A Global Study Comparing Pulsed Field Ablation With Electrographic Flow Mapping Versus Posterior Wall Ablation for Persistent Atrial Fibrillation

Inclusion Criteria:

1. ≥ 18 years of age, or older if required by local law

2. Have symptomatic drug-refractory1, persistent AF2, confirmed by both:

• Documentation, such as physician note, of persistent continuous AF for > 7 daysand ≤ 365 days and the arrhythmia symptoms

• Documentation, within 180 days of enrollment date of either:

• A 24-hour continuous ECG recording confirming continuous AF or

• Two (2) ECGs (from any regulatory cleared rhythm monitoring device)showing continuous AF taken at least 7 days apart

3. Willing and capable of providing informed consent

4. Willing and capable of participating in all follow-up assessments and testingassociated with this clinical investigation at an approved clinical investigationalcenter

5. Willing to receive LUX-Dx™ insertable cardiac monitor (ICM) during the study oralready has a LUX-Dx™ ICM that was inserted ≤ 6 months (i.e., within 180 days) ofconsent, and willing to comply to the LUX-Dx Latitude Clarity transmissioninstructions

Exclusion Criteria:

1. Any of the following atrial conditions:

2. Left atrial anteroposterior diameter ≥ 5.5 cm, or if1 LA diameter notavailable, non-indexed volume >100 ml (physician note or imaging)

3. Any prior left atrial ablation

4. Any prior atrial surgery

5. Current atrial myxoma

6. Current left atrial thrombus

7. Any PV abnormality, stenosis, or stenting (common and middle PVs areadmissible)

8. Any of the following cardiovascular conditions:

9. History of sustained ventricular tachycardia or any ventricular fibrillation

10. Severe right ventricular dysfunction with documented echocardiography and/orhemodynamic data, per Investigator's discretion

11. AF that is secondary to electrolyte imbalance, thyroid disease, alcohol, orother reversible / non-cardiac causes

12. Cardiac devices and implants:

• Current or anticipated pacemaker, implantable cardioverter defibrillatoror cardiac resynchronization therapy devices
• Implantable loop recorder, other than LUX-Dx
• Interatrial baffle, patent foramen ovale or atrial septal defect closuredevice or patch
• Any left atrial appendage closure or occlusion device

5. Presence of any of the following valvular conditions:

• Any prosthetic heart valve, stenotic valves, ring or repair
• Moderate to severe mitral valve stenosis
• More than moderate mitral regurgitation

6. Hypertrophic or amyloid cardiomyopathy

7. Any IVC filter, known inability to obtain vascular access or othercontraindication to femoral access

8. Awaiting cardiac transplantation or other planned cardiac surgery within thenext 12 months

9. Severe right ventricular dysfunction with documented echocardiography and/orhemodynamic data.

10. Any of the following conditions at Baseline:

11. Heart failure associated with NYHA Class III or IV

12. Most recent documented LVEF < 40% within the previous 12 months

13. Body Mass Index (BMI) > 45.0

14. Known coagulopathy or bleeding disorder

15. Contraindication to, or unwillingness to use systemic anticoagulation, oracceptable alternatives, pre-, intra- and post-procedure to achieve adequateanticoagulation

16. Women who are confirmed to be pregnant or lactating at the time of the ablationprocedure

17. Severe lung disease, severe pulmonary hypertension, or any lung diseaseinvolving abnormal blood gases or requiring supplemental oxygen

18. Active malignancy (other than squamous cell carcinoma)

19. Clinically significant gastrointestinal problems involving the esophagus orstomach including severe or erosive esophagitis, uncontrolled gastric reflux,gastroparesis, esophageal candidiasis or active gastroduodenal ulceration

20. Known active systemic infection

21. Untreated diagnosed obstructive sleep apnea with apnea hypopnea indexclassification of severe (>30 pauses per hour) as per the guidelines

22. Predicted life expectancy less than one year per investigator medical judgement

23. Subjects who are currently enrolled in another investigational study orregistry that would directly interfere with the current study, except when thesubject is participating in a mandatory governmental registry, or a purelyobservational registry with no associated treatments; each instance must bebrought to the attention of the Sponsor to determine eligibility

24. Required use of phosphodiesterase inhibitors within 24 hours of the ablationprocedure

25. Uncontrolled hypertension (SBP > 160 mmHg or DBP > 95 mmHg on two (2) BPmeasurements at baseline assessment not attributable to white coat syndrome perInvestigator opinion

26. CHA2DS2-VASc score ≥ 5

27. Known allergic drug reaction to nitroglycerin (excluding hypotension)

28. Unwillingness to receive, or unable to tolerate, a subcutaneous, chronicallyinserted LUX-Dx ICM device

29. Any of the following congenital conditions:

30. Congenital heart disease with any clinically significant residual anatomic orconduction abnormality

31. History of known congenital methemoglobinemia

32. History of known G6PD deficiency

33. Any of the following conditions in the medical history:

34. Solid organ or hematologic transplant, or currently being evaluated for atransplant

35. Any prior history or current evidence of hemi-diaphragmatic paralysis orparesis

36. Any documented history of Prinzmetal Angina or severe non-revascularizablecoronary disease

37. Renal insufficiency if an estimated glomerular filtration rate (eGFR) is < 30mL / min / 1.73 m2, or with any history of renal dialysis or renal transplant

38. Any other general health condition 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 orits interpretation.

39. Any of the following events less than or equal to 90 days of the consent date:

40. Myocardial infarction (MI), unstable angina or coronary intervention

41. Any cardiac surgery

42. Heart failure hospitalization

43. Pericarditis or symptomatic pericardial effusion

44. Gastrointestinal bleeding

45. Stroke, TIA, or intracranial bleeding

46. Any active non-neurologic thrombus and/or thromboembolic event

47. Carotid stenting or endarterectomy

48. Uncontrolled diabetes mellitus or a recorded HbA1c > 8.0%