title: Association of post-cardioversion transcardiac concentration gradient of soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) and inflammatory biomarkers to atrial fibrillation recurrence.
abstract: OBJECTIVE
  Soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) has been shown to have both pro- and anti-apoptotic activities and is associated to better prognosis in heart failure. The aim of this study was to determine the transcardiac concentration gradient of sTRAIL and inflammatory biomarkers after AF cardioversion and assess their relation to AF recurrence.
  
  
  METHODS
  We measured transcardiac gradients (coronary sinus concentration minus aortic root concentration) of sTRAIL, C-reactive protein (hsCRP) and interleukin-6 (IL-6) in patients with non-valvular AF after electrical cardioversion. Six-month AF recurrence was the study endpoint.
  
  
  RESULTS
  There were no differences in sTRAIL and hsCRP concentrations in peripheral venous blood between patients with and without AF recurrence (p=0.066 and 0.149, respectively), while IL-6 was higher in patients with recurrence (p=0.032). Only sTRAIL showed a significant transcardiac gradient [3 pg/mL (IQR 1-4 pg/mL); p=0.01]. sTRAIL gradient was 4 pg/mL (IQR 3-5 pg/mL) in patients without recurrence versus -1 pg/mL (IQR -2-1 pg/mL) in those with recurrence (p<0.001). IL-6 (p=0.281) and hsCRP (p=0.979) aortic concentrations were not significantly different from coronary sinus concentrations. In multivariate analysis, sTRAIL transcardiac gradient (beta -0.81, p=0.004) remained a negative predictor of AF recurrence.
  
  
  CONCLUSIONS
  This study demonstrates the existence of a significant transcardiac sTRAIL concentration gradient in patients with non-valvular AF, inversely associated to AF recurrence. These results suggest production of sTRAIL by the heart and a protective role against substrate-altering processes in AF-prone atria. This could have implications for TRAIL-targeting therapies currently under development.
authors.affiliation: Department of Cardiology, Athens General Hospital "G. Gennimatas", Athens, Greece.
authors.forename: Spyridon
authors.initials: S
authors.lastname: Deftereos
authors.affiliation: Department of Cardiology, Athens General Hospital "G. Gennimatas", Athens, Greece; Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT, USA. Electronic address: ggiann@med.uoa.gr.
authors.forename: Georgios
authors.initials: G
authors.lastname: Giannopoulos
authors.affiliation: Department of Cardiology, Athens General Hospital "G. Gennimatas", Athens, Greece.
authors.forename: Charalambos
authors.initials: C
authors.lastname: Kossyvakis
authors.affiliation: Department of Cardiology, Athens General Hospital "G. Gennimatas", Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Raisakis
authors.affiliation: Department of Cardiology, Athens General Hospital "G. Gennimatas", Athens, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Angelidis
authors.affiliation: 2nd Department of Cardiology, Evangelismos General Hospital, Athens, Greece.
authors.forename: Michalis
authors.initials: M
authors.lastname: Efremidis
authors.affiliation: Department of Cardiology, Athens General Hospital "G. Gennimatas", Athens, Greece.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Panagopoulou
authors.affiliation: Department of Cardiology, Athens General Hospital "G. Gennimatas", Athens, Greece.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kaoukis
authors.affiliation: Department of Cardiology, General Hospital of Mesologgi, Mesologgi, Greece.
authors.forename: Andreas
authors.initials: A
authors.lastname: Theodorakis
authors.affiliation: Department of Cardiology, General Hospital of Chalkida, Chalkida, Greece.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Toli
authors.affiliation: Department of Cardiology, General Hospital of Mesologgi, Mesologgi, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Zavitsanakis
authors.affiliation: Department of Cardiology, General Hospital of Chalkida, Chalkida, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Mantas
authors.affiliation: Department of Cardiology, Athens General Hospital "G. Gennimatas", Athens, Greece.
authors.forename: Vlasios
authors.initials: V
authors.lastname: Pyrgakis
authors.affiliation: 1st Department of Cardiology, University of Athens Medical School, Hippokration Hospital, Athens, Greece.
authors.forename: Christodoulos
authors.initials: C
authors.lastname: Stefanadis
authors.affiliation: Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Cleman
mesh_terms: D000368:Aged; D017209:Apoptosis; D001281:Atrial Fibrillation / Q000097:blood* / Q000473:pathology / Q000628:therapy*; D015415:Biomarkers / Q000097:blood; D004554:Electric Countershock; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012995:Solubility; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000097:blood*
chemical_list: D015415:Biomarkers; D053221:TNF-Related Apoptosis-Inducing Ligand
keywords: Apoptosis; Atrial fibrillation; C-reactive protein; Interleukin-6; Recurrence; sTRAIL