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

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

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.

Study Overview

• Status: Terminated
• Conditions: Atrial Fibrillation; Ventricular Tachycardia
• Intervention / Treatment: Diagnostic test: EP Study

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 Type: Observational
• Enrollment (Actual): 32

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients with early-onset AF are referred to our Vanderbilt AF Precision Medicine Clinic and undergo clinical genetic testing with a CM/arrhythmia panel and a comprehensive clinical evaluation including a cardiac MRI. 50% of patients are referred to undergo AF ablation to treat symptomatic AF. For all eligible patients, the study will be described either in person, or be contacted via phone with an approved phone script. If interested, participants sign the written informed consent (paper option or e-consent option).

Description

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 Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pathogenic variant in TTN; 50 patients with a pathogenic variant in TTN	Diagnostic test: EP Study; 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.; Other Names: Mapping
Pathogenic variant in other cardiomyopathy genes; 50 patients with a pathogenic variant in other cardiomyopathy genes	Diagnostic test: EP Study; 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.; Other Names: Mapping
Genotype-negative controls; 100 genotype-negative controls	Diagnostic test: EP Study; 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.; Other Names: Mapping

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VT Inducibility	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.	At the time of procedure
Low voltage substrate	The primary endpoint is the presence of low voltage (yes/no) in the basal LV.	At the time of procedure
Presence of ventricular arrhythmias per specific site	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.	At the time of procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Site of origin for ventricular arrhythmias	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.	At the time of procedure
Evaluation of electrogram potentials	Secondary analyses will explore multicomponent electrograms and fractionated potentials that can be created by scar.	At the time of procedure
Presence of low voltage	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.	At the time of procedure

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Investigators: Principal Investigator: Moore B Shoemaker, MD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2023
• Primary Completion (Actual): April 28, 2026
• Study Completion (Actual): April 28, 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): May 6, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: genomics; catheter ablation
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Tachycardia; Pathological Conditions, Signs and Symptoms; Atrial Fibrillation; Tachycardia, Ventricular
• Other Study ID Numbers: 231260

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