Non-invasive Characterization of the Mechanisms of Atrial Fibrillation Maintenance

Study Overview
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Brief Summary
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Currently available antiarrhythmic drugs for the treatment of atrial fibrillation (AF) have a limited efficacy and often cause long-term side effects. Pulmonary vein isolation is the therapy of choice in drug-refractory patients. Recent studies have shown that ablation have a greater efficacy in patients in whom AF is maintained hierarchically and after ablation of rotors. The non-invasive identification of specific mechanism of AF maintenance in each patient could allow the selection of the most appropriate treatment.

Detailed Description
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The MAIN GOAL of this project is to clinically validate the technology for the noninvasive identification of the mechanisms responsible for maintenance of AF by body surface electrical mapping. To achieve this goal, noninvasive mapping of the atrial activity will be correlated with simultaneous endocardial mapping (high density contact catheters) using advanced signal analyses techniques (Dominant frequency, phase and causality mapping, inverse solution problem). These analyses will be performed in patients with different mechanisms of maintenance of AF (e.g. paroxysmal, persistent, valvular) undergoing AF ablation for clinical indication. Both endocardial and body surface mapping results will be correlated with biomarkers levels, MRI scans and AF outcomes of AF ablation at 6 months and 1 year after the procedure. Wide antrum circumferential pulmonary vein isolation with demonstration of bidirectional block will be performed using standard cooled-tip radiofrequency catheters. In patients with mitral stenosis, PBMV will be performed according to Inoue´s technique followed by wide antrum circumferential pulmonary vein isolation. In all patients, MRI/CT scans and fibrosis biomarkers will be obtained at baseline, 6 months and 1 year post ablation.

Official Title
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PERSONALIZE-AF: Non-invasive Characterization of the Mechanisms of Atrial Fibrillation

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Procedure: Pulmonary vein ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with paroxysmal AF symptomatic and refractory to at least one antiarrhythmic medication. Patients with persistent AF symptomatic and refractory to at least one antiarrhythmic medication. Patients with severe mitral stenosis (mitral valve area ≤1.5 cm2, stage D) and favorable valve morphology in the absence of left atrial thrombus or moderate-to-severe mitral regurgitation. Patients must be able and willing to provide written informed consent to participate in the study. Prior anticoagulation for> 4 weeks or transesophageal echocardiogram excluding intracardiac thrombi (in patients with paroxysmal AF). Exclusion Criteria: Patients with inadequate anticoagulation levels. Patients with left atrial thrombus, tumor, or another abnormality which precludes catheter introduction on TEE prior to the procedure. Patients with moderate-to-severe mitral regurgitation. Patients with contraindications to systemic anticoagulation with heparin or coumadin. Prior atrial fibrillation ablation. Patients who are or may potentially be pregnant. Contraindication for adenosine administration; Current enrollment in another investigational drug or device study. Pacemaker or Implantable Cardioverter Defibrillator.

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| - Patients with paroxysmal AF.<br>Patients with AF episodes that terminates spontaneously or with intervention in less than seven days with clinical indication of pulmonary vein ablation. | Procedure: Pulmonary vein ablation<br>* Simultaneous biatrial endocardial electroanatomical mapping by high-density basket catheter (64 pin) and customized body surface mapping (57 electrodes) followed by circumferential pulmonary vein ablation.<br>* Other names: Mitral Valvuloplasty in patients with severe mitral stenosis;|
| - Patients with persistent AF.<br>Patients with AF episodes that fails to self-terminate within seven days or require pharmacologic or electrical cardioversion to restore sinus rhythm with clinical indication of pulmonary vein ablation.. | Procedure: Pulmonary vein ablation<br>* Simultaneous biatrial endocardial electroanatomical mapping by high-density basket catheter (64 pin) and customized body surface mapping (57 electrodes) followed by circumferential pulmonary vein ablation.<br>* Other names: Mitral Valvuloplasty in patients with severe mitral stenosis;|
| - Patients with mitral stenosis.<br>- Patients with mitral stenosis and clinical indication for AF ablation undergoing percutaneous balloon mitral valvuloplasty (PBMV) with clinical indication of pulmonary vein ablation.. | Procedure: Pulmonary vein ablation<br>* Simultaneous biatrial endocardial electroanatomical mapping by high-density basket catheter (64 pin) and customized body surface mapping (57 electrodes) followed by circumferential pulmonary vein ablation.<br>* Other names: Mitral Valvuloplasty in patients with severe mitral stenosis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from atrial fibrillation off antiarrhythmic medications in patients with either paroxysmal, persistent AF or valvular stenosis AF. |  | 12 months post-first ablation procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from atrial fibrillation on or off antiarrhythmic medication post-first ablation procedure and after redo procedures. |  | at 6 and 12 months | 
| Freedom from atrial fibrillation and other atrial arrhythmias post-first ablation procedure and after redo procedures. |  | at 6 and 12 months | 
| Incidence of peri-procedural complications |  | during ablation procedure and 12 months after | 
| Procedure duration |  | Duration of ablation procedure, and valvuloplasty if indicated, in minutes | 
| Body surface recording analysis by 120 disposable electrodes distributed over the patient's chest and connected to the polygraph. |  | During ablation procedure, and valvuloplasty if indicated | 
| Electroanatomic reconstruction and recordings of electrical activity: a three-dimensional reconstruction of atrium and coronary sinus is obtained using high density catheters and an electroanatomic navigation system. |  | During ablation procedure, and valvuloplasty if indicated | 
| Atrial fibrosis determination using late gadolinium enhancement-MRI |  | At 6 and 12 months | 
| Fluoroscopy time |  | During ablation procedure, and valvuloplasty if indicated, in minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atrial Fibrillation, Pulmonary Vein Ablation, Mitral stenosis, Body surface mapping