Substrate Ablation and Remodelling in Non-paroxysmal Atrial Fibrillation (AF)

Study Overview
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Brief Summary
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The investigators hypothesise that modification of the Atrial Fibrillation (AF) substrate by radiofrequency ablation would improve single procedure success rates for Radio Frequency Ablation (RFA) for Non-paroxysmal AF when compared to that achieved with short-term peri-procedural anti-arrhythmic drug therapy alone.

Official Title
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Substrate Modification With Ablation and Antiarrhythmic Drugs in Non-Paroxysmal Atrial Fibrillation

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Procedure: Pulmonary vein isolation (PVI)
* Procedure: Pulmonary vein isolation + linear lesions
* Drug: Pharmacological Substrate modification


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ongoing symptoms (European Heart Rhythm Association Class 2 or above) in spite of treatment with rate control medication Non-paroxysmal atrial fibrillation, as pre-classified as Persistent AF: AF requiring Electrical/ Chemical cardioversion or that lasting >7 days. These patients may be in AF or in sinus Rhythm at the time of their initial assessment and/ or at the time of their ablation. Continuous Persistent AF: These patients are persistently in AF with or without antiarrhythmic drug therapy, as confirmed on a 24 hour Holter. They may have undergone previous cardioversion(s). Sustained Paroxysmal AF with underlying substrate: Patients with Individual AF episode(s) lasting >12 hours but less than 7 days plus one or more of the following: Age >65 years 21 Individual AF episode(s) lasting >24 hours Significant left atrial dilatation of >45 mm on Echo (Parasternal Long Axis view) Obesity (Body Mass Index >30), and/ or history suggestive of sleep apnoea Diabetes Mellitus requiring hypoglycaemic drugs and/or Insulin Exclusion Criteria: Inability or unwillingness to receive oral anticoagulation with warfarin Previous Ablation procedure for AF Unwillingness or inability to complete the required follow up arrangements Presence of long standing persistent AF with continuous AF longer than 12 months. This includes patients in whom sinus rhythm may have been maintained following electrical cardioversion for a period of less than 1 week at a stretch. Documented typical atrial flutter Prior prosthetic mitral valve replacement or severe structural cardiac abnormality Contraindications and/ or prior intolerance to both Amiodarone and Flecainide. Reversible cause for atrial fibrillation Known hypertrophic or infiltrative cardiomyopathy

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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pulmonary vein isolation<br>Patients will undergo pulmonary venous isolation plus pharmacological substrate modification | Procedure: Pulmonary vein isolation (PVI)<br>* Using a 4mm irrigated tip radiofrequency ablation catheter a series of lesions >2 mm outside pulmonary vein (PV) ostia will be made to encircle and electrically isolate the pulmonary veins in two ipsilateral pairs (wide area circumferential ablation, WACA). A 20-pole PV mapping catheter will be used to confirm electrical isolation. If the patient is in atrial fibrillation at this stage, sinus rhythm would be restored with electrical cardioversion and PVI would be confirmed in sinus rhythm<br>Drug: Pharmacological Substrate modification<br>* at least 6 weeks therapy with oral amiodarone prior to the ablation procedure and 6 weeks post.<br>|
| Experimental: Pulmonary vein isolation + Linear Lesions<br>Patients will undergo pulmonary venous isolation plus both pharmacological and interventional substrate modification | Procedure: Pulmonary vein isolation + linear lesions<br>* Using a 4mm irrigated tip radiofrequency ablation catheter a series of lesions >2 mm outside PV ostia will be made to encircle and electrically isolate the pulmonary veins in two ipsilateral pairs (wide area circumferential ablation, WACA)34. A 20-pole PV mapping catheter will be used to confirm electrical isolation. Once PVI has been achieved, patients will go onto to receive additional linear ablation lesions. These will include a left atrial roof line, mitral isthmus line, (including ablation inside the coronary sinus if necessary), and ablation on the cavotricuspid isthmus. If the patient is in atrial fibrillation at this stage, the acute end-point would be signal obliteration at the ablated area. Once sinus rhythm is restored with electrical cardioversion, PVI would be confirmed in sinus rhythm and conduction block across the LA roof line, Mitral line and CTI will then be verified with appropriate pacing manoeuvres.<br>Drug: Pharmacological Substrate modification<br>* at least 6 weeks therapy with oral amiodarone prior to the ablation procedure and 6 weeks post.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from atrial fibrillation/ atrial tachycardia at 6 months following a single procedure. | Defined as >30 sec of AF/ atrial tachycardia identified on ECG or ambulatory ECG monitoring following a 3 month blanking period. | 12 months |