Mechanistic insights to pro-arrhythmogenesis of short-QT syndrome associated with KCNQ1 gene mutation

Idiopathic short QT (SQT) syndrome is a recently identified, genetically heterogeneous condition characterized by abbreviated QT intervals and an increased susceptibility to arrhythmia and sudden death. In this computer simulation study, we identify the mechanisms by which cellular electrophysiological changes in the SQT syndrome associated with V307L KvLQT1 (KCNQ1) gene mutation (the gene coding the slowly activated rectifier potassium channel current (IKs)) increase arrhythmia-risk in human ventricle. Our simulations have shown that V307L gene mutation increases transmural heterogeneity of ventricular repolarisation that leads to an increased tissue’s vulnerability for uni-directional conduction block favorable to re-entrant arrhythmia. It also increases tissue’s susceptibility to sustain re-entry. This study provided novel mechanistic insights toward understandings of pro-arrhythmogenesis in patients with SQT syndrome subjected to V307L gene mutation.