VEin of MArshall Ethanolization Vs Extended Pulmonary Vein PULSEd Field Ablation After Failed PVI for Persistent AF (VEMAPULSE)

Comparison Between VEin of MArshall Ethanol Infusion Versus Extended Pulmonary Vein PULSEd Field Ablation After Failed Pulmonary Vein Isolation in Patients with Persistent Atrial Fibrillation

The goal of this clinical trial is to compare two ablation techniques to treat patients with persistent atrial fibrillation (irregular and often very rapid heart rhythm). An ablation is a procedure during which some scars are made on the inside of the heart to break up the electrical signals that cause the irregular heartbeat. In this trial researchers will compare a new technique, which uses tiny electric shocks to make the scars, to the standard technique, which uses heat.

The main question the trial aims to answer is:

• Does the new technique work as well as the standard technique to prevent the irregular heartbeat from returning within one year of the procedure?

Participants will:

• Undergo an ablation with either the new or the standard technique
• Visit the hospital 1, 3, 6, 9 and 12 months after the procedure for a check-up
• Wear a device to register their heart rhythm for 24 hours before the 3 month visit and for 72 hours before the 6, 9 and 12 month visit
• Record their heart rhythm at home every week
• Complete a questionnaire 3, 6, 9 and 12 months after the procedure

Study Overview

• Status: Recruiting
• Conditions: Persistent Atrial Fibrillation
• Intervention / Treatment: Procedure: Pulsed field ablation with posterior wall isolation; Procedure: Radiofrequency ablation and vein of Marshall ethanolization

Detailed Description

Background

Pulmonary vein isolation (PVI) remains the cornerstone of catheter ablation for the treatment of atrial fibrillation (AF). However, in patients with persistent AF, recurrence occurs in 20% to 50% of the patients. These patients often need additional ablation beyond PVI in the index procedure or in a redo procedure. During redo procedures, optimal management of AF has not been validated yet. Different strategies are used but without strong scientific background and without uniformity.

In the case of PV reconnection, PV re-isolation alone seems to be the gold standard in healthy atria, but with moderate success in patients with dilated left atrium or scar zones.

Different recent studies show a potential impact of posterior wall isolation; however with discordant results. This could be in part related to low rate of durable posterior wall isolation and also due to potential risk of esophageal fistula limiting the use of RF ablation at the posterior wall. The use of pulsed field energy could improve lesion durability and avoid any risk of fistula.

On the other hand, ethanol infusion in the vein of Marshal has also been shown to improve the success rate of persistent AF ablation but requires significant experience and may be time-consuming.

Rationale

Currently, there are no clear ablation endpoints in the case of AF recurrence post PVI. Especially for patients with persistent AF since substrate ablation beyond PVI does not seem to improve the success rate during a first procedure. However, this could be related to inappropriate patient selection. Indeed, PVI-resistant patients present those with worst prognosis with respect to AF recurrence. Additionally, when durable PVI is observed following recurrence in patients with persistent AF, case ablation beyond PVI seems reasonable and necessary.

The aim of this trial is to compare two strategies with clear endpoints, to avoid potential bias. The gold standard, PVI, is also respected in both groups In one group, PFA re-isolation of PVs and of the posterior wall has the advantage of a clear straight forward approach, with short-lasting procedures and which does not require high level technical skills.

In the second group, radiofrequency guided PV re-isolation will be performed in combination with mitral, aided by vein of Marshall ethanol infusion, and dome lines until bidirectional block. A Vein of Marshall is present in ~90% of the patients and strongly facilitates block at the mitral line (almost 100%) while a dome transection reduces the risk of further left atrial tachyarrhythmia.

Hypothesis

The hypothesis of this study is that the efficacy of a straightforward strategy of PV re-isolation (if necessary) and additional posterior wall isolation using the PFA FARAPULSETM catheter is comparable to that of a more complex and time consuming RF strategy aiming at vein of Marshall ethanol infusion and linear lesions at the roof and at the mitral line.

Design

This is a prospective, randomized (1:1), open label, blinded endpoint study (PROBE). Eligible subjects, who sign the study informed consent form, with persistent AF will be randomized into one of two study arms. In the pulsed field ablation (PFA) arm, patients will be treated using the FARAPULSETM catheter, aiming at pulmonary vein (PV) re-isolation (if necessary) and isolation of the posterior wall. In the radiofrequency (RF) group, patients will receive ethanol infusion in the vein of Marshall, followed by re-isolation of the PV (if necessary), dome and mitral lines with aim at bidirectional block.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Emma Christiaen; Phone Number: 003250453293; Email: emma.christiaen@azsintjan.be

Study Locations

• Belgium
  • Brugge, Belgium, 8000
    • Recruiting
    • AZ Sint-Jan Brugge AV
    • Contact: Emma Christiaen; Email: emma.christiaen@azsintjan.be
    • Contact: Sébastien Knecht, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Symptomatic persistent atrial fibrillation (AF) despite a first PVI. Persistent AF is defined as the presence of AF lasting ≥7 days (i.e. in case of new onset AF one has to wait for 7 days)

Exclusion Criteria:

• Persistent AF lasting ≥ 12 months
• Advanced valvular heart disease
• Left atrial (LA) volume >150mL
• LA diameter (PS-LAX) >60mm
• Septal wall diameter >15mm
• Life expectancy <1 year
• Weight >150 kg
• Any contra indication to catheter ablation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pulsed field ablation with posterior wall isolation	Procedure: Pulsed field ablation with posterior wall isolation; Extended pulmonary vein isolation including posterior wall isolation using pulsed field ablation
Active Comparator: Radiofrequency ablation and vein of Marshall ethanolization	Procedure: Radiofrequency ablation and vein of Marshall ethanolization; Radiofrequency pulmonary vein re-isolation (when necessary), vein of Marshall ethanol infusion with roof and mitral lines

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Atrial tachyarrhythmia recurrence within 12 months	Percentage of patients with any atrial tachyarrhythmia recurrence (> 30 sec) from 2 months (blanking period) to 12 months after the ablation procedure	2-12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and procedural related adverse event	Occurrence of vascular complications, tamponade, transient ischemic attack/stroke and other adverse events during and after the procedure, and within 12 months post procedure	During procedure-12 months
Duration of the ablation procedure	Duration of the ablation procedure in both groups	During procedure
Fluoroscopy time	Fluoroscopy time	During procedure
Fluoroscopy dose	Fluoroscopy dose during the procedure	During procedure
Effect of the procedure on quality of life	Results of the 36-Item Short Form Survey Instrument (SF-36) before and 3, 6, 9 and 12 months post procedure. The scores range from 0 to 100. A higher score corresponds with a better outcome.	3, 6, 9, 12 months
Incidence of repeat ablation	Percentage of patients who need another ablation within 12 months post procedure	12 months
Unscheduled visits and hospitalization	Number of unscheduled visits and hospitalization within 12 months post procedure	12 months

Collaborators and Investigators

• Sponsor: Sebastien Knecht
• Collaborators: Boston Scientific Corporation
• Investigators: Principal Investigator: Sébastien Knecht, MD, PhD, AZ Sint-Jan Brugge AV

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2024
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: April 16, 2024
• First Submitted That Met QC Criteria: April 22, 2024
• First Posted (Actual): April 25, 2024

Study Record Updates

• Last Update Posted (Estimated): October 9, 2024
• Last Update Submitted That Met QC Criteria: October 7, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: CIV-24-01-045634

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No