Minimal T-wave representation and its use in the assessment of drug arrhythmogenicity.

ABSTRACT

BACKGROUND: Recently, numerous models and techniques have been developed for analyzing and extracting features from the T wave which could be used as biomarkers for drug-induced abnormalities. The majority of these techniques and algorithms use features that determine readily apparent characteristics of the T wave, such as duration, area, amplitude, and slopes. METHODS: In the present work the T wave was down-sampled to a minimal rate, such that a good reconstruction was still possible. The entire T wave was then used as a feature vector to assess drug-induced repolarization effects. The ability of the samples or combinations of samples obtained from the minimal T-wave representation to correctly classify a group of subjects before and after receiving d,l-sotalol 160 mg and 320 mg was evaluated using a linear discriminant analysis (LDA). RESULTS: The results showed that a combination of eight samples from the minimal T-wave representation can be used to identify normal from abnormal repolarization significantly better compared to the heart rate-corrected QT interval (QTc). It was further indicated that the interval from the peak of the T wave to the end of the T wave (Tpe) becomes relatively shorter after IKr inhibition by d,l-sotalol and that the most pronounced repolarization changes were present in the ascending segment of the minimal T-wave representation. CONCLUSIONS: The minimal T-wave representation can potentially be used as a new tool to identify normal from abnormal repolarization in drug safety studies.