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33rd International Congress on Electrocardiology

International Society of Electrocardiology

Assessing Pharmacologically Induced Changes in Repolarization for Cardiac Safety

Meeting Abstract

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  • corresponding author presenting/speaker R. L. Lux - University of Utah, Salt Lake City, Utah
  • J. W. Mason - University of Utah, Salt Lake City, Utah

33rd International Congress on Electrocardiology. Cologne, 28.06.-01.07.2006. Düsseldorf, Köln: German Medical Science; 2007. Doc06ice012

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/ice2006/06ice012.shtml

Published: February 8, 2007

© 2007 Lux et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

Mandatory testing of newly developed drugs to assess cardiac safety has promoted recent interest in and need for improved methods to detect ventricular repolarization change. The rate corrected QT interval (QTc) is the standard for detecting pharmacologically induced repolarization change in the setting of drug testing for cardiac safety. However, QT interval is a low signal-to-noise (SNR) measurement that results in high standard deviations of measurements; and, rate dependency of repolarization is complex, nonstationary, and varies within and across subjects, thus making rate “correction” difficult if not confounding. We present a novel approach to repolarization assessment that is more robust than QTc, is nearly rate independent, and provides a means to statistically detect pharmacologically induced repolarization changes within and between subjects. The approach is based on a magnitude function of the ECG, the root-mean-square (RMS) of all leads measured. The interval between the peaks of the R and T waves in the RMS ECG has been shown experimentally to provide a robust, high SNR estimate of mean ventricular action potential duration and the width of the RMS ECG T wave, as defined by second derivative inflection points, has been experimentally shown to provide a robust estimate of repolarization time dispersion. In this presentation, we compare and contrast the ability of these measurements and QTc to detect changes in repolarization induced by known pharmacological agents.