title: Sertindole causes distinct electrocardiographic T-wave morphology changes.
abstract: Sertindole's propensity to prolong the QT interval relates to blockade of the KCNH2 (HERG) encoded Ikr potassium channel, but there has been limited detailed data on T-wave morphology changes. Digital 12-lead ECG was recorded at baseline and at steady-state in 37 patients switched to sertindole. ECG was analyzed for quantitative T-wave morphology changes and Fridericia-corrected QT duration (QTcF). Prominent T-wave morphology changes occurred during sertindole treatment and in some cases without concomitant prolongation of the QTcF interval. Four patients developed notched T-waves during sertindole treatment. Mean QTc prolongation was 19 ms. The mean effect size was higher for T-wave morphology combination score (MCS) (ES=1.92; 95% CI: 1.35-2.49) compared to the mean effect size for QTcF (ES=0.88; 95% CI: 0.52-1.24). The use of T-wave morphology analysis may become clinically relevant, particularly if shown to be associated with drug-induced arrhythmia risk.
authors.affiliation: Unit for Psychiatric Research, Aalborg Psychiatric Hospital, Aarhus University Hospital, Mølleparkvej 10, PO Box 210, DK-9100 Aalborg, Denmark. jin@rn.dk
authors.forename: Jimmi
authors.initials: J
authors.lastname: Nielsen
authors.forename: Claus
authors.initials: C
authors.lastname: Graff
authors.forename: Thomas
authors.initials: T
authors.lastname: Hardahl
authors.forename: Mads P
authors.initials: MP
authors.lastname: Andersen
authors.forename: Jens
authors.initials: J
authors.lastname: Kristoffersen
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Struijk
authors.forename: Egon
authors.initials: E
authors.lastname: Toft
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Meyer
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects* / Q000627:therapeutic use; D007211:Indoles / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D012559:Schizophrenia / Q000188:drug therapy
chemical_list: D014150:Antipsychotic Agents; D007093:Imidazoles; D007211:Indoles; C066304:sertindole