Simulation of re-entrant wave dynamics in a 2-D sheet of human ventricle with KCNJ2-linked variant 3 short QT syndrome

Recent studies suggested that short QT syndrome is liable to cause malignant ventricular arrhythmia possibly due to high-frequency re-entrant waves. Our goal was to study the dynamical behaviours of rotors associated with a KCNJ2-linked variant 3 short QT syndrome. A two-dimensional sheet model of human ventricular tissue was implemented to create a short QT syndrome substrate. Electrical action potential of each node was simulated by the ten Tusscher et al. model, which was modified to incorporate changes of hi based on experimentally observed data of Kir2.1 function, including WT, WT-D172N and D172N scenarios. Using the model, the minimal length of the S2 stimulus which provided a sufficient substrate for maintaining rotors was computed. It was shown that WT-D172N and D172N mutant I
_k1
led to abbreviated APD and ERP, resulting in a reduced minimal length of the S2 stimulus to sustain re-entry. This suggested that with the SQT3 Kir2.1 mutation, reentry can be more easily initiated and sustained as compared to the WT condition. This study provides novel insights into the ionic bases of an increased incidence of ventricular fibrillation associated with short QT syndrome, which may cause sudden cardiac death.