Outcome of Different Ablation Strategies In Persistent and Long-Standing Persistent Atrial Fibrillation

Study Overview
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Brief Summary
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Specific Aim: This prospective randomized study aims to compare the impact of three different catheter ablation approaches on long-term procedure outcome in terms of arrhythmia recurrence in persistent (PeAF) and long-standing persistent atrial fibrillation (LSPAF) patients. The three strategies to be evaluated are 1) ablation at sources guided by FIRMap (using RhythmView™ Workstation from TOPERA), 2) ablation at sources guided by FIRMap + conventional pulmonary vein antrum isolation (PVAI) and 3) Extended PVAI plus ablation of non-PV triggers and complex fractionated atrial electrograms (CFAE).

Detailed Description
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Specific Aim: This prospective randomized study aims to compare the impact of three different catheter ablation approaches on long-term procedure outcome in terms of arrhythmia recurrence in persistent (PeAF) and long-standing persistent atrial fibrillation (LSPAF) patients. The three strategies to be evaluated are 1) ablation at sources guided by FIRMap (using RhythmView™ Workstation from TOPERA), 2) ablation at sources guided by FIRMap + conventional pulmonary vein antrum isolation (PVAI) and 3) Extended PVAI plus ablation of non-PV triggers and complex fractionated atrial electrograms (CFAE). Hypothesis: Extended PVAI plus ablation of non-PV triggers and CFAE results in better long-term procedure outcome in PeAF and LSPAF patients. Background: The limited success rate of conventional ablation approaches in LSPAF has led to the search for the ideal ablation strategy (1). The main problem in the settings of PeAF and LSPAF is the lack of information on the best targets to ablate to achieve freedom from arrhythmia (2). Some strategies aim at elimination of AF triggers; some solely target CFAE for atrial substrate modification whereas others elect for isolation of PVs plus posterior wall along with ablation of non-PV triggers demonstrated by high-dose isoproterenol challenge with or without CFAEs. (2). The last option has been shown to be the best option so far in improving the freedom from AF at long-term follow-up (2, 3). Recently Narayan et al, by using a computational mapping system that identifies 'rotors' (organized reentrant circuits or focal impulses), were able to achieve a success rate of 82.4% following ablation of rotors plus PVAI, at a median follow-up of 273 days, in a primarily paroxysmal AF population (4). The results of this study are promising and need to be tested in patients with PeAF and LSPAF. Objective: To compare the long-term efficacy and safety of different ablation approaches in PeAF and LSPAF patients. Study Design: This prospective study will enroll 120 consecutive PeAF/LSPAF patients and consenting patients will be randomized to any of the 3 groups (40 per group); Group 1: ablation at sources guided by FIRMap (using RhythmView™ Workstation from TOPERA) Group 2: ablation at sources guided by FIRMap + conventional pulmonary vein antrum isolation (PVAI) Group 3: Extended PVAI plus ablation of non-PV triggers and complex fractionated atrial electrograms (CFAE) Patients will be randomized to different treatment groups after the risks and benefits of each one are discussed in detail with them.

Official Title
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Outcome of Different Ablation Strategies In Persistent and Long-Standing Persistent Atrial Fibrillation

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Procedure: radiofrequency catheter ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: ≥ 18 years Patients presenting with persistent or long-standing persistent AF Undergoing first ablation procedure Ability to provide written informed consent Exclusion Criteria: Reversible causes of atrial arrhythmia such as hyperthyroidism, pneumonia, pulmonary embolism, sarcoidosis and excessive alcohol consumption Prior ablation procedures Pregnancy

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: Arm I<br>ablation at sources guided by FIRMap (using RhythmView™ Workstation from TOPERA) Intervention: AF ablation | Procedure: radiofrequency catheter ablation<br>* Radiofrequency catheter ablation of atrial fibrillation with or without being guided by FIRMap (using RhythmView™ Workstation from TOPERA)<br>* Other names: RFCA;|
| Active Comparator: Arm II<br>ablation at sources guided by FIRMap (using RhythmView™ Workstation from TOPERA) + conventional pulmonary vein antrum isolation (PVAI) Intervention: AF ablation | Procedure: radiofrequency catheter ablation<br>* Radiofrequency catheter ablation of atrial fibrillation with or without being guided by FIRMap (using RhythmView™ Workstation from TOPERA)<br>* Other names: RFCA;|
| Active Comparator: Arm III<br>Extended PVAI plus ablation of non-PV triggers and complex fractionated atrial electrograms (CFAE) Intervention: AF ablation | Procedure: radiofrequency catheter ablation<br>* Radiofrequency catheter ablation of atrial fibrillation with or without being guided by FIRMap (using RhythmView™ Workstation from TOPERA)<br>* Other names: RFCA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence of atrial arrhythmia | Any episode of AF/AT > 30 sec will be considered as a recurrence. Episodes that occur during the first 2 months after the procedure (blanking period) will not be considered as recurrence. | 1 year post-ablation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Procedural complications | complications associated with prolonged use of radiofrequency (RF) energy such as atrioesophageal fistula, perforation, cardiac tamponade, major hemorrhagic events | 48 hours | 
| Acute success | AF termination, organization into AT or ≥10 % slowing | Intra-procedural |