Left Atrial Appendage Closure With Versus Without Pulsed Field Ablation in Atrial Fibrillation Patients With Mild Symptoms and High Stroke Risk (REVERSE-OPTION)

Left Atrial Appendage Closure and Pulsed Field Ablation Procedure Versus Left Atrial Appendage Closure Alone in Persistent Atrial Fibrillation Patients With Mild Symptoms and High Risk of Stroke: A Prospective, Multicenter, Single-Blind, Randomized Controlled Pilot Study

This study is a prospective, multicenter, single-blinded, randomized controlled trial to investigate whether concomitant left atrial appendage closure (LAAC) and pulsed field ablation (PFA) is more effective than LAAC alone in improving the outcomes in persistent atrial fibrillation (AF) patients with high risk of stroke.

Emerging data show that some-especially those with persistent AF, high AF burden, or early atrial re-modelling-have high stroke and heart failure risks. This pilot study aims to assess whether combining LAAC and PFA improves outcomes more than LAAC alone in persistent AF patients at high stroke risk. Fifty participants will be randomly assigned in a 1:1 ratio to the LAAC or LAAC plus PFA group, with group allocation blinded.

Baseline assessments included cardiopulmonary exercise testing (CPET), the Atrial Fibrillation Effect on QualiTy-of-life questionnaire (AFEQT) , and brain magnetic resonance imaging (MRI). In the LAAC group, patients will undergo electrical cardioversion followed by LAAC under general anesthesia; if sinus rhythm could not be achieved by the end of procedure, pharmocol cardioversion will be tried to restore it. In the LAAC plus PFA group, pulmonary vein isolation (PVI) and posterior wall isolation (PWI) will be performed using the FARAPULSE system, then LAAC will be done. If sinus rhythm could not be restored after PFA, cardioversion will be performed. Additional ablation is allowed only if a clear arrhythmia mechanism is identified; empirical ablation is prohibited. Follow-up occurs every two months with 7-day Holter monitoring. CPET, AFEQT, and brain MRI will be repeated at 6 months. During the blanking period, antiarrhythmic drugs may be used except amiodarone due to its long half-life. Ablation is not recommended within the first two months. Crossover to ablation is permitted only for patients with documented AF/AFL/AT recurrence and worsened symptoms (AFEQT score drop ≥10 points from baseline). At crossover or redo-ablation, AFEQT, CPET, and brain MRI will be repeated.

Study Overview

• Status: Recruiting
• Conditions: ATRIAL APPENDAGE CLOSURE for ATRIAL FIBRILLATION; PFA Ablation and LAAC Procedures
• Intervention / Treatment: Procedure: LAAC plus PFA for persistent AF with high risk of stroke; Procedure: LAAC for persistent AF with high risk of stroke

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chenyang Jiang; Phone Number: 86-13857190051; Email: cyjiang@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • Sir Run Run Shaw Hospital
      • Contact: Chenyang Jiang; Phone Number: 86-13857190051; Email: cyjiang@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years old.
2. Subjects diagnosed with persistent AF with duration more than 3 months.
3. Subjects with AFEQT score >70 .
4. Subjects with CHA2DS2-VA score ≥2.
5. Subjects who are willing and capable of providing ICF and participating in all testing associated with this study.

Exclusion Criteria:

1. AF that is secondary to electrolyte imbalance, thyroid disease, alcohol, or other reversible/non-cardiac causes.
2. Subjects with the history of AF ablation, LAA surgically closed or otherwise excluded or the LAA anatomy does not accommodate a Closure Device.
3. Left atrial anteroposterior diameter ≥ 5.5 cm.
4. Heart failure with a NYHA III/IV and/or LVEF ≤35% within 3 months prior to the procedure.

