Tailored vs. Anatomical Ablation Strategy for Persistent Atrial Fibrillation

Study Overview
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Brief Summary
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Atrial Fibrillation (AF) ablation is typically performed in predefined anatomic regions of the left atrium without attempting to identify patient-specific areas of interest. This procedure is referred to as Pulmonary Vein Isolation (PVI). The hypothesis in this Study is that a tailored ablation strategy targeting areas of spatio-temporal dispersion in combination with PVI is superior to an anatomical ablation strategy targeting PVI alone for the treatment of persistent AF.

Official Title
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Tailored vs. Anatomical Ablation Strategy for Persistent Atrial Fibrillation

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Procedure: Dispersion ablation + PVI
* Device: VX1
* Procedure: PVI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 18 years of age or older candidates for a first AF ablation Symptomatic AF, refractory to at least one antiarrhythmic medication Persistent or long-standing persistent AF with documentation of (ECG, Holter, physician's letter): AF duration of ≥ 3 months and ≤ 5 years (≥ 3 months and < 1 year in the United States) or 1 effective cardioversion followed by AF recurrence lasting ≥ 3 months Continuous anticoagulation with warfarin (INR 2-3) or NOAC for > 4 weeks prior to ablation Patients must be able and willing to provide written informed consent to participate in the clinical trial At least 60% of patients (224 patients) in persistent AF ≥ 6 months including at least 15% (56 patients) of long-standing persistent AF ≥ 12 months Exclusion Criteria: Paroxysmal and short-standing AF < 3 months Long-standing persistent AF > 5 years (≥ 1 year in the United States) ≥ 2 previous ineffective cardioversion sessions in case of undetermined AF duration Severe obesity (BMI > 40) Very dilated Left Atrium (LA)(e.g. LA diameter > 60 mm and/or LA surface > 40 cm2 determined by 2D echocardiography) Patients with AF secondary to an obvious reversible cause Inadequate anticoagulation as defined in the inclusion criteria LA thrombus on Transesophageal Echocardiography (TEE) or CT Scan prior to procedure Contraindications to anticoagulation (heparin, warfarin or NOAC) Patients who are or may potentially be pregnant Previous surgical or catheter ablation for AF Any cardiac surgery within the past 2 months (60 days) (includes PCI) Myocardial infarction within the past 2 months (60 days) Previous atrioventricular valve surgery History of blood clotting or bleeding abnormalities Documented arterial thromboembolic event (including TIA) within the past 12 months (365 days) Rheumatic Heart Disease Chronic severe Heart Failure (NYHA functional class IV and/or LVEF < 25%) Awaiting cardiac transplantation or other cardiac surgery within the next 12 months (365 days) Unstable angina within the past month Acute illness or active systemic infection or sepsis AF secondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac cause Diagnosed atrial myxoma Significant severe pulmonary disease, (e.g. patients with restrictive pulmonary disease, constrictive or chronic obstructive pulmonary disease in GOLD stage IV) or any other disease or malfunction of the lungs or respiratory system that produces chronic symptoms (e.g. unstable or untreated sleep apnea) Significant congenital anomaly or medical problem that in the opinion of the investigator would preclude enrollment Enrollment in an investigational study evaluating another device, biologic, or drug Presence of intramural thrombus, tumor or other abnormality or condition that precludes vascular access, or manipulation of the catheter Life expectancy or other disease processes likely to limit survival to less than 12 months Acute Covid-19 infection (fever and/or biological inflammatory syndrome, and positive test documented)

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: Randomized Controlled Trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tailored<br>Tailored ablation strategy | Procedure: Dispersion ablation + PVI<br>* Ablation of spatio-temporal dispersion electrograms in combination with pulmonary vein antrum isolation<br>Device: VX1<br>* VX1-based dispersion mapping<br>|
| Active Comparator: Anatomical<br>Anatomical ablation strategy | Procedure: PVI<br>* Pulmonary vein antrum isolation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from documented AF after one ablation procedure | Freedom from documented AF episodes > 30 seconds, with or without anti-arrhythmic drugs (AADs), 12 months after a single index ablation procedure | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from documented AF/AT after one or two ablation procedures | Freedom from documented AF/AT episodes > 30 seconds, after one or two procedures, with or without AADs, at 12 months | 12 months | 
| Freedom from documented AF/AT after one ablation procedure | Freedom from documented AF/AT episodes > 30 seconds, with or without AADs, 12 months after a single ablation procedure | 12 months | 
| Incidence of complications (safety composite endpoint) | Incidence of complications at 12 months: death, cerebrovascular events, or serious treatment-related adverse event | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Persistent Atrial Fibrillation, Catheter Ablation, Electrogram dispersion