Multiscale cardiac modelling reveals the origins of notched T waves in long QT syndrome type 2

Arash Sadrieh, Luke Domanski, Joe Pitt-Francis, Stefan A Mann, Emily C Hodkinson, Chai-Ann Ng, Matthew D Perry, John A Taylor, David Gavaghan, Rajesh N Subbiah, Jamie I Vandenberg and Adam P Hill ()
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Arash Sadrieh: Victor Chang Cardiac Research Institute
Luke Domanski: CSIRO eResearch and Computational and Simulation Sciences
Joe Pitt-Francis: University of Oxford
Stefan A Mann: Victor Chang Cardiac Research Institute
Emily C Hodkinson: Victor Chang Cardiac Research Institute
Chai-Ann Ng: Victor Chang Cardiac Research Institute
Matthew D Perry: Victor Chang Cardiac Research Institute
John A Taylor: CSIRO eResearch and Computational and Simulation Sciences
David Gavaghan: University of Oxford
Rajesh N Subbiah: Victor Chang Cardiac Research Institute
Jamie I Vandenberg: Victor Chang Cardiac Research Institute
Adam P Hill: Victor Chang Cardiac Research Institute

Nature Communications, 2014, vol. 5, issue 1, 1-11

Abstract: Abstract The heart rhythm disorder long QT syndrome (LQTS) can result in sudden death in the young or remain asymptomatic into adulthood. The features of the surface electrocardiogram (ECG), a measure of the electrical activity of the heart, can be equally variable in LQTS patients, posing well-described diagnostic dilemmas. Here we report a correlation between QT interval prolongation and T-wave notching in LQTS2 patients and use a novel computational framework to investigate how individual ionic currents, as well as cellular and tissue level factors, contribute to notched T waves. Furthermore, we show that variable expressivity of ECG features observed in LQTS2 patients can be explained by as little as 20% variation in the levels of ionic conductances that contribute to repolarization reserve. This has significant implications for interpretation of whole-genome sequencing data and underlies the importance of interpreting the entire molecular signature of disease in any given individual.

Date: 2014
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DOI: 10.1038/ncomms6069

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