A novel normalization of vectorcardiogram to enhance markers of differences between hERG and multichannel drugs

Abstract

Torsade de Pointes is a polymorphic ventricular tachyarrhythmia potentially fatal that has been observed in a large number of common commercial drugs. Current markers used in pharmacological regulation do not have enough sensitivity/specificity. In this work, we present a novel technique for normalizing cardiac loops using principal component analysis. Then, using quaternionic techniques, the angular velocity of the cardiac electrical vector is obtained. This velocity is used to obtain highly efficient complementary parameters for determining the risk of certain drugs that differentially block repolarization ion channels. The results showed that the drugs that predominantly block human ether-`a-go-go-related gene (hERG) channels show significant variations (p < 0.001) at the time of the highest plasma concentration. Also, a symmetry trend in angular velocity is observed. Moreover, the temporal parameters obtained showed greater efficiency as alternative measures to the standards. We hope that these insights will contribute significantly to the development of safe drug therapies.