title: Adenosine-guided pulmonary vein isolation for the treatment of paroxysmal atrial fibrillation: an international, multicentre, randomised superiority trial.
abstract: BACKGROUND
  Catheter ablation is increasingly used to manage atrial fibrillation, but arrhythmia recurrences are common. Adenosine might identify pulmonary veins at risk of reconnection by unmasking dormant conduction, and thereby guide additional ablation to improve arrhythmia-free survival. We assessed whether adenosine-guided pulmonary vein isolation could prevent arrhythmia recurrence in patients undergoing radiofrequency catheter ablation for paroxysmal atrial fibrillation.
  
  
  METHODS
  We did this randomised trial at 18 hospitals in Australia, Europe, and North America. We enrolled patients aged older than 18 years who had had at least three symptomatic atrial fibrillation episodes in the past 6 months, and for whom treatment with an antiarrhythmic drug failed. After pulmonary vein isolation, intravenous adenosine was administered. If dormant conduction was present, patients were randomly assigned (1:1) to additional adenosine-guided ablation to abolish dormant conduction or to no further ablation. If no dormant conduction was revealed, randomly selected patients were included in a registry. Patients were masked to treatment allocation and outcomes were assessed by a masked adjudicating committee. Patients were followed up for 1 year. The primary outcome was time to symptomatic atrial tachyarrhythmia after a single procedure in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT01058980.
  
  
  RESULTS
  Adenosine unmasked dormant pulmonary vein conduction in 284 (53%) of 534 patients. 102 (69·4%) of 147 patients with additional adenosine-guided ablation were free from symptomatic atrial tachyarrhythmia compared with 58 (42·3%) of 137 patients with no further ablation, corresponding to an absolute risk reduction of 27·1% (95% CI 15·9-38·2; p<0·0001) and a hazard ratio of 0·44 (95% CI 0·31-0·64; p<0·0001). Of 115 patients without dormant pulmonary vein conduction, 64 (55·7%) remained free from symptomatic atrial tachyarrhythmia (p=0·0191 vs dormant conduction with no further ablation). Occurrences of serious adverse events were similar in each group. One death (massive stroke) was deemed probably related to ablation in a patient included in the registry.
  
  
  CONCLUSIONS
  Adenosine testing to identify and target dormant pulmonary vein conduction during catheter ablation of atrial fibrillation is a safe and highly effective strategy to improve arrhythmia-free survival in patients with paroxysmal atrial fibrillation. This approach should be considered for incorporation into routine clinical practice.
  
  
  BACKGROUND
  Canadian Institutes of Health Research, St Jude Medical, Biosense-Webster, and M Lachapelle (Montreal Heart Institute Foundation).
authors.affiliation: Montreal Heart Institute and Montreal Health Innovations Coordinating Centre, Department of Medicine, Université de Montréal, Montreal, QC, Canada. Electronic address: lmacle@mac.com.
authors.forename: Laurent
authors.initials: L
authors.lastname: Macle
authors.affiliation: Montreal Heart Institute and Montreal Health Innovations Coordinating Centre, Department of Medicine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Khairy
authors.affiliation: University of Western Australia and Hollywood Private Hospital, Perth, WA, Australia.
authors.forename: Rukshen
authors.initials: R
authors.lastname: Weerasooriya
authors.affiliation: Royal Jubilee Hospital, Victoria, BC, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Novak
authors.affiliation: Southlake Regional Health Centre, Newmarket, ON, Canada.
authors.forename: Atul
authors.initials: A
authors.lastname: Verma
authors.affiliation: University Hospital Eppendorf, Hamburg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Willems
authors.affiliation: Herz-Zentrum, Bad Krozingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Arentz
authors.affiliation: Deutsches Herz-Zentrum Munchën, Munich, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Deisenhofer
authors.affiliation: Libin Cardiovascular Institute, Calgary, AB, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Veenhuyzen
authors.affiliation: Cliniques Universitaires St-Luc, Brussels, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Scavée
authors.affiliation: Hôpital Haut-Lévèque, Bordeaux, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Jaïs
authors.affiliation: KH der Elisabethinen, Linz, Austria.
authors.forename: Helmut
authors.initials: H
authors.lastname: Puererfellner
authors.affiliation: Montreal Heart Institute and Montreal Health Innovations Coordinating Centre, Department of Medicine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Levesque
authors.affiliation: Montreal Heart Institute and Montreal Health Innovations Coordinating Centre, Department of Medicine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Andrade
authors.affiliation: Montreal Heart Institute and Montreal Health Innovations Coordinating Centre, Department of Medicine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Lena
authors.initials: L
authors.lastname: Rivard
authors.affiliation: Montreal Heart Institute and Montreal Health Innovations Coordinating Centre, Department of Medicine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Guerra
authors.affiliation: Montreal Heart Institute and Montreal Health Innovations Coordinating Centre, Department of Medicine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Dubuc
authors.affiliation: Montreal Heart Institute and Montreal Health Innovations Coordinating Centre, Department of Medicine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Thibault
authors.affiliation: Montreal Heart Institute and Montreal Health Innovations Coordinating Centre, Department of Medicine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Mario
authors.initials: M
authors.lastname: Talajic
authors.affiliation: Montreal Heart Institute and Montreal Health Innovations Coordinating Centre, Department of Medicine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Denis
authors.initials: D
authors.lastname: Roy
authors.affiliation: Montreal Heart Institute and Montreal Health Innovations Coordinating Centre, Department of Medicine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Stanley
authors.initials: S
authors.lastname: Nattel
mesh_terms: D000241:Adenosine; D000889:Anti-Arrhythmia Agents; D001281:Atrial Fibrillation / Q000601:surgery*; D017115:Catheter Ablation / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D061646:Operative Time; D016016:Proportional Hazards Models; D011667:Pulmonary Veins / Q000187:drug effects* / Q000601:surgery; D055502:Secondary Prevention; D016896:Treatment Outcome
chemical_list: D000889:Anti-Arrhythmia Agents; D000241:Adenosine