Clinical trial NCT05986526: The PIFPAF-PFA Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Persistent Atrial Fibrillation
Keywords: Pulmonary vein isolation
Pulsed field ablation
Left atrial posterior wall isolation
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2023-08-14
Enrollment: 206
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Persistent atrial fibrillation documented on a 12 lead ECG, Holter monitor or implantable cardiac device within last 2 years of enrollment
2. Persistent atrial fibrillation is defined as a sustained episode lasting \> 7 days
3. Candidate for ablation based on current atrial fibrillation guidelines
4. 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
5. Age of 18 years or older on the date of informed consent
6. Signed informed consent

Exclusion Criteria:

1. Previous left atrial ablation or left atrial surgery
2. Left atrial diameter \>60 mm in the parasternal long axis
3. Patients with paroxysmal atrial fibrillation
4. Patients with persistent atrial fibrillation lasting \>3 years
5. AF due to reversible causes (e.g. hyperthyroidism, cardiothoracic surgery)
6. Intracardiac thrombus
7. Pre-existing pulmonary vein stenosis or pulmonary vein stent
8. Pre-existing hemidiaphragmatic paralysis
9. Contraindication to anticoagulation or radiocontrast materials
10. Prior mitral valve surgery
11. Severe mitral regurgitation or moderate/severe mitral stenosis
12. Myocardial infarction during the 3-month period preceding the consent date
13. Ongoing triple antithrombotic/anticoagulation therapy
14. Cardiac surgery during the 3-month interval preceding the informed consent date or scheduled cardiac surgery/ transcatheter aortic valve implantation
15. Significant congenital heart defect (including atrial septal defects or pulmonary vein abnormalities but not including a patent foramen ovale)
16. NYHA class III or IV congestive heart failure
17. Left ventricular ejection fraction (LVEF) \<35%
18. Hypertrophic cardiomyopathy (wall thickness \>1.5 cm)
19. Significant chronic kidney disease (eGFR \<30 ml/min)
20. Uncontrolled hyperthyroidism
21. Cerebral ischemic event (stroke or TIA) during the 6-month interval preceding the informed consent date
22. Ongoing systemic infections
23. History of cryoglobulinemia
24. Cardiac amyloidosis
25. Pregnancy (to exclude pregnancy a blood test (HCG) is performed in women \< 50 years before inclusion)
26. Life expectancy less than one year per physician opinion
27. Currently participating in any other clinical trial, which may confound the results of this trial
28. Unwilling or unable to comply fully with the study procedures and follow-up

