Evaluation of the Impact of Pulsed Field Ablation on Autonomic Nervous System Modulation in Paroxysmal Atrial Fibrillation (GPfIRE)

A Prospective Randomized Study for the Evaluation of the Impact of Point-by-Point Pulse Field Ablation on Autonomic Nervous System Modulation in Paroxysmal Atrial Fibrillation

The objective of this clinical trial is to evaluate the impact of pulse field (PF) energy, both alone and in combination with radiofrequency (RF) energy, on vagal modulation during point-by-point pulmonary vein isolation (PVI) in patients with paroxysmal atrial fibrillation (PAF). The effect of PF energy on ganglionated plexi (GP) will be assessed using heart rate variability (HRV) as a surrogate marker. Participants will be randomized into three groups: the PF-only group and the Hybrid group (PF posterior/RF anterior) as the experimental arms, and the RF-only group as the control arm. HRV will be measured before and 24 hours after the PVI procedure. Additionally, cardio and neuro biomarkers (Troponin and S100B) will be measured pre-procedure and 20 minutes post-ablation. All participants will be followed for 12 months, with 24-hour Holter-ECG evaluations scheduled at 3, 6, and 12 months after the initial ablation procedure.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation (AF); Paroxysmal AF
• Intervention / Treatment: Procedure: PF-only PVI; Procedure: Hybrid PVI; Procedure: RF-only PVI

• Study Type: Interventional
• Enrollment (Estimated): 105
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chiara Valeriano, MD; Phone Number: +34 697539354; Email: chiara.valeriano91@gmail.com

Study Locations

• Belgium
  • Aalst, Belgium, 9300
    • Recruiting
    • OLV Hospital
    • Contact: Hedwig Batjoens, MSc; Phone Number: +32 53 72 44 49; Email: hedwig.batjoens@olvz-aalst.be

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Symptomatic Paroxysmal Atrial Fibrillation (AF) that terminates spontaneously or with intervention within 7 days of onset
• Age range: 18-70 years
• Willing and capable of providing informed consent
• Able and willing to comply with all pre-, post-, and follow-up testing and requirements

Exclusion Criteria:

• Previously diagnosed Persistent AF (> 7 days in duration)
• Previous LA ablation
• Previous cardiac surgery
• Myocardial Infarction within the previous 3 months
• Severely compromised Left Ventricular Ejection Fraction (LVEF<40%)
• Presence of implanted pacemaker or Implantable Cardioverter-Defibrillator (ICD) or other implanted metal cardiac device that may interfere with the pulsed electric field energy
• Acute illness, active systemic infection, or sepsis
• Presence of intracardiac thrombus, myxoma, tumor, interatrial baffle or patch or other abnormality that precludes catheter introduction or manipulation.
• Severe mitral regurgitation
• Woman who are pregnant, lactating, or who are planning to become pregnant during the course of the clinical investigation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-only; The PF-only arm includes patients with a clinical indication for ablation to manage their paroxysmal atrial fibrillation, who will undergo PVI using only PF energy	Procedure: PF-only PVI; It consists in performing a point-by-point PVI using the Dual Energy THERMOCOOL SMARTTOUCH™ SF (DE STSF) ablation catheter with the TRUPULSE™ generator, employing only PF energy for ablation
Experimental: Hybrid (PF posterior/RF anterior); The Hybrid arm includes patients with a clinical indication for ablation to manage their paroxysmal atrial fibrillation, who will undergo PVI using both PF and RF energy	Procedure: Hybrid PVI; It consists in performing a point-by-point PVI using the Dual Energy THERMOCOOL SMARTTOUCH™ SF (DE STSF) ablation catheter with the TRUPULSE™ generator, employing both PF and RF energy for ablation. Specifically, PF energy is used for the posterior segments and RF energy for the anterior segments of the pulmonary veins
Active Comparator: RF-only; The RF-only arm includes patients with a clinical indication for ablation to manage their paroxysmal atrial fibrillation, who will undergo PVI using only RF energy	Procedure: RF-only PVI; It consists in performing a point-by-point PVI using the Dual Energy THERMOCOOL SMARTTOUCH™ SF (DE STSF) ablation catheter with the TRUPULSE™ generator, employing only RF energy for ablation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute HRV variation (PF-only vs. RF-only arm)	It is the acute difference in the HRV variation (Δ SDNN: baseline/1-day after ablation) between the PF-only arm and the control arm (RF-only).	from enrolment to the day after the ablation procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute HRV variation (Hybrid vs. RF-only arm)	The secondary endpoint is the acute difference in the HRV variation (Δ SDNN: baseline/1-day after ablation) between the Hybrid arm and the control arm (RF-only)	from enrolment to the day after the ablation procedure

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute difference in biomarker release	It measures the change in blood levels of the neuro-biomarker S100B (Δ S100B) and the cardiac injury biomarker Troponin (Δ Troponin), both measured before and immediately (~ 20 minutes) after the ablation	Peri-procedural: from procedure start (after groin puncture) to its end (before sheaths removal)
Atrial arrhythmia recurrences and atrial fibrillation burden	It measures any difference between the study arms in terms of AT/AF/AFL documented recurrences and AF burden during the effective evaluation period (Day 91-Day 365)	from day 91 to day 365 post-ablation
Acute difference in resting Heart Rate (HR)	Acute difference in average resting HR (Δ HR: baseline/1-day after ablation) between the investigational arms compared to the control arm	from enrolment to the day after the ablation procedure
HRV variation across the follow-up period	It measures the HRV change at 3, 6 and 12 months after the ablation procedure to assess the durability of the vagal modulation	from the first follow-up (3-month) visit until the last one (12-month)

Collaborators and Investigators

• Sponsor: VZW Cardiovascular Research Center Aalst
• Collaborators: Biosense Webster, Inc.
• Investigators: Principal Investigator: Tom De Potter, MD, Cardiovascular Research Center Aalst

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: October 15, 2024
• First Submitted That Met QC Criteria: October 15, 2024
• First Posted (Actual): October 17, 2024

Study Record Updates

• Last Update Posted (Actual): July 10, 2025
• Last Update Submitted That Met QC Criteria: July 8, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: ganglionated plexi; heart rate variability; paroxysmal atrial fibrillation; pulmonary vein isolation; vagal modulation; pulsed field; dual-energy focal ablation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: GPfIRE01-BWI-CS-012; CIV-24-02-046139-RS01 (Other Identifier: Eudamed)

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