Outcomes of an Optimized Workflow With PulseSelect Pulsed Field Ablation (PFA) System in Paroxysmal and Persistent Atrial Fibrillation

This study will include subjects with a diagnosis of recurrent symptomatic Paroxysmal and Persistent AF. Following the index ablation procedure and hospital discharge, all study subjects will be followed at 7 days, 2 months, 6 months, and 12 months and will be exited from the study at the conclusion of the 12-month follow-up visit.

• PulseSelect Pulse Field Ablation (PFA) System (Device): Adult subjects with recurrent symptomatic paroxysmal AF or persistent AF will be enrolled and undergo ablation with the PulseSelect™ PFA system.

Primary outcomes

• Safety: Number of Participants with at Least One Primary Safety Event [Up to 6 months post procedure]: Primary Safety events are: Within 7 days of ablation procedure: * Heart block requiring a pacemaker * Major bleeding requiring transfusion * Myocardial infarction * Permanent phrenic nerve paralysis * Pulmonary edema * Severe pericarditis * Significant pericardial effusion/tamponade * Stroke/cerebrovascular accident (CVA) * Systemic/pulmonary embolism requiring intervention * Transient ischemic attack (TIA) * Vagal nerve injury resulting in esophageal dysmotility or gastroparesis * Vascular access complications requiring intervention * Acute Kidney Injury (AKI) requiring dialysis, new hospitalization greater than 48 hours, or prolongation of hospitalization greater than 48 hours beyond the expected discharge * Death Within 3 months post-ablation: \- Atrioesophageal fistula/Esophageal perforation (procedure and PulseSelect PFA Loop Catheter related) Within 6 months post-ablation: \- Pulmonary vein stenosis (≥70% diameter reduction)
• Effectiveness: Number of Participants with Treatment Success [Up to 12 months post procedure]: Treatment success is defined as freedom from documented recurrence of AF, AT, or AFL based on electrocardiographic data up to the 12-month follow-up and excluding a 90-day blanking period. Treatment failure is defined as any of the following components: * Acute procedural failure (see definition below) * Documented AF/AT/AFL after the 90-day post-ablation blanking period * Any subsequent AF catheter or surgical ablation in the LA, including repeat PVI ablation at any time during the study. * Direct current cardioversion for AF/AT/AFL recurrences after the 90-day blanking period. * Use of a Class I or III AAD at a higher daily dose than the pre-ablation maximum daily dose after the 90-day blanking period. * Initiation of a new Class I or III AAD after the 90-day blanking period. * Re-initiation after the 90-day blanking period of any dose of a Class I or III AAD that was failed or was not tolerated prior to the ablation procedure.

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

1. Adults who are ≥18 and ≤80 years of age on the day of enrollment (or older than 18 if required by local law)
2. A diagnosis of recurrent symptomatic paroxysmal or persistent AF:

   Symptomatic paroxysmal AF: AF that terminates spontaneously or with intervention within 7 days of onset, documented by the following:
   1. Physician's note indicating at least 2 symptomatic paroxysmal AF episodes occurring within 12 months prior to enrollment; AND
   2. at least 1 ECG documented AF episode from any form of rhythm monitoring within 12 months prior to enrollment.

   Symptomatic persistent AF: Continuous AF sustained beyond 7 days and less than 1 year, documented by the following:
   1. Physician's note indicating at least 1 symptomatic persistent AF episode occurring within 12 months prior to enrollment; AND
   2. any 24-hour continuous ECG recording documenting continuous AF within 12 months prior to enrollment; OR 2 ECGs from any form of rhythm monitoring taken at least 7 days apart, both showing continuous AF within 12 months prior to enrollment
3. Willing and able to comply with all baseline and follow-up evaluations for the full length of the study.

