Ablation of Fibrotic Areas in Patients With Persistent Atrial Fibrillation.

Study Overview
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Brief Summary
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Brief summary: The objective of this study is to compare two different ablation strategies in participants with persistent atrial fibrillation and fibrotic areas in the left atrium. The participant will be randomized to pulmonary vein isolation or pulmonary vein isolation plus ablation of fibrotic areas.

Detailed Description
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Background: Atrial fibrillation (AF) is the most common arrhythmia in clinical practice with a prevalence of 2-3 percent in the population. Catheter ablation performing pulmonary vein isolation (PVI) is an established treatment, which aim to eliminate triggers from the pulmonary veins. This treatment is successful in most patients with paroxysmal AF. In many patients, especially the patients with persistent AF, this treatment is not sufficiently to achieve freedom from arrhythmia and symptoms. There are several studies showing that fibrosis in the left atrium (LA) is an independent factor to relapse in AF after PVI. The fibrotic areas can be detected by measuring the voltage in the left atrium and creating a voltage map. There are non-randomized studies that suggest better results regarding reduction of arrhythmia burden after ablating the low voltage areas (LVAs). This ablation strategy is commonly used in clinical praxis although there are no randomized studies in this field. Aim: The objective of this study is to compare two different ablation strategies in participants with persistent atrial fibrillation and fibrotic areas in the left atrium. The participant will be randomized to PVI versus PVI plus ablation of LVAs. The primary endpoint is freedom of atrial arrhythmias after 1 to 2 ablation procedures within 6 months measured at 12 months after the first ablation procedure without antiarrhythmic drugs. Secondary endpoints will be atrial arrhythmia burden, health related quality of life measured by AFEQT score, and RAND 36 and periprocedural complications; death, stroke/ TIA, tamponade, atrio-esophageal fistula, and atrioventricular block. Study design: Randomized controlled multicenter trial. The study will be single blinded. All the participants will undergo PVI and the substrate map will be collected during atrial pacing. The patients with LVA will be randomized in a 1:1 fashion to; PVI plus ablation of LVA or PVI alone. Follow up visits will be at 3, 6, 12, 18 and 24 months. Before ablation and at every follow up visit the participants will fill in arrhythmia symptom specific questionnaires (AFEQT and ASTA) and questionnaire about quality of life (RAND 36). The participants will register arrhythmia with a heart monitoring system if symptoms of arrhythmia and two times daily during two weeks before every follow up visit.

Official Title
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Individually DEsigned Ablation of Low Voltage Areas in Patients With Persistent Atrial Fibrillation, a Randomized Controlled Multicenter Trial

