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.Findings 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.Interpretation 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.Funding Canadian Institutes of Health Research, St Jude Medical, Biosense-Webster, and M Lachapelle (Montreal Heart Institute Foundation).
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Adenosine testing to identify patients in need of additional ablation remains controversial after evaluation in several reports.
“Adenosine testing to identify patients in need of additional ablation remains controversial after evaluation in several reports.739,[742][743][744]”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [742]
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- Authors
- Macle, L., Khairy, P., Weerasooriya, R., Novak, P., Verma, A., Willems, S., Arentz, T., Deisenhofer, I., Veenhuyzen, G., Scavée, C., Jaïs, P., Puererfellner, H., Levesque, S., Andrade, J. G., Rivard, L., Guerra, P. G., Dubuc, M., Thibault, B., Talajic, M., Roy, D., & Nattel, S.
- Affiliations
- Montreal Heart Institute (CA)
- The University of Western Australia (AU)
- Royal Jubilee Hospital (CA)
- Southlake Regional Health Center (CA)
- Universität Hamburg (DE)
- Universitäts-Herzzentrum Freiburg-Bad Krozingen (DE)
- Deutsches Herzzentrum München (DE)
- Libin Cardiovascular Institute of Alberta (CA)
- Cliniques Universitaires Saint-Luc (BE)
- Corresponding author
- Macle, Laurent
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2015-08
- Volume
- 386
- Issue
- 9994
- Pages
- 672-679
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W1873062171
- Cited by
- 226
- References
- 30
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 10 · 2023: 11 · 2022: 11 · 2021: 16 · 2020: 30 · 2019: 26 · 2018: 20 · 2017: 43 · 2016: 31 · 2015: 11
- FWCI
- 25.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Digital Access to Libraries (submittedVersion)
- FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Funders
- St. Jude Medical
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Arrhythmias and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac pacing and defibrillation studies
- Keywords
- paroxysmal atrial fibrillation, adenosine, pulmonary vein isolation, radiofrequency catheter ablation, arrhythmia recurrence, arrhythmia-free survival, antiarrhythmic drug failure, atrial fibrillation recurrence prevention
- MeSH terms
- Adenosine, Anti-Arrhythmia Agents, Atrial Fibrillation, Female, Humans, Male, Middle Aged, Pulmonary Veins, Proportional Hazards Models, Treatment Outcome, Catheter Ablation, Secondary Prevention, Operative Time
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