Drug-induced symmetry effects on ventricular repolarization dynamics

Abstract

The detection of proarrhythmic effects of many current drugs has prompted the search for complementary non-invasive markers of cardiotoxicity risk. Indices based on studies of cardiac vector dynamics have emerged. We use quaternions to quantify symmetry changes in cardiac vector velocity during ventricular repolarization, which could signal the arrhythmia risk. Principal component analysis is used to homogenize the information and reduce the space to three dimensions. A comparison with the ratio of normalized areas of the repolarization loop (T-wave) and two standard measurements was made: QT and T peak-end intervals. Assessment was conducted by comparing 52 healthy subjects with patients undergoing treatment with Sotalol: 7 recordings with Torsade de Pointes events and 15 without arrhythmic effects. Significant differences (p ¡ 5E-4) were found in both phases of repolarization in terms of absolute velocities and areas. The ratio between the maximums of each parameter in both halves of the T-wave showed a trend towards 1 in the proximity of an arrhythmic event. Angular velocity ratios reached a sensitivity/specificity pair of 100 (95%CI: 59–100)/90 (95%CI: 79–97) with an AUC of 98.6 (95%CI: 95.7–100) in the comparison of healthy population with at-risk patients. Linear discriminant analysis improved the classification by reaching sensitivity and specificity values of 100 (95%CI: 59–100) and 96 (5%CI: 87–100), respectively. The high performance of the method exceeded the diagnostic power of standard measurements, thus showing its potential to contribute to drug evaluation methods. Further research with a larger number of events is required to generalize the method.