Multitarget Pulse Field Ablation Guided by Endocardial and Non-invasive Atrial Driver Mapping (PFA+ADM) Pilot Study. Development of an Ablation Strategy to Improve the Efficacy of Long Standing Atrial Fibrillation Ablation in Patients With High Comorbidity Burden or Heart Failure

NCT ID: NCT07118488

Last Updated: 2025-08-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-31
• Study Completion Date: 2027-07-31

Brief Summary

To assess the efficacy and safety of a percutaneous ablation strategy that targets multiple extrapulmonary structures as the Cox-Maze IV.

Detailed Description

Persistent and long-standing atrial fibrillation (PsAF and LSAF) remain significant clinical challenges, particularly in patients with heart failure or high comorbidity burden, where the arrhythmia is often more sustained, complex, and resistant to conventional ablation approaches. Despite advancements in ablation technology, pulmonary vein isolation (PVI) alone has shown limited success in this subgroup. Current guidelines acknowledge the need for additional ablation targets beyond the pulmonary veins (PVs), yet evidence remains scarce and optimal strategies undefined.

This single-arm, prospective pilot study investigates a novel ablation strategy that combines multi-target pulsed field ablation (PFA) with both endocardial intracavitary electrogram (EGM) mapping and non-invasive body surface mapping (BSM) to guide the identification and ablation of extra-PV atrial fibrillation drivers. This approach is designed to emulate the multilevel strategy of the surgical Cox-Maze IV, aiming for comprehensive arrhythmia substrate modification while minimizing procedural risk.

The PFA+ADM protocol leverages recent advances in:

• Pulsed Field Ablation (PFA): a non-thermal modality offering selective myocardial ablation with reduced risk to adjacent tissues (e.g., esophagus, phrenic nerve).
• Non-invasive Driver Mapping (ADM): Electrocardiographic imaging (ECGi) with torso vests capable of reconstructing 3D epicardial activation patterns and identifying high-frequency or rotational driver sites.
• Intracardiac Electrogram Analysis: High-resolution EGM signals captured during atrial fibrillation are analyzed to localize driver activity, complex fractionated atrial electrograms (CFAEs), or high dominant frequency regions.

Study Workflow

After informed consent, participants will undergo implantation of an insertable cardiac monitor (ICM) to allow for continuous AF burden tracking. The ablation procedure includes:

1. Baseline Electroanatomical Mapping: Creation of 3D maps of both atria using a high-density mapping catheter.

2. Non-invasive Driver Mapping: Performed using vest-based ECGi systems to non-invasively identify arrhythmogenic sources beyond the PVs.

3. Intracavitary Driver Mapping: Electrograms are analyzed for spectral content, including dominant frequency (DF) and organization index (OI), to confirm rotational or focal drivers.

4. Pulmonary Vein Isolation (PVI): Executed using PFA technology.

5. Targeted Extra-PV Ablation: Ablation of extrapulmonary targets guided by overlap between invasive and non-invasive driver maps. PFA will be used to eliminate identified high-frequency or rotational driver regions.

6. Post-ablation Re-mapping: Repeat non-invasive and invasive mapping to assess residual driver activity and efficacy of lesion sets.

7. Iterative Ablation (if necessary): Further lesion delivery at persistent driver sites, up to a clinically acceptable endpoint, defined as elimination or reduction in dominant frequency by at least 2 Hz or disappearance of driver behavior.

8. Follow-up Assessments: Clinical evaluations and ICM-based rhythm analysis at 3, 6, and 12 months.

Technical Specifics and Rationale

Rationale for Multitarget Approach:

Atrial remodeling in patients with PsAF/LSPsAF is often diffuse and multifocal. Standard PVI addresses the initiating triggers of paroxysmal AF but fails to control perpetuating mechanisms in persistent forms. The multitarget strategy aims to:

• Capture and eliminate active drivers that are not pulmonary in origin.
• Address atrial regions exhibiting consistent high-frequency reentry.
• Improve patient outcomes by personalizing ablation strategy based on individual driver distributions.

Advantages of PFA Technology:

PFA uses irreversible electroporation to ablate cardiomyocytes without significant collateral damage. This is especially relevant when targeting extrapulmonary sites near vulnerable structures (e.g., posterior wall near esophagus, Bachmann's bundle near the aorta). Additionally, PFA has demonstrated faster lesion creation and potentially shorter procedure times with comparable or superior efficacy in preclinical and early clinical data.

Integration of ECGi and EGM-based Mapping:

Simultaneous use of non-invasive ECG imaging and invasive mapping enables comprehensive localization of potential drivers, enhancing ablation precision. The goal is to improve arrhythmia control without significantly increasing procedural complexity or risk.

Patient Profile and Unmet Needs:

This trial targets patients often excluded or underrepresented in clinical trials-those with heart failure or multiple comorbidities who have higher recurrence rates post-ablation. These patients also tend to have more advanced atrial myopathy and may benefit from a more aggressive substrate modification strategy, if delivered safely.

