Defining the Risk of Ventricular Tachycardia in Genetic Forms of Early-onset Atrial Fibrillation

Recruiting

• Conditions: Ventricular Tachycardia; Atrial Fibrillation

• Registration Number: NCT06647459
• Lead Sponsor: Vanderbilt University Medical Center

Brief Summary

To use programmed ventricular stimulation at the time of AF ablation to define the prevalence and mechanism of inducible ventricular tachycardia (VT); pace-mapping to define the site of origin of ventricular arrhythmias; and voltage mapping to define low voltage scar substrate in the basal LV in patients with pathogenic TTN variants compared to genotype-negative controls.

Detailed Description

Participants will undergo AF ablation according to standard, contemporary techniques. The procedure will be performed under general anesthesia. As part of routine standard of care in patients with early-onset AF or patients who have PVCs, we will also test for inducibility of VT using a standardized pacing protocol. The research protocol will include LV mapping and identification of low voltage substrate using electroanatomical mapping as described below.

Study Timeline

• Study Start: 2023-12-13
• Study First Submitted: 2024-10-15
• Study First Submitted QC: 2024-10-15
• Study First Posted: 2024-10-17
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-05
• Last Update Posted: 2025-01-07
• Primary Completion: 2026-01-01
• Study Completion: 2027-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Adults aged 18 and older
2. Diagnosed with AF before age 60
3. Scheduled for catheter-based AF ablation (de-novo or repeat)
4. Able to provide written, informed consent
5. P/LP variant in TTN or other CM gene (cases) or identified as a genotype-negative control.

Exclusion Criteria

1. Diagnosed with a genetic CM or arrhythmia syndrome prior to AF
2. VUS in 'possibly pathogenic' subgroup (control group only)
3. Pacemaker or ICD
4. Previous PVC or VT ablation
5. LVEF <20%
6. Prosthetic mitral or aortic valve
7. Contraindication to heparin
8. Prior myocardial infarction.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
VT Inducibility	At the time of procedure	The primary endpoint is induction of sustained VT that is determined to be reentrant or likely-reentrant. Sustained VT will be defined as VT lasting 30 seconds or requiring termination with burst pacing or cardioversion due to hemodynamic instability.
Presence of ventricular arrhythmias per specific site	At the time of procedure	The primary endpoint is the occurrence (yes/no) of ventricular arrhythmias (PVCs, NSVT, sustained VT) that are mapped to the basal LV as defined above.
Low voltage substrate	At the time of procedure	The primary endpoint is the presence of low voltage (yes/no) in the basal LV.

Secondary Outcome Measures

Name	Time	Method
Site of origin for ventricular arrhythmias	At the time of procedure	Secondary analyses will explore the rate of ventricular arrhythmias in other segments of the LV and RV and will compare the site of origin for ventricular arrhythmias in the group of participants with pathogenic variants in other CM genes.
Evaluation of electrogram potentials	At the time of procedure	Secondary analyses will explore multicomponent electrograms and fractionated potentials that can be created by scar.
Presence of low voltage	At the time of procedure	Other secondary analyses will compare the presence of low voltage and the other secondary endpoints in the group of participants with pathogenic variants in other CM genes.

Trial Locations

Locations (1)

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States