Effects of island-distribution of mid-cardiomyocytes on ventricular electrical excitation associated with the KCNQ1-linked short QT syndrome.

AIMS

Short QT syndrome (SQTS) is a new genetic disorder of the electrical system of the heart. To date, there are six gene mutations in ion channels underlying SQTS. However, functional effects of spatial heterogeneities, such as island-distribution of mid-cardiomyocytes (M island) on ventricular electrical excitation in SQTS condition are poorly understood or even not understood at all. Therefore, this study used computational modelling to investigate such possible effects.

METHODS

The spatial heterogeneities of ventricular tissue was studied by using ten Tusscher et al.

MODEL

The model was modified to simulate changes to IKs based on experimental observations of KCNQ1 V307L mutation in SQT2 condition. Cell models were coupled to construct a strand tissue, among which 35% were mid-cardiomyocytes, either distributed in island form or in band form, 25% were endocardial (ENDO), and the rest part were epicardial (EPI) cells.

RESULTS

In simulations, the QT interval was shortened due to the KCNQ1 V307L mutation. The model with M band form failed to reproduce a markedly increase in the T-wave height. However, the model with M island form was able to produce a markedly increased T-wave height with the V307L mutation, matching the major features of SQT clinical ECGs.

CONCLUSIONS

This study substantiates a causal link between the M island and T-wave amplitude in the KCNQ1-linked short QT syndrome.