Data Handling and Interim Analysis

Data will be collected prospectively, including electrogram recordings, ECGi maps, procedural data, imaging, and follow-up rhythm status. An interim analysis is planned after the first 25 patients to evaluate safety and refine the mapping-ablation workflow if necessary. Data from ICMs will be analyzed to calculate daily AF burden, detect arrhythmia recurrence, and correlate clinical outcomes with procedural findings.

Safety is evaluated both acutely and in follow-up, with predefined thresholds for major complications (≤5%). The use of PFA is expected to significantly reduce thermal injury risks. Procedural metrics such as total duration, fluoroscopy time, and energy delivery time will also be recorded.

This pilot study will serve as a foundation for larger multicenter trials by assessing the feasibility and clinical benefit of this precision-guided, multitarget ablation strategy in a high-risk AF population. Its results may help redefine ablation endpoints beyond pulmonary vein isolation and facilitate the integration of novel technologies into routine clinical practice.

Conditions

Persistent Atrial Fibrillation Longstanding

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single Arm - Multitarget PFA Ablation

Pulmonary vein isolation plus extra pulmonary drivers ablation based on EGM findings (rotational and high frequency sites)

Group Type: EXPERIMENTAL

Multitarget PFA Ablation

Intervention Type: PROCEDURE

• Informed consent gave by the patient.
• Implantable loop recorder procedure
• Clinical procedure starts
• Electrophysiologycal study
• Non-invasive map is obtained.
• Electroanatomical map of both atria is generated.
• Intracavitary electrogram (EGM) driver assessment
• Pulmonary vein isolation
• Extra pulmonary drivers ablation based on EGM findings (rotational and high frequency sites).
• Non-invasive map is obtained to assess ablation impact on driver distribution.
• Remap and extra pulmonary lesions are carried out until activity. At drivers sites disappears or decreases in at least 2 hertz or up to physician criteria.
• Patient follow up

Interventions

Multitarget PFA Ablation

• Informed consent gave by the patient.
• Implantable loop recorder procedure
• Clinical procedure starts
• Electrophysiologycal study
• Non-invasive map is obtained.
• Electroanatomical map of both atria is generated.
• Intracavitary electrogram (EGM) driver assessment
• Pulmonary vein isolation
• Extra pulmonary drivers ablation based on EGM findings (rotational and high frequency sites).
• Non-invasive map is obtained to assess ablation impact on driver distribution.
• Remap and extra pulmonary lesions are carried out until activity. At drivers sites disappears or decreases in at least 2 hertz or up to physician criteria.
• Patient follow up

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Age between 18 and 80.
• Ability and willingness to follow the study protocol, including informed consent.
• Symptomatic long-standing AF for at least one month, documented by ECG or dual-chamber device recordings.
• History of failure, intolerance, or refusal of antiarrhythmic drug therapy.
• New York Heart Association (NYHA) functional class II or III, or left ventricular dysfunction (LVEF ≤ 50%) or a CHA2DS2-VASc score of 4 or more.
• Optimal medical treatment for heart failure for at least three months for patients with left ventricular dysfunction.

Exclusion Criteria

• Left atrial diameter >5.5 cm.
• Previous left atrial ablation or surgery.
• Lack of anticoagulation therapy for 3 weeks prior to the procedure.
• Pulmonary vein stents or stenosis.
• Pre-existing diaphragmatic paralysis.
• Cardiac valve prosthesis or significant valve disease.
• Recent cardiac surgery or interventions within the past 3 months.
• Unstable angina, NYHA Class IV heart failure.
• Pulmonary hypertension or rheumatic heart disease.
• Blood clotting disorders.
• Contraindications to chronic anticoagulation.
• Active infection or hypertrophic cardiomyopathy.
• Reversible causes of AF, such as hyperthyroidism or sleep apnea.
• Stroke or TIA in the past 6 months.
• History of thromboembolic events or evidence of intracardiac thrombus.
• Women of childbearing age
• Life expectancy less than 12 months.
• Participation in another clinical trial.
• Allergy to adhesives.
• Inability to comply with study procedures.
• Inability to provide personal consent.
• NYHA Class IV heart failure.
• Left ventricular ejection fraction ≤ 25%.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundacion para la Innovacion en Biomedicina (FIBMED)

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Angel Arenal, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital General Universitario Gregorio Marañón

Locations

Hospital General Universitario Gregorio Marañon

Madrid, Madrid, Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

Angel Arenal, MD, PhD

Role: CONTACT

arenal@secardiologia.es

0034915868290

Gonzalo Ricardo Ríos-Muñoz, MSc, PhD

Role: CONTACT

grios@ing.uc3m.es

Facility Contacts

Angel Arenal, MD, PhD

Role: primary

arenal@secardiologia.es

0034915868290

Other Identifiers

PFA+ADM

Identifier Type: -

Identifier Source: org_study_id