title: Whole Blood Gene Expression Differentiates between Atrial Fibrillation and Sinus Rhythm after Cardioversion.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.|Thrombosis and Atherosclerosis Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.|Department of Medical Sciences, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4K1, Canada.
authors.forename: Kripa
authors.initials: K
authors.lastname: Raman
authors.affiliation: Division of Internal Medicine, Department of Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.|Cardiovascular Research Institute Basel, University Hospital Basel, Spitalstrasse 2, 4031, Basel, Switzerland.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Aeschbacher
authors.affiliation: Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.|Cardiovascular Research Institute Basel, University Hospital Basel, Spitalstrasse 2, 4031, Basel, Switzerland.|Cardiology Division, Department of Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.|Division of Cardiology, Hamilton General Hospital, Hamilton Health Sciences, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.
authors.forename: Matthias
authors.initials: M
authors.lastname: Bossard
authors.affiliation: Division of Internal Medicine, Department of Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.|Cardiovascular Research Institute Basel, University Hospital Basel, Spitalstrasse 2, 4031, Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hochgruber
authors.affiliation: Division of Internal Medicine, Department of Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.|Cardiovascular Research Institute Basel, University Hospital Basel, Spitalstrasse 2, 4031, Basel, Switzerland.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Zimmermann
authors.affiliation: Cardiology Division, Department of Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.
authors.forename: Beat A
authors.initials: BA
authors.lastname: Kaufmann
authors.affiliation: Cardiovascular Research Institute Basel, University Hospital Basel, Spitalstrasse 2, 4031, Basel, Switzerland.
authors.forename: Katrin
authors.initials: K
authors.lastname: Pumpol
authors.affiliation: Cardiology Division, Department of Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.|Cardiology Division, Kantonsspital Bruderholz, 4101, Bruderholz, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Rickenbacker
authors.affiliation: Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.|Thrombosis and Atherosclerosis Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.|Department of Pathology and Molecular Medicine, McMaster University, Michael G. DeGroote School of Medicine, 1280 Main Street West, Hamilton, ON, L8S 4K1, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Paré
authors.affiliation: Division of Internal Medicine, Department of Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.|Cardiovascular Research Institute Basel, University Hospital Basel, Spitalstrasse 2, 4031, Basel, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Conen
mesh_terms: D000368:Aged; D001146:Arrhythmia, Sinus / Q000097:blood* / Q000235:genetics*; D001281:Atrial Fibrillation / Q000097:blood* / Q000235:genetics* / Q000628:therapy; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D015331:Cohort Studies; D003710:Demography; D003937:Diagnosis, Differential; D004554:Electric Countershock; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000097:blood; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers; D026901:Membrane Transport Proteins; C000631432:PDK4 protein, human; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D020097:Natriuretic Peptide, Brain; C120109:SLC25A20 protein, human; D017346:Protein Serine-Threonine Kinases