, Netherlands
Hovdenes, Jan; Department of Anesthesia and Intensive Care, Oslo University Hospital, Rikshospitalet, Oslo, Norway
Rylander, Christian; Anaesthesiology and Intensive Care Medicine, Department of Surgical Sciences, Uppsala University and Uppsala University Hospital, 715 85, Uppsala, Sweden
Wise, Matt P; Adult Critical Care, University Hospital of Wales, Cardiff, UK
Nielsen, Niklas; Department of Clinical Sciences Lund, Anesthesia and Intensive Care, Helsingborg Hospital, Lund University, Svart‑brödragränden 3, 251 87, Helsingborg, Sweden
Devaux, Yvan ; Cardiovascular Research Unit, Department of Precision Health, Luxembourg Institute of Health, Strassen, Luxembourg. yvan.devaux@lih.lu
V.S. is funded by the Heart Foundation Daniel Wagner of Luxembourg (YMCA project). Y.D. is funded by the Ministry of Higher Education and Research of Luxembourg and the Heart Foundation Daniel Wagner.
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