Left Atrial Appendage Closure With Versus Without Pulsed Field Ablation in Atrial Fibrillation Patients With Mild Symptoms and High Stroke Risk

• LAAC plus PFA for persistent AF with high risk of stroke (Procedure): 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.
• LAAC for persistent AF with high risk of stroke (Procedure): 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.

Primary outcomes

• Change in peak VO₂ from baseline to 6 months as assessed by CPET [6 months]: Change in peak oxygen uptake (peak VO₂) measured by cardiopulmonary exercise testing (CPET) at the 6-month visit compared with baseline.

Secondary outcomes

• The change of AFEQT at 6-month visit compared to baseline. [6 months]: 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
• Symptomatic AF recurrence at 6 month visit after blanking period. [6 months]
• The change in CBF over 6 months. [6 months]: Change in cerebral blood flow (CBF) from baseline to 6 months as assessed by arterial spin labeling brain magnetic resonance imaging (MRI)
• The incidence of composite clinical events [6 MONTHS]: 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.
• AF burden determined by 7 d Holter during the follow-up visits. [6 MONTHS]
• Echocardiology parameters [6 MONTHS]: LVEF, LA diameter, left atrial strain (LASr, LASct, LASI)
• Cognitive function: MoCA scale [6 MONTHS]: 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).

Other outcomes

• 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. [6 MONTHS]: 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).
• The change of NT-proBNP/BNP at 6 month compared to baseline. [6 MONTHS]
• the imaging assessment [6 months]: 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.

Sex: All, ages: 18 Years to any

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.