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

NCT06647459 | Terminated DMC

• 1 other identifier: 231260
• Study Type: observational
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Ventricular Tachycardia; Atrial Fibrillation

Keywords

catheter ablation; genomics

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• Low voltage substrate

  The primary endpoint is the presence of low voltage (yes/no) in the basal LV.

  At the time of procedure

Secondary Outcomes (3)

• Site of origin for ventricular arrhythmias

  At the time of procedure

• Evaluation of electrogram potentials

  At the time of procedure

• Presence of low voltage

  At the time of procedure

Study Arms (3)

Pathogenic variant in TTN

50 patients with a pathogenic variant in TTN

Diagnostic Test: EP Study

Pathogenic variant in other cardiomyopathy genes

50 patients with a pathogenic variant in other cardiomyopathy genes

Diagnostic Test: EP Study

Genotype-negative controls

100 genotype-negative controls

Diagnostic Test: EP Study

Interventions

EP Study DIAGNOSTIC_TEST

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.

Also known as: Mapping

Genotype-negative controls; Pathogenic variant in TTN; Pathogenic variant in other cardiomyopathy genes

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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).

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Tachycardia, Ventricular; Atrial Fibrillation

Condition Hierarchy (Ancestors)

Tachycardia; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Moore B Shoemaker, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: October 15, 2024
• First Posted: October 17, 2024
• Study Start: December 13, 2023
• Primary Completion: April 28, 2026
• Study Completion: April 28, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)