Pulsed Field Ablation Noninferior to Conventional Thermal Ablation for Paroxysmal Atrial Fibrillation
Key findings
- The multicenter, randomized ADVENT trial compared pulsed field ablation (n=305) with conventional thermal ablation (radiofrequency ablation, n=167 or cryoballoon ablation, n=135) in the treatment of drug-refractory paroxysmal atrial fibrillation
- Pulsed-field ablation was noninferior to thermal ablation with respect to a composite of initial procedural failure, documented atrial tachyarrhythmia after a three-month blanking period, antiarrhythmic drug use, cardioversion or repeat ablation
- Pulsed-field ablation was also noninferior with respect to the primary safety endpoint of device- and procedure-related serious adverse events at one year, and it was superior with respect to change in the cross-sectional area of the pulmonary veins
- One procedure-related death occurred in a patient who underwent pulsed field ablation; it occurred as a result of catheter manipulation and was unrelated to the delivery of pulsed-field energy
- The Farapulse system studied in this registrational trial was approved by the FDA in January 2024
Pulsed-field ablation (PFA) is a unique new alternative to standard-of-care thermal ablation for patients with drug-refractory paroxysmal atrial fibrillation. In this approach, microsecond-scale, high-voltage electrical fields cause irreversible destabilization of cell membranes, culminating in cellular necrosis.
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Preclinical and clinical studies have shown that pulsed-field ablation allows myocardial tissue to be preferentially ablated with limited effects such as atrioesophageal fistula, hemidiaphragmatic paralysis, and pulmonary vein stenosis.
Moussa Mansour, MD, director of the Atrial Fibrillation Program, and the Jeremy Ruskin and Dan Starks endowed chair in Cardiology at Massachusetts General Hospital, and colleagues conducted ADVENT, a multicenter, randomized, single-blind trial comparing PFA with conventional thermal ablation. In The New England Journal of Medicine, they report noninferiority of PFA with respect to both efficacy and safety.
Methods
Prior to enrollment, one to three roll-in patients were treated at each center to ensure operator familiarity with the pentaspline PFA catheter. Then, between March 1, 2021, and June 3, 2022, the researchers enrolled adults ≤75 years of age who had symptomatic paroxysmal atrial fibrillation refractory to at least one antiarrhythmic drug.
607 patients were randomly assigned to undergo either PFA (n=305) or conventional thermal ablation (n=302, including 167 assigned to radiofrequency ablation and 135 to cryoballoon ablation).
After hospital discharge, oral anticoagulation was continued according to standard guidelines, and class I or III antiarrhythmic drugs (except amiodarone) were permitted during the three-month blanking period. (By convention, arrhythmias following any form of myocardial ablation are not considered during the first three months.) Patients were followed for a total of one year.
The trial was funded by the manufacturer of the PFA system, Farapulse, which was later acquired by Boston Scientific.
Efficacy
The primary efficacy endpoint was freedom from a composite of:
- Initial procedural failure to achieve pulmonary vein isolation with the use of the assigned treatment method
- Documented atrial tachyarrhythmia lasting 30 seconds or longer after the blanking period
- Use of class I or III antiarrhythmic drug or cardioversion after the blanking period
- Use of amiodarone at any time post-procedure
- Repeat ablation at any time during follow-up
Treatment results were:
- PFA group—204 had success (were free of the composite of events), 80 had failure, and 21 had censored data
- Thermal ablation group—194 had success, 85 had failure, and 23 had censored data
The estimated probability of treatment success was 73.3% for PFA and 71.3% for thermal ablation. PFA met the prespecified criterion for noninferiority to thermal ablation with a posterior probability of more than 0.999.
Outcomes in the two groups were also similar when alternative definitions of treatment success were applied, which allowed for repeat ablation or continued use of antiarrhythmic drugs.
Safety
The primary safety endpoint was device- or procedure-related serious adverse events, which occurred in six patients in the PFA group and four who underwent thermal ablation. The estimated incidence was 2.1% vs. 1.5%, and these findings, too, met the criterion for noninferiority with a posterior probability of more than 0.999.
The secondary safety endpoint was the mean change in the cross-sectional area of the pulmonary veins. Narrowing of the pulmonary vein ostia was greater in the thermal ablation group: −1.18 cm2 (12.0%) versus −0.18 cm2 (0.9%) with PFA. This result met the criterion for superiority.
Adverse events of special interest were:
- Pericardial tamponade—2 patients in the PFA group; one of them underwent emergency sternotomy and lengthy resuscitation but had multiorgan failure and died on day 10
- Symptoms of pulmonary vein stenosis—None in either group
- Persistent phrenic-nerve injury—2 patients who underwent cryoballoon ablation
- Asymptomatic ischemic phenomena detected in a brain MRI substudy—3/33 patients in the PFA group and 0/37 who underwent thermal ablation
- Procedure-related clinical stroke—1 patient who underwent radiofrequency ablation
Based on these findings, the FDA approved the Farapulse system in January 2024.
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