Catheter Ablation Compared With Pharmacological Therapy for Atrial Fibrillation - a Randomized Multicentre Study Comparing Atrial Fibrillation Ablation Strategy With Optimized Conventional Pharmacological Strategy After 12 Months Follow-up.

It is a randomized, open-label, multi-centre trial in which patients with symptomatic paroxysmal or persistent atrial fibrillation will be randomized to treatment with either catheter ablation for pulmonary vein isolation or optimized conventional pharmacological therapy. Patients will receive an implantable cardiac monitor, Reveal XT, implanted subcutaneously, before a two month "Run-in" period from which the basic atrial fibrillation burden will be defined, which will provide an objective basis to assess the AF burden for 3 years.

After initiation of randomized therapy, patients will be followed at 3, 6, 9, 12, 18, 24, 30, 36 and 48 months. In case of intolerable symptomatic atrial fibrillation despite allocated treatment, subjects will be switched to the alternative regimen, on patient's request.

The ablation will consist of pulmonary vein isolation for both paroxysmal and persistent atrial fibrillation. A linear lesion at the left atrial roof is optional for patients with recurrence after a first procedure or primarily for patients with persistent atrial fibrillation only. A second ablation procedure may be undertaken at earliest 3 months after the first procedure, if symptoms persists or recurs. Epicardial off-pump ablation may be offered after failed attempts of transvenous catheter ablation at earliest 3 months after latest procedure. If the second transvenous ablation procedure fails, patients may be offered i) a third transvenous ablation procedure or ii) an epicardial off-pump procedure. In case the patient declines a third intervention despite recurrence, the patient should continue on the same anti-arrhythmic drugs. If new previously untested drugs are prescribed, the patient will be defined as a change of treatment (and failed ablation). Ablation may be performed using radiofrequency energy with irrigated tip or with cryo-energy using the Arctic Front™ Cardiac CryoAblation Catheter. A complete pulmonary vein isolation will be defined by documenting PV entrance block in each vein using a circular mapping catheter.

Anti-arrhythmic drugs remaining to be tested for rate and rhythm control may include previously tested tolerable antiarrhythmic drugs if dosages were inadequate. Optimized anti-arrhythmic drug therapy includes testing of all available anti-arrhythmic drugs at adequate dosages, including amiodarone 600 mg once daily for 7-10 days, and 100-200 mg once daily thereafter; sotalol: 80-160 mg twice daily; flecainide 100 to 150 mg twice daily or the entire dose as slow-release formula once daily; propafenone 300 mg twice daily; and disopyramide 250-375mg twice daily, and potentially new antiarrhythmic drugs commercially available during the study period.

A monitor will verify that data recorded on the procedure forms are correct through quarterly communication, review of catheterization reports and medical records. In accordance with applicable regulations a monitor (study nurse from Uppsala) will contact the site prior to the start of the study to review with the site staff protocol, study requirements and their responsibilities to satisfy study requirements, if needed. When reviewing data collection procedures the discussion will also include identification, agreement and documentation of data items for which the case record forms (CRF), patient files (paper or database), tracings of investigations, and questionnaires, will serve a source document. The investigator and the head of the medical institution agrees should allow the monitor direct access to all relevant documents whenever needed and in an event of an audit. To ensure compliance the monitor may conduct a quality assurance audit, which can occur at any time during or after completion of the study.