Paper Info
Title
Sensitivity analysis of the QT and JTpeak intervals from a high-resolution human left-ventricular wedge model
Abstract
There is an interest in looking at sub-intervals of the QT in the Comprehensive in-vitro Proarrhythmia Assay (CiPA) initiative. Here, we performed a sensitivity analysis of JT peak and T-wave morphology (TWM) parameters computed on transmural ECGs, generated by a highresolution human left-ventricular wedge model, with a modified version of the ten Tusscher 2006 cardiac cell model, with respect to the block of the slow and rapid potassium channels (IKs and IKr), and the late sodium channel (NaL), from 0% to 90%. Moreover, we simulated the effects of Dofitilide and Ranolazine. TWM parameters were QT interval (QT), T-peak to T-end (TpTe), T amplitude (Tamp), J to T-peak (JTpeak), Flatness Score (FS), Asymmetry Score (AS), average APD90 (APD90avg), APD Dispersion (APD90Disp) and standard deviation of the repolarization times (s <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">p</sub> ). Sensitivities were computed as the percentage variation normalized at 50% block and they varied across ion channels and amount of block. QT interval, JTpeak and APD90avg performed similarly across channels (0.29). TpTe and s <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">p</sub> provided similar sensitivities (0.80 for both IKr and NaL, and 0.13 for IKs). AS resulted with the highest sensitivity to NaL block (8.35). Morover, the wedge model was capable to simulate the effects of the drugs. In conclusion, TWM parameters reflected ion channel alterations with different proportions.
Year
DOI
Venue
2017
10.22489/CinC.2017.062-263
2017 Computing in Cardiology (CinC)
Keywords
Field
DocType
NaL block,TWM parameters,ion channel alterations,sensitivity analysis,Comprehensive in-vitro Proarrhythmia Assay,T-wave morphology parameters,transmural ECGs,Tusscher 2006 cardiac cell model,slow potassium channels,rapid potassium channels,late sodium channel,average APD90,APD Dispersion,APD90Disp,ion channels,subintervals,QT peak intervals,JT peak intervals,high-resolution human left-ventricular wedge model,Dofitilide,Ranolazine
QT interval,Internal medicine,Proarrhythmia,Cardiology,Wedge (mechanical device),Ranolazine,Repolarization,Potassium channel,Sodium channel,Standard deviation,Mathematics
Conference
Volume
ISSN
ISBN
44
2325-8861
978-1-5386-4555-0
Citations 
PageRank 
References 
0
0.34
0
Authors
6
Name
Order
Citations
PageRank
Massimo W Rivolta104.73
Roberto Sassi213919.26
Viatcheslav Gurev332.09
John Jeremy Rice47111.16
Coeli M. Lopes500.34
Jean-Philippe Couderc6436.67