Atrial Fibrillation: Ablation or Surgical Treatment II: FAST II

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare two invasive treatments of symptomatic paroxysmal atrial fibrillation: Percutaneous radiofrequency catheter ablation and mini invasive thoracoscopic radiofrequency ablation in patients referred for a first time invasive treatment for atrial fibrillation. The hypothesis is, that mini invasive thoracoscopic radiofrequency ablation as a first time invasive treatment is more effective compared to a percutaneous catheter based technique in patients with symptomatic paroxysmal atrial fibrillation refractory or intolerant to at least one antiarrhythmic drug.

Detailed Description
-----------------
Atrial fibrillation is characterized by disorganized, rapid, and irregular contraction of the atria. Its effects on hemodynamic and thromboembolic events result in significant morbidity, mortality, impaired quality of life, hospitalizations, and health-cost. It is the most common sustained cardiac arrhythmia. Over six million Europeans suffer from this arrhythmia. The prevalence is estimated to at least double in the next 50 years and is probably underestimated due to asymptomatic atrial fibrillation. The prevalence increases with age and affects men more often. Atrial fibrillation is treated medically with varying results and there are no definitive long term curative treatments. The main goal aims at reducing symptoms and preventing disabling complications. Treatment normally includes antithrombotic, rhythm, and/or rate management, New non-pharmacological interventions have evolved over the last decades in order to prevent paroxysmal atrial fibrillation and/or reduce symptoms. The main focus of non-pharmacological intervention has been on percutaneous radiofrequency catheter ablation and surgical maze ablation. Both approaches aim at minimizing the impact of triggers from the pulmonary veins by electrical isolation of the veins. Studies comparing antiarrhythmic drug and radiofrequency ablation indicate that radiofrequency ablation has a higher efficacy rate, a lower rate of complications, and in selected patients radiofrequency ablation reduced the risk of atrial fibrillation recurrence after one year by 65 % compared with antiarrhythmic drug. In a recently published paper the success rate after a mean of 1.3 radiofrequency ablation procedures per patient varied from 57.7% to 75.4% with higher success rates in patients with paroxysmal atrial fibrillation as compared to persistent/permanent atrial fibrillation. European Society of Cardiology recommends that radiofrequency ablation is reserved for patients who remain symptomatic despite optimal therapy and failed at least one antiarrhythmic drug. Dr. James Cox introduced the Cox-maze surgical operation for atrial fibrillation in 1987, later modified to Cox-maze III also known as the cut and sew maze. It is highly successful in restoring sinus rhythm, with 90-96 % being free from atrial fibrillation at a mean follow-up of 5.4 years. Due to its complexity and technical difficulty the procedure has not been widely adopted. Mini invasive procedures for pulmonary vein isolation have been developed and can now be performed either through mini thoracotomies or using totally thoracoscopic approach. These procedures also hold the advantage of left atrial appendage excision or exclusion. The thoracoscopic maze ablation has shown promising results in small studies in patients with recurrence of atrial fibrillation after earlier catheter based radiofrequency ablation, after a mean follow-up of 11 months 84 % of the patients remain in sinus rhythm. However long-term results are still unknown. The procedure still needs to be compared head to head with catheter based radiofrequency ablation before it should be offered as a standard treatment of atrial fibrillation. The rationale for eliminating atrial fibrillation with radiofrequency ablation include a potential improvement in quality of life, decreased stroke risk, decreased heart failure risk and improved survival.

Official Title
-----------------
Atrial Fibrillation: Ablation or Surgical Treatment II: FAST II A Randomized Study Comparing Non-pharmacologic Therapy in Patients With Drug-refractory Atrial Fibrillation Referred for a First Time Invasive Treatment.

Conditions
-----------------
Paroxysmal Atrial Fibrillation.

Intervention / Treatment
-----------------
* Procedure: Percutaneous radiofrequency catheter ablation
* Procedure: Mini invasive thoracoscopic radiofrequency ablation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Recurrent symptomatic paroxysmal atrial fibrillation Previously failed one or more antiarrhythmic or beta-blocker medication (treatment > 30 days) or if any contraindications against treatment with these drug. Patient is willing and able to attend the scheduled follow-up visits Signed informed consent Exclusion Criteria: Persistent or permanent atrial fibrillation Previously atrial fibrillation ablation procedure Atrial fibrillation secondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac cause Severe underlying heart disease (congenital heart disease, significant valvular disease, cardiomyopathy with LVEF < 35 %, angina pectoris/ ischemic heart disease). Severe enlargement of left atrium (> 45mm) Patient with pacemaker Failure to obtain informed consent Pregnant or breastfeeding women. Patient unable to undergo TEE or with documented left atrial thrombus Patients with co-morbid conditions who, in the opinion of the investigator, constitute increased risk of general anesthesia or port access, e.g. pleural fibrosis, chronic obstructive pulmonary disease (FEV1 < 1.5 L/s). Known internal carotid artery stenosis (> 80 %). Patients, who are enrolled in another clinical trial Life expectancy less than one year Previously TIA/stroke

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Mini invasive thoracoscopic radiofrequency ablation<br>Video-assisted thoracoscopic radiofrequency ablation | Procedure: Mini invasive thoracoscopic radiofrequency ablation<br>* Video-assisted thoracoscopic approach for electrical isolation of the pulmonary veins bilaterally and left atrial appendage excision or exclusion.<br>* Other names: Mini invasive mini maze;|
| Active Comparator: Percutaneous ablation<br>Percutaneous radiofrequency catheter ablation | Procedure: Percutaneous radiofrequency catheter ablation<br>* Percutaneous radiofrequency catheter ablation around the rights and lefts pulmonary veins, with complete circumferential ablation.<br>* Other names: Atrial fibrillation ablation;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from atrial fibrillation with or without antiarrhythmic drug. | Determined by seven days Holter monitoring, ECG, and patient interviews. An episode of atrial fibrillation/flutter/tachycardia is defined as more than 30 seconds of atrial fibrillation observed on Holter monitoring/telemetry or ECG | 12 month follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life | Comparison of quality of life before ablation and at follow-up, by 4 different quality of life questionnaires AFEQT, AF-QoL-18, GAD-7 and PHQ-9. | 12 month follow-up | 
| Procedural complications | Thromboembolic events (TIA,Stroke), Mortality, Tamponade, need for thoracotomy, bleeding, infection, esophageal fistula, embolic events, death , pneumothorax and hemothorax. | 12 month follow-up | 
| Health economics (cost-effectiveness analysis) |  | 12 month follow-up | 
| Reduction in atrial fibrillation burden |  | 12 month follow-up | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Percutaneous radiofrequency catheter ablation, Mini invasive thoracoscopic radiofrequency ablation