Exclusion Criteria:

1. Long-standing persistent AF (continuous AF that is sustained >12 months)
2. Paroxysmal AF patients: AF that required three (3) or more distinct cardioversions in the preceding 12 months.
3. Paroxysmal AF: LA anteroposterior diameter > 5.0 cm (by MRI, CT, or TTE) Persistent AF: LA anteroposterior diameter > 5.5 cm (by MRI, CT, or TTE)
4. Any of the following procedures, implants, or conditions at baseline: prior left atrial catheter or surgical ablation, prior left atrial percutaneous interventions including left atrial appendage occlusion, and septal closure devices
5. Planned LAA closure procedure or implant of a permanent pacemaker, biventricular pacemaker, loop recorder/insertable cardiac monitor (ICM), or any type of implantable cardiac defibrillator (with or without biventricular pacing function) for any time during the follow-up period
6. Presence of a permanent pacemaker, biventricular pacemaker, loop recorder/insertable cardiac monitor (ICM), or any type of implantable cardiac defibrillator (with or without biventricular pacing function)
7. Patient who is not on oral anticoagulation therapy for at least 3 weeks prior to the ablation procedure
8. Contraindication to or unwillingness to use systemic anticoagulation
9. Presence of any pulmonary vein stents
10. Known pre-existing pulmonary vein stenosis
11. Prior valvular (surgical or percutaneous) procedure including prosthetic, bioprosthetic, valve replacement, valve repair or valvuloplasty, and any prior atriotomy
12. Moderate to severe mitral valve or aortic stenosis
13. Moderate to severe mitral regurgitation (i.e., 3+ or 4+ MR)
14. Any cardiac surgery, myocardial infarction, PCI / PTCA or coronary artery stenting which occurred during the 3-month interval preceding the consent date
15. Unstable angina
16. NYHA Class III or IV congestive heart failure or documented left ventricular ejection fraction (LVEF) less than or equal to 40% measure by acceptable cardiac testing (e.g. TTE), or planned transplant or left ventricular assist device (LVAD)
17. Severe lung disease, primary pulmonary hypertension, or any lung disease abnormal blood gases or requiring supplemental oxygen
18. Rheumatic heart disease
19. Severe thrombocytosis, thrombocytopenia, or any bleeding or clotting disorder
20. Documented left atrial thrombus on imaging
21. Active systemic infection or sepsis
22. Hypertrophic cardiomyopathy
23. Known reversible causes of AF, including but not limited to uncontrolled hyperthyroidism, severe untreated obstructive sleep apnea, and acute alcohol toxicity
24. Any cerebral ischemic event (strokes or TIAs) which occurred during the 6-month interval preceding the consent date
25. Carotid stenting or endarterectomy
26. History of thromboembolic event within the past 6 months or evidence of intracardiac thrombus at the time of the procedure
27. Any woman known to be pregnant or breastfeeding, or any woman of childbearing potential who is not on a reliable form of birth regulation method or abstinence
28. Patient with life expectancy that makes it unlikely 12 months of follow-up will be completed
29. Current or anticipated participation in any other clinical trial of a drug, device or biologic during the duration of the study not pre-approved by Medtronic
30. Known allergies or hypersensitivities to adhesives
31. Body mass index > 40 kg/m2
32. Atrial myxoma
33. Significant restrictive or obstructive pulmonary disease or chronic respiratory condition.
34. Renal insufficiency with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2, or any history of renal failure requiring dialysis or renal transplant
35. Solid organ or hematologic transplant, or currently being evaluated for an organ transplant
36. Presence of intramural thrombus, tumor, or other abnormality that precludes vascular access, catheter introduction, or manipulation
37. Known drug or alcohol dependency
38. Significant congenital anomaly or medical problem that, in the opinion of the investigator, would preclude enrollment in this study or compliance with follow-up requirements or would impact the scientific soundness of the clinical trial results
39. Amyloid heart disease (cardiac amyloidosis)

• Jason Andrade, Prof., Principal investigator, Vancouver General Hospital
• Gerhard Hindricks, Prof., Principal investigator, German Heart Center Charite