The PIFPAF-PFA Study

Study Overview
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Brief Summary
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Pulmonary vein isolation (PVI) is very effective for rhythm control in patients with paroxysmal atrial fibrillation (AF), but less successful in patients with persistent AF. Adding posterior wall ablation (PWA) to PVI is among the most promising ablation strategies to improve arrhythmiafree outcome in patients with persistent AF. Patients with left atrial posterior wall scar may benefit most from adding PWA to PVI. With previous ablation technology, posterior wall isolation (PWI) was difficult to achieve and increased the risk of procedural complications. With pulsed-field ablation (PFA), a technology is now available which is both very effective and safe for complete ablation of the posterior wall. The aim of this trial therefore is to compare the efficacy and procedural safety of two ablation strategies for the treatment of persistent AF using PFA: PVI only versus PVI with added PWA. The endpoint of atrial arrhythmia recurrence within 12 months will be assessed by an implantable cardiac monitor (ICM) with remote monitoring capabilities.

Official Title
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Pulmonary Vein Isolation With Pulsed-Field Ablation With Versus Without Posterior Wall Ablation in Patients With Symptomatic Persistent Atrial Fibrillation - A Multi-Center Randomized Clinical Trial: The PIFPAF-PFA Study

Conditions
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Persistent Atrial Fibrillation

Intervention / Treatment
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* Procedure: Pulmonary vein isolation without posterior wall ablation
* Procedure: Pulmonary vein isolation with posterior wall ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Persistent atrial fibrillation documented on a 12 lead ECG, Holter monitor or implantable cardiac device within last 2 years of enrollment Persistent atrial fibrillation is defined as a sustained episode lasting > 7 days Candidate for ablation based on current atrial fibrillation guidelines Continuous anticoagulation with Vitamin-K-Antagonists or a NOAC for ≥4 weeks prior to the ablation; or a transesophageal echocardiography and/or CT scan that excludes left atrial thrombus ≤48 hours before the ablation procedure Age of 18 years or older on the date of informed consent Signed informed consent Exclusion Criteria: Previous left atrial ablation or left atrial surgery Left atrial diameter >60 mm in the parasternal long axis Patients with paroxysmal atrial fibrillation Patients with persistent atrial fibrillation lasting >3 years AF due to reversible causes (e.g. hyperthyroidism, cardiothoracic surgery) Intracardiac thrombus Pre-existing pulmonary vein stenosis or pulmonary vein stent Pre-existing hemidiaphragmatic paralysis Contraindication to anticoagulation or radiocontrast materials Prior mitral valve surgery Severe mitral regurgitation or moderate/severe mitral stenosis Myocardial infarction during the 3-month period preceding the consent date Ongoing triple antithrombotic/anticoagulation therapy Cardiac surgery during the 3-month interval preceding the informed consent date or scheduled cardiac surgery/ transcatheter aortic valve implantation Significant congenital heart defect (including atrial septal defects or pulmonary vein abnormalities but not including a patent foramen ovale) NYHA class III or IV congestive heart failure Left ventricular ejection fraction (LVEF) <35% Hypertrophic cardiomyopathy (wall thickness >1.5 cm) Significant chronic kidney disease (eGFR <30 ml/min) Uncontrolled hyperthyroidism Cerebral ischemic event (stroke or TIA) during the 6-month interval preceding the informed consent date Ongoing systemic infections History of cryoglobulinemia Cardiac amyloidosis Pregnancy (to exclude pregnancy a blood test (HCG) is performed in women < 50 years before inclusion) Life expectancy less than one year per physician opinion Currently participating in any other clinical trial, which may confound the results of this trial Unwilling or unable to comply fully with the study procedures and follow-up

