Effectiveness Study of Circumferential vs. Segmental Ablation in Paroxysmal Atrial Fibrillation

Study Overview
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Brief Summary
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This is a PI-initiated study that aims to evaluate the efficacy of two different methods of paroxysmal atrial fibrillation (PAF) ablation. There are currently two strategies for PAF ablation that are routinely performed by electrophysiology clinicians: (1) circumferential pulmonary vein ablation (CPVA) and (2) segmental pulmonary vein isolation (SPVI). However, it is not known if one approach is better than the other. This randomized study will evaluate and compare the efficacy of CPVA versus SPVI in subjects undergoing ablation for paroxysmal atrial fibrillation only. Subjects will have a 50/50 chance of receiving either the CPVA or SPVI ablation method.

Detailed Description
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Despite more than a decade of clinical experience and investigation, the optimal approach to ablation of paroxysmal atrial fibrillation (PAF) still remains controversial. There are currently two strategies for ablation of PAF: (1) circumferential pulmonary vein ablation (CPVA) and (2) segmental pulmonary vein isolation (SPVI). There are advantages and disadvantages associated with each method. In the CPVA method (1), contiguous ablation lesions are created to encircle the two left and right pulmonary veins (PVs), guided by a three-dimensional (3D) electroanatomic mapping system (Carto, Biosense Webster, Inc. or ESI NavX, St. Jude, Inc.) with a 3D left atrial (LA) geometry created either by using the mapping catheter or by importing a pre-recorded 3D computed tomography (CT) image. In the SPVI method (2), electrical potentials recorded at the PV ostium, that represent myocardial connections between the LA and PVs, are ablated at the PV ostium or just proximal to the PV ostium in the PV antrum. In this approach, ablation is performed segmentally at multiple sites around the PV ostium or antrum, until mapping with a circular catheter demonstrates pulmonary vein isolation. The reported success rates for SPVI for prevention of recurrence of PAF range from 60-87% (2-4) with most recurrences associated with recovery of PV conduction. Therefore, the success of SPVI for treatment of PAF appears to be related to in large part to permanent elimination of the triggers of AF. In a retrospective study by Sawhney et al, overall 5-year outcome after SPVI for PAF was similar to that for short-term follow up less than or equal to 2 years. However, late recurrences after 2 years did occur (up to 22.5%) and repeat ablation was often required to maintain freedom from symptomatic PAF (5). Even though success rates for CPVA have been reported to be higher (up to 90%), most CPVA procedures previously reported included left atrial linear ablation (LALA), additional ablation lesions or lines connecting the mitral valve to the posterior pulmonary veins or along the roof of the left atrium. Thus the success of CPVA may be due in part to ablation of substantially larger amounts of atrial tissue (6-7). However, additional ablation (LALA) may cause potential pro-arrhythmic effects that lead to development of atypical left atrial flutter (8). Compared to SPVI, CPVA resulted in higher success rates and lower fluoroscopy time in one study by Arentz et al (9). However, that study included subjects with both PAF and persistent AF, and those with persistent AF have potentially different underlying mechanisms. Furthermore, two other randomized studies comparing the efficacy of PVI and CPVA have shown conflicting results (10-11). Thus, we will initiate this randomized controlled study to evaluate the efficacy of CPVA versus SPVI in subjects undergoing ablation of paroxysmal atrial fibrillation only.

Official Title
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Evaluating the Efficacy of Circumferential Pulmonary Vein Ablation (CPVA) Versus Segmental Pulmonary Vein Isolation (SPVI) in Paroxysmal Atrial Fibrillation

Conditions
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Paroxysmal Atrial Fibrillation, Atrial Arrhythmia

Intervention / Treatment
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* Procedure: Circumferential Pulmonary Vein Ablation
* Procedure: Segmental Pulmonary Vein Isolation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with paroxysmal atrial fibrillation, whose episodes have never been documented to exceed 48 hours duration Patients with a clinical indication for ablation Patients greater than 18 years of age. Patients willing and able to give informed consent. Patients with concurrent atrial fibrillation and atrial flutter are allowed. Exclusion Criteria: Patients with medical conditions that would limit participation for the entire duration of the study. Patients that are pregnant (all females of child-bearing potential must have a negative pregnancy test within 1 week of enrollment). Patients having undergone prior AF ablation Patients with paroxysmal atrial fibrillation whose episodes last greater than 48 hours Patients with persistent AF

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Circumferential Pulmonary Vein Ablation<br>Contiguous ablation lesions will be performed to encircle the two left and right pulmonary veins (PVs), guided by 3D electroanatomic mapping (Carto, Biosense Webster, Inc. or ESI NavX, St. Jude, Inc.) with a 3D LA geometry created either by using the roving mapping catheter or by importing a pre-recorded 3D CT image of the left atrium. After completion of the circumferential ablation, PV isolation will be confirmed by the mapping catheter, and further focal ablation performed as required until electrical PV isolation is confirmed (entrance block at a minimum). | Procedure: Circumferential Pulmonary Vein Ablation<br>* Contiguous ablation lesions will be performed to encircle the two left and right pulmonary veins (PVs) of the left atrium, guided by 3D electroanatomic mapping. After completion of the circumferential ablation, PV isolation will be confirmed by the mapping catheter, and further focal ablation performed as required until electrical PV isolation is confirmed.<br>* Other names: atrial fibrillation ablation;|
| Active Comparator: Segmental Pulmonary Vein Isolation<br>Electrical potentials recorded in the pulmonary vein (PV) ostium using a circular mapping catheter, representing myocardial connections between the left atrium and PVs will be ablated at or just proximal to the PV ostium in the PV antrum. Ablation will be performed segmentally at multiple sites guided by the mapping catheter around the PV ostium or antrum, until mapping demonstrates elimination of all PV potentials (entrance block at a minimum). | Procedure: Segmental Pulmonary Vein Isolation<br>* Electrical potentials recorded in the pulmonary vein (PV) ostium using a circular mapping catheter, representing electrical connections between the left atrium and PVs will be ablated at or just proximal to the PV ostium in the PV antrum. Ablation will be performed segmentally at multiple sites guided by the mapping catheter until mapping demonstrates elimination of all PV potentials.<br>* Other names: atrial fibrillation ablation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Atrial Fibrillation Recurrence | Recurrence of atrial fibrillation (AF) will be defined as any ECG documented symptomatic AF, or asymptomatic AF lasting >30 seconds on Mobile Outpatient Cardiac Telemetry (MCOT) monitoring. Subjects will be scheduled for clinic visits at 1, 6, 12 and 24 months post ablation. In addition, mobile outpatient telemetry will be performed for at least seven days at 6, 12 and 24 months post-procedure to detect recurrence of asymptomatic atrial fibrillation. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary Vein Stenosis | A CT scan of the left atrium and pulmonary veins will be routinely performed 3 months after ablation to assess for any evidence of pulmonary vein stenosis | 3 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PAF, atrial fibrillation, paroxysmal atrial fibrillation, arrhythmia, atrial fibrillation ablation, circumferential ablation, CPVA, segmental ablation, PVI, pulmonary vein isolation