Modelling of short QT syndrome in a heterogeneous model of the human ventricular wall

Aims A percentage of sudden cardiac death events occur in individuals with structurally normal hearts due to an abnormality in the ion channel activity. While the majority of these hereditary syndromes are well-established, little is known about the significance of the short QT syndrome. Methods This study is based on discovered insights into the molecular basis of the originally described form of this disease. A biophysically detailed model of cellular electrophysiology was adapted to emulate the behaviour of cells affected by the short QT syndrome. Simulations were performed in single cell and homogeneous as well as heterogeneous anisotropic multi-cellular environment describing the human left ventricle. Results The short QT mutation increased the activity of the repolarizing outward potassium current IKr. The heterogeneous abbreviation of the action potential duration decreased the dispersion of repolarization in heterogeneous tissue. Repolarization was homogenized and the final repolarization was shifted to epicardial sites. The transmural ECG showed a shortened QT interval and a T wave with reduced amplitude. Conclusion The altered characteristics of the mutant IKr current were consistent with experimental findings. The heterogeneous reduction of the action potential duration and the reduced T wave amplitude need to be verified by measurements.