title: Application of probabilistic analysis for precisely correcting the QT interval for heart rate in telemetered common marmosets.
abstract: BACKGROUND
  QT intervals are strongly influenced by preceeding heart rate history and are also characterized by rate-independent variability, leading to difficulty in precise rate-correction of the raw QT interval. The present study elucidates a novel analytical method that effectively addresses this problematic phenomenon in telemetered common marmosets.
  
  
  METHODS
  ECGs were collected from telemetered common marmosets (male and female) and analyzed by computerized algorithms. Descriptive statistics were calculated from the mean of QT intervals for 5-ms increments of RR. The QT interval was corrected for the RR interval by applying Bazett's, Fridericia's, and individual probabilistic QT rate-correction formulae.
  
  
  RESULTS
  The linear regression of log-transformed QT and RR intervals derived from a probabilistic approach yielded a well-correlated QT-RR fit. Assessed as the slope of the QTc-RR interval, application of individual probabilistic QT rate-corrections resulted in the most effective dissociation of the effects of rate from the raw QT interval, compared to generic rate-correction formulae. Using individual corrections, the QTc was stable while the interquartile range (IQR) of the QTc distribution was stable, spanning 5-10 ms for each subject over all physiological RR intervals. Heart rate variability distributions were centered about unity during both photoperiods and sinus arrhythmia was far less pronounced compared with measurements in dogs.
  
  
  CONCLUSIONS
  Probabilistic QT rate-correction eliminated the confounding effects of heart rate and provided a stable QTc baseline. These results indicate that application of this method of analysis in telemetered common marmosets results in a high degree of sensitivity for the consistent detection of small (5-10 ms) changes in the QTc interval.
authors.affiliation: Safety Assessment Dept. Chugai Pharmaceutical Co., Ltd. 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Honda
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Komatsu
authors.forename: Henry H
authors.initials: HH
authors.lastname: Holzgrefe
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yamada
authors.forename: Takehito
authors.initials: T
authors.lastname: Isobe
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kimura
authors.forename: Toshio
authors.initials: T
authors.lastname: Itoh
authors.forename: Norikazu
authors.initials: N
authors.lastname: Tamaoki
authors.forename: Mitsuyasu
authors.initials: M
authors.lastname: Tabo
mesh_terms: D000818:Animals; D002144:Callithrix / Q000502:physiology*; D004562:Electrocardiography / Q000379:methods / Q000592:standards / Q000706:statistics & numerical data; D005260:Female; D006339:Heart Rate / Q000502:physiology*; D008133:Long QT Syndrome / Q000175:diagnosis / Q000503:physiopathology*; D008297:Male; D015233:Models, Statistical; D013045:Species Specificity; D013686:Telemetry / Q000379:methods* / Q000592:standards / Q000706:statistics & numerical data