Re-ablation of Persistent Atrial Fibrillation (Re-AF)

Re-ablation of Persistent Atrial Fibrillation: a Randomized Study, Evaluating Vein of Marshall Ethanol Ablation in Combination With Block of Mitral and Tricuspid Isthmuses and Dome Line

Pulmonary vein re-isolation plus Vein of Marshall ethanol ablation in combination with block of mitral and tricuspid isthmuses and dome line will be compared to pulmonary vein re-isolation alone in patients undergoing re-ablation for persistent atrial fibrillation in this investigator initiated, randomized, patient-assessor blinded multicenter trial. Patients are followed with standard ECG at 3 months, with standard ECG, 5-days' ECG monitoring and quality of life assessment after 12 months, with standard ECG and quality of life assessment after 24 months, through patient files at 60 months after the ablation.

Primary endpoint: Change in AFEQT score between baseline and 12 months.

Study Overview

• Status: Not yet recruiting
• Conditions: Atrial Fibrillation, Persistent
• Intervention / Treatment: Procedure: Intervention; Procedure: Control

Detailed Description

This study is a prospective, patient and assessor blinded, 1:1 randomized superiority trial.

Consecutive patients referred for re-ablation of symptomatic PsAF after previous PVI will be included. All preoperative procedures will be conducted according to the department's standard operational procedures for AF ablation. In all patients, an electro anatomical map (CARTO™, Biosense Webster, Diamond Bar, CA, or EnSite X™, Abbott Laboratories, Abbott Park, IL) of the LA with a multipolar mapping catheter (PENTARAY™ or OCTARAY™, Biosense Webster, Diamond Bar, CA, or Advisor™ HD Grid, Abbott Laboratories, Abbott Park, IL) will be constructed and reconnection of PVs will be assessed in sinus rhythm. If reconnection is present, re-PVI will be performed and confirmed with the multipolar mapping catheter. Patients in atrial fibrillation will undergo cardioversion to sinus rhythm prior to mapping. After mapping and confirming isolation of the PVs, patients will be randomized using the Redcap Database software to intervention or control. The intervention group will undergo VOM ethanol ablation including supplementary LA and coronary sinus ablation, if needed to achieve mitral isthmus block plus creation of dome line and cavotricuspid isthmus (CTI) block. VOM ablation, mitral and CTI ablation and dome line will not be performed in control group and patients in control group will undergo no further ablation. The energy source used will be radiofrequency ablation or pulsed field ablation, at the discretion of the physician. However, radiofrequency should be preferred near coronary arteries. For dome line, focal PFA is preferred. All post-procedural work-up and follow-up will be the same for both randomization groups and assessment of outcomes will be performed by personnel blinded to randomization.

Patients are followed with standard ECG at 3 months, with standard ECG, 5-days' ECG monitoring and quality of life assessment after 12 months, with standard ECG and quality of life assessment after 24 months, through patient files at 60 months after the ablation.

Primary endpoint: Change in AFEQT score between baseline and 12 months.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Peter Lukac, MD, PhD; Phone Number: +45 40293641; Email: peteluka@rm.dk
• Study Contact Backup: Name: Mads Brix Kronborg, MD, PhD, DMSc; Phone Number: + 45 29896776; Email: madskron@rm.dk

Study Locations

• Denmark
  • Danmark
    • Århus N, Danmark, Denmark, 8250
      • Department of Cardiology, Aarhus University Hospital
      • Contact: Peter Lukac, MD, PhD; Phone Number: +45 40293641; Email: peteluka@rm.dk
      • Contact: Mads Brix Lukac, MD, PhD, DMSc; Phone Number: +45 29896776; Email: madskron@rm.dk
• Netherlands
  • Leiden, Netherlands, 2333
    • Department of Cardiology, Leiden University Medical Center
    • Contact: Sebastiaan Piers, MD, PhD; Phone Number: +31 71 526 20 20; Email: S.R.D.Piers@lumc.nl
• Sweden
  • Stockholm, Sweden, 17176
    • Department of Cardiology, Karolinska University Hospital, Stockholm
    • Contact: Finn Åkerström, MD, PhD; Phone Number: +46 734646045; Email: finn.akerstrom@regionstockholm.se

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Previous pulmonary vein isolation for atrial fibrillation
• Indication for catheter ablation with at least two episodes of symptomatic PsAF during the last 12 months
• Age > 18 years
• Expected survival > 12 months
• Able to provide informed consent

Exclusion Criteria:

• Previous extrapulmonary atrial ablation other than cavotricuspid isthmus line, roof- or dome line or posterior wall isolation/ablation
• Atypical atrial flutter in addition to atrial fibrillation
• Atrial fibrillation secondary to a transient abnormality
• Uncontrolled hypertension
• Acute coronary syndrome, cardiac surgery, or TIA/stroke within the last 3 months
• Planned cardiac surgery within 1 year
• Dialysis or severe renal failure
• Active substance or alcohol abuse (>14 units/week)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: vein re-isolation plus VOM ablation and block of mitral and tricuspid isthmuses and dome line; pulmonary vein re-isolation plus Vein of Marshall ethanol ablation in combination with block of mitral and tricuspid isthmuses and dome line	Procedure: Intervention; pulmonary vein re-isolation plus Vein of Marshall ethanol ablation in combination with block of mitral and tricuspid isthmuses and dome line
Active Comparator: vein re-isolation; pulmonary vein re-isolation	Procedure: Control; pulmonary vein re-isolation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Atrial fibrillation effect on quality of life (AFEQT) score	A score with a scale from 0 to 100. The higher score signifies less disability	between baseline and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Freedom from documented atrial arrhythmia	As documented on a standard ECG or Holter, after 3 months blanking period, on or off antiarrhythmic drugs	12, 24 and 60 months
Freedom from documented persistent atrial arrhythmia	duration 7 days or longer or cardioverted, after 3 months blanking period, on or off antiarrhythmic drugs	at 12 and 24 months and 5 years
Freedom from direct-current cardioverted atrial arrhythmia	after 3 months blanking period, on or off antiarrhythmic drugs	at 12 and 24 months and 5 years
Number of direct current-cardioversions and sustained atrial arrhythmia episodes	after 3 months blanking period, on or off antiarrhythmic drugs	at 12 and 24 months and 5 years
Freedom from accepted chronic atrial fibrillation	i.e. when cardioversion is not considered or indicated	at 12 and 24 months and 5 years.
Freedom from re-ablation procedure	reablation procedure because of atrial arrhythmia	at 12 and 24 months and 5 years.
Change in Atrial fibrillation effect on quality of life (AFEQT) score	A score with a scale from 0 to 100. The higher score signifies less disability	between baseline and 24 months and between baseline and 5 years.

Collaborators and Investigators

• Sponsor: Aarhus University Hospital
• Collaborators: Karolinska University Hospital; Leiden University Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2032

Study Registration Dates

• First Submitted: February 20, 2025
• First Submitted That Met QC Criteria: February 20, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 26, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Radiofrequency ablation; Persistent atrial fibrillation; Pulsed field ablation; Vein of Marshall alcohol ablation; Cavotricuspid isthmus line; Mitral isthmus line; Dome line; Pulmonary vein re-isolation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: 1-10-72-153-24

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No