| A new ECG biomarker for drug toxicity: a combined signal processing and computational modeling study. | |
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MedLine Citation:
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PMID: 21096447 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 (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. |
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Authors:
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Xiao Jie; Blanca Rodriguez; Esther Pueyo |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference Volume: 2010 ISSN: 1557-170X ISO Abbreviation: Conf Proc IEEE Eng Med Biol Soc Publication Date: 2010 |
Date Detail:
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Created Date: 2010-11-24 Completed Date: 2011-03-30 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 101243413 Medline TA: Conf Proc IEEE Eng Med Biol Soc Country: United States |
Other Details:
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Languages: eng Pagination: 2565-8 Citation Subset: IM |
Affiliation:
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Computing Laboratory, Oxford University, OX1 3QD, UK. xiao.jie@comlab.ox.ac.uk |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Action Potentials Algorithms Anti-Arrhythmia Agents / pharmacology, toxicity* Biological Markers Computer Simulation Electrocardiography / methods* Humans Ion Channels / chemistry Ions Models, Statistical Signal Processing, Computer-Assisted Software Sotalol / pharmacology Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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U24 HL096556-03/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anti-Arrhythmia Agents; 0/Biological Markers; 0/Ion Channels; 0/Ions; 3930-20-9/Sotalol |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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