Upfront Pulsed Field Ablation Shows Efficacy in Persistent Afib

First-line treatment with pulsed field ablation (PFA) reduced the risk of recurrence of atrial arrhythmia among patients with persistent atrial fibrillation (Afib), the randomized AVANT GUARD trial showed.

Among untreated patients at 12 months, short- and long-term treatment success was observed in 56% of those who received PFA with the Farapulse pentaspline catheter system compared with 30% of those who received upfront antiarrhythmic drug therapy (HR for composite treatment failure 0.46, 95% CI 0.33-0.65), reported Oussama Wazni, MD, of the Cleveland Clinic, at the Heart Rhythm Society annual meeting held in Chicago.

These results were simultaneously published in the New England Journal of Medicine.

The PFA arm also met a prespecified safety performance goal, with safety events, namely device- or procedure-related serious adverse events, occurring in 5.1% of patients (upper confidence limit of 8.6%) in the randomized PFA arm combined with a separate PFA-assigned cohort.

“The current trial affirms that ablation with the pentaspline PFA catheter is an effective intervention to control rhythm,” Wazni and colleagues wrote. “In this patient population with more advanced atrial fibrillation, the risk of recurrence of arrhythmia was lower with an initial ablation procedure than with antiarrhythmic-drug therapy.”

“These latest results show that we are continuing to move the needle in terms of treatment since persistent atrial fibrillation patients are typically sicker and have more profound effects of the disease,” Wazni said in a press release. “We look forward to subsequent studies further down the line including a 3-year follow-up as the next step.”

In the trial, short-term treatment success was defined as procedural success in the PFA group and the absence of ablation during the blanking period in the antiarrhythmic drug group. Long-term treatment success was defined as freedom from recurrence of atrial arrhythmias, repeat ablation, or need for antiarrhythmic drugs from 90 days through 12 months in the PFA group, and freedom from amiodarone use at any time. Continuous rhythm monitoring was conducted using a LUX-Dx insertable cardiac monitor.

Persistent Afib, characterized as a single episode lasting more than 7 days, is associated with worse clinical outcomes compared with paroxysmal Afib.

“For patients with paroxysmal atrial fibrillation, catheter ablation is established as a safe and superior alternative to antiarrhythmic drugs as a first-line therapy,” Wazni and team noted. “However, patients with persistent atrial fibrillation often have substantial electrical and structural remodeling, which leads to worse procedural outcomes with thermal-based ablation techniques than in patients with paroxysmal atrial fibrillation.”

The Farapulse is a single-shot system with configurable flower or basket shapes and 20 electrodes; it has been FDA approved for paroxysmal Afib since 2024 and for drug-refractory persistent Afib since last summer. Competing systems, namely the PulseSelect and Volt, are also on the market for PFA treatment of both paroxysmal and persistent Afib.

The expectation with PFA technology is that its non-thermal means of tissue ablation would reduce the risk of unintended damage to nearby collateral structures, thereby making it safer than radiofrequency-based ablation.

Although there was ultimately no significant excess of serious adverse events associated with PFA in AVANT GUARD (25% vs 21% for drug therapy), the trial had been paused after six procedure-related strokes were observed, one of which was related to inadvertent introduction of air from the deflectable sheath.

After the 3-week pause, enrollment was allowed to resume with an amended study protocol, with modifications including the exclusion of patients with CHA2DS2-VASc scores ≥4 and new requirements that patients undergo screening for left atrial thrombus within 24 hours before PFA, receive uninterrupted anticoagulation for at least 4 weeks before PFA, and have a minimum activated clotting time of 350 seconds before ablation.

Wazni and colleagues reported that no neurologic events were observed after these protocol modifications.

“Even so, these results highlight the importance of balancing the risks and benefits of earlier intervention as part of the shared decision-making process,” they cautioned. “The patients’ more extensive medical history in our trial may have had a negative effect on absolute efficacy in the PFA group and may also have contributed to the risk of periprocedural adverse events, since the risks of intervention are enhanced in older, frailer patients with more coexisting illnesses.”

The AVANT GUARD trial enrolled patients from 2023 to 2025 from the U.S., Europe, and Asia. After an initial roll-in phase, the investigators randomized 310 adults 2:1 to PFA or antiarrhythmic drug therapy. A separate 100-patient cohort was assigned to PFA for the safety analysis.

Patients who were assigned to the PFA group underwent pulmonary vein isolation (PVI) and posterior wall ablation with the Farawave PFA catheter. Controls randomized to medical therapy were prescribed daily antiarrhythmic drugs in accordance with local clinical practice and established guideline-directed therapy (thus excluding amiodarone); a 90-day blanking period was allowed for dose adjustment and did not count Afib as a failure of treatment.

Baseline characteristics were comparable between the groups. Mean age was nearly 68 years, and about 30% were women. Baseline body mass index was around 31.

The mean procedure time was 85 minutes in the PFA group. A mean of 45 applications were performed for PVI, along with 25 applications for posterior wall ablation. Cavotricuspid isthmus ablation was performed in 8.2% of patients.

As for drug therapy, patients were prescribed on average 1.2 unique antiarrhythmic drugs at 1.6 unique doses during the 90-day blanking period. Flecainide was the most frequently prescribed antiarrhythmic drug (57.2%) at a median daily dose of 200 mg, followed by sotalol (28.2%) at a median dose of 240 mg.

Secondary efficacy outcomes supporting PFA versus antiarrhythmic drug therapy included:

• Amiodarone use: 1% vs 3%
• Nonprotocol ablation: <1% vs 6%
• Recurrence of a symptomatic atrial tachyarrhythmia (lasting for at least 30 seconds): 2% vs 3%
• Recurrence of asymptomatic atrial tachyarrhythmias (lasting for at least 1 hour): 30% vs 46%
• Median atrial arrhythmia burden at 1 year: 0% vs 0.2%
• A burden of atrial tachyarrhythmia >0.1%: 35% vs 53%

PFA’s effect could have been underestimated since patients in the drug group were allowed to get ablation after failure of medical therapy, Wazni and colleagues noted.

Prolonged follow-up is still needed for this group, they acknowledged, adding that these findings may not be generalizable to other types of catheters, ablation energy sources, or lesion sets.