The purpose of this study is to assess how safe VARIPULSE catheter system is for treatment of a heart rhythm disease called persistent atrial fibrillation (PsAF) in participants who are having a catheter ablation procedure (treat heart rhythm disease). This includes isolation of pulmonary vein and superior vena cava (heart veins; PVI and SVCI), with or without another technique called posterior wall isolation (PWI). Also, to assess how safe it is for participants who are having a catheter ablation procedure and at the same time receiving another procedure called left atrial appendage occlusion (LAAO; to reduce stroke risk). Additionally, to assess how well VARIPULSE catheter system works over a long period of time for treatment of PsAF in participants undergoing catheter ablation.

Inclusion criteria:

• Participant has been diagnosed with symptomatic persistent atrial fibrillation (PsAF), which is defined as continuous atrial fibrillation (AF) sustained beyond 7 days in duration and less than 365 days in duration, documented by: i. A physician's note documenting diagnosis of symptomatic PsAF, as defined above; and ii. Two electrocardiograms (ECGs) showing continuous AF, with electrocardiogram taken at least 7 days apart (electrocardiograms cannot be greater than (>) 365 days prior to enrollment); or iii. A 24-hour arrhythmia monitor documenting continuous AF within the last 365 days
• Participant is aged 18 - 80 years at the time of informed consent
• Participant is willing and capable of providing informed consent
• Participant is able and willing to comply with all pre-, post- and follow-up testing and requirement

Left atrial appendage occlusion (LAAO) concomitant subset:

- Participant is clinically indicated for a LAAO procedure

Exclusion criteria:

• Participant has continuous AF > 365 days (longstanding persistent AF)
• Participant has AF secondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac cause (for example, untreated documented obstructive sleep apnea, acute alcohol toxicity, etc.)
• Participant has had previous surgical or catheter ablation for AF
• Participant is known to require ablation outside the left atrium (LA), superior vena cava (SVC), and the cavotricuspid isthmus (CTI) region (for example, atrioventricular reentrant tachycardia, atrioventricular nodal reentry tachycardia, ventricular tachycardia and Wolff-Parkinson-White)
• Participant has severe dilatation of the LA (left atrial diameter [LAD] > 50 millimeters [mm]) of the antero-posterior diameter confirmed by imaging performed within 180 days prior to enrollment
• Participant has LA thrombus confirmed by imaging within 48 hours prior to the procedure
• Participant has severely compromised left ventricular ejection fraction (left ventricle ejection fraction [LVEF] less than [<] 40 percent [%]) confirmed by imaging performed within 180 days prior to enrollment
• Participant has uncontrolled heart failure or New York heart association (NYHA) Class III or IV functional classification
• Participant has a history of blood clotting, bleeding abnormalities or contraindication to anticoagulation (for example, heparin)
• Participant has had a thromboembolic event (including transient ischemic attack [TIA]) within the past 180 days prior to enrollment
• Participant has had a percutaneous coronary intervention or acute myocardial infarction (MI) within past 60 days prior to enrollment
• Participant has had coronary artery bypass grafting (CABG) surgery within the past 180 days prior to enrollment
• Participant has had valvular cardiac surgical/percutaneous procedure (that is, ventriculotomy, atriotomy, valve repair or replacement and presence of a prosthetic valve)
• Participant has unstable angina within past 6 months prior to enrollment
• Participant has anticipated cardiac transplantation, cardiac surgery, or other major surgery within the next 365 days post-procedure
• Participant has significant pulmonary disease (for example, restrictive pulmonary disease, constrictive or chronic obstructive pulmonary disease) or any other disease or malfunction of the lungs or respiratory system that produces severe chronic symptoms
• Participant has a significant congenital anomaly (for example, atrial septal defects [ASDs]) including repaired defects or medical problems that in the opinion of the Investigator would preclude enrollment in this study
• Participant has an existing diagnosis of pulmonary vein stenosis (PVS)
• Participant has a pre-existing hemi-diaphragmatic paralysis
• Participant has an acute illness, active systemic infection, or sepsis
• Participant has an intracardiac thrombus, myxoma, tumor, interatrial baffle or patch or other abnormality that precludes catheter introduction or manipulation
• Participant has severe mitral regurgitation (Regurgitant volume greater than or equal to [>=] 60 milliliters [mL]/beat, Regurgitant fraction >= 50%, and/or Effective regurgitant orifice area >= 0.40 square centimeter [cm^2])
• Participant has an implanted metal cardiac device (other than coronary stents, implanted pacemaker, implantable cardioverter-defibrillator [ICD], implantable loop recorder [ILR]) that may interfere with the pulsed field (PF) energy field
• Participant has a condition that precludes vascular access (such as inferior vena cava [IVC] filter) - Participant is currently enrolled in an investigational study evaluating another device or drug
• Participant is pregnant, lactating, or is of child-bearing potential and plans on trying to become pregnant during the course of the clinical investigation
• Participant has a life expectancy of less than 365 days
• Participant has contraindications for the devices used in the study, as indicated in the respective instructions for use (IFUs)
• Participant has contraindications for the ablation of the SVC

LAAO concomitant subset:

• Participant is contraindicated for a LAAO procedure per the instructions of use of the planned LAAO device
• Participant with prior LAAO procedure (attempted or successful)

The data sharing policy of Johnson & Johnson Innovative Medicine is available at www.innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu.