• The primary end point of the study was freedom from recurrent atrial tachyarrhythmias ([AT], both AF and regular atrial tachycardia) during a 12 months follow-up. The first analysis was scheduled to be performed after the last enrolled patient complete
  

• Presence of SR during 1-month intervals
  
• Percent of patients totally free of AF
  
• Number of cardioversions
  
• LV function
  
• Incidence of cardiovascular hospitalization
  
• Overall morbidity
  
• Left atrial size and function
  
• Thromboembolic and bleeding complications
  
• Efficacy and safety of two 3D mapping systems
  
• Efficacy and safety of two ablation catheters
  
• Procedure duration, length of hospital stay
  

Antiarrhythmic drug therapy (ADT) is currently considered as first-line therapy in patients with paroxysmal atrial fibrillation (AF).1 However antiarrhythmic drugs are frequently ineffective and can have serious potential adverse effects, thus often offsetting any advantage offered by the maintenance of sinus rhythm (SR).2,3 Data from our and other laboratories suggest that pulmonary vein ablation techniques may be a curative alternative for AF, obviating the need for ADT and/or anticoagulation in many patients.4-8 However, only preliminary and frequently non-randomized data exists for an evidence-based evaluation of catheter ablation as compared to conventional antiarrhythmic drug therapyADT.4,8 Thus, we conducted a controlled randomized trial (the Ablation for Paroxysmal Atrial Fibrillation [APAF] trial) to determine the long-term efficacy of circumferential pulmonary vein ablation (CPVA) in patients with paroxysmal AF as compared with ADT with flecainide, sotalol or amiodarone.

Methods: One hundred ninety-eight patients (age, 56±10 years) with PAF (duration, 6±5 years, mean AF episodes 3.4/month), were randomized to CPVA or to ADT with flecainide, sotalol or amiodarone. Ablation was randomly performed with the use of a standard or an irrigated tip catheter and with CARTO or NavX non fluoroscopic 3D systems guidance. Cardiac rhythm was assessed with daily transtelephonic transmissions over a 12-month follow-up. Crossovers to CPVA were allowed after 3 months of ADT.

Results: By Kaplan-Meier analysis, 86% of patients in the CPVA group and 22% in the ADT group were free from recurrent atrial tachyarrhythmias ([AT] P<0.001); a repeat ablation was performed in 9% of patients in the CPVA group for recurrent AF (6%) or atrial tachycardia (3%). At 1 year, 93% and 35% of the CPVA and ADT groups were AT-free. Lower left ejection fraction, arterial hypertension and age independently predicted AF recurrences in the ADT group. CPVA was associated with a significant decrease in left atrial diameter (15±10%, P<0.01) and with fewer number of cardiovascular hospitalizations (p<0.01). Ablation with an irrigated tip catheter was more effective (P=0.03) with either the CARTO or NavX system (P=0.08). One transient ischemic attack and one pericardial effusion occurred in the CPVA group; side effects of ADT were reported in 23 patients.

Conclusions: Compared to ADT, CPVA can safely and effectively cure PAF in over 93% of the patients at one-year follow-up.

Inclusion Criteria:

1. Age 18-70 years
2. History of symptomatic paroxysmal AF lasting more than 6 months. Paroxysms of AF are intended as recurrent self-terminating episodes lasting less than 7 days and occurring more than 2 times every month.

Exclusion Criteria:

1. Pregnancy
2. NYHA functional class III or IV
3. Left atrial size > 65 mm
4. Left ventricular (LV) ejection fraction < 35%
5. Contraindication to anticoagulation with warfarin
6. History of myocardial infarction within six months of the procedure
7. Prior catheter or surgical ablation attempt for AF
8. Inability or unwillingness to provide written informed consent
9. Life expectancy less than 1 year
10. Significant comorbid conditions such as: cancer (not cured), end stage renal disease (creatinine clearance < 20 mL/h), severe chronic obstructive lung disease, cirrhosis, etc)
11. Anticipated cardiac surgery for congenital, valvular, aortic or coronary heart disease.
12. Presence of left atrial thrombus.
13. Prior antiarrhythmic drug therapy with amiodarone, sotalol and flecainide at optimal doses (target 200 mg, 240 mg, 200 mg daily respectively
14. AF burden < 2 episodes/month
15. WPW
16. Expected survival < 1 year

17. Contraindications for antiarrhythmics therapy including flecainide, sotalol or amiodarone not listed above:

    • LV hypertrophy (LV mass index > 125g/m2)
    • thyroid dysfunction (hyperthyroidism or uncontrolled hypothyroidism or thyroid cancer)
    • liver dysfunction (ALT or AST >2x the reference values)
    • Interstitial lung disease with DLCO<70% of predicted or severe asthma.
    • QT interval exceeding 400 msec
    • Symptomatic sinus node or atrioventricular node dysfunction unless a pacemaker had been implanted
    • Evidence of stress-induced myocardial ischemia