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Linking a novel mutation to its short QT phenotype through multiscale computational modelling

This paper is available in a repository.
This paper is available in a repository.

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Abstract

The aim of this work was to assess the link between a newly identified KCNQ1 mutation and the short QT syndrome clinically observed in the patients. We applied two human Action Potential models. the ten Tusscher-Panfilov (TTP) and the O'Hara Rudy (ORd). We also simulated the effects of adrenergic stimulation on action potential, since the basal adrenergic tone should likely affect the 1ks influence on QTc in vivo. Finally, we simulated the pseudo ECG taking into account the heterogeneity of the cardiac wall. Simulations predict a shortening of the action potential consistent with the patient phenotype: using the TTP model the shortening was largely more pronounced (e.g. from 397 to 297 ms in M cells) than with the ORd (e.g. from 332 to 318 ms in M cells). When simulating the β-adrenergic stimulation, the APD shortening was enhanced in ORd model. Pseudo ECG results confirm the reduction of the QT interval caused by mutation.