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aMAZE

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

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Year of Publication: 2024

Authors: Dhanunjaya R. Lakkireddy, MD; David J. Wilber, MD; Suneet Mittal, ..., PhD; Randall J. Lee

Journal: JAMA

Citation: JAMA. 2024;331(13):1099-1108. doi:10.1001/jama.2024.3026

Link: https://doi.org/10.1001/jama.2024.3026

Clinical Question

Does percutaneous left atrial appendage ligation adjunctive to pulmonary vein isolation improve outcomes compared to pulmonary vein isolation alone in patients with nonparoxysmal atrial fibrillation?

Bottom Line

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, but met prespecified safety criteria and demonstrated high rates of closure.

        Major Points
        Multicenter, prospective, open-label, randomized clinical trial using 2:1 randomization
610 patients with nonparoxysmal atrial fibrillation enrolled from 53 US sites
Primary effectiveness of 64.3% vs 59.9% (difference 4.3%, 95% CI -4.2% to 13.2%) did not meet superiority criterion
Primary safety met with 3.4% serious adverse event rate at 30 days, below 10% threshold
84% complete left atrial appendage closure achieved at 12 months
Bayesian adaptive design with predictive probabilities for interim analyses

      

Design

Study Type: Multicenter, prospective, open-label, randomized clinical trial

Randomization: 1

Blinding: Open-label (no blinding described)

Enrollment Period: October 2015 to December 2019

Follow-up Duration: 12 months after pulmonary vein isolation

Centers: 53

Countries: United States

Sample Size: 610

Analysis: Bayesian adaptive analysis with multiple imputation for missing data, binomial distribution modeling with beta prior distributions

Inclusion Criteria

Documented symptomatic nonparoxysmal atrial fibrillation (7 days to 3 years of continuous atrial fibrillation)
Unsuccessful treatment with at least 1 class I/III antiarrhythmic drug
Eligible and planned to undergo catheter ablation

Exclusion Criteria

Left atrial diameter greater than 6 cm
New York Heart Association class IV heart failure
Body mass index greater than 40
Prior opening/entry into the pericardial space
Documented thromboembolic event, myocardial infarction, or unstable angina within 3 months of enrollment

Arms

Field	Left atrial appendage ligation plus pulmonary vein isolation	Control
Intervention	LARIAT device left atrial appendage ligation via percutaneous subxiphoid approach within 30 days, followed by pulmonary vein isolation using radiofrequency ablation with contact force sensing irrigated catheters	Pulmonary vein isolation alone using radiofrequency ablation with contact force sensing irrigated catheters guided by electroanatomical mapping
Duration	LAA ligation within 30 days, PVI within next 30 days	PVI within 30 days of randomization

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Freedom from documented atrial arrhythmias greater than 30 seconds duration 12 months after pulmonary vein isolation	Primary	59.9%	64.3%	4.40%	0.835 posterior probability
Complete left atrial appendage closure (0 mm) at 12 months	Secondary	N/A	84%
≤5 mm residual communication at 12 months	Secondary	N/A	99%
Technical success (≤1 mm) immediately after procedure	Secondary	N/A	87%
Primary safety composite at 30 days	Adverse	N/A	3.4% (95% CI: 2.0% to 5.0%)		1.0 posterior probability
Bleeding	Adverse	N/A	2.2%
Serious injury to cardiac structure requiring surgical intervention	Adverse	N/A	0.8%
Vascular injury requiring intervention	Adverse	N/A	0.3%

Subgroup Analysis

No significant treatment effect differences across prespecified baseline variables. Incomplete left atrial appendage closure was not associated with efficacy outcomes.

Criticisms

Open-label design without blinding
Uneven 2:1 randomization ratio may have affected power calculations
23 of 378 patients exited study prior to 30-day post-LAA ligation assessment
Neither left atrial appendage electrical isolation nor its relationship to closure were measured
Patients unevenly distributed between nonparoxysmal AF classifications, with most having early persistent AF
Study population may have had insufficient left atrial enlargement to benefit from volume reduction
Combined procedural adverse event rate numerically higher but not statistically different than PVI alone

Funding

AtriCure, Inc

Based on: aMAZE (JAMA, 2024)

Authors: Dhanunjaya R. Lakkireddy, MD; David J. Wilber, MD; Suneet Mittal, ..., PhD; Randall J. Lee

Citation: JAMA. 2024;331(13):1099-1108. doi:10.1001/jama.2024.3026

Content summarized and formatted by NeuroTrials.ai.

aMAZE

(2024)

Objective

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

Study Summary

• Percutaneous left atrial appendage ligation plus pulmonary vein isolation did not meet prespecified efficacy criteria for freedom from atrial arrhythmias at 12 months (64.3% vs 59.9%, difference 4.3%)
• The combination met prespecified safety criteria with 30-day serious adverse event rate of 3.4%
• High rates of complete left atrial appendage closure (84%) were achieved at 12 months

Intervention

Percutaneous left atrial appendage ligation using LARIAT device plus pulmonary vein isolation

Inclusion Criteria

Documented symptomatic nonparoxysmal atrial fibrillation (7 days to 3 years duration), unsuccessful treatment with at least 1 class I/III antiarrhythmic drug, eligible for catheter ablation

Study Design

Arms: Left atrial appendage ligation plus pulmonary vein isolation vs pulmonary vein isolation alone

Patients per Arm: 404 patients (LAA ligation + PVI) vs 206 patients (PVI alone)

Outcome

• Primary effectiveness: 64.3% freedom from atrial arrhythmias in combination group vs 59.9% in PVI alone (not statistically superior)
• Primary safety: 3.4% serious adverse event rate at 30 days, meeting prespecified goal
• Complete LAA closure achieved in 84% of patients at 12 months

Bottom Line

Major Points

Multicenter, prospective, open-label, randomized clinical trial using 2:1 randomization
610 patients with nonparoxysmal atrial fibrillation enrolled from 53 US sites
Primary effectiveness of 64.3% vs 59.9% (difference 4.3%, 95% CI -4.2% to 13.2%) did not meet superiority criterion
Primary safety met with 3.4% serious adverse event rate at 30 days, below 10% threshold
84% complete left atrial appendage closure achieved at 12 months
Bayesian adaptive design with predictive probabilities for interim analyses

Study Design

Study Type: Multicenter, prospective, open-label, randomized clinical trial
Randomization: Yes
Blinding: Open-label (no blinding described)
Sample Size: 610
Follow-up: 12 months after pulmonary vein isolation
Centers: 53
Countries: United States

Primary Outcome

Definition: Freedom from documented atrial arrhythmias greater than 30 seconds duration 12 months after pulmonary vein isolation

Control	Intervention	HR/OR	P-value
59.9%	64.3%	- (-4.2% to 13.2%)	0.835 posterior probability

Limitations & Criticisms

Open-label design without blinding
Uneven 2:1 randomization ratio may have affected power calculations
23 of 378 patients exited study prior to 30-day post-LAA ligation assessment
Neither left atrial appendage electrical isolation nor its relationship to closure were measured
Patients unevenly distributed between nonparoxysmal AF classifications, with most having early persistent AF
Study population may have had insufficient left atrial enlargement to benefit from volume reduction
Combined procedural adverse event rate numerically higher but not statistically different than PVI alone

Citation

JAMA. 2024;331(13):1099-1108. doi:10.1001/jama.2024.3026

View Original Publication →

aMAZE

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

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

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