Persistent Atrial Fibrillation
Conditions
Keywords
Pulmonary vein isolation, Pulsed field ablation, Left atrial posterior wall isolation
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.
Interventions
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
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
Sponsors
Insel Gruppe AG, University Hospital Bern
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to first recurrence of any atrial tachyarrhythmia day 91-365 | Day 91-365 post-ablation | Time to first recurrence of atrial tachyarrhythmia (atrial fibrillation \[AF\], atrial flutter \[AFL\] or atrial tachycardia \[AT\]) between day 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of time with cardiac arrhythmia (arrhythmia burden) for each participant between day 91-365 evaluated based on continuous ICM | Day 91-365 post-ablation | Key secondary efficacy endpoint |
| Treatment-emergent adverse events: Cardiac tamponade requiring drainage | Day 0-90 post-ablation | Number of patients with cardiac tamponade requiring drainage after PVI |
| Treatment-emergent adverse events: Persistent phrenic nerve palsy lasting >24 hours | Day 0-90 post-ablation | Number of patients with persistent phrenic nerve palsy lasting \>24 hours after PVI |
| Treatment-emergent adverse events: Serious vascular complication requiring intervention | Day 0-90 post-ablation | Number of patients with serious vascular complications requiring intervention after PVI |
| Treatment-emergent adverse events: Stroke or TIA | Day 0-90 post-ablation | Number of patients with stroke or TIA after PVI |
| Treatment-emergent adverse events: Atrioesophageal fistula | Day 0-90 post-ablation | Number of patients with atrioesophageal fistula after PVI |
| Treatment-emergent adverse events: Death | Day 0-90 post-ablation | Number of patients with fatal outcome/death after PVI |
| Time to first recurrence of any atrial tachyarrhythmia day 0-365 | Day 0-365 post-ablation | Time to first recurrence of atrial tachyarrhythmia (atrial fibrillation \[AF\], atrial flutter \[AFL\] or atrial tachycardia \[AT\]) between day 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) |
| Time to first recurrence of any atrial tachyarrhythmia day 0-90 | Day 0-90 post-ablation | Time to first recurrence of atrial tachyarrhythmia (atrial fibrillation \[AF\], atrial flutter \[AFL\] or atrial tachycardia \[AT\]) between day 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) |
| Total procedure time | Day 0, during procedure | Procedural endpoint; \[min\] |
| Total left atrial indwelling time | Day 0, during procedure | Procedural endpoint; \[min\] |
| Total fluoroscopy time | Day 0, during procedure | Procedural endpoint; \[min\] |
| Total radiation dose | Day 0, during procedure | Procedural endpoint; Calculated by multiplying the absorbed radiation dose (air kerma) by the cross-sectional area of the X-ray beam \[cG\*cm2\] |
| Change in hs-troponin on Day 1 post-ablation compared with pre-procedural hs-troponin | Pre-procedural (day -1 or day 0) to day 1 post-ablation | Procedural endpoint; \[ng/L\] |
| Post-ablation 3D electro-anatomical mapping: Proportion of isolated veins | Day 0, shortly after ablation | Procedural endpoint |
| Post-ablation 3D electro-anatomical mapping: Posterior wall ablation success rate | Day 0, shortly after ablation | Procedural endpoint; experimental group only |
| Percentage of time with cardiac arrhythmia (arrhythmia burden) for each participant between day 0-90 evaluated based on continuous ICM | Day 0-90 post-ablation | Secondary endpoint during follow-up |
| Percentage of time with cardiac arrhythmia (arrhythmia burden) for each participant between day 0-365 evaluated based on continuous ICM | Day 0-365 post-ablation | Secondary endpoint during follow-up |
| Percentage of time with cardiac arrhythmia (arrhythmia burden) for each participant between day 365 until explantation or end of life (EOL) of the ICM | Day 365 post-ablation to explantation of ICM or end of life of ICM (up to 4 years after implantation of ICM) | Secondary endpoint during follow-up |
| Correlation of AF burden to symptoms and quality of life changes | Day 0-365 post-ablation | Secondary endpoint during follow-up; Quality of life will 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 |
| Time to first recurrence of atrial flutter/ atrial tachycardia day 91-365 | Day 91-365 post-ablation | Secondary endpoint during follow-up |
| Time to first recurrence of atrial flutter/ atrial tachycardia day 0-90 | Day 0-90 post-ablation | Secondary endpoint during follow-up |
| Time to first recurrence of atrial flutter/ atrial tachycardia day 0-365 | Day 0-365 post-ablation | Secondary endpoint during follow-up |
| Time to first recurrence of persistent or paroxysmal atrial fibrillation day 91-365 | Day 91-365 post-ablation | Secondary endpoint during follow-up |
