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.

Please refer to the uploaded study protocol

Inclusion Criteria:

• Age ≥ 18 years
• Diagnosis of SCVF as per current criteria
• Willingness to provide written informed consent

Exclusion Criteria:

- SCVF patients < age 18

Cohort study of SCVF probands