gms | German Medical Science

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.