Congenital Short QT Syndrome (SQTS) is a rare but dangerous condition involving abbreviated ventricular
repolarization and an increased risk of atrial and ventricular arrhythmias. Taking the example of the first
identified SQTS mutation, N588K-hERG, we consider briefly the basic science approaches used to obtain
an understanding of the mechanism(s) of arrhythmogenesis in this form of the syndrome. A combination of
recombinant channel electrophysiology and in silico simulations has provided insights into causality
between the identified mutation, accelerated repolarization and increased susceptibility to re-entry in
N588K-hERG-linked SQTS. Subsequent studies employing a transgenic rabbit model or human induced
pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) have further demonstrated mechanisms
predisposing to re-entry, spiral wave activity and arrhythmia in intact tissue. The complementarity between
the findings made using these different approaches gives confidence that, collectively, they have identified
major arrhythmia mechanisms and their potential mitigation by Class I antiarrhythmic drugs in this form of
SQTS.
Effects of Taurine-Magnesium Coordination Compound on Type 2 Short QT Syndrome: A Simulation Study
