Sex-Based Disparities in the Electrophysiological Substrate for Atrial Fibrillation and Its Impact on Clinical Outcomes

DISPARITY-AF is a prospective, single-center, observational registry designed to characterize the sex-based disparities in the electrophysiological substrate driving Atrial Fibrillation (AF). While standard Pulmonary Vein Isolation (PVI) is the cornerstone of AF ablation, women consistently experience lower long-term success rates. This study tests the hypothesis that women harbor a significantly higher burden of unmapped, extra-pulmonary vein (extra-PV) AF initiation sites compared to men.

In 100 consecutive patients undergoing first-time PVI, comprehensive biatrial repolarization mapping will be performed using programmed electrical stimulation (PES) to measure the atrial effective refractory period (AERP) in multiple atrial sites immediately after successful PVI. All mapping systems and multielectrode catheters utilized in this study are clinically approved and used routinely in our center. Identified steep repolarization gradients (SRGs) and AF initiation sites will be documented but not ablated. Patients will undergo intensive 1-year clinical follow-up to test the secondary hypothesis that patients with untreated extra-PV SRG/AF initiation sites have a significantly higher rate of AF recurrence.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation (AF)
• Intervention / Treatment: Device: Identifying extra-PV SRG sites

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

Contacts and Locations

• Study Contact: Name: Anat Milman, MD; Phone Number: +972-54-3166651; Email: anatmi@shamir.gov.il
• Study Contact Backup: Name: Ofir Mitz; Email: ofirm@shamir.gov.il

Study Locations

• Israel
  • Be’er Ya‘aqov, Israel
    • Recruiting
    • Shamir Medical Center
    • Contact: Anat Milman, MD; Phone Number: +972-54-3166651; Email: anatmi@shamir.gov.il
    • Contact: Ofir Mitz; Email: ofirm@shamir.gov.il

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age 18 years or older.
• Male or Female sex.
• Symptomatic paroxysmal or persistent AF indicated for a first-time catheter ablation.
• Ability to provide written informed consent.

Exclusion Criteria:

• Prior catheter ablation for AF or surgical MAZE.
• Long-standing persistent AF (>12 months).
• Presence of intracardiac thrombus or contraindication to systemic anticoagulation.
• Pregnant women and patients not able to provide an informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: PVI ablation and identifying extra-PV SRG sites; Men and women undergoing first time PVI ablation for identification of extra-PV SRG sites.	Device: Identifying extra-PV SRG sites; After performing PVI as standard of care, mapping of both atria will be performed to locate extra-PV SRG sites.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spatial distribution and frequency of extra-PV sites and AF initiation sites in both atria following standard PVI.	Number of extra-PV sites and AF initiations for every patient (N per patient)	During procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Freedom from AF and AT at one year.	Number of patients with recurrence is defined as any documented AF, AT or atrial flutter lasting ≥30 seconds using ECG and holter monitoring.	During 12 month follow up period.

Collaborators and Investigators

• Sponsor: Anat Milman

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2026
• Primary Completion (Estimated): April 19, 2027
• Study Completion (Estimated): April 19, 2028

Study Registration Dates

• First Submitted: April 28, 2026
• First Submitted That Met QC Criteria: May 5, 2026
• First Posted (Actual): May 12, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: May 31, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; Ablation; Sex; Gender; Disparity
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Pathological Conditions, Signs and Symptoms; Behavior; Sexual Behavior; Atrial Fibrillation; Coitus
• Other Study ID Numbers: DISPARITY-AF

Drug and device information, study documents

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