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Opstal, Jurren M. van; Verduyn, S. Cora; Winckels, Stephan K.G.; Leerssen, Hendrik M.; Leunissen, Jet D.M.; Wellens, Hein J.J.; Vos, Marc A.

doi:10.1023/a:1015302415323

Cited by 19 publications

(4 citation statements)

References 38 publications

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“…This is consistent with the experimental study in dog ventricles where the mean JT area increased by 90.0% following administration of class III antiarrhythmic drugs [5]. Furthermore, in our results, the percentage increase in the mean JT area was nearly three times greater than that in mean QTc interval, suggesting a better sensitivity to drug-induced changes in JT area.…”

Section: Discussionsupporting

confidence: 93%

“…The heart rate-corrected QT interval, QTc, was calculated using Bazett’s formula. JT area of each beat was computed as the area between the curve and the baseline from J-point to the end point of the T-wave [5]. The baseline referred to the isoelectric segment preceding QRS complex.…”

Section: Methodsmentioning

confidence: 99%

“…JT area, i.e., total area of the T-wave, has been shown to be an indicator of temporal and spatial dispersion of repolarization as administration of class III antiarrhythmic drugs (drugs that block potassium channels) increased both JT area and dispersion of repolarization in dogs [5]. The goal of this study is to evaluate the predictive value of JT area as a surrogate/supplemental ECG biomarker for drug-induced toxicity using both signal processing and computational modeling approaches.…”

Section: Introductionmentioning

confidence: 99%

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A new ECG biomarker for drug toxicity: A combined signal processing and computational modeling study

Xiao

Rodríguez

Pueyo

2010

2010 Annual International Conference of the IEEE Engineering in Medicine and Biology

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QT prolongation is the only clinically proven, yet insufficient, electrocardiogram (ECG) biomarker for drug-induced cardiac toxicity. The goal of this study is to evaluate whether JT area, i.e., total area of the T-wave, can serve as an ECG biomarker for drug-induced cardiac toxicity using both signal processing and computational modeling approaches. An ECG dataset that contained recordings from patients under control and sotalol condition was analyzed. In order to relate sotalol-induced ECG changes to its effect on ion channel level, i.e., blockade of the rapid component of the delayed rectifier potassium channel (IKr), varied degrees of IKr blockade were simulated in a slab of ventricular tissue. The mean JT area increased by 36.5% following the administration of sotalol in patients. Simulations in the slab tissue showed that sotalol increased action potential duration preferentially in the midmyocardium, which led to increased transmural dispersion of repolarization and JT area. In conclusion, JT area reflects the transmural dispersion of repolarization and may be a potentially useful surrogate/supplemental ECG biomarker to assess drug safety.

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Section: Discussionsupporting

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A new ECG biomarker for drug toxicity: A combined signal processing and computational modeling study

Xiao

Rodríguez

Pueyo

2010

2010 Annual International Conference of the IEEE Engineering in Medicine and Biology

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“…In terms of T-wave morphology, increased JT area (total area of the T-wave) has been reported (Thomsen et al 2006 a , b ), representing increased interventricular dispersion of repolarization (van Opstal et al 2002). T-wave area-based parameters have been shown to be indices as effective as QT interval for identification of sotalol-induced repolarization changes (Couderc et al 2003).…”

Section: Biomarkers Of Drug-induced Arrhythmic Riskmentioning

confidence: 99%

Arrhythmic risk biomarkers for the assessment of drug cardiotoxicity: from experiments to computer simulations

Corrias

Xiao

Romero

et al. 2010

Phil. Trans. R. Soc. A.

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In this paper, we illustrate how advanced computational modelling and simulation can be used to investigate drug-induced effects on cardiac electrophysiology and on specific biomarkers of pro-arrhythmic risk. To do so, we first perform a thorough literature review of proposed arrhythmic risk biomarkers from the ionic to the electrocardiogram levels. The review highlights the variety of proposed biomarkers, the complexity of the mechanisms of drug-induced pro-arrhythmia and the existence of significant animal species differences in drug-induced effects on cardiac electrophysiology. Predicting drug-induced pro-arrhythmic risk solely using experiments is challenging both preclinically and clinically, as attested by the rise in the cost of releasing new compounds to the market. Computational modelling and simulation has significantly contributed to the understanding of cardiac electrophysiology and arrhythmias over the last 40 years. In the second part of this paper, we illustrate how state-of-the-art open source computational modelling and simulation tools can be used to simulate multi-scale effects of drug-induced ion channel block in ventricular electrophysiology at the cellular, tissue and whole ventricular levels for different animal species. We believe that the use of computational modelling and simulation in combination with experimental techniques could be a powerful tool for the assessment of drug safety pharmacology.

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Cellular Basis for the Repolarization Waves of the ECG

Antzelevitch¹

2004

Dynamic Electrocardiography

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Abstract: Changes in dispersion of ventricular repolarization are reflected by alterations in JT-area. This non-invasive parameter may therefore be used to indicate changes in heterogeneity in ventricular repolarization.

Cited by 19 publications

References 38 publications

A new ECG biomarker for drug toxicity: A combined signal processing and computational modeling study

A new ECG biomarker for drug toxicity: A combined signal processing and computational modeling study

Arrhythmic risk biomarkers for the assessment of drug cardiotoxicity: from experiments to computer simulations

Cellular Basis for the Repolarization Waves of the ECG

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