Ground-Breaking Electroporation-based Intervention for PERSistent Atrial Fibrillation Treatment (BEAT PERS-AF)

Inclusion Criteria:

1. Patients with drug-resistant symptomatic persistent AF meeting all the followingcriteria:
2. Persistent: continuous drug resistant AF that is sustained beyond 7 days (butless than 1 year).
3. Frequency: At least one (1) documented episode by a recording such as ECG, EM,Holter monitor or telemetry strip within 6 months of enrolment.
4. Drug failed: Failed AAD treatment, meaning therapeutic failure of at least one (1) AAD (Class I to IV) for efficacy and / or intolerance.
5. Patients who are ≥ 18 and ≤ 75 years of age on the day of enrollment.
6. Patient who are willing and capable of:
7. Providing informed consent to undergo study procedures AND
8. Participating in all examinations and follow-up visits and tests associated withthis clinical study.
9. Patient having a smart phone compatible with the Event Monitor device.
10. Highly effective contraception for women of childbearing potential.
11. Effective oral anticoagulation >3 weeks prior to planned ablation procedure
12. Patient affiliated to or beneficiary of national health security scheme for Frenchparticipants.

Exclusion Criteria:

• 1. AF that is any of the following:

1. Paroxysmal AF by diagnosis or that terminates spontaneously within 7 days ofonset
2. Secondary to electrolyte imbalance, thyroid disease, alcohol or other reversible / non-cardiac causes 2. Any of the following atrial conditions:
3. Left atrial anteroposterior diameter ≥ 5.5 cm (by MRI, CT or TTE)
4. Any prior atrial endocardial or epicardial ablation procedure, other than rightsided cavotricuspid isthmus ablation or for right sided SVT
5. Any prior atrial surgery
6. Intra-atrial septal patch or interatrial shunt
7. Atrial myxoma
8. Current LA thrombus
9. LA appendage closure, device or occlusion, past or anticipated
10. Any PV abnormality, stenosis or stenting (common and middle PVs are admissible)
11. At any time, one (1) or more of the following cardiovascular procedures,implants or conditions: a. Sustained ventricular tachycardia or any ventricular fibrillation b.Hemodynamically significant valvular disease: i. Valvular disease that is symptomaticii. Valvular disease causing or exacerbating congestive heart failure iii. Aorticstenosis: if already characterized, valve area < 1.5cm or gradient > 20 mm Hg iv.Mitral stenosis: if already characterized, valve area < 1.5cm or gradient > 5 mm Hg v.Aortic or mitral regurgitation associated with abnormal LV function or hemodynamicmeasurements c. Hypertrophic cardiomyopathy d. Any prosthetic heart valve, ring orrepair including balloon aortic valvuloplasty e. Pacemaker, implantable cardioverterdefibrillator or cardiac resynchronization therapy devices f. Any inferior vena cava (IVC) filter, known inability to obtain vascular access or other contraindication tofemoral access g. History of rheumatic fever h. History of congenital heart diseasewith any residual anatomic or conduction abnormality 4. Any of the followingprocedures, implants or conditions: a. At baseline: i. New York Heart Association (NYHA) Class III/IV ii. Left ventricularejection fraction (LVEF) < 40% iii. Symptomatic hypotension iv. Uncontrolledhypertension (SBP > 160 mmHg or DBP > 95 mmHg on two BP measurements at baselineassessment) v. Symptomatic resting bradycardia vi. Implantable loop recorder orinsertable cardiac monitor, b. Within the 3 months preceding the Consent Date: i.Myocardial infarction ii. Unstable angina iii. Percutaneous coronary intervention iv.Heart failure hospitalization v. Pericarditis or symptomatic pericardial effusion vi.Gastrointestinal bleeding c. Within the 6 months preceding the Consent Date: i. Heartsurgery ii. Stroke, TIA or intracranial bleeding iii. Any thromboembolic event iv.Carotid stenting or endarterectomy 5. Diagnosed disorder of blood clotting or bleedingdiathesis 6. Contraindication to, or unwillingness to use, systemic anticoagulation 7.Contraindication to both CT and MRI 8. Sensitivity to contrast media not controllableby premedication 9. Women who are pregnant, lactating, or who are planning to becomepregnant during the anticipated study period 10. Medical conditions that would preventparticipation in the study, interfere with assessment or therapy, significantly raisethe risk of study participation, or modify outcome data or its interpretation,including but not limited to:
12. Body Mass Index (BMI) > 40.0
13. Solid organ or hematologic transplant, or currently being evaluated for an organtransplant
14. Severe lung disease, pulmonary hypertension, or any lung disease involvingabnormal blood gases or requiring supplemental oxygen
15. Renal insufficiency with an estimated glomerular filtration rate (eGFR) < 30mL/min/1.73 m2, or any history of renal dialysis or renal transplant
16. Active malignancy or history of treated malignancy within 24 months of enrollment (other than cutaneous basal cell or squamous cell carcinoma)
17. Clinically significant gastrointestinal problems involving the esophagus orstomach including severe or erosive esophagitis, uncontrolled gastric reflux,gastroparesis, esophageal candidiasis or active gastroduodenal ulceration
18. Active systemic infection
19. COVID-19 disease
20. Current confirmed, active COVID-19 disease ii. Current positive test forSARS-CoV-2 iii. Confirmed COVID-19 disease not clinically resolved at least 3months prior to the Consent Date. i. Other uncontrolled medical conditions that may modify device effect or increaserisk, including uncontrolled diabetes mellitus (HgbA1c > 8.0% if test result alreadyobtained), untreated obstructive sleep apnea or active alcohol abuse j. Predicted lifeexpectancy less than one (1) year 11. Clinically significant psychological conditionthat in the Investigator's opinion would prohibit the subject's ability to meet theprotocol requirements/ Patient under legal protection 12. Current or anticipatedenrollment in any other clinical study. 13. Employees / family members of:
21. FARAPULSE or any of its affiliates or contractors
22. The Investigator, sub-Investigators, or their medical office or practice, orhealthcare organizations at which study procedures may be performed.