Cardiac regulation and electrocardiographic factors contributing to the measurement of repolarization variability

Cellular and macroelectrical instability within the heart ventricles during repolarization is described as a potential triggering mechanism of life-threatening arrhythmias. Although this phenomenon was observed in animal and in vitro studies, significant efforts have been put into the design of computerized technologies to quantify very subtle variations of the repolarization signal from the surface electrocardiograms. These technologies aim at capturing repolarization instability of ventricular repolarization while controlling for the normal variability. Currently, the methods have focused on the autonomic regulation of the heart rate as a primary confounding factor (such as in the QT variability index). However, there are other factors that can influence the measurements of beat-to beat variability of the repolarization segment. Among them, the amplitude of the repolarization signal, the selected lead, and the heart vector orientation are very important and too often neglected in clinical investigations. We will discuss these factors and provocatively describe why they should be cautiously considered to avoid erroneous measurements of repolarization instability.