Deliver mOre aPplications for More Durable Pulmonary Vein IsOlation

Overview

Pulmonary vein isolation (PVI) by catheter ablation (CA) has become a widely accepted interventional treatment for patients with symptomatic atrial fibrillation (AF) despite anti-arrhythmic drugs (AAD). Classic thermal ablation modalities use radiofrequency energy or cryo-energy to create cardiac tissue lesions. Irreversible electroporation (IRE) using pulsed field energy (PFA) is a novel technology for cardiac tissue ablation. Initial studies have shown favorable outcome data in patients with AF treated by performing PVI using PFA. However, the freedom of AF has not yet proven superior to existing thermal ablation methods and appears similarly associated with suboptimal lesion durability, leading to electrical reconnection. The purpose of this study is to determine if freedom of atrial fibrillation may be improved by delivering more and better targeted pulsed field ablations.

Detailed description

Pulmonary vein isolation (PVI) by catheter ablation (CA) has become a widely accepted interventional treatment for patients with symptomatic atrial fibrillation (AF) despite anti-arrhythmic drugs (AAD). Classic thermal ablation modalities use radiofrequency energy or cryo-energy to create cardiac tissue lesions. Irreversible electroporation (IRE) using pulsed field energy (PFA) is a novel technology for cardiac tissue ablation. Initial studies have shown favorable outcome data in patients with AF treated by performing PVI using PFA. However, the freedom of AF has not yet proven superior to existing thermal ablation methods and appears similarly associated with suboptimal lesion durability, leading to electrical reconnection. The purpose of this study is to determine if freedom of atrial fibrillation may be improved by delivering more and better targeted pulsed field ablations. Patients will undergo the standard catheter ablation procedure in accordance with good clinical practice, performing pulmonary vein islolation (PVI) with the FARAPULSE cardiac ablation system. In the control group PVI will be performed with 4 basket- and 4 flower-shaped applications of the catheter, while in the study group 2 olive-, 4 basket-, and 6 flower shaped applications will be delivered at each vein. All other procedural steps will be the same between groups. Patients will be randomized in a 1:1 fashion with a block size of 4 to the study arm or the usual care (control) arm. The primary study parameter for efficacy is the freedom of atrial arrhythmias after the 2-month blanking period up to 18 months after the procedure. The secondary study outcomes include the extent and position of pulmonary vein reconnection observed during redo procedures that are performed due to arrhythmia recurrence, which constitutes a study endpoint. Furthermore, the study also evaluates arrhythmia burden after the procedure in centers that routinely use photoplethysmographic remote monitoring as standard care for all their ablation patients.

Interventions

• Device Pulmonary vein isolation by percutaneous endocardial catheter ablation using the FARAPULSE pulsed high voltage electrical field system in patients with atrial fibrillation
  Standard of care 4 pulsed electrical field applications in basket shape and 4 applications in flower shape
• Device Pulmonary vein isolation by percutaneous endocardial catheter ablation using a pentaspline pulsed high voltage electrical field system in patients with atrial fibrillation
  Experimental treatment delivering 2 pulsed electrical field applications in olive shape, 4 in basket shape and 6 applications in flower shape

Primary outcome measures

• Freedom of atrial fibrillation after a 2-month blanking period up to 18 months post procedure. [Time frame: Baseline, month 3, month 6, month 12, month 18]

Secondary outcome measures (4)

• Procedural-up-to-30 days and 30 days up-to 18 months safety of increasing PFA application numbers [Time frame: From procedure to 18-month follow-up]
• Quality of life differences between groups [Time frame: Baseline, month 3, month 6, month 12, month 18]
• The potential for hemolysis in relation to application number [Time frame: Post procedure every 24 hours, up to 5 days post procedure for each individual patient]
• The durability of pulmonary vein isolation in case of a redo procedure [Time frame: Month 3, month 6, month 12, month 18.]

