Pulsed-Field Ablation With/Without Electrogram Mapping (PEAK-AF)

Pulsed-Field Ablation With/Without Electrogram Mapping of Key Substrates for Non-paroxysmal Atrial Fibrillation: A Prospective Multicenter Randomized Study (PEAK-AF Study)

Pulsed field ablation (PFA) has demonstrated favorable safety and efficacy in atrial fibrillation ablation, particularly for pulmonary vein isolation (PVI). However, the optimal PFA-based ablation strategy for non-paroxysmal atrial fibrillation remains uncertain. In addition to anatomical lesion sets such as PVI and posterior wall isolation (PWI), Electrogram Mapping of Key Substrates may allow identification of residual arrhythmogenic areas that contribute to the maintenance of atrial fibrillation. In the investigators' previously completed single-center cohort study, adjunctive ablation targeting key substrates identified by electrogram mapping on top of PVI+PWI was feasible and associated with improved rhythm outcomes.

This prospective multicenter randomized controlled study is designed to compare PFA-based PVI+PWI alone versus PVI+PWI plus adjunctive ablation guided by Electrogram Mapping of Key Substrates in patients with non-paroxysmal atrial fibrillation, in order to evaluate the efficacy and safety of this strategy in a broader and more rigorous clinical setting.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-paroxysmal Atrial Fibrillation
• Intervention / Treatment: Procedure: PFA-based PVI+PWI plus adjunctive ablation guided by Electrogram Mapping of Key Substrates; Procedure: PFA-based PVI+PWI alone

Detailed Description

Pulsed field ablation (PFA) has emerged as a promising energy source for atrial fibrillation ablation because of its myocardial selectivity and favorable safety profile. Previous studies have demonstrated high procedural success and encouraging clinical outcomes for PFA-based pulmonary vein isolation (PVI), particularly in patients with paroxysmal atrial fibrillation. However, in patients with non-paroxysmal atrial fibrillation, the underlying arrhythmogenic substrate is often more complex and extends beyond the pulmonary veins, and the optimal lesion set for PFA-based ablation in this population remains to be established.

Posterior wall isolation (PWI) is commonly added to PVI in an effort to improve substrate modification in non-paroxysmal atrial fibrillation. Nevertheless, recurrence after PVI+PWI remains common, suggesting that additional mechanisms outside conventional anatomical targets may play an important role in arrhythmia maintenance. Electrogram Mapping of Key Substrates provides a strategy to identify localized abnormal electrophysiological regions that may represent critical drivers or perpetuators of atrial fibrillation and may therefore serve as adjunctive ablation targets beyond standard anatomical lesion sets.

In the investigators' previous studies of catheter ablation for persistent atrial fibrillation, substrate modification guided by electrogram characteristics showed promising efficacy. More specifically, in the investigators' completed single-center cohort study of PFA for non-paroxysmal atrial fibrillation, adjunctive ablation based on Electrogram Mapping of Key Substrates in addition to PVI+PWI was shown to be feasible and was associated with favorable rhythm control outcomes. These findings support the hypothesis that a strategy incorporating electrogram-defined key substrate identification may provide incremental benefit over PVI+PWI alone.

However, whether adjunctive ablation guided by Electrogram Mapping of Key Substrates improves clinical outcomes in a reproducible manner has not yet been validated in a prospective multicenter randomized controlled trial. Given the potential influence of operator experience and center-level variability on substrate-based ablation, a multicenter randomized design is necessary to provide more robust evidence regarding the efficacy, safety, and generalizability of this strategy.

