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.

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.