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: Pulmonary vein isolation without posterior wall ablation<br>Pulmonary vein isolation without left atrial posterior wall ablation | Procedure: Pulmonary vein isolation without posterior wall ablation<br>* Pulmonary vein isolation with Pulsed field ablation without left atrial posterior wall ablation. At the end of the procedure, an implantable cardiac monitor will be implanted for the purpose of continuous arrhythmia monitoring<br>|
| Active Comparator: Pulmonary vein isolation with posterior wall ablation<br>Pulmonary vein isolation with left atrial posterior wall ablation | Procedure: Pulmonary vein isolation with posterior wall ablation<br>* Pulmonary vein isolation with Pulsed field ablation with left atrial posterior wall ablation. At the end of the procedure, an implantable cardiac monitor will be implanted for the purpose of continuous arrhythmia monitoring<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first recurrence of any atrial tachyarrhythmia | Time to first recurrence of atrial tachyarrhythmia (atrial fibrillation [AF], atrial flutter [AFL] or atrial tachycardia [AT]) between days 91 and 365 post ablation as detected on an implantable cardiac monitor (ICM). AF, AFL or AT will qualify as a recurrence after ablation if it lasts 120 seconds or longer on the ICM (the minimum programmable episode interval) | Days 91 to 365 post-ablation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events: Cardiac tamponade | Number of patients with cardiac tamponade requiring drainage after PVI | Days 0 to 30 post-ablation | 
| Incidence of treatment-emergent adverse events: Persistent phrenic nerve palsy | Number of patients with persistent phrenic nerve palsy lasting >24 hours after PVI | Days 0 to 30 post-ablation | 
| Incidence of treatment-emergent adverse events: Serious vascular complication | Number of patients with serious vascular complications requiring intervention after PVI | Days 0 to 30 post-ablation | 
| Incidence of treatment-emergent adverse events: Stroke or TIA | Number of patients with stroke or TIA after PVI | Days 0 to 30 post-ablation | 
| Incidence of treatment-emergent adverse events: Atrioesophageal fistula | Number of patients with atrioesophageal fistula after PVI | Days 0 to 30 post-ablation | 
| Incidence of treatment-emergent adverse events: Death | Number of patients with fatal outcome/death after PVI | Days 0 to 30 post-ablation | 
| Total procedure time | Procedural endpoint | Day 0, during procedure | 
| Total left atrial indwelling time | Procedural endpoint | Day 0, during procedure | 
| Total fluoroscopy time | Procedural endpoint | Day 0, during procedure | 
| Total radiation dose | Procedural endpoint | Day 0, during procedure | 
| Change in hs-Troponin on day 1 post-ablation | Procedural endpoint | Day 1 post-ablation | 
| Pre-ablation 3D electro-anatomical mapping: Number of participants with scar as a region that demonstrated reproducibly an area of > 0.5×0.5 cm on the posterior wall with voltage less than 0.5 mV | Procedural endpoint | Day 0, shortly before ablation | 
| Post-ablation 3D electro-anatomical mapping: Proportion of isolated veins | Procedural endpoint | Day 0, shortly after ablation | 
| Post-ablation 3D electro-anatomical mapping: Proportion of isolated carinas | Procedural endpoint | Day 0, shortly after ablation | 
| Post-ablation 3D electro-anatomical mapping: Lesion size | Procedural endpoint | Day 0, shortly after ablation | 
| Post-ablation 3D electro-anatomical mapping: Posterior wall ablation success rate | Procedural endpoint | Day 0, shortly after ablation | 
| Time to first recurrence of any atrial tachyarrhythmia in patients with versus without left atrial posterior wall scar | Secondary endpoint during follow-up | Day 0 to 36 months post-ablation | 
| Time to first recurrence of any atrial tachyarrhythmia in patients with left atrial posterior wall scar and posterior wall ablation versus without posterior wall ablation | Secondary endpoint during follow-up | Day 0 to 36 months post-ablation | 
| Percentage of time with cardiac arrhythmia (arrhythmia burden) for each participant between days 0-90 evaluated based on continuous ICM | Secondary endpoint during follow-up | Day 0 to 90 post-ablation | 