Therefore, the present study is designed as a prospective multicenter randomized controlled trial to compare two PFA-based ablation strategies in patients with non-paroxysmal atrial fibrillation:

1. PVI+PWI alone; and
2. PVI+PWI plus adjunctive ablation guided by Electrogram Mapping of Key Substrates.

The primary objective of this study is to determine whether the addition of ablation targeting key substrates identified by electrogram mapping improves rhythm outcomes compared with PVI+PWI alone. The study will also assess procedural characteristics and safety outcomes to further define the role of Electrogram Mapping of Key Substrates in optimizing PFA-based ablation strategies for non-paroxysmal atrial fibrillation.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200030
    • Shanghai Jiao Tong University School of Medicine, Shanghai Chest Hospital
  • Shanghai, China, 200127
    • Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine Shanghai
  • Hubei
    • Wuhan, Hubei, China, 430014
      • The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology
  • Jiangsu
    • Changshu, Jiangsu, China, 215516
      • Changshu Hospital of Traditional Chinese Medicine
    • Xuzhou, Jiangsu, China, 221009
      • Xuzhou Central Hospital
  • Shandong
    • Jinan, Shandong, China, 271100
      • Jinan City People's Hospital
    • Jinan, Shandong, China, 250001
      • Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine
  • Zhejiang
    • Wenling, Zhejiang, China, 317500
      • Wenling Hospital of Traditional Chinese Medicine
    • Yuhuan, Zhejiang, China, 317600
      • Yuhuan Second People's Hospital
• United States
  • New York
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1. Patients with documented drug-resistant symptomatic persistent AF meeting all three of the following criteria:a. Patient is refractory or intolerant to at least one Class I/III antiarrhythmic agentb. ECG-documented episode of persistent AF lasting longer than 7 days c. Holter within 90 days of the Enrollment Date demonstrating 24 hours of continuous AF2. Patients who are ≥ 18 years and <80 years 3. Patient participation requirements:a. Is willing and capable of providing Informed Consent to undergo study proceduresb. Is willing to participate in all examinations and follow-up visits and tests associated with this clinical study.

Exclusion Criteria:

• 1. AF that is:a. Paroxysmal (longest AF episode < 7days)b. Secondary to electrolyte imbalance, thyroid disease, alcohol abuse or other reversible / non-cardiac causes2. Left atrial anteroposterior diameter ≥ 60 mm as documented by transthoracic echocardiography (TTE) or computed tomography (CT)3. Any of the following cardiac conditions:a. Clinically significant arrhythmias other than AF, AFL or ATb. NYHA Class IV CHFc. Atrial or ventricular septal defect closured. Atrial myxomae. History of congenital heart disease with any residual anatomic or conduction abnormality4. Any of the following within 3 months of enrollment:a. Myocardial infarctionb. Unstable anginac. Percutaneous coronary interventiond. Heart surgery (e.g. coronary artery bypass grafting, ventriculotomy, atriotomy)e. Heart failure hospitalizationf. Stroke or TIAg. Clinically significant bleedingh. Pericarditis or pericardial effusioni. Left atrial thrombus 5. History of blood clotting or bleeding abnormalities.6. Contraindication to, or unwillingness to use, systemic anticoagulation 7. Sensitivity to contrast media not controlled by premedication8. Women of childbearing potential who are pregnant, lactating or not using birth control9. Medical conditions that would prevent participation in the study, interfere with assessment or therapy, significantly raise the risk of study participation, or confound data or its interpretation, including but not limited toa. Body mass index (BMI) > 40 transplantb. Severe lung disease, pulmonary hypertension, or any lung disease involving abnormal blood gases or significant dyspneac. Renal insufficiency with an estimated creatinine clearance < 30 mL/min/1.73 m2, or any history of renal dialysis or renal transplant d. Active malignancy or history of treated cancer within 24 months of enrollmente. Clinically significant gastrointestinal problems involving the esophagus, stomach and/or untreated acid refluxf. Clinically significant infectiong. Predicted life expectancy less than one year10. Current or anticipated enrollment in any other clinical study

