Grant: Project Grant

Short-coupled ventricular fibrillation (SCVF) is a recently discovered, primary electrical disorder. Primary electrical disorders cause dangerous heart rhythms and are a common cause of unexplained sudden cardiac death. Affected patients are at very high risk of recurrent arrhythmia. Our previous work showed that a large proportion of SCVF is actually caused by circulating autoantibodies in the blood. These autoantibodies bind to a specific cardiac potassium channel, TREK-1, resulting in cellular changes that promotes arrhythmia. The only known effective medication for SCVF, quinidine, can neutralize the effect of these antibodies. To elaborate and confirm our initial results, we propose a large multicenter center study enrolling patients from different Canadian provinces. Eligible patients will undergo repeat blood tests over 12 months to test for anti-TREK-1 autoantibodies. This will be compared with the disease severity. The proposed study will also allow to determine the possibility of different manifestations between men and women as well as between various ethnic groups. A second part of this project includes laboratory experiments using cardiac cells that will be created from reprogrammed human inducible pluripotent stem cells (hiPSC). These cells can be differentiated into different cardiac cell types. We will then study the effect of anti-TREK-1 on the electrical properties of these different cell types. The results of these experiments could help to identify which cardiac cell type is responsible for SCVF. The anticipated results of this proposed project will improve our understanding of SCVF and may permit us to predict the clinical course. Future episodes of ventricular fibrillation may be preventable by timely adjustment of medication or referral for special invasive procedures in cardiac electrophysiology. Our results may also allow us to provide effective family screening identifying other individuals being potentially at risk.