Combined Pulsed-field Ablation (PFA) and Left Atrial Appendage Occlusion Using Watchman Flx or Amulet

Study Overview
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Brief Summary
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AF ablation is an established treatment option for non-valvular atrial fibrillation (NVAF). While AF ablation helps to maintain cardiac rhythm in sinus, the stroke risk associated with AF persists after ablation. Oral anticoagulant (OAC) therapy is currently the standard therapy before and after successful ablation. Percutaneous LAA Occlusion (LAAO) has been emerged as an alternative to oral anticoagulants for stroke prophylaxis in patients who refused or contraindicated to OAC. As both AF ablation and percutaneous LAAO require transseptal access from to left atrium, combining the two procedures into one single procedure may provide a straightforward strategy aiming at concomitant rhythm control as well as stroke prevention, without the additional risk of multiple procedures. It is showed in previous studies that this approach is feasible and safe. Pulsed-field ablation (PFA) is a non-thermal ablation technology that uses high amplitude pulsed electrical fields to ablate tissues through the mechanism of irreversible electroporation. Irreversible electroporation is the application of high electric field to a cell with a resultant increased permeability of the membrane and downstream cell death. Success with PFA depends upon the proximity of the electrode to the target tissue, but not necessarily upon contact. Therefore, with PFA the transseptal access for successful AF ablation is less demanding. Moreover, PFA would induce less pulmonary ridge edema compared to conventional ablation techniques and could potentially causes less PDL. Watchman Flx (Boston Scientific) and Amulet (Abbott) are the two most commonly used LAAO devices. The two devices have different designs, deployment requirements and occlusion results. Both devices have been used in combined procedure. However, there is no data of combined AF ablation and LAAO using the PFA technique, and of combined AF ablation comparing the use of Watchman Flx versus Amulet device. In this randomized controlled study, we aim to assess the feasibility and compare the peri-procedural outcomes and LAA occlusion result of combined AF ablation (using the PFA technique), and LAAO using either the Watchman Flx or the Amulet device.

Detailed Description
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Atrial fibrillation (AF) is the most common cardiac arrythmia globally. Its prevalence ranges between 2-4% worldwide. It is associated with significant morbidity and mortality. AF ablation is an established treatment option for non-valvular atrial fibrillation (NVAF). While AF ablation helps to maintain cardiac rhythm in sinus, the stroke risk associated with AF persists after ablation. Oral anticoagulant (OAC) therapy is currently the standard therapy before and after successful ablation. Percutaneous LAA Occlusion (LAAO) has been emerged as an alternative to oral anticoagulants for stroke prophylaxis in patients who refused or contraindicated to OAC . As both AF ablation and percutaneous LAAO require transseptal access from to left atrium, combining the two procedures into one single procedure may provide a straightforward strategy aiming at concomitant rhythm control as well as stroke prevention, without the additional risk of multiple procedures. It is showed in previous studies that this approach is feasible and safe. However, the current AF ablation techniques (radiofrequency ablation and cryoballoon ablation) requires a less posterior transseptal access while LAAO requires a posterior-inferior transseptal access. This could potentially make LAAO after same procedure AF ablation using the same transseptal access more challenging. Besides, current ablation techniques would induce edema over pulmonary ridge, which could potentially result in significant peri-device leak (PDL) post LAAO after edema subsided. Pulsed-field ablation (PFA) is a non-thermal ablation technology that uses high amplitude pulsed electrical fields to ablate tissues through the mechanism of irreversible electroporation. Irreversible electroporation is the application of high electric field to a cell with a resultant increased permeability of the membrane and downstream cell death. Success with PFA depends upon the proximity of the electrode to the target tissue, but not necessarily upon contact. Therefore, with PFA the transseptal access for successful AF ablation is less demanding. Moreover, PFA would induce less pulmonary ridge edema compared to conventional ablation techniques and could potentially causes less PDL. Watchman Flx (Boston Scientific) and Amulet (Abbott) are the two most commonly used LAAO devices. The two devices have different designs, deployment requirements and occlusion results. Both devices have been used in combined procedure. However, there is no data of combined AF ablation and LAAO using the PFA technique, and of combined AF ablation comparing the use of Watchman Flx versus Amulet device. In this randomized controlled study, we aim to assess the feasibility and compare the peri-procedural outcomes and LAA occlusion result of combined AF ablation (using the PFA technique), and LAAO using either the Watchman Flx or the Amulet device.

