title: Analyses of dynamic beat-to-beat QT-TQ interval (ECG restitution) changes in humans under normal sinus rhythm and prior to an event of torsades de pointes during QT prolongation caused by sotalol.
abstract: BACKGROUND
  Restitution through intracardiac pacing has been used to assess arrhythmia vulnerability. We examined whether analyses of sequential beat-to-beat QT and TQ interval measures can be used to quantify ECG restitution changes under normal sinus rhythm.
  
  
  METHODS
  The QT, R-R and TQ intervals were examined 22.5 hour Holter monitoring before and after oral sotalol in normal male and female volunteers. Additionally, comparisons were made to those observed in the time-matched dataset prior to torsades de pointes in a heart diseased patient that received a single dose of sotalol.
  
  
  RESULTS
  Sotalol increased QT, R-R and TQ intervals 71, 101, and 125 ms after 160 mg (n = 38) and 194, 235, and 135 ms after 320 mg (n = 19) during maximum plasma concentrations, respectively. The percentage of beats with a QT/TQ ratio >1 was reduced 25% over the entire 22.5 hours after sotalol and the lower TQ interval boundary (5th quantile) was increased 22-30%. In contrast, 99% of the beats prior to torsades de pointes had a QT/TQ ratio > 1 and the median TQ interval was below the lower 98% confidence bounds of normals before and after sotalol.
  
  
  CONCLUSIONS
  ECG restitution changes are quantifiable under varying states (nocturnally, beta-adrenergic blockade, QT prolongation) in healthy subjects.
authors.affiliation: Pfizer Global Research and Development, Groton, Connecticut 06340, USA. anthony.a.fossa@pfizer.com
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Fossa
authors.forename: Todd
authors.initials: T
authors.lastname: Wisialowski
authors.forename: Kimberly
authors.initials: K
authors.lastname: Crimin
authors.forename: Eric
authors.initials: E
authors.lastname: Wolfgang
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Couderc
authors.forename: Martin
authors.initials: M
authors.lastname: Hinterseer
authors.forename: Stefan
authors.initials: S
authors.lastname: Kaab
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zareba
authors.forename: Fabio
authors.initials: F
authors.lastname: Badilini
authors.forename: Nenad
authors.initials: N
authors.lastname: Sarapa
mesh_terms: D000293:Adolescent; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D015716:Electrocardiography, Ambulatory; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D013015:Sotalol / Q000494:pharmacology*; D018709:Statistics, Nonparametric; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000503:physiopathology*
chemical_list: D000889:Anti-Arrhythmia Agents; D013015:Sotalol