Characterization of Arrhythmia Substrate to Ablate Persistent Atrial Fibrillation

Study Overview
=================
Brief Summary
-----------------
A multicentre, parallel group, two arm, single-blinded randomized clinical trial, assessing the efficacy of a patient-tailored catheter ablation (CA) strategy guided by atrial scar mapping in addition to pulmonary vein isolation (PVI) when compared to PVI alone in patients with persistent atrial fibrillation (AF).

Detailed Description
-----------------
The optimal CA strategy for persistent AF remains unknown. Current data highlight the need for a better understanding of the substrate and mechanisms of arrhythmia maintenance in this population. Atrial scar-based catheter ablation has recently emerged as a promising strategy for ablation of AF. However, the available data has limitations that preclude definitive conclusions regarding the utility of this strategy (no data from multicenter, randomized studies available). Further research is needed to assess the role of scar-based ablation for persistent AF. The Investigators hypothesize that catheter ablation of persistent AF (PeAF) tailored to abolish abnormal atrial substrate identified by intracardiac atrial scar mapping in addition to pulmonary vein isolation (PVI) will result in higher procedural success rates when compared to PVI alone. The study will recruit 502 patients with PeAF (251 per treatment arm) who are candidates for CA ablation of AF according to the treating physician (and in agreement with current practice guidelines). Subjects will be recruited over a 42 month period. The total duration of the study is 60 months. Prior to undergoing catheter ablation subjects will be seen by the investigator/ research assistant and the following data will be collected: i. Age and sex ii. Structural heart disease if present iii. CHADS2VASc score iv. DR-FLASH score v. NYHA class vi. Current medications vii. Duration of uninterrupted AF viii. Height and weight ix. Echocardiogram and other cardiac imaging results (within previous 12 months, including assessment of left ventricular ejection fraction, left atrial volume and valve function) x. ECG, Holter or loop monitor recording (within past 36 months) documenting AF. Subjects will be randomly assigned in a 1:1 ratio to undergo wide area circumferential ablation for pulmonary vein isolation (PVI- control arm) or wide area circumferential ablation PVI and scar ablation (experimental arm). Randomization will be stratified by centre and by sex. Subjects will be randomized prior to the procedure. Enrolled subjects will have a clinical follow-up visit at 3, 6, 12 and 18 months after the ablation procedure. A 14-day continuous ambulatory ECG monitor will be completed at each visit. The results of monitoring will be interpreted at a centralized core lab, and the results will be adjudicated by an arrhythmia specialist blinded to treatment group. A total of three questionnaires will be administered throughout the study, each at a specific time point. The Quality of Life (EQ-5D), CCS-Severity of AF scale, and Atrial Fibrillation Effect on Quality of life (AFEQT) will be completed at baseline, and at the 12-month and 18 month visit. Concomitant medical therapy will be selected according to the treating physician. All subjects will be maintained on systemic oral anticoagulation for at least 2 months following catheter ablation.

Official Title
-----------------
Characterization of Arrhythmia Substrate to Ablate Persistent Atrial Fibrillation (Coast-AF) Randomized Clinical Trial

Conditions
-----------------
Atrial Fibrillation

Intervention / Treatment
-----------------
* Procedure: Catheter ablation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥18 years ; Subjects with symptomatic persistent AF AND clinically indicated catheter ablation for AF At least one episode of AF that is sustained beyond 3 months in duration ; documented on 12-lead ECG, Holter monitor, loop monitor or trans-telephonic monitor (TTM) within 36 months of enrollment in the study; Modified DR-FLASH score >=4 4. Subjects must be able to provide informed consent. Exclusion Criteria: History of previous catheter ablation for AF or left atrial flutter; History of previous surgical ablation for AF; Known intracardiac thrombus; Contraindication to systemic oral anticoagulation therapy; Reversible causes of AF; Hypertrophic cardiomyopathy; Severe valvular disease (mitral/aortic stenosis or regurgitation); Subjects that are pregnant or breastfeeding; Comorbid condition with life expectancy < 1 year

Ages Eligible for Study
-----------------
Minimum Age: 18 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
Interventional Model Description: Prospective, parallel arm randomized clinical trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pulmonary Vein Isolation<br>Wide area circumferential catheter ablation for pulmonary vein isolation | Procedure: Catheter ablation<br>* Wide area circumferential catheter ablation for pulmonary vein isolation of persistent atrial fibrillation<br>* Other names: Atrial Fibrillation Ablation;|
| Experimental: Pulmonary Vein Isolation and scar ablation<br>Wide area circumferential catheter ablation for pulmonary vein isolation and scar ablation | Procedure: Catheter ablation<br>* Wide area circumferential catheter ablation for pulmonary vein isolation of persistent atrial fibrillation<br>* Other names: Atrial Fibrillation Ablation;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of documented (>30s) AF, atrial flutter or atrial tachycardia occuring from day 91 to 18 months post ablation | Documented AF, Aflutter or AT by ECG, holter or external loop monitoring and has a duration of at least 30 seconds | day 91 post ablation to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AF burden | Documented amount of AF | At 12 months and 18 months | 
| Need for repeat ablation procedure for AF, AFl or AT | Documented by ECG, holter or ECG loop recorder | Up to 18 months | 
| Need for emergency room visits or hospitalization | Hospital admission for > 24 hours and emergency room admission | Up to 18 months | 
| Incidence of any ECG documented AF with 90 days of ablation | Symptomatic or asymptomatic AF | up to 90 days | 
| Time to first recurrence at 18 months according to sex and atrial scar extent | Recurrence of AF, AFl or AT | 18 months | 
| Composite safety outcome | Procedure related complications at any time (stroke, PV stenosis, pericarditis, cardiac perforation, major bleeding) and/or death | Up to 18 months | 
| Total ablation delivery time | RF ablation time | Day of ablation procedure | 
| Total procedure duration | Start of ablation to end of ablation | Day of ablation procedure | 
| Quality of life analyses | Using EQ-5D general quality of life score, and AF severity scale (symptoms and functionality) | 18 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
AF ablation, Pulmonary vein isolation, Atrial scar ablation