Clinical Research Directory

MEdical Treatment in Idiopathic Ventricular Fibrillation Patients

A person who has experienced a cardiac arrest with no apparent cause is at risk of having recurrent cardiac arrest. Hence an implantable cardioverter-defibrillator (ICD) is recommended on empirical grounds. Today, there is no uniform way of approaching prevention of recurrence in idiopathic ventricular fibrillation (IVF) patients, beside ICD implantation. Better reatment and risk stratification tools are needed Medical treatment in these patients has never been assessed systematically, but at least some patients with no apparent diagnosis are on betablocker treatment. It is not known if low-doselow dose betablocker treatment is beneficial in these patients. This study investigates the effect of betablocker treatment to reduce arrhythmic burden in IVF patients. No predictors for appropriate ICD therapy have been identified in patients with IVF. It is also explored if toxicological and/or genetic profiles, together with in depth machine learning simulation data on repolarization patterns from IVF-ECGs compared to controls, can be used as risk stratification tools. Lastly, QOL in IVF patients and the impact of beta blocker treatment will be investigated.

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.