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PLoS One. 2016 Jun 22;11(6):e0157550. doi: 10.1371/journal.pone.0157550. eCollection 2016.

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

Author information

1
Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.
2
Thrombosis and Atherosclerosis Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.
3
Department of Medical Sciences, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4K1, Canada.
4
Division of Internal Medicine, Department of Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.
5
Cardiovascular Research Institute Basel, University Hospital Basel, Spitalstrasse 2, 4031, Basel, Switzerland.
6
Cardiology Division, Department of Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.
7
Division of Cardiology, Hamilton General Hospital, Hamilton Health Sciences, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.
8
Cardiology Division, Kantonsspital Bruderholz, 4101, Bruderholz, Switzerland.
9
Department of Pathology and Molecular Medicine, McMaster University, Michael G. DeGroote School of Medicine, 1280 Main Street West, Hamilton, ON, L8S 4K1, Canada.

Abstract

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.

PMID:
27332823
PMCID:
PMC4917233
DOI:
10.1371/journal.pone.0157550
[Indexed for MEDLINE]
Free PMC Article

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