Official Title
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Combined Pulsed-field Ablation (PFA) and Left Atrial Appendage Occlusion Using Watchman Flx or Amulet: A Randomized Controlled Study

Conditions
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Combined Pulsed-field Ablation (PFA)

Intervention / Treatment
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* Device: Combined Pulsed-field Ablation (PFA) + Left Atrial Appendage Occlusion (LAAO)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Paroxysmal or persistent non- valvular atrial fibrillation CHADS2-VASc >=2 Age >=18; and able to give written consent Exclusion Criteria: are in permanent atrial fibrillation are not eligible for 3 months of oral anticoagulant post ablation has left Atrial thrombus identified by pre-procedure TEE or during procedure had received prior left atrial appendage closure procedure (percutaneous or surgical) are planned to receive concomitant ablation procedure or structural heart interventions other than AF ablation and LAAO (e.g SVT ablation, Aflutter ablation, PFO closure, leadless pacemaker, ASD Closure, etc) patient whom refused or cannot tolerate procedural or post procedural follow-up TEE

Ages Eligible for Study
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Minimum Age: 19 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: Watchman Flx<br>Watchman Flx device to be used for LAAO | Device: Combined Pulsed-field Ablation (PFA) + Left Atrial Appendage Occlusion (LAAO)<br>* Pulsed-field ablation (PFA) is a non-thermal ablation technology that uses high amplitude pulsed electrical fields to ablate tissues through the mechanism of irreversible electroporation Percutaneous LAA Occlusion (LAAO) has been emerged as an alternative to oral anticoagulants for stroke prophylaxis in patients who refused or contraindicated to OAC<br>|
| Active Comparator: Amulet<br>Amulet device to be used for LAAO | Device: Combined Pulsed-field Ablation (PFA) + Left Atrial Appendage Occlusion (LAAO)<br>* Pulsed-field ablation (PFA) is a non-thermal ablation technology that uses high amplitude pulsed electrical fields to ablate tissues through the mechanism of irreversible electroporation Percutaneous LAA Occlusion (LAAO) has been emerged as an alternative to oral anticoagulants for stroke prophylaxis in patients who refused or contraindicated to OAC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of >=moderate peri-device leak (i.e. >=3mm) on follow-up TEE | Rate of >=moderate peri-device leak (i.e. >=3mm) on follow-up TEE | 45-90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LAAO technical success rate | successful device implantation without device related complication and peri-device leak >5mm | Baseline | 
| Rate of procedural related complications | stroke, pericardial effusion, device embolization, mortality | baseline, 45-90 days, 6-months, 12-months | 
| Total ablation time | Total ablation time | baseline, 45-90 days, 6-months, 12-months | 
| LAAO procedural time | LAAO procedural time | baseline, 45-90 days, 6-months, 12-months | 
| Need of additional transseptal puncture for LAAO | Need of additional transseptal puncture for LAAO | baseline, 45-90 days, 6-months, 12-months | 
| Number of device recapture (full or partial) | Number of device recapture (full or partial) | baseline, 45-90 days, 6-months, 12-months | 
| Number of device used | Number of device used | baseline, 45-90 days, 6-months, 12-months | 
| PFA acute technical success | electric isolation of 4 pulmonary veins) by pre-ablation and post ablation mapping | baseline, 45-90 days, 6-months, 12-months | 
| AF ablation procedural success | AF ablation procedural success, defined as no ECG, holter, or rhythm strip documentation of recurrence of AF, AT, Aflutter lasting more than 30 seconds at 1 year | baseline, 45-90 days, 6-months, 12-months | 
| Number of Participants with 1-year clinical events | bleeding or thromboembolic event | baseline, 45-90 days, 6-months, 12-months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transesophageal echocardiog, Combined Pulsed-field Ablation (PFA), Left Atrial Appendage Occlusion (LAAO), Atrial fibrillation (AF), Oral anticoagulant (OAC), non-valvular atrial fibrillation (NVAF)