Pulmonary Vein Isolation With or Without Left Atrial Appendage Ligation in Atrial Fibrillation: The aMAZE Randomized Clinical Trial

Abstract

Importance: Left atrial appendage elimination may improve catheter ablation outcomes for atrial fibrillation.

Objective: To assess the safety and effectiveness of percutaneous left atrial appendage ligation adjunctive to catheter pulmonary vein isolation for nonparoxysmal atrial fibrillation.

Design, setting, and participants: This multicenter, prospective, open-label, randomized clinical trial evaluated the safety and effectiveness of percutaneous left atrial appendage ligation adjunctive to planned pulmonary vein isolation for nonparoxysmal atrial fibrillation present for less than 3 years. Eligible patients were randomized in a 2:1 ratio to undergo left atrial appendage ligation and pulmonary vein isolation or pulmonary vein isolation alone. Use of a 2:1 randomization ratio was intended to provide more device experience and safety data. Patients were enrolled from October 2015 to December 2019 at 53 US sites, with the final follow-up visit on April 21, 2021.

Interventions: Left atrial appendage ligation plus pulmonary vein isolation compared with pulmonary vein isolation alone.

Main outcomes and measures: A bayesian adaptive analysis was used for primary end points. Primary effectiveness was freedom from documented atrial arrythmias of greater than 30 seconds duration 12 months after undergoing pulmonary vein isolation. Rhythm was assessed by Holter monitoring at 6 and 12 months after pulmonary vein isolation, symptomatic event monitoring, or any electrocardiographic tracing obtained through 12 months after pulmonary vein isolation. Primary safety was a composite of predefined serious adverse events compared with a prespecified 10% performance goal 30 days after the procedure. Left atrial appendage closure was evaluated through 12 months after pulmonary vein isolation.

Results: Overall, 404 patients were randomized to undergo left atrial appendage ligation plus pulmonary vein isolation and 206 were randomized to undergo pulmonary vein isolation alone. Primary effectiveness was 64.3% with left atrial appendage ligation and pulmonary vein isolation and 59.9% with pulmonary vein isolation only (difference, 4.3% [bayesian 95% credible interval, -4.2% to 13.2%]; posterior superiority probability, 0.835), which did not meet the statistical criterion to establish superiority (0.977). Primary safety was met, with a 30-day serious adverse event rate of 3.4% (bayesian 95% credible interval, 2.0% to 5.0%; posterior probability, 1.0) which was less than the prespecified threshold of 10%. At 12 months after pulmonary vein isolation, complete left atrial appendage closure (0 mm residual communication) was observed in 84% of patients and less than or equal to 5 mm residual communication was observed in 99% of patients.

Conclusions and relevance: Percutaneous left atrial appendage ligation adjunctive to pulmonary vein isolation did not meet prespecified efficacy criteria for freedom from atrial arrhythmias at 12 months compared with pulmonary vein isolation alone for patients with nonparoxysmal atrial fibrillation, but met prespecified safety criteria and demonstrated high rates of closure at 12 months.

Trial registration: ClinicalTrials.gov Identifier: NCT02513797.

Figure 1.. Flow of Participants in a Study of Pulmonary Vein Isolation (PVI) With or Without Left Atrial Appendage (LAA) Ligation in Atrial Fibrillation

At 30- and 90-day follow-up, the following assessments were used: medication review, physical examination, electrocardiogram, Atrial Fibrillation Effect on Quality of Life questionnaire, international normalized ratio, CHA₂DS₂-VASc score (30-day only), and adverse event/serious adverse event assessment. At 180- and 365-day follow-up, the following assessments were used: medication review, physical examination, 24-h Holter monitoring, electrocardiogram, transesophageal echocardiogram (365-day only), Atrial Fibrillation Effect on Quality of Life questionnaire, international normalized ratio, CHA₂DS₂-VASc score, and adverse event/serious adverse event assessment. ^aSee eTable 2 in Supplement 1 for more information. ^bRandomized in a 2:1 ratio. Enrollment was completed on December 13, 2019. Participants who consented prior to receipt of the official enrollment closure notification were allowed to continue to be screened, randomized, and treated per protocol.

Figure 2.. Freedom From Recurrent Atrial Arrhythmias by Treatment Group After Ablation

Number of patients at risk was counted from the actual day after pulmonary vein isolation (PVI) and thus the Kaplan-Meier curve is not truncated at day 365. Of note, there were 7 patients across treatment groups whose final end point assessment visits were performed beyond the 365-day visit window due to various factors (including the COVID-19 pandemic). Recurrences in the initial 90-day blanking period were excluded from analysis. (This was a post hoc analysis and not prespecified per the statistical analysis plan.)