Sadrieh, Arash and Domanski, Luke and Pitt-Francis, Joe and Mann, Stefan A and Hodkinson, Emily C and Ng, Chai-Ann and Perry, Matthew D and Taylor, John A and Gavaghan, David and Subbiah, Rajesh N and Vandenberg, Jamie I and Hill, Adam P (2014) Multiscale cardiac modelling reveals the origins of notched T waves in long QT syndrome type 2. Nature Communications, 5. p. 5069. ISSN 2041-1723 (OA)
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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.
(NHMRC grants 1006016, 1019693; ARC grant FT110100075).
| Item Type: | Article |
|---|---|
| Keywords: | DOAJ publication |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 21 Jan 2016 05:40 |
| Last Modified: | 18 May 2016 23:41 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/207 |
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