Pulsed Field Ablation (PFA) vs Anti-Arrhythmic Drug (AAD) Therapy as a First Line Treatment for Persistent Atrial Fibrillation

Inclusion Criteria: 1. Age ≥ 18 years of age, or older if specified by local law 2. Have symptomatic persistent AF, confirmed by both: a. Documentation, within 180 days of randomization, or treatment assignment for roll-in subjects, of either: i. A 24-hour continuous ECG recording (from any regulatory cleared rhythm monitoring device) confirming continuous AF, OR ii. Two ECGs (from any regulatory cleared rhythm monitoring device) showing continuous AF taken at least 7 days apart b. Documentation, such as physician note, of persistent continuous AF for \> 7 days and ≤ 365 days 3. Willing and capable of providing informed consent 4. Willing and capable of participating in all testing associated with this clinical investigation at an approved clinical investigational center 5. Willing to receive LUX-Dx™ insertable cardiac monitor (ICM) during the study or already has a LUX-Dx™ ICM that was inserted ≤ 6 months(i.e., within 180 days of consent Exclusion Criteria: 1. Treated with AAD (Class I or III) ≤ 6 months (i.e., within 180 days) before enrollment, 1. More than 7-day history of therapeutic AAD use (Class I or III), or 2. ≥ 24 hours amiodarone, i Note Pill-in-the-pocket AAD use, is permitted. 2. Treated with AAD ( Class I or III) \> 6 months (i.e., more than 180 days) before enrollment and experienced AAD failure (adverse drug effects or frequent AF episodes) 3. Contraindication to, or unwillingness to use, AADs (Class I and III, excluding amiodarone) 4. Contraindication to PFA treatment 5. Contraindication to, or unwillingness to use, systemic anticoagulation, or acceptable alternatives, pre-, intra-, and post-procedure to achieve adequate anticoagulation. 6. Any of the following atrial conditions: 1. Left atrial (LA) anteroposterior diameter ≥ 5.5 cm, or, if LA diameter not available, non-indexed volume \>100 ml, as documented by physician note or imaging (Note: if both values are available, only the LA diameter will be used to confirm eligibility criteria) 2. Any prior atrial endocardial, epicardial or surgical ablation procedure for arrhythmia, other than right sided cavotricuspid isthmus ablation or for right sided supraventricular tachycardia 3. Current atrial myxoma 4. Any PV abnormality, stenosis, or stenting (common and middle PVs are admissible) 5. Current left atrial thrombus 7. Any of the following cardiovascular conditions: 1. History of sustained ventricular tachycardia or any ventricular fibrillation 2. AF that is secondary to electrolyte imbalance, thyroid disease, alcohol, or other reversible / non-cardiac causes 3. Current or anticipated pacemaker, implantable cardioverter defibrillator or cardiac resynchronization therapy devices, interatrial baffle, atrial septal patch, atrial septal defect closure device, or patent foramen ovale occluder 4. Valvular disease that is any of the following: i. Symptomatic, ii. Causing or exacerbating congestive heart failure, iii. Associated with abnormal left ventricular (LV) function or hemodynamic measurements 5. Hypertrophic cardiomyopathy 6. Cardiac amyloidosis 7. Any prosthetic heart valve, ring or repair including balloon aortic valvuloplasty 8. Any inferior vena cava (IVC) filter, known inability to obtain vascular access or other contraindication to femoral access 9. Rheumatic heart disease 10. Congenital heart disease with any clinically significant residual anatomic or conduction abnormality 11. Awaiting cardiac transplantation or other cardiac surgery within the next 12 months 8. Any of the following conditions identified during screening assessments 1. Heart failure associated with New York Heart Association (NYHA) Class IV 2. Left Ventricle Ejection Fraction (LVEF) \< 40% 3. Uncontrolled hypertension (Systolic Blood Pressure \> 160 mmHg or Diastolic Blood Pressure \> 95 mmHg on two (2) BP measurements during screening 9. Any of the following events 90 days prior to randomization (or Index procedure for PFA Assigned or roll-in subjects): 1. Myocardial infarction (MI), unstable angina or coronary intervention 2. Cardiac surgery 3. Heart failure hospitalization 4. Pericarditis or symptomatic pericardial effusion 5. Gastrointestinal bleeding 6. Stroke, TIA, or intracranial bleeding 7. Non-neurologic thromboembolic event 8. Carotid stenting or endarterectomy 10. Known coagulopathy disorder (e.g., von Willbrand's disease, hemophilia) 11. Unwillingness to receive, or unable to tolerate, a subcutaneous, chronically inserted LUX-Dx™ ICM device 12. Women of childbearing potential who are pregnant, lactating, not using a reliable form of contraception, or who are planning to become pregnant during the anticipated study period 13. Body Mass Index (BMI) \> 45 14. Solid organ or hematologic transplant, or currently being evaluated for a transplant 15. Any prior history or current evidence of hemi-diaphragmatic paralysis or paresis 16. Severe lung disease, or any lung disease involving abnormal blood gases or requiring supplemental oxygen 17. Severe pulmonary hypertension during screening assessment 18. Renal insufficiency if an estimated glomerular filtration rate (eGFR) is \< 30 mL / min / 1.73 m2, or with any history of renal dialysis or renal transplant 19. Active malignancy at enrollment (other than cutaneous basal cell or squamous cell carcinoma) 20. Clinically significant gastrointestinal problems involving the esophagus or stomach including severe or erosive esophagitis, uncontrolled gastric reflux, gastroparesis, esophageal candidiasis or active gastroduodenal ulceration 21. Known active systemic infection 22. Uncontrolled diabetes mellitus or a recorded HgbA1c \> 8.0% in the 90 days prior to randomization (or Index procedure for PFA Assigned or roll-in subjects) 23. Untreated diagnosed obstructive sleep apnea with apnea hypopnea index classification of severe (\>30 pauses per hour) 24. Predicted life expectancy less than one (1) year 25. Currently enrolled in another investigational study or registry that would directly interfere with this study, except when the subject is participating in a mandatory governmental registry, or a purely observational registry with no associated treatments; each instance must be brought to the attention of the Sponsor to determine eligibility 26. Health conditions that, in the investigator's medical opinion, would prevent participation in the study, interfere with assessment or therapy, significantly raise the risk of study participation, or modify outcome data or its interpretation 27. Has operational LUX-Dx ICM that was inserted more than 6 months (i.e., \>180 days) prior to enrollment 28. Has operational ICM other than a LUX-Dx ICM and does not express a willingness to receive a LUX-Dx ICM for the study 29. Individuals who may require an ablation, besides the PV and PW, in the left atrium including, but not limited to, those with Left-Sided Atrioventricular Reentrant Tachycardia (AVRT), Left-Sided Atrial Tachycardia (AT), or Atypical Left-Sided Atrial Flutter. 30. AAD (Class I and III) Drug Naïve Subjects (as defined in criterion #1 and #2), who are PFA Assigned (Non-Roll-in), PFA randomized, or Roll-in with a CHA2DS2-VASc Score ≥ 4