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)
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)
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)
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).
Metadata
Keywords: | DOAJ publication |
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Subjects: | R Medicine > R Medicine (General) |
Depositing User: | Repository Administrator |
Date Deposited: | 21 Jan 2016 05:40 |
Last Modified: | 18 May 2016 23:41 |
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Filename: Sadrieh 2014 notched T waves _Nature Comms OA.pdf