Clinical trial NCT06647459: Defining the Risk of Ventricular Tachycardia in Genetic Forms of Early-onset Atrial Fibrillation
Official title: Defining the Risk of Ventricular Tachycardia in Genetic Forms of Early-onset Atrial
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Ventricular Tachycardia
Atrial Fibrillation
Keywords: catheter ablation
genomics
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2024-10-17
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: VT Inducibility
timeFrame: At the time of procedure
measure: Presence of ventricular arrhythmias per specific site
timeFrame: At the time of procedure
measure: Low voltage substrate
timeFrame: At the time of procedure
Secondary outcomes:
measure: Site of origin for ventricular arrhythmias
timeFrame: At the time of procedure
measure: Evaluation of electrogram potentials
timeFrame: At the time of procedure
measure: Presence of low voltage
timeFrame: At the time of procedure
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Moore B Shoemaker, MD
role: PRINCIPAL_INVESTIGATOR
References: