Computational analysis of long QT syndrome type 2 and the therapeutic effects of KCNQ1 antibodies

Figures

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  Figure 1.. The fitted curve of the relationship between the voltage shift and the concentration of KCNQ1 antibody.

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  Figure 2.. Simulation results of action potentials. (A–C) Steady-state action potentials of ENDO, MCELL, and EPI cells under homozygous (red) conditions. (D–F) Steady-state action potentials of ENDO, MCELL, and EPI cells under wild-type (black) and heterozygous (orange) conditions. (G) APD90 of EPI, MCELL, and ENDO cells under wild-type (black) and heterozygous (orange) conditions. (H) Effective refractory period (ERP) of EPI, MCELL, and ENDO under wild-type (black) and heterozygous (orange) conditions. The asterisks (‘*’) in the bottom two panels indicate failure of repolarization.

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  Figure 3.. Simulated pseudo-electrocardiogram (ECG) results and the restitution properties of ECG. (A and B) Spatiotemporal maps of excitation wave propagation under wild-type and heterozygous conditions. (C and D) The corresponding pseudo-ECGs under wild-type and heterozygous conditions.

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  Figure 4.. The restitution properties of QT interval. (A and B) Simulated pseudo-ECG results for wild-type and heterozygous conditions over a BCL range of 600–1500 ms. Arrows indicate the gradual prolongation of QT intervals as BCL increases. (C and D) Changes of QT, QTc, ΔQT, and ΔQTc as BCL increases. Black and orange traces indicate wild-type and heterozygous conditions, respectively. (E) The QTc ratio of heterozygous long QT (LQT) to wild-type, that is, QTcHETE/QTcWT.

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  Figure 5.. Visualization of the vulnerable window (VW) and its distribution. (A and B) Panels from left to right show in order of the bidirectional conduction block (S2 applied too early), the unidirectional conduction block (within the VW), and the bidirectional conduction (S2 applied too late). (C) Distribution of VWs under wild-type (black) and heterozygous (orange) conditions. (D) Comparison of the average VW width under different conditions. The average VW widths for the wild-type and heterozygous groups were 5.22 and 31.10 ms, respectively.

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  Figure 6.. Propagation of excitation waves in the three-dimensional (3D) human left ventricular wedge model: (A) wild-type and (B) heterozygous conditions.

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  Figure 7.. Simulation results of the action of KCNQ1 antibody on cellular action potentials and pseudo-electrocardiograms (ECGs). (A–C) Steady-state action potentials of (A) ENDO, (B) MCELL, and (C) EPI under different conditions, including the wild-type (gray), heterozygous (orange), heterozygous with 60 µg/mL KCNQ1 antibody (green), and heterozygous with 300 µg/mL KCNQ1 antibody (blue). (D) Pseudo-ECGs under wild-type (gray), heterozygous (orange), and heterozygous with 60 µg/mL KCNQ1 antibody (green) conditions. (E) Pseudo-ECGs under wild-type (gray), heterozygous (orange), and heterozygous with 300 µg/mL KCNQ1 antibody (blue) conditions.

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  Figure 8.. Propagation of excitation waves in the ventricular wedge with the application of KCNQ1 antibodies. (A) Wild-type condition. (B) Heterozygous condition. (C) Heterozygous group with 300 µg/mL KCNQ1 antibody.

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  Figure 9.. Vulnerable windows (VWs) under different conditions. (A) Distributions of VWs under different conditions. (B) The comparison of average VW width under different conditions.