| Time to first recurrence of persistent or paroxysmal atrial fibrillation day 0-90 | Day 0-90 post-ablation | Secondary endpoint during follow-up |
| Time to first recurrence of persistent or paroxysmal atrial fibrillation day 0-365 | Day 0-365 post-ablation | Secondary endpoint during follow-up |
| Average heart rate as recorded by the ICM in months 1, 2 and 3 after ablation | Months 1, 2 and 3 post-ablation | Secondary endpoint during follow-up |
| Hospital or emergency room admission due to atrial arrhythmia recurrence | Day 0-365 post-ablation | Incidence rate |
| Repeat ablation due to recurrence of atrial arrhythmias | Day 0-365 post-ablation | Incidence rate |
| Electrical cardioversion due to recurrence | Day 0-365 post-ablation | Incidence rate |
| Reinitiation or continuation of antiarrhythmic drug therapy day 91-365 | Day 0-365 post-ablation | Incidence rate |
| Number of reconnected pulmonary veins evaluated during redo procedures | During redo procedures between day 1 to 36 months post-ablation | Secondary endpoint during follow-up |
| Sites of reconnection (anterior, posterior, superior, inferior) of the pulmonary veins evaluated during redo procedures | During redo procedures between day 1 to 36 months post-ablation | Secondary endpoint during follow-up |
| Size of antral scar area (cm²) of the pulmonary veins evaluated during redo procedures | During redo procedures between day 1 to 36 months post-ablation | Secondary endpoint during follow-up |
| Number of reconnected posterior walls evaluated during redo procedures | During redo procedures between day 1 to 36 months post-ablation | Secondary endpoint during follow-up |
| Sites of reconnection of the posterior wall evaluated during redo procedures | During redo procedures between day 1 to 36 months post-ablation | Secondary endpoint during follow-up |
| Size of the scar area (cm²) of the posterior wall evaluated during redo procedures | During redo procedures between day 1 to 36 months post-ablation | Secondary endpoint during follow-up |
| EQ-5D-5L Composite score month 3 | Day 90 post-ablation | Quality of life wil be measured with the EQ-5D-5L questionnaire where higher scores mean better outcomes. Composite score month 3. |
| EQ-5D-5L Composite score month 12 | Day 365 post-ablation | Quality of life wil be measured with the EQ-5D-5L questionnaire where higher scores mean better outcomes. Composite score month 12. |
| EQ-5D-5L Visual analogue scale month 3 | Day 90 post-ablation | Quality of life wil be measured with the EQ-5D-5L questionnaire where higher scores mean better outcomes. Visual analogue scale month 3. |
| EQ-5D-5L Visual analogue scale month 12 | Day 365 post-ablation | Quality of life wil be measured with the EQ-5D-5L questionnaire where higher scores mean better outcomes. Visual analogue scale month 12. |
| AFEQT month 3 | Day 90 post-ablation | Quality of life wil be measured with the AFEQT questionnaire. |
| AFEQT month 12 | Day 365 post-ablation | Quality of life wil be measured with the AFEQT questionnaire. |
| Stroke or transient ischemic attack day 0-365 | Day 0-365 post-ablation | Incidence rate |
| All-cause death day 0-365 | Day 0-365 post-ablation | Incidence rate |
| Time to first episode of atrial tachyarrhythmia day 91-365 lasting ≥1 hour | Day 91-365 post-ablation | Time to first recurrence of atrial tachyarrhythmia (atrial fibrillation \[AF\], atrial flutter \[AFL\] or atrial tachycardia \[AT\]) between day 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) |
| Time to first episode of atrial tachyarrhythmia day 91-365 lasting ≥6 hour | Day 91-365 post-ablation | Time to first recurrence of atrial tachyarrhythmia (atrial fibrillation \[AF\], atrial flutter \[AFL\] or atrial tachycardia \[AT\]) between day 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) |
| Time to first episode of atrial tachyarrhythmia day 91-365 lasting ≥1 day | Day 91-365 post-ablation | Time to first recurrence of atrial tachyarrhythmia (atrial fibrillation \[AF\], atrial flutter \[AFL\] or atrial tachycardia \[AT\]) between day 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) |
| Time to first episode of atrial tachyarrhythmia day 91-365 lasting ≥2 days | Day 91-365 post-ablation | Time to first recurrence of atrial tachyarrhythmia (atrial fibrillation \[AF\], atrial flutter \[AFL\] or atrial tachycardia \[AT\]) between day 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) |
| Time to first episode of atrial tachyarrhythmia day 91-365 lasting ≥7 days | Day 91-365 post-ablation | Time to first recurrence of atrial tachyarrhythmia (atrial fibrillation \[AF\], atrial flutter \[AFL\] or atrial tachycardia \[AT\]) between day 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) |
Countries
Switzerland
Contacts
PRINCIPAL_INVESTIGATORLaurent Roten, MD
Inselspital, University Hospital Bern
Outcome results
None listed