5. Any of the following events within 90 days of the Consent Date:

   • Myocardial infarction, unstable angina or coronary intervention or any cardiac surgery
   • Pericarditis or symptomatic pericardial effusion
   • Gastrointestinal bleeding
   • Stroke, TIA, or intracranial bleeding or any non-neurologic thromboembolic event
6. Contraindication to, or unwillingness to use systemic anticoagulation.
7. Subjects with contraindications or not tolerate to EP procedure, general anaesthesia, or the tests included in the study, like CPET, MRI.
8. Subjects cannot be removed from Class I/III AAD for reasons other than atrial arrhythmia.
9. Women of childbearing potential who are pregnant or lactating.
10. Renal insufficiency if an eGFR is < 30 mL/min/1.73 m2, or with any history of renal dialysis or renal transplant.
11. Predicted life expectancy is less than 12 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LAAC+PFA group; LAAC plus PFA	Procedure: LAAC plus PFA for persistent AF with high risk of stroke; Pulmonary vein isolation (PVI) and posterior wall isolation (PWI) will be performed using the FARAPULSE system, then LAAC will be done. If sinus rhythm could not be restored after PFA, cardioversion will be performed. Additional ablation is allowed only if a clear arrhythmia mechanism is identified; empirical ablation is prohibited.
Active Comparator: LAAC group; LAAC alone	Procedure: LAAC for persistent AF with high risk of stroke; Patients will undergo electrical cardioversion followed by LAAC under general anesthesia; if sinus rhythm could not be achieved by the end of procedure, pharmocol cardioversion will be tried to restore it.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in peak VO₂ from baseline to 6 months as assessed by CPET	Change in peak oxygen uptake (peak VO₂) measured by cardiopulmonary exercise testing (CPET) at the 6-month visit compared with baseline.	6 months
The change in CBF over 6 months.	Change in cerebral blood flow (CBF) from baseline to 6 months as assessed by arterial spin labeling brain magnetic resonance imaging (MRI)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change of AFEQT at 6-month visit compared to baseline.	The change of Atrial Fibrillation Effect on QualiTy-of-life questionnaire (AFEQT) at 6-month visit compared to baseline, range: 0-100; higher scores indicate better quality of life	6 months
Symptomatic AF recurrence at 6 month visit after blanking period.		6 months
The incidence of composite clinical events	The incidence of composite clinical events, including death from cardiovascular causes, stroke (either ischemic or hemorrhagic), major bleeding or hospitalization with worsening of heart failure (unplanned hospitalization and/or intravenous use of diuretics) or acute coronary syndrome.	6 MONTHS
AF burden determined by 7 d Holter during the follow-up visits.		6 MONTHS
Echocardiology parameters	LVEF, LA diameter, left atrial strain (LASr, LASct, LASI)	6 MONTHS
Cognitive function: MoCA scale	Change in Montreal Cognitive Assessment (MoCA) total score from baseline to 6 months, MoCA total score ranges from 0 to 30, with higher scores indicating better cognitive function. The outcome will be summarized as the mean change (6-month minus baseline).	6 MONTHS

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Actionable AF recurrence rate at 6 months, defined as occurrence of any cardioversion, ablation or AAD treatment for AF post blanking period.		6 MONTHS
The change of Clinical Frailty Scale Health.	The Clinical Frailty Scale (CFS) ranges from 1 to 9, with higher scores indicating worse frailty. The outcome will be summarized as the mean change (6-month minus baseline).	6 MONTHS
The change of NT-proBNP/BNP at 6 month compared to baseline.		6 MONTHS
the imaging assessment	Baseline and 6-month multimodal brain MRI, including three-dimensional T1-weighted imaging (3D T1), T2 fluid-attenuated inversion recovery (T2-FLAIR), with optional diffusion tensor imaging (DTI). DTI is an exploratory imaging endpoint.	6 months

Collaborators and Investigators

• Sponsor: Sir Run Run Shaw Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): December 15, 2026
• Study Completion (Estimated): January 31, 2027

Study Registration Dates

• First Submitted: January 27, 2026
• First Submitted That Met QC Criteria: March 4, 2026
• First Posted (Actual): March 6, 2026

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Carbohydrates; Membrane Proteins; Glycoproteins; Glycoconjugates; Antigens; Antigens, Surface; Desmogleins; Desmosomal Cadherins; Cadherins; Cell Adhesion Molecules; Membrane Glycoproteins; Autoantigens; Desmoglein 1
• Other Study ID Numbers: SRRSH-ER-2026-Research-0108

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No