Effect of Percentage Reduction in Action Potential Duration of M-cells on Reentry in Short QT Syndrome

Ponnuraj Kirthi Priya and Srinivasan Jayaraman
Tata Consultancy Services


Increase in transmural dispersion of repolarisation along with a diminished QT interval have been known to aid in the development of arrhythmia during KCNQ1-linked short QT syndrome type 2 (SQTS2). However, the percentage by which action potential duration (APD) shortens in the different cell types that make up the ventricular wall are not fully understood. In this study, the percentage of APD shortening of M-cells was varied to determine the conditions under which re-entry occurs during SQTS2. A 2D transmural section of the heart with anisotropic properties is considered. Slight modifications to the TP06 equations are used to simulate the electrophysiology of the endocardial (endo), midmyocardial (M) and epicardial (epi) cells. A discrete network of 250x100 cells are interconnected using gap junction conductances and from this, a pseudo ECG is generated. On pacing the tissue with premature beats in the midst of normal pacing pulses and on including SQTS2 conditions, it is observed that re-entry is sustained for a longer duration when the APD shortening in M-cells is more compared to the epi or endo cells while the percentage reduction in APD of M-cells is about 5% to 7% lesser than that in epi and endo cells. Further, when the percentage reduction in APD of M-cells is similar to epi or endo cells, no re-entry is generated. This analysis highlights the key role of percentage reduction in APD of M-cells compared to epi and endo cells in maintaining the re-entrant waves.