Prospective trial comparing the efficacy and safety of CryoBalloonAblation (CBA) to standardized medication for treatment of early onset persistent atrial fibrillation (AF) without structural heart disease. The value of CBA in these patients has never been studied; the endpoints for persistent patients are much easier than for paroxysmal patients. Reduction in left atrial (LA) size will be compared versus patients on drug therapy and versus failing patients.

The total AF history should be shorter than 24 months. Symptomatic patients can be included if they have had within the last year at least 2 episodes of documented AF, lasting minimal 30 sec. One episode in the entire history should have lasted more than 48 h, requiring electrical or pharmacological cardioversion or stopped spontaneously after more than 7 days.

All patients eligible for the study will sign informed consent, have an echocardiogram prior to inclusion to exclude severe left ventricular dysfunction, to rule out significant valve abnormalities, left ventricular hypertrophy and to assess the LA volume and diameter.

Prior to randomization, and after inclusion it is suggested to the local investigators to perform an MRI-scan or CT scan of the LA and pulmonary veins (in both branches of the study ) in eligible patients to assess the anatomy and the left atrial volume. The results should not influence the strategy of treatment.

Inclusion Criteria:

• > 21 years and legally capable
• First documentation or history of symptomatic AF more than 30 sec within the last 2 years
• Twice AF within the last year
• One episode cardioverted after more than 48 hours or spontaneously terminated after more than 7 days
• Eligible for at least one first step drug therapy (sotalol, propafenone, or flecainide) and for amiodarone
• Left ventricular ejection fraction estimated > 45%
• LA diameter < 50 mm (parasternal short axis) and LA volume less than 100 ml (apical view, Area Length method;)
• CHADS2 ≤ 2
• Failed AAD strategy, or untreated with AAD
• No use of Amiodarone in the previous 3 months (except IV or oral for 7 days)
• Informed consent

Exclusion Criteria:

• Age > 75 yrs
• CHF
• Ischemic heart disease as known in the history
• (Severe) Left ventricular hypertrophy as shown on echo (IVSd or PWd > 14 mm)
• Hyperthyroidism
• Congenital heart disease
• Hypertrophic Cardiomyopathy, Arrhythmogenic Right ventricular Cardiomyopathy, channelopathies
• Contra-indications to AAD
• Long QT syndrome
• Received already adequately dosed all level 1 drugs (sotalol, propafenone, and flecainide)
• Pure (typical) atrial flutter as documented on one occasion