A randomized controlled trial of pulsed field ablation vs antiarrhythmic therapy as a first-line treatment for persistent atrial fibrillation: The AVANT GUARD trial rationale and design

Oussama M Wazni; Kyoung-Ryul Julian Chun; Anish Amin; Ante Anic; Olujimi A Ajijola; Douglas N Gibson; Moussa Mansour; Kevin Makati; Jonathan Chrispin; Mattias Duytschaever; Devi G Nair; Jonathan P Piccini; Andrea Natale; Giovanni Raciti; Scott Wehrenberg; Sheryl McCammon; Elizabeth M Albrecht; Ania Garlitski; Brad S Sutton; Jason G Andrade; AVANT GUARD Investigators

doi:10.1016/j.hroo.2025.12.011

A randomized controlled trial of pulsed field ablation vs antiarrhythmic therapy as a first-line treatment for persistent atrial fibrillation: The AVANT GUARD trial rationale and design

Heart Rhythm O2. 2025 Dec 23;7(3):561-574. doi: 10.1016/j.hroo.2025.12.011. eCollection 2026 Mar.

Authors

Oussama M Wazni¹, Kyoung-Ryul Julian Chun², Anish Amin³, Ante Anic⁴, Olujimi A Ajijola⁵, Douglas N Gibson⁶, Moussa Mansour⁷, Kevin Makati⁸, Jonathan Chrispin⁹, Mattias Duytschaever¹⁰, Devi G Nair¹¹, Jonathan P Piccini¹², Andrea Natale^{13

14}, Giovanni Raciti¹⁵, Scott Wehrenberg¹⁵, Sheryl McCammon¹⁵, Elizabeth M Albrecht¹⁵, Ania Garlitski¹⁵, Brad S Sutton¹⁵, Jason G Andrade¹⁶; AVANT GUARD Investigators

Affiliations

¹ Cleveland Clinic, Cleveland, Ohio.
² Cardioangiologisches Centrum Bethanien, Frankfurt, Germany.
³ Riverside Methodist Hospital, Columbus, Ohio.
⁴ Split University Clinical Hospital, Split, Croatia.
⁵ Ronald Reagan UCLA Medical Center, Los Angeles, California.
⁶ Scripps Clinic and Prebys Cardiovascular Institute, San Diego, California.
⁷ Massachusetts General Hospital, Boston, Massachusetts.
⁸ St. Joseph's Hospital - Baycare, Lutz, Florida.
⁹ Johns Hopkins University School of Medicine, Baltimore, Maryland.
¹⁰ AZ Sint-Jan Brugge, Bruges, Belgium.
¹¹ St. Bernards Medical Center & Arrhythmia Research Group, Jonesboro, Arkansas.
¹² Duke University, Durham, North Carolina.
¹³ Texas Cardiac Arrhythmia Research, St. David's Medical Center, Austin, Texas.
¹⁴ Department of Bioscience and Prevention, Division of Cardiology, University of Tor Vergata, Rome, Italy.
¹⁵ Boston Scientific Corp, St. Paul, Minnesota.
¹⁶ University of British Columbia, Vancouver, British Columbia, Canada.

Abstract

Background: Recent studies have established catheter ablation as a safe and superior alternative to antiarrhythmic drugs (AADs) as a first-line therapy in patients with paroxysmal atrial fibrillation (AF). There are no randomized controlled trials assessing this strategy in patients with persistent AF.

Objective: This study aims to establish the safety and effectiveness of pulsed field ablation (PFA) as a first-line treatment for persistent AF compared with AAD therapy.

Methods: AVANT GUARD (A Prospective Randomized Multicenter Global Study Comparing Pulsed Field Ablation vs Anti-Arrhythmic Drug Therapy as a First Line Treatment for Persistent Atrial Fibrillation) is a multicenter, global, pivotal investigational device exemption study that compares the safety and effectiveness of PFA with the pentaspline PFA catheter to AADs as first-line therapy for patients with persistent AF. All patients will receive an implantable cardiac monitor.

Results: The primary safety end point, evaluated in PFA subjects, is a composite of defined acute and chronic device- and procedure-related serious adverse events. The primary effectiveness end point, evaluated in randomized PFA and AAD subjects at 12-month follow-up, is a composite of acute and chronic treatment success including freedom from atrial arrhythmia recurrence lasting ≥30 seconds (symptomatic) or ≥1 hour (asymptomatic), electrical cardioversion, or (re)ablation.

Conclusion: AVANT GUARD will help fill a critical gap in our understanding of treatment approaches and disease progression for patients with persistent AF by providing a direct comparison between ablation using PFA versus AAD treatment as a first-line therapy with continuous monitoring to assess outcomes.

Keywords: Antiarrhythmic drugs; Catheter ablation; First-line therapy; Persistent atrial fibrillation; Pulsed field ablation; Randomized controlled trial.