Idiopathic Ventricular Fibrillation, Short-coupled Ventricular Fibrillation
Conditions
Keywords
SCVF, anti-TREK-1 antibodies, IVF
Brief summary
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.
Detailed description
Please refer to the uploaded study protocol
Interventions
OTHERRepeat plasma screening for the presence or absence of anti-TREK-1 autoantibodies
Semiquantitative measure of circulating anti-TREK-1 autoantibodies in plasma of study participants using a peptid microarray
GENETICDPP6 risk haplotype
Systematic genetic screening for the Dutch DPP6 risk haplotype in all study participants and correlation of results with the presence or absence of anti-TREK-1 autoantibodies
Sponsors
Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Diagnosis of SCVF as per current criteria * Willingness to provide written informed consent
Exclusion criteria
\- SCVF patients \< age 18
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Presence of anti-TREK-1 autoantibodies at three different time points | 12 months | Plasma concentrations of anti-TREK-1 autoantibodies (semiquantitative measure using a peptide microarray at three predefined time points |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time-dependent variability of plasma concentrations of anti-TREK-1 autoantibodies | 12 months | Repeat plasma sampling to assess the presence/absence of anti-TREK-1 autoantibodies and time-dependent variability of antibody expression |
| Impact of anti-TREK-1 autoantibodies on disease severity | 12 months | Correlation of the presence (plasma concentration) of anti-TREK-1 autoantibodies with recurrent VF, electrical storm and appropriate ICD therapies |
Countries
Canada, Netherlands
Contacts
CONTACTMarina Sanchez, PhD
CONTACTPaule Banville, Study coordinator
PRINCIPAL_INVESTIGATORChristian Steinberg, MD
Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
Outcome results
None listed