Inclusion Criteria- Over the preceding 6 months have:
1. ≥2 paroxysmal (electrocardiographic documentation of at least 1) AF episodes lasting ≥1 hour in duration: (that terminate spontaneously within 7 days or cardioversion is performed within 48h of AF onset): or
2. electrocardiographic documentation of 1 persistent AF episode: (sustained for ≥7 days or cardioversion is performed more than 48h after AF onset): or
3. electrocardiographic documentation of 1 longstanding persistent AF episode: (continuous AF of duration >1 year).
- Warrant active therapy (within the past 3 months) beyond simple ongoing observation
- Be eligible for catheter ablation and ≥2 sequential rhythm control and/or ≥2 rate control drugs.
- Be ≥65 yrs of age, or <65 yrs with one or more of the following risk factors for stroke: Hypertension (treated and/or defined as a BP >140/90 mmHg) , Diabetes (treated and/or defined as a fasting glucose ≥126 mg/dl) , Congestive heart failure (including systolic or diastolic heart failure), Prior stroke, TIA or systemic emboli, Atherosclerotic vascular disease (previous MI, peripheral arterial disease or aortic plaque), LA size >5.0 cm (or volume index ≥40 cc/m2), or EF ≤35.
- Have the capacity to understand and sign an informed consent form.
- Be ≥18 years of age.
- NOTE- Subjects <65 yrs of age whose only risk factor is hypertension must have a second risk factor or LV hypertrophy to qualify.Patients receiving new drug therapy initiated within the previous 3 months may continue that therapy if randomized to the drug therapy arm. Patients may have documented atrial flutter in addition to atrial fibrillation and remain eligible for enrollment.
Exclusion Criteria- Lone AF in the absence of risk factors for stroke in patients <65 years of age
- Patients who in the opinion of the managing clinician should not yet receive any therapy for AF
- Patients who have failed >2 membrane active anti-arrhythmic drugs at a therapeutic dose due to inefficacy or side effects (Table 5.2.2)
- An efficacy failure of full dose amiodarone treatment >8 weeks duration at any time
- Reversible causes of AF including thyroid disorders, acute alcohol intoxication, recent major surgical procedures, or trauma
- Recent cardiac events including MI, PCI, or valve or bypass surgery in the preceding 3 months
- Hypertrophic obstructive cardiomyopathy (outflow track)
- Class IV angina or Class IV CHF (including past or planned heart transplantation)
- Other arrhythmias mandating anti-arrhythmic drug therapy (i.e. VT, VF)
- Heritable arrhythmias or increased risk for torsade de pointes with class I or III drugs
- Prior LA catheter ablation with the intention of treating AF
- Prior surgical interventions for AF such as the MAZE procedure
- Prior AV nodal ablation
- Patients with other arrhythmias requiring ablative therapy
- Contraindication to appropriate anti-coagulation therapy
- Renal failure requiring dialysis
- Medical conditions limiting expected survival to <1 year
- Women of childbearing potential (unless post-menopausal or surgically sterile)
- Participation in any other clinical mortality trial (Participation in other non-mortality trials should be reviewed with the clinical trial management center)
- Unable to give informed consent
- NOTE- Prior ablation of the cavo-tricuspid isthmus alone is not an exclusion if the patient develops subsequent recurrent AF. Planned atrial flutter ablation in combination with the left atrial ablation is not an exclusion.