Grant proposal was sent to NIH 3 times but did not score well enough to receive funding

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.

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.

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.

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).