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

Author

Listed:
  • Arash Sadrieh

    (Victor Chang Cardiac Research Institute
    St Vincent’s Clinical School, University of New South Wales)

  • Luke Domanski

    (CSIRO eResearch and Computational and Simulation Sciences)

  • Joe Pitt-Francis

    (University of Oxford)

  • Stefan A Mann

    (Victor Chang Cardiac Research Institute
    St Vincent’s Clinical School, University of New South Wales)

  • Emily C Hodkinson

    (Victor Chang Cardiac Research Institute
    St Vincent’s Clinical School, University of New South Wales)

  • Chai-Ann Ng

    (Victor Chang Cardiac Research Institute
    St Vincent’s Clinical School, University of New South Wales)

  • Matthew D Perry

    (Victor Chang Cardiac Research Institute
    St Vincent’s Clinical School, University of New South Wales)

  • John A Taylor

    (CSIRO eResearch and Computational and Simulation Sciences)

  • David Gavaghan

    (University of Oxford)

  • Rajesh N Subbiah

    (Victor Chang Cardiac Research Institute
    St Vincent’s Clinical School, University of New South Wales)

  • Jamie I Vandenberg

    (Victor Chang Cardiac Research Institute
    St Vincent’s Clinical School, University of New South Wales)

  • Adam P Hill

    (Victor Chang Cardiac Research Institute
    St Vincent’s Clinical School, University of New South Wales)

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.

Suggested Citation

  • 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 & Adam P H, 2014. "Multiscale cardiac modelling reveals the origins of notched T waves in long QT syndrome type 2," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6069
    DOI: 10.1038/ncomms6069
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    Cited by:

    1. William A. Ramírez & Alessio Gizzi & Kevin L. Sack & Simonetta Filippi & Julius M. Guccione & Daniel E. Hurtado, 2020. "On the Role of Ionic Modeling on the Signature of Cardiac Arrhythmias for Healthy and Diseased Hearts," Mathematics, MDPI, vol. 8(12), pages 1-19, December.

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