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

• Published in: Annals of noninvasive electrocardiology 2017-05, Vol.22 (3), p.e12413-n/a
• Main Authors: Shakibfar, Saeed, Graff, Claus, Kanters, Jørgen K., Nielsen, Jimmi, Schmidt, Samuel, Struijk, Johannes J.
• Format: Article
• Language: English
• Subjects: Abnormalities; Adolescent; Adult; Algorithms; Anti-Arrhythmia Agents - pharmacology; Biomarkers; Cardiac arrhythmia; Discriminant analysis; electrocardiogram; Electrocardiography; Electrocardiography - drug effects; Electrocardiography - statistics & numerical data; Feature extraction; Heart - drug effects; Heart rate; Humans; Male; Middle Aged; Original; Pharmacovigilance; QT interval; Reference Values; repolarization; Sotalol - pharmacology; T wave; Tpeak‐Tend; Young Adult
• ISSN: 1082-720X; 1542-474X
• DOI: 10.1111/anec.12413

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.