Whole Blood Gene Expression Differentiates between Atrial Fibrillation and Sinus Rhythm after Cardioversion

Raman, K. and Aeschbacher, S. and Bossard, M. and Hochgruber, T. and Zimmermann, A. J. and Kaufmann, B. A. and Pumpol, K. and Rickenbacker, P. and Pare, G. and Conen, D.. (2016) Whole Blood Gene Expression Differentiates between Atrial Fibrillation and Sinus Rhythm after Cardioversion. PLoS One, 11 (6). e0157550.

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Official URL: https://edoc.unibas.ch/62150/

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BACKGROUND: Treatment to restore sinus rhythm among patients with atrial fibrillation (AF) has limited long-term success rates. Gene expression profiling may provide new insights into AF pathophysiology. OBJECTIVE: To identify biomarkers and improve our understanding of AF pathophysiology by comparing whole blood gene expression before and after electrical cardioversion (ECV). METHODS: In 46 patients with persistent AF that underwent ECV, whole blood samples were collected 1-2 hours before and 4 to 6 weeks after successful cardioversion. The paired samples were sent for microarray and plasma biomarker comparison. RESULTS: Of 13,942 genes tested, expression of SLC25A20 and PDK4 had the strongest associations with AF. Post-cardioversion, SLC25A20 and PDK4 expression decreased by 0.8 (CI 0.7-0.8, p = 2.0x10-6) and 0.7 (CI 0.6-0.8, p = 3.0x10-5) fold respectively. Median N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations decreased from 127.7 pg/mL to 44.9 pg/mL (p = 2.3x10-13) after cardioversion. AF discrimination models combining NT-proBNP and gene expression (NT-proBNP + SLC25A20 area under the curve = 0.88, NT-proBNP + PDK4 AUC = 0.86) had greater discriminative capacity as compared with NT-proBNP alone (AUC = 0.82). Moreover, a model including NT-proBNP, SLC25A20 and PDK4 significantly improved AF discrimination as compared with other models (AUC = 0.87, Net Reclassification Index <0.56, p>5.8x10-3). We validated the association between SLC25A20 and PDK4 with AF in an independent sample of 17 patients. CONCLUSION: This study demonstrates that SLC25A20, PDK4, and NT-proBNP have incremental utility as biomarkers discriminating AF from sinus rhythm. Elevated SLC25A20 and PDK4 expression during AF indicates an important role for energy metabolism in AF.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Cardiovascular Molecular Imaging (Kaufmann)
UniBasel Contributors:Kaufmann, Beat
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1932-6203 (Electronic) 1932-6203 (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:31 May 2020 17:22
Deposited On:31 May 2020 17:22

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