A New ECG Biomarker for Drug Toxicity: a Combined Signal Processing and Computational Modeling Study.
2010 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC)
2565 - 2568.
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 (I-Kr), varied degrees of I-Kr 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.
|Title:||A New ECG Biomarker for Drug Toxicity: a Combined Signal Processing and Computational Modeling Study|
|Location:||Buenos Aires, ARGENTINA|
|Keywords:||TORSADES-DE-POINTES, LONG-QT-SYNDROME, T-WAVE, REPOLARIZATION, PROLONGATION, SOTALOL, TISSUE, DOGS|
|UCL classification:||UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
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