title: The use of beat-to-beat electrocardiogram analysis to distinguish QT/QTc interval changes caused by moxifloxacin from those caused by vardenafil.
abstract: QT correction factors (QTc) can cause errors in the interpretation of drug effects on cardiac repolarization because they do not adequately differentiate changes when heart rate or autonomic state deviates from the baseline QT/RR interval relationship. The purpose of our study was to determine whether the new method of QT interval dynamic beat-to-beat (QTbtb) analysis could better discriminate between impaired repolarization caused by moxifloxacin and normal autonomic changes induced by subtle reflex tachycardia after vardenafil. Moxifloxacin produced maximum mean increases of 13-14 ms in QTbtb, QTcF, and QTcI after 4 h. After vardenafil administration, a 10-ms effect could be excluded at all time points with QTbtb but not with QTcF or QTcI. Subset analysis of the vardenafil upper pharmacokinetic quartile showed that the upper bound of QTcF and QTcI was >10 ms, whereas that of QTbtb was <8 ms. This study demonstrated that newer methods of electrocardiogram (ECG) analysis can differentiate changes in the QT interval to improve identification of proarrhythmia risk.
authors.affiliation: iCardiac Technologies, Rochester, New York, USA. anthony.fossa@icardiac.com
authors.forename: A A
authors.initials: AA
authors.lastname: Fossa
authors.forename: G
authors.initials: G
authors.lastname: Langdon
authors.forename: J-P
authors.initials: JP
authors.lastname: Couderc
authors.forename: M
authors.initials: M
authors.lastname: Zhou
authors.forename: B
authors.initials: B
authors.lastname: Darpo
authors.forename: F
authors.initials: F
authors.lastname: Wilson
authors.forename: R
authors.initials: R
authors.lastname: Wallis
authors.forename: J D
authors.initials: JD
authors.lastname: Davis
mesh_terms: D000890:Anti-Infective Agents / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D001341:Autonomic Nervous System / Q000187:drug effects / Q000503:physiopathology; D001372:Aza Compounds / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology; D018592:Cross-Over Studies; D004562:Electrocardiography / Q000187:drug effects* / Q000379:methods*; D005260:Female; D024841:Fluoroquinolones; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology; D008133:Long QT Syndrome / Q000139:chemically induced*; D008297:Male; D000077266:Moxifloxacin; D058986:Phosphodiesterase 5 Inhibitors / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology; D010879:Piperazines / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology; D010919:Placebos; D011804:Quinolines / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology; D013450:Sulfones / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology; D013610:Tachycardia / Q000139:chemically induced; D014227:Triazines / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology; D000069058:Vardenafil Dihydrochloride
chemical_list: D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D007093:Imidazoles; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D010919:Placebos; D011804:Quinolines; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride; D000077266:Moxifloxacin