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 days and ≤ 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 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, and willing to comply to the LUX-Dx Latitude Clarity transmission instructions
Exclusion Criteria:
1. Any of the following atrial conditions:
1. Left atrial anteroposterior diameter ≥ 5.5 cm, or if1 LA diameter not available, non-indexed volume \>100 ml (physician note or imaging)
2. Any prior left atrial ablation
3. Any prior atrial surgery
4. Current atrial myxoma
5. Current left atrial thrombus
6. Any PV abnormality, stenosis, or stenting (common and middle PVs are admissible)
2. Any of the following cardiovascular conditions:
1. History of sustained ventricular tachycardia or any ventricular fibrillation
2. Severe right ventricular dysfunction with documented echocardiography and/or hemodynamic data, per Investigator's discretion
3. AF that is secondary to electrolyte imbalance, thyroid disease, alcohol, or other reversible / non-cardiac causes
4. Cardiac devices and implants:
* Current or anticipated pacemaker, implantable cardioverter defibrillator or cardiac resynchronization therapy devices
* Implantable loop recorder, other than LUX-Dx
* Interatrial baffle, patent foramen ovale or atrial septal defect closure device 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 other contraindication to femoral access
8. Awaiting cardiac transplantation or other planned cardiac surgery within the next 12 months
9. Severe right ventricular dysfunction with documented echocardiography and/or hemodynamic data.
3. Any of the following conditions at Baseline:
1. Heart failure associated with NYHA Class III or IV
2. Most recent documented LVEF \< 40% within the previous 12 months
3. Body Mass Index (BMI) \> 45.0
4. Known coagulopathy or bleeding disorder
5. Contraindication to, or unwillingness to use systemic anticoagulation, or acceptable alternatives, pre-, intra- and post-procedure to achieve adequate anticoagulation
6. Women who are confirmed to be pregnant or lactating at the time of the ablation procedure
7. Severe lung disease, severe pulmonary hypertension, or any lung disease involving abnormal blood gases or requiring supplemental oxygen
8. Active malignancy (other than squamous cell carcinoma)
9. Clinically significant gastrointestinal problems involving the esophagus or stomach including severe or erosive esophagitis, uncontrolled gastric reflux, gastroparesis, esophageal candidiasis or active gastroduodenal ulceration
10. Known active systemic infection
11. Untreated diagnosed obstructive sleep apnea with apnea hypopnea index classification of severe (\>30 pauses per hour) as per the guidelines
12. Predicted life expectancy less than one year per investigator medical judgement
13. Subjects who are currently enrolled in another investigational study or registry that would directly interfere with the current 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
14. Required use of phosphodiesterase inhibitors within 24 hours of the ablation procedure
15. Uncontrolled hypertension (SBP \> 160 mmHg or DBP \> 95 mmHg on two (2) BP measurements at baseline assessment not attributable to white coat syndrome per Investigator opinion
16. CHA2DS2-VASc score ≥ 5
17. Known allergic drug reaction to nitroglycerin (excluding hypotension)
18. Unwillingness to receive, or unable to tolerate, a subcutaneous, chronically inserted LUX-Dx ICM device
4. Any of the following congenital conditions:
1. Congenital heart disease with any clinically significant residual anatomic or conduction abnormality
2. History of known congenital methemoglobinemia
3. History of known G6PD deficiency
5. Any of the following conditions in the medical history:
1. Solid organ or hematologic transplant, or currently being evaluated for a transplant
2. Any prior history or current evidence of hemi-diaphragmatic paralysis or paresis
3. Any documented history of Prinzmetal Angina or severe non-revascularizable coronary disease
4. 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
5. 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 or its interpretation.
6. Any of the following events less than or equal to 90 days of the consent date:
1. Myocardial infarction (MI), unstable angina or coronary intervention
2. Any cardiac surgery
3. Heart failure hospitalization
4. Pericarditis or symptomatic pericardial effusion
5. Gastrointestinal bleeding
6. Stroke, TIA, or intracranial bleeding
7. Any active non-neurologic thrombus and/or thromboembolic event
8. Carotid stenting or endarterectomy
9. Uncontrolled diabetes mellitus or a recorded HbA1c \> 8.0%