Eligibility criteria

Inclusion criteria

• Be scheduled for PVI with the use of the FARAPULSE catheter ablation system AND
• Have paroxysmal atrial fibrillation (PAF) documented in the last 6 months prior to enrolment OR
• Had persistent atrial fibrillation but maintained in SR or converted to paroxysmal by antiarrhythmic drugs with no more than 1 cardioversion beyond 7 days in the past

Exclusion criteria

• Cerebrovascular accident (CVA) in the last 6 months
• More than moderate valvular disease that would require intervention
• Cardiac catheter/surgical intervention in the last 3 months or scheduled
• Atrial septal defect (ASD)/ patent foramen ovale (PFO) closure in the past
• Left atrial appendage (LAA) closure in the past
• Mechanical mitral valve
• Non-adherence to oral anticoagulation in the 3 weeks prior to ablation
• Renal disease with known eGFR<45 ml
• Left atrial volume index (LAVI) >50 ml/m2 or left atrial diameter (LAD) >50 mm
• Known contra-indication for catheter ablation
• Known contra-indication for deep sedation or general anesthesia
• Known pregnancy

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Netherlands · 1 center

• St. Antonius Hospital — Nieuwegein

Publications

• Boersma L, Andrade JG, Betts T, Duytschaever M, Purerfellner H, Santoro F, Tzeis S, Verma A. Progress in atrial fibrillation ablation during 25 years of Europace journal. Europace. 2023 Aug 2;25(9):euad244. doi: 10.1093/europace/euad244. PMID 37622592
• Kawamura I, Neuzil P, Shivamurthy P, Kuroki K, Lam J, Musikantow D, Chu E, Turagam MK, Minami K, Funasako M, Petru J, Choudry S, Miller MA, Langan MN, Whang W, Dukkipati SR, Koruth JS, Reddy VY. How does the level of pulmonary venous isolation compare between pulsed field ablation and thermal energy ablation (radiofrequency, cryo, or laser)? Europace. 2021 Nov 8;23(11):1757-1766. doi: 10.1093/euro PMID 34151947
• Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, Akar JG, Badhwar V, Brugada J, Camm J, Chen PS, Chen SA, Chung MK, Cosedis Nielsen J, Curtis AB, Davies DW, Day JD, d'Avila A, Natasja de Groot NMS, Di Biase L, Duytschaever M, Edgerton JR, Ellenbogen KA, Ellinor PT, Ernst S, Fenelon G, Gerstenfeld EP, Haines DE, Haissaguerre M, Helm RH, Hylek E, Jackman WM, Jalife J, Kalman JM, Kautz PMID 29016840
• Koruth J, Verma A, Kawamura I, Reinders D, Andrade JG, Deyell MW, Mehta N, Reddy VY. PV Isolation Using a Spherical Array PFA Catheter: Preclinical Assessment and Comparison to Radiofrequency Ablation. JACC Clin Electrophysiol. 2023 May;9(5):652-666. doi: 10.1016/j.jacep.2023.01.022. Epub 2023 Feb 3. PMID 36842871
• Futing A, Reinsch N, Howel D, Brokkaar L, Rahe G, Neven K. First experience with pulsed field ablation as routine treatment for paroxysmal atrial fibrillation. Europace. 2022 Jul 21;24(7):1084-1092. doi: 10.1093/europace/euac041. PMID 35513354
• Verma A, Asivatham SJ, Deneke T, Castellvi Q, Neal RE 2nd. Primer on Pulsed Electrical Field Ablation: Understanding the Benefits and Limitations. Circ Arrhythm Electrophysiol. 2021 Sep;14(9):e010086. doi: 10.1161/CIRCEP.121.010086. Epub 2021 Sep 20. PMID 34538095
• Reddy VY, Neuzil P, Koruth JS, Petru J, Funosako M, Cochet H, Sediva L, Chovanec M, Dukkipati SR, Jais P. Pulsed Field Ablation for Pulmonary Vein Isolation in Atrial Fibrillation. J Am Coll Cardiol. 2019 Jul 23;74(3):315-326. doi: 10.1016/j.jacc.2019.04.021. Epub 2019 May 11. PMID 31085321
• Hartl S, Reinsch N, Futing A, Neven K. Pearls and Pitfalls of Pulsed Field Ablation. Korean Circ J. 2023 May;53(5):273-293. doi: 10.4070/kcj.2023.0023. PMID 37161743

Identifiers

NCT: NCT07021313 · NL88354.100.24

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