| Percentage of time with cardiac arrhythmia (arrhythmia burden) for each participant between days 91-365 evaluated based on continuous ICM | Secondary endpoint during follow-up | Day 91 to 365 post-ablation | 
| Percentage of time with cardiac arrhythmia (arrhythmia burden) for each participant between days 365 until explantation or end of life (EOL) of the ICM | Secondary endpoint during follow-up | Day 365 post-ablation to explantation of ICM or end of life of ICM (up to 4 years after implantation of ICM) | 
| Correlation of AF burden to symptoms and quality of life changes | Secondary endpoint during follow-up; Quality of life wil be measured with the EQ-5D-5L questionnaire where higher scores mean better outcomes; Symptoms will be measured with the AFEQT (Atrial Fibrillation Effect on Quality-of-life) questionnaire where higher scores mean worse outcomes | Day 0 and months 3 and 12 post-ablation | 
| Reduction of percentage of time with cardiac arrhythmia (AF burden) by > 90% post ablation procedure | Secondary endpoint during follow-up | Day 0 to 36 months post-ablation | 
| Comparison of the prevalence of the type of arrhythmia recurrence during follow-up being AF or organized atrial arrhythmias (AFL or AT) | Secondary endpoint during follow-up | Day 0 to 36 months post-ablation | 
| Time to first recurrence of atrial tachyarrhythmia between days 91 and 365 evaluated based on continuous ICM in patients with presence of scar on the PW based on the preablation voltage map versus patients with no scar on the PW | Secondary endpoint during follow-up | Day 91 to 365 post-ablation | 
| Number of participants with persistent or paroxysmal AF during follow-up | Secondary endpoint during follow-up | Day 0 to 36 months post-ablation | 
| Average heart rate as recorded by the ICM in months 1, 2 and 3 after ablation | Secondary endpoint during follow-up | Months 1, 2 and 3 after ablation | 
| Proportion of patients admitted to the hospital or emergency room because of documented recurrence of atrial arrhythmias | Secondary endpoint during follow-up | Day 0 to 36 months post-ablation | 
| Proportion of patients undergoing a repeat ablation procedure because of documented recurrence of atrial arrhythmias | Secondary endpoint during follow-up | Day 0 to 36 months post-ablation | 
| Number of participants reinitiating of antiarrhythmic drugs during follow-up | Secondary endpoint during follow-up | Day 0 to 36 months post-ablation | 
| Number of participants with electrical cardioversion during follow-up | Secondary endpoint during follow-up | Day 0 to 36 months post-ablation | 
| Number of reconnected pulmonary veins evaluated during redo procedures | Secondary endpoint during follow-up | During redo procedures between day 1 to 36 months post-ablation | 
| Sites of reconnection (anterior, posterior, superior, inferior) of the pulmonary veins evaluated during redo procedures | Secondary endpoint during follow-up | During redo procedures between day 1 to 36 months post-ablation | 
| Size of antral scar area (cm²) of the pulmonary veins evaluated during redo procedures | Secondary endpoint during follow-up | During redo procedures between day 1 to 36 months post-ablation | 
| Number of reconnected posterior walls evaluated during redo procedures | Secondary endpoint during follow-up | During redo procedures between day 1 to 36 months post-ablation | 
| Sites of reconnection of the posterior wall evaluated during redo procedures | Secondary endpoint during follow-up | During redo procedures between day 1 to 36 months post-ablation | 
| Size of the scar area (cm²) of the posterior wall evaluated during redo procedures | Secondary endpoint during follow-up | During redo procedures between day 1 to 36 months post-ablation | 
| Evolution of Quality of Life after 3 and 12 months | Secondary endpoint during follow-up; Quality of life wil be measured with the EQ-5D-5L questionnaire where higher scores mean better outcomes | Day 0 and months 3 and 12 post-ablation | 
| Number of participants with stroke including TIA after 3, 12, 24 and 36 months | Secondary endpoint during follow-up | Months 3, 12, 24 and 36 post-ablation | 
| Number of participants with cardiovascular or non-cardiovascular death after 3, 12, 24 and 36 months | Secondary endpoint during follow-up | Months 3, 12, 24 and 36 post-ablation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary vein isolation, Pulsed field ablation, Left atrial posterior wall isolation