In patients with persistent atrial fibrillation (AF), ligation of the left atrial appendage (LAA) appears to be safe and technically successful, but it was not superior to standard treatment in reducing recurrent atrial arrhythmias, new trial data show.
David J. Wilber, MD, of Loyola University Chicago, presented results of the aMAZE trial Sunday at the American Heart Association Scientific Sessions 2021 virtual meeting. He and DJ Lakkireddy, MD, MBBS, of the Kansas City Heart Institute, are the trial’s national co-primary investigators.
Ablation of persistent AF by pulmonary vein antral isolation (PVAI) alone has historically led to suboptimal outcomes. Adjunct strategies targeting sites outside the pulmonary vein antra to improve outcomes, including the foci or substrate in the LAA, have been the subject of recent intense investigation, Wilber said in his presentation.
The LAA is a critical structure in the maintenance of persistent and longstanding AF. The aMAZE trial investigators hypothesized that LAA ligation with the LARIAT System (AtriCure Inc.) adjunctive to PVAI would decrease the recurrence of atrial arrhythmia in patients with persistent AF. The trial’s objective was to evaluate the additional efficacy of this treatment in decreasing the 12-month rate of recurrent atrial arrhythmias following initial ablation therapy with an acceptable safety profile.
The prospective trial randomized 610 patients at 53 U.S. sites to LARIAT plus PVAI or PVAI alone (control) in a 2:1 ratio. In the treatment group, LARIAT ligation was performed 30 days before PVAI.
To be eligible, patients had to have prior failed antiarrhythmic therapy, planned initial AF ablation and persistent AF (defined as 7 days to 3 years of continuous AF). The study had a Bayesian adaptive, superiority design.
The primary effectiveness endpoint was freedom from documented atrial arrhythmias at 12 months post-procedure with no new or increased dosage of Class I or III antiarrhythmic medication. The primary safety endpoint was a composite of predefined 30-day post-LARIAT serious adverse events compared to a performance goal. Technical success was considered successful LARIAT placement to achieve effective LAA ligation (defined as (≤1 ± 1 mm diameter residual communication).
The trial randomized 404 patients to the treatment arm and 206 to the control arm. In the treatment arm, 378 patients underwent LARIAT LAA ligation, and 372 were available at 30-day follow-up for safety assessment. The primary endpoint was performed in the modified intention-to-treat population with evaluable data.
At baseline, both arms had similar patient characteristics. The mean age of all patients was 66.6 ± 8.12 years, 27% were women, and the patients’ mean body mass index was 31.29 ± 4.55 kg/m2. The majority of patients had AF between 7 days and 6 months in duration (79%). The patients’ mean left atrial volume was 137.55 ± 38.85 cm3; however, the volume was numerically lower in the treatment group (135.3 ± 38.35 cm3) than in the control group (141.9 ± 39.55 cm3).
At 30 days after undergoing LARIAT ligation, 3.4% (95% Bayesian credible interval [CrI]: 2.0%, 5.0%) of patients experienced a primary safety endpoint event. This rate was below the pre-specified performance goal of 10%, and the primary safety endpoint was met with a Bayesian posterior probability of 1 (>0.957). The most commonly reported safety event was bleeding (defined as the need for at least 2 units of packed red blood cells [PRBC] within the first 2 postoperative days, or organ structure or injury requiring intervention or that was fatal), reported in eight patients (2.2%). Three patients (0.8%) experienced serious injury to cardiac or related structure requiring surgical intervention, and one patient (0.3%) experienced vascular injury requiring surgical treatment, hospital admission or PRBC.
Patients in the treatment arm also experienced high LAA closure rates (85% to 99%) at 12 months post-PVAI. Residual communication diameter was 0 mm (100% closure) in 84% of patients, ≤1 ± 1 mm (technical success) in 85%, and ≤5 mm in 99% at 12 months.
Turning to the primary effectiveness endpoint, the rate of freedom from atrial arrhythmias at 12 months was 64.3% in the treatment group and 59.9% in the control group (difference: 4.3%; 95% Bayesian CrI: -4.2%, 13.2%). This failed to meet the criterion for superiority. The Bayesian posterior probability of superiority was 0.835, but the probability had to be >0.977 to declare primary effectiveness endpoint success.
Prespecified subgroup analyses measured primary effectiveness by baseline AF duration and left atrial volume.
In patients with early persistent AF (7 days to <6 months), freedom from atrial arrhythmias at 12 months was 66% in the treatment group and 58.5% in the control group, which also did not meet the prespecified Bayesian posterior probability of superiority (difference: 7.5%; p=0.084; 95% Bayesian CrI: -0.022, 0.174; posterior probability = 0.931).
In patients with early persistent AF and increased left atrial volume (defined as >133 cm3, which was the median volume among study patients), 65.8% of patients in the treatment group were free from atrial arrhythmias as 12 months as compared to 53.4% of the control group. This, too, did not meet the Bayesian posterior probability of superiority (difference: 12.4%; p=0.093; 95% Bayesian CrI: -0.021, 0.263; posterior probability = 0.952).
Wilber concluded that the LARIAT System appears to be safe and technically successful but that it was not superior to PVAI alone in reducing recurrent atrial arrhythmias in patients with persistent AF undergoing initial AF ablation.
The subgroup analyses do suggest that patients with early persistent AF and larger left atrial volumes might experience improved rhythm control with adjunctive LAA ligation, Wilber said, but he added, “Further investigation is required to verify these exploratory observations.”
The trial was sponsored and funded by AtriCure Inc. The LARIAT LAA Exclusion System has clearance under Section 510(k) of the U.S. Food, Drug and Cosmetics Act for use where the soft tissue is being approximated or ligated with a pre-tiered suture loop. The data presented in this trial were not reviewed by the U.S. Food and Drug Administration, the study investigators disclosed.