Pulmonary Vein Isolation Alone or in Combination With Substrate Modulation After Electric Cardioversion Failure

Study Overview
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Brief Summary
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This study aims at assessing whether electric cardioversion can act as a discriminant factor between patients requiring Pulmonary Vein Isolation (PVI) procedure alone or PVI procedure combined with substrate modulation. All included patients will undergo an electric cardioversion, then: Patients with electric cardioversion success will be treated as per Standard of Care and according to ESC recommendations (2020). A prospective registry will be implemented for these patients. Patients with electric cardioversion failure will be randomized in the study between 2 ablative procedures: PVI procedure alone PVI procedure combined with substrate modulation

Detailed Description
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Atrial fibrillation (AF) is the most common heart rhythm disorder. It is the result of uncoordinated action of the atrial myocardial cells, causing rapid and irregular contraction of the heart's atria. The AF prevalence in adults is currently estimated to be between 2% and 4% and is expected to increase by a factor of 2.3 in the next few years, due to the increased longevity of the general population and the increased search for undiagnosed AF. Increased age is an important risk factor for AF, but other increased comorbidities, including hypertension, diabetes, heart failure, coronary artery disease, chronic renal failure, obesity, and obstructive sleep apnoea syndrome, are also important; modifiable risk factors contribute strongly to the development and progression of AF (ESC Guideline, 2020). The European Society of Cardiology (ESC) recommended pulmonary vein isolation (PVI) (Class IA) as first-line ablative strategy for persistent AF (Class IA) (ESC Guideline, 2020). However, PVI alone is only effective in treating about 40% to 60% of patients with persistent AF in the general population (unselected). If we apply this strategy to all patients (PVI alone), we accept to re-do ablative procedure in up to 60% of patients. The second feasible strategy is to treat patients with persistent AF by PVI combined with substrate modulation (ESC Class IIb). This strategy, when done well, by creating irreversible lesions (Marshall-PLAN) can effectively treat 70% to 80% of AF patients. But this implies that the investigator will be doing unnecessary substrate modulation in up to 40% of patients, which can lead to increased risks associated with the ablative procedure, longer procedure times, multiple lesions, etc… In addition, incorrect or incomplete substrate modulation is pro-arrhythmic and leads to recurrences in the form of left atrial flutters, tolerance of which, is generally poor. Both ablative strategies have been widely validated in large numbers of published studies. The problem is to know when and for which patients to apply one or the other of the two strategies. Electric cardioversion could help in selecting the most appropriate strategy.

Official Title
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Pulmonary Vein Isolation Alone or in Combination With Substrate Modulation After Electric Cardioversion Failure in Patients With Persistent Atrial Fibrillation: a Randomized, Multicentric, and Comparative Study

Conditions
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Persistent Atrial Fibrillation

