This study is to assess the effectiveness and safety of using cryoballoon ablation comparing with anti-arrhythmic drug therapy as initial treatment for naive patients with persistent atrial fibrillation.

Subjects with persistent atrial fibrillation with no history of treatment with anti-arrhythmic drugs are randomized 1:1 to either an anti-arrhythmic drug or pulmonary vein isolation using the cryoballoon catheter.

Inclusion Criteria:

• Documentation of symptomatic persistent AF: Defined as having a continuous episode lasting longer than 7 days but less than 1 year documented by consecutive ECG recordings OR Defined as having a continuous episode lasting longer than 7 days but less than 1 year documented by an ECG recording and one doctor note indicating patient had symptoms consistent with AF
• Age 18 -75 years old
• Structurally normal heart with LVEF ≥50%, interventricular septum thickness ≤ 12 mm, and left atrial diameter <46 mm (short axis) as obtained by transthoracic echocardiography. •
• Normal ECG parameters when measured in sinus rhythm (QRS width ≤120 ms in a 12-channel surface ECG, QTc interval <440 ms, and PQ interval ≤210 ms).

Exclusion Criteria:

• History of AF treatment with class I or III antiarrhythmic drug, including sotalol, with the intention to prevent an AF recurrence. However, patients pretreated with above AAD for less than 7 days with the intention to convert an AF episode are allowed.
• left atrial ablation or surgical procedure (including left atrial appendage closures)
• Presence or likely implant of a permanent pacemaker, biventricular pacemaker, loop recorder, or any type of implantable cardiac defibrillator (with or without biventricular pacing function) within 12 months
• Presence of any pulmonary vein stents
• Presence of any pre-existing pulmonary vein stenosis
• Pre-existing hemidiaphragmatic paralysis
• Presence of any cardiac valve prosthesis
• +3 and +4 mitral valve regurgitation or stenosis
• Any cardiac surgery, myocardial infarction, percutaneous coronary intervention (PCI) / percutaneous transluminal coronary angioplasty (PTCA) or coronary artery stenting which occurred during the 3 month interval preceding e consent date
• Unstable angina
• New York Heart Association (NYHA) Class II, III or IV congestive heart failure
• Primary pulmonary hypertension
• Rheumatic heart disease
• Thrombocytosis, thrombocytopenia
• Any condition contraindicating chronic anticoagulation
• Active systemic infection
• Hypertrophic cardiomyopathy
• Cryoglobulinemia
• Uncontrolled hyperthyroidism
• Any cerebral ischemic event (strokes or transient ischemic attacks (TIAs)) which occurred during the 6 month interval preceding the consent date
• Any woman known to be pregnant or breastfeeding.
• Life expectancy less than one year
• 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
• Active intracardiac thrombus
• Known drug or alcohol dependency
• Unwilling or unable to comply fully with study procedures and follow-up
• Significant Chronic Kidney Disease-estimated Glomerular Filtration Rate(CKD-eGFR) <30umol/L