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Procedure: Radio frequency ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ECG-documented persistent or long-standing persistent atrial fibrillation according to European Society of Cardiology (ESC) definition Symptoms e. g. palpitations, dyspnea, tiredness that is due to the atrial fibrillation. Suitable candidate for catheter ablation. Tried one or more antiarrhythmic drugs or unwilling to try antiarrhythmic drugs Age ≥18 years. Exclusion Criteria: LA dimension >55 mm as determined by an echocardiography within the previous year Acute coronary syndrome or coronary artery bypass surgery within 12 weeks Severe aortic or mitral valvular heart disease using the ESC guidelines Congenital heart disease Prior surgical or percutaneous AF ablation procedure or atrioventricular-nodal ablation Medical condition likely to limit survival to < 1 year New York Heart Association (NYHA) class IV heart failure symptoms Contraindication to oral anticoagulation Renal failure requiring dialysis AF due to reversible cause Pregnant and fertile women without anticonception History of non-compliance to medical therapy Unable or unwilling to provide informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomization 1:1
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pulmonary vein isolation plus substrate modification<br>Pulmonary vein isolation plus ablation of low voltage areas in the left atrium | Procedure: Radio frequency ablation<br>* Two different radio frequency ablation procedures<br>|
| Active Comparator: Pulmonary vein isolation<br>Pulmonary vein isolation | Procedure: Radio frequency ablation<br>* Two different radio frequency ablation procedures<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Freedom from Atrial Arrhythmia | Freedom from documented atrial arrhythmias >30 seconds at 12 months after 1 or 2 ablation procedures within 6 months without antiarrhythmic drugs | From 3 months (blanking period) to 12 months after the first ablation procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Freedom from Atrial Arrhythmia after 1 Ablation Procedure without Antiarrhythmic Drugs (AAD) | Freedom from documented atrial arrhythmias >30 seconds at 12 months after 1 ablation procedure without antiarrhythmic drugs | From 3 months (blanking period) to 12 months after the first ablation procedure | 
| Number of Participants with Freedom from Atrial Arrhythmia after 1 Ablation Procedure with/ without AAD | Freedom from documented atrial arrhythmias >30 seconds at 12 months after 1 ablation procedure with or without antiarrhythmic drugs | From 3 months (blanking period) to 12 months after the first ablation procedure | 
| Number of Participants with Freedom from Atrial Arrhythmia after 1 or 2 Ablation Procedures with/ without AAD | Freedom from documented atrial arrhythmias >30 seconds at 12 months after 1 or 2 ablation procedures with or without antiarrhythmic drugs | From 3 months (blanking period) to 12 months after the first ablation procedure | 
| Number of Participants with Freedom from Atrial Fibrillation | Freedom from documented atrial fibrillation >30 seconds at 12 months after 1 or 2 ablation procedures without antiarrhythmic drugs | From 3 months (blanking period) to 12 months after the first ablation procedure | 
| Number of Participants with Freedom from Symptomatic Atrial Arrhythmias | Freedom from documented symptomatic atrial arrhythmias >30 seconds at 12 months after 1 or 2 ablation procedures with or without antiarrhythmic drugs | From 3 months (blanking period) to 12 months after the first ablation procedure | 
| Number of Participants with Freedom from Atrial Arrhythmias without AAD | Freedom from documented atrial arrhythmias >30 seconds at 24 months after 1 or several ablation procedures without antiarrhythmic drugs | From 3 months (blanking period) to 24 months after the first ablation procedure | 
| Number of Participants with Freedom from Atrial Arrhythmias with or without AAD | Freedom from documented symptomatic atrial arrhythmias >30 seconds at 24 months after 1 or several ablation procedures with or without antiarrhythmic drugs | From 3 months (blanking period) to 24 months after the first ablation procedure | 
| Arrhythmia Burden | Number of Registrations with Remote Heart Monitor / Number of Registrations with Atrial Arrhythmia with Remote Heart Monitor | From 3 months (blanking period) to 12 months and 24 months after the first ablation procedure | 
| Time to First Recurrens | Time from first ablation procedure to first documented recurrens of atrial arrhythmias | From first ablation procedure to 24 months | 
| Number of Repeat Procedures | Number of repeat procedures | 12 and 24 months after the first ablation procedure | 
| Changes in Quality of Life Measures: Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) Overall Score and Subscale Scores | AFEQT is a 21 questions atrial fibrillation specific health related quality of life questionnaire. Overall Score (calculated from 18 of the questions) and subscale scores in three domains: symptoms, daily activities, and treatment concern. Score ranges from 0 to 100 points. Higher scores mean a better outcome. | Baseline, 12 and 24 months after the first ablation procedure | 
| Changes in Quality of Life Measures: RAND 36 (Research ANd Development) 36 All Domains | RAND 36 (developed by RAND corporation) is a 36 questions health related quality of life questionnaire. The RAND 36 is divided into 8 domains: Physical functioning, role physical, role emotional, bodily pain, vitality, general health, social functioning and mental health. Score range from 0 to 100 points. Higher scores mean a better outcome. | Baseline,12 and 24 months after the first ablation procedure | 
| Number of Participants with Adverse Events/ Complications | Complications related to the ablation procedure: Cardiac perforation, stroke, transitory ischemic attack (TIA), systemic embolic events, atrio-esophageal fistula, major bleeding, atrioventricular block, groin hematoma requiring vascular surgery or extended hospitalization. | 12 and 24 months after the first ablation procedure | 
| Number of Participants With All-cause Mortality | Number of Participants With All-cause Mortality | 12 and 24 months after the first ablation procedure | 
| Procedure time | Time from start of groin punction to withdrawal of the catheters | Immediately after the procedure | 
| Fluoroscopy time | Total fluoroscopy time during the procedure | Immediately after the procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Catheter ablation, Low voltage