Intervention / Treatment
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* Procedure: Pulmonary Vein Isolation (PVI) alone
* Procedure: PVI procedure associated with substrate modulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria * Criteria to be validated before performing electric cardioversion: Persistent AF (continuous for at least 7 days without interruption according to information transmitted by the cardiologist and the patient), symptomatic and resistant to anti-arrhythmic treatment including amiodarone; Life expectancy > 5 years; Female or male between 18 and 80 years of age. Affiliation to a health insurance system; Patient informed of the study and having signed informed consent * Criteria to be validated prior to randomization on the day of ablation (these patients may be randomized): Patient with failed electric cardioversion i.e. in AF, confirmed by 24-H holter. Exclusion Criteria: *Criteria to be validated before performing electric cardioversion (the study cannot be proposed to patients corresponding to these criteria): Current hyperthyroidism; Pregnant or breastfeeding woman; Patient with a BMI greater than 30; Patient with severe COPD; Patient with hypertrophic heart disease; Patient with a mechanical mitral valve; Contraindications to anticoagulants; TIA/stroke less than 6 months old; Psychiatric illness affecting follow-up; Left auricle volume > 220ml ; Left Ventricular Ejection Fraction (LVEF) < 40% ; Uncontrolled ischaemic heart disease (angina, myocardial ischaemia) Patients under legal protection * Criteria to be validated before randomization, on the day of ablation (these patients cannot be randomized): Patient in normal sinus rhythm 4-6 weeks after electric cardioversion: these patients are included in the study registry. Patient with complete absence of sinus rhythm (less than 10 seconds) after 3 electric cardioversion attempts: these patients will discontinue from the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: The study procedure is the electric cardioversion as a discriminant factor between patients requiring PVI procedure alone or PVI procedure combined with substrate modulation. This electric cardioversion will be performed in all included patients up to 6 weeks before the ablative procedure. On the day of the ablative procedure: If the patient presents with a Sinus Rhythm (= successful electric cardioversion, approximately 70% of patients) the patient will be treated as per SoC in accordance with ESC recommendations. It is recommended to perform PVI procedure alone in these patients. A prospective registry for these patients will be established for this study. If the patient presents with AF (= failure of electric cardioversion, approximately 30% of patients), randomization will be carried out according to the 2 strategies: Group 1: PVI procedure alone in accordance with ESC recommendations Group 2: PVI procedure associated with substrate modulation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PVI procedure alone<br>If the patient presents with AF (= failure of electric cardioversion, approximately 30% of patients), randomization will be carried out according to : - Group 1: PVI procedure alone in accordance with ESC recommendations | Procedure: Pulmonary Vein Isolation (PVI) alone<br>* PVI procedures correspond to point-by-point 50W AI-guided RF applications (400 posterior LA wall, and 550 elsewhere). The PVI will be validated by the absence of any activity recorded inside the PV encirclement by a multipolar catheter (either a Lasso catheter or a Pentaray catheter) (entrance block) and by the non-capture of the LA despite pacing maneuvers from inside the encirclement (exit block). The bidirectional block will be validated again after a 15-minutes waiting period.<br>|
| Experimental: PVI procedure combined with substrate modulation<br>If the patient presents with AF (= failure of electric cardioversion, approximately 30% of patients), randomization will be carried out according to : - Group 2: PVI procedure associated with substrate modulation | Procedure: PVI procedure associated with substrate modulation<br>* PVI procedure associated with substrate modulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year sinus rhythm maintenance rate | Rate of patients with sinus rhythm (yes/no) at 1 year after a single ablative procedure | At 1 year after ablation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of patients with sinus rhythm (randomized patients) | Rate of patients with sinus rhythm during 1 year after ablation and after a single ablative procedure. | At 1 year after ablation | 
| Rate of patients with sinus rhythm (registry patients) | Rate of patients with sinus rhythm during 1 year after ablation and after a single ablative procedure. | At 1 year after ablation | 
| Rate of patients with sinus rhythm (randomized and registry patients, strategy PVI procedure alone) | Rate of patients with sinus rhythm during 1 year after ablation and after a single ablative procedure. | At 1 year after ablation | 
| Duration (in minutes) of ablative procedure | Duration (in minutes) of ablative procedure | On the day of the ablative procedure | 
| Duration (in minutes) of radiofrequency use | Duration (in minutes) of radiofrequency use | On the day of the ablative procedure | 
| Duration (in minutes) of Fluoroscopy | Duration (in minutes) of Fluoroscopy | On the day of the ablative procedure | 
| Duration (in days) of hospitalization | Duration (in days) of hospitalization | From date of surgery until the date of discharge from hospital assessed up to 1 day | 
| Evaluation of major complications rate | Tamponade and/or stroke rate out of the blanking period and up to 1-year follow-up | Up to 1 year | 
| Evaluation of drug treatment use rate or electric cardioversion in the blanking period | Number of patients using drug treatment and/or electric cardioversion during the blanking period (first 3 months after ablation) between the two strategies (randomized patients) | At three months after ablation | 
| Evaluation of the minor complications rate between the two strategies after 1-year follow-up (randomized patients) | Occurrence of a false aneurysm or fistulas at the puncture sites and/or occurrence of a post-ablation pericardial reaction | up to 1-year follow-up |