Primary outcomes:
measure: Time to first recurrence of any atrial tachyarrhythmia
timeFrame: Days 91 to 365 post-ablation
Secondary outcomes:
measure: Incidence of treatment-emergent adverse events: Cardiac tamponade
timeFrame: Days 0 to 90 post-ablation
measure: Incidence of treatment-emergent adverse events: Persistent phrenic nerve palsy
timeFrame: Days 0 to 90 post-ablation
measure: Incidence of treatment-emergent adverse events: Serious vascular complication
timeFrame: Days 0 to 90 post-ablation
measure: Incidence of treatment-emergent adverse events: Stroke or TIA
timeFrame: Days 0 to 90 post-ablation
measure: Incidence of treatment-emergent adverse events: Atrioesophageal fistula
timeFrame: Days 0 to 90 post-ablation
measure: Incidence of treatment-emergent adverse events: Death
timeFrame: Days 0 to 90 post-ablation
measure: Total procedure time
timeFrame: Day 0, during procedure
measure: Total left atrial indwelling time
timeFrame: Day 0, during procedure
measure: Total fluoroscopy time
timeFrame: Day 0, during procedure
measure: Total radiation dose
timeFrame: Day 0, during procedure
measure: Change in hs-Troponin on day 1 post-ablation
timeFrame: Day 1 post-ablation
measure: 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
timeFrame: Day 0, shortly before ablation
measure: Post-ablation 3D electro-anatomical mapping: Proportion of isolated veins
timeFrame: Day 0, shortly after ablation
measure: Post-ablation 3D electro-anatomical mapping: Proportion of isolated carinas
timeFrame: Day 0, shortly after ablation
measure: Post-ablation 3D electro-anatomical mapping: Lesion size
timeFrame: Day 0, shortly after ablation
measure: Post-ablation 3D electro-anatomical mapping: Posterior wall ablation success rate
timeFrame: Day 0, shortly after ablation
measure: Time to first recurrence of any atrial tachyarrhythmia in patients with versus without left atrial posterior wall scar
timeFrame: Day 0 to 36 months post-ablation
measure: 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
timeFrame: Day 0 to 36 months post-ablation
measure: Percentage of time with cardiac arrhythmia (arrhythmia burden) for each participant between days 0-90 evaluated based on continuous ICM
timeFrame: Day 0 to 90 post-ablation
measure: Percentage of time with cardiac arrhythmia (arrhythmia burden) for each participant between days 91-365 evaluated based on continuous ICM
timeFrame: Day 91 to 365 post-ablation
measure: Percentage of time with cardiac arrhythmia (arrhythmia burden) for each participant between days 365 until explantation or end of life (EOL) of the ICM
timeFrame: Day 365 post-ablation to explantation of ICM or end of life of ICM (up to 4 years after implantation of ICM)
measure: Correlation of AF burden to symptoms and quality of life changes
timeFrame: Day 0 and months 3 and 12 post-ablation
measure: Reduction of percentage of time with cardiac arrhythmia (AF burden) by > 90% post ablation procedure
timeFrame: Day 0 to 36 months post-ablation
measure: Comparison of the prevalence of the type of arrhythmia recurrence during follow-up being AF or organized atrial arrhythmias (AFL or AT)
timeFrame: Day 0 to 36 months post-ablation
measure: 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
timeFrame: Day 91 to 365 post-ablation
measure: Number of participants with persistent or paroxysmal AF during follow-up
timeFrame: Day 0 to 36 months post-ablation
measure: Average heart rate as recorded by the ICM in months 1, 2 and 3 after ablation
timeFrame: Months 1, 2 and 3 after ablation
measure: Proportion of patients admitted to the hospital or emergency room because of documented recurrence of atrial arrhythmias
timeFrame: Day 0 to 36 months post-ablation
measure: Proportion of patients undergoing a repeat ablation procedure because of documented recurrence of atrial arrhythmias
timeFrame: Day 0 to 36 months post-ablation
measure: Number of participants reinitiating of antiarrhythmic drugs during follow-up
timeFrame: Day 0 to 36 months post-ablation
measure: Number of participants with electrical cardioversion during follow-up
timeFrame: Day 0 to 36 months post-ablation
measure: Number of reconnected pulmonary veins evaluated during redo procedures
timeFrame: During redo procedures between day 1 to 36 months post-ablation
measure: Sites of reconnection (anterior, posterior, superior, inferior) of the pulmonary veins evaluated during redo procedures
timeFrame: During redo procedures between day 1 to 36 months post-ablation
measure: Size of antral scar area (cm²) of the pulmonary veins evaluated during redo procedures
timeFrame: During redo procedures between day 1 to 36 months post-ablation
measure: Number of reconnected posterior walls evaluated during redo procedures
timeFrame: During redo procedures between day 1 to 36 months post-ablation
measure: Sites of reconnection of the posterior wall evaluated during redo procedures
timeFrame: During redo procedures between day 1 to 36 months post-ablation
measure: Size of the scar area (cm²) of the posterior wall evaluated during redo procedures
timeFrame: During redo procedures between day 1 to 36 months post-ablation
measure: Evolution of Quality of Life after 3 and 12 months
timeFrame: Day 0 and months 3 and 12 post-ablation
measure: Number of participants with stroke including TIA after 3, 12, 24 and 36 months
timeFrame: Months 3, 12, 24 and 36 post-ablation
measure: Number of participants with cardiovascular or non-cardiovascular death after 3, 12, 24 and 36 months
timeFrame: Months 3, 12, 24 and 36 post-ablation
Other outcomes:
Locations:
city: Baden
country: Switzerland
facility: Cantonal Hospital Baden
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Bern
country: Switzerland
facility: Inselspital, University Hospital Bern
city: Lausanne
country: Switzerland
facility: University Hospital Lausanne
city: St. Gallen
country: Switzerland
facility: Cantonal Hospital St. Gallen
city: Zürich
country: Switzerland
facility: University Hospital Zürich
Study officials:
affiliation: Inselspital, University Hospital Bern
name: Laurent Roten, MD
role: PRINCIPAL_INVESTIGATOR
References: