Role of Anti-TREK-1 Autoantibodies in SCVF

Short-coupled ventricular fibrillation (SCVF) is a lethal, primary electrical disorder and an important cause of unexplained cardiac arrest.1 Recent work from our group suggests that a substantial proportion of SCVF cases is associated to circulating autoantibodies targeting TREK-1, a cardiac potassium channel, resulting in an abnormal gain-of-function which is the prerequisite for the SCVF phenotype.2 This proposal is a translational multicenter study to validate anti-TREK-1 autoantibodies as a diagnostic and prognostic biomarker in a large, diversified cohort of SCVF patients (Figure 1). Functional, cellular experiments in patient-derived hiPSC cardiomyocytes and Purkinje cells will be performed to explore the cell type-specific role of TREK-1 in arrhythmogenesis, while single-nuclear RNA sequencing (snRNA-seq) will allow us to establish the transcriptomic profile (Figure 1). These results will identify the cellular substrate for SCVF.

NCT Number	NCT06943365
Lead Sponsor	Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
Conditions	Short-coupled Ventricular Fibrillation, Idiopathic Ventricular Fibrillation
Enrollment	300 participants
Start Date	2025-05-01
Primary Completion	2027-07-31 (estimated)
Study Completion	2028-12-31 (estimated)
Updated on ClinicalTrials.gov	2026-06-16