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EGM; PFA-based PVI+PWI plus adjunctive ablation guided by Electrogram Mapping of Key Substrates: Participants randomized to this arm will undergo pulsed-field ablation (PFA)-based pulmonary vein isolation (PVI) and posterior wall isolation (PWI), followed by adjunctive ablation targeting key atrial substrates identified by predefined electrogram mapping criteria.	Procedure: PFA-based PVI+PWI plus adjunctive ablation guided by Electrogram Mapping of Key Substrates; In the experimental arm, electrogram mapping will be performed before pulmonary vein isolation (PVI) and posterior wall isolation (PWI) to identify key atrial substrates for adjunctive ablation. Mapping may be conducted using machine learning-assisted electrogram mapping, operator-guided electrogram mapping, or a combination of both, based on the same predefined criteria for target identification. Electrogram analysis will then be performed to identify target regions with the following characteristics: 1)Spatial-temporal dispersion activation; 2)Short cycle length activity; 3)Focal activity. After completion of electrogram mapping and target identification, all participants in the experimental arm will undergo standard PFA-based PVI and PWI. Adjunctive pulsed-field ablation will subsequently be delivered to the electrogram-defined key substrates identified during the pre-ablation mapping phase.
Active Comparator: PWI; Participants randomized to this arm will undergo pulsed-field ablation (PFA)-based pulmonary vein isolation (PVI) and posterior wall isolation (PWI) without adjunctive ablation guided by electrogram mapping of key substrates.	Procedure: PFA-based PVI+PWI alone; Ablation will be performed using a pulsed-field ablation system. Participants in this arm will undergo standard pulmonary vein isolation and posterior wall isolation only, without additional substrate ablation guided by electrogram mapping.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
composite of major safety events	The safety endpoint is a composite of major safety events including cardiac tamponade or perforation, peripheral or organ thromboembolism, stroke or transient ischemic attack (TIA), diaphragmatic paralysis, block, pericarditis, hemolysis, myocardial infarction, PV stenosis, atrioesophageal fistula, and death. The endpoint includes events occurring within 30 days of the index or reassessment procedures.	adverse events occurring within 30 days of the index or reassessment procedures.
freedom from any AF/AT	The feasibility primary endpoint was defined as freedom from any AF/AT episodes lasting more than 30 seconds after the blanking period without anti-arrhythmic drugs at 3 months, 6 months, 12 months and 36 months respectively after the procedure.	freedom from any AF/AT at 3 months, 6 months, 12 months and 36 months respectively after the procedure; adverse events occurring within 30 days of the index or reassessment procedures.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AF recurrence	freedom from any documented AF episode lasting more than 30 seconds after the blanking period without anti-arrhythmic drug treatment at 3 months, 6 months, 12 months and 36 months respectively	freedom from any AF at 3 months, 6 months, 12 months and 36 months respectively after the procedure
AT recurrence	any documented AT episode lasting more than 30 seconds after the blanking period without anti-arrhythmic drug treatment at 3 months, 6 months, 12 months and 36 months respectively.	freedom from any AT at 3 months, 6 months, 12 months and 36 months respectively after the procedure

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
AF termination	procedural AF termination	AF termination immediately during ablation, including AF terminated to sinus rhythm/atrial tachycardia
difference of freedom from any AF/AT between patients with/without procedural AF termination	freedom from any AF/AT episodes lasting more than 30 seconds after the blanking period without anti-arrhythmic drugs at 3 months, 6 months, 12 months and 36 months respectively after the procedure in patients with/without procedural AF termination	freedom from any AF/AT at 3 months, 6 months, 12 months and 36 months respectively after the procedure; adverse events occurring within 30 days of the index or reassessment procedures

Collaborators and Investigators

• Sponsor: Xu Liu
• Collaborators: Shanghai Chest Hospital, Shanghai Jiao Tong University School Of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2024
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: April 13, 2026
• First Submitted That Met QC Criteria: April 13, 2026
• First Posted (Actual): April 21, 2026

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: catheter ablation; persistent atrial fibrillation; non-paroxysmal atrial fibrillation; pulsed field ablation; electrogram mapping; key substrate ablation; eletrogram-guided ablation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Pathological Conditions, Signs and Symptoms; Atrial Fibrillation
• Other Study ID Numbers: PEAK-AF Study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The individual participant data (IPD) from this study will not be shared publicly due to concerns regarding patient confidentiality and the sensitive nature of medical data. Given the potential risks of identifying participants from detailed clinical information, the data will remain confidential and will not be made available for public sharing. Additionally, the study involves proprietary methodologies and ongoing analyses that are part of the intellectual property of the institution. As such, sharing the IPD at this stage could compromise the integrity of the study's findings and its future applications.

Drug and device information, study documents

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