Variability of heart rate correction methods for the QT interval

Abstract

Aims To compare variability of heart rate-corrected QT intervals (QT c ) using three different methods in a study of low-dose oral haloperidol. Methods In a randomized, double-blind, placebo-controlled, crossover trial, we studied QT interval pharmacodynamics of single doses of oral haloperidol (10 mg) in 16 healthy subjects. Heart rate correction of the QT interval was performed using Bazett's, Fridericia's and subject-specific correction methods. The subjectspecific correction was performed using linear mixed modelling of placebo period QT vs RR data from each study subject. Results The subject-specific correction, in the form of QT c = QT/RR a , yielded a correction term a (slope of the log-transformed QT vs RR relationship) that ranged from 0.23 to 0.38 in individual subjects, i.e. the fixed correction term a = 0.5 of Bazett's correction was outside and the fixed correction term a = 0.33 of Fridericia's correction inside the range of individual values. The mean absolute slope of the QT c vs RR regression line using the subject-specific correction was significantly lower than the mean slopes obtained using either Bazett's or Fridericia's corrections. All three methods revealed a statistically significant greater mean QT c on haloperidol than on placebo at 10 h post-drug administration. The mean QT (95% CI) was 421.6 (410.8, 432.4), and 408.4 (398.6, 417.8) on haliperidol and placebo, respectively, using the subject-specific correction method (P = 0.0053). The mean QT c (95% CI) was 425.4 (414.3, 436.5) and 403.1 (394.3, 411.9) on haliperidol and placebo, respectively, using Bazett's correction (P = 1.7 ¥ 10 -5 ) and 423.1 (412.6, 433.6) and 408.2 (398.6, 417.8) on haliperidol and placebo, respectively, using Fridericia's correction (P = 7.7 ¥ 10 -4 ). Raw P-values were calculated using a paired t-test. Bonferroni-corrected P-values were calculated by multiplying the raw Pvalues by 13. Conclusion Haloperidol caused a statistically significant mean QT c prolongation using the three correction methods. The QT c intervals were less dependent on RR intervals using the subject-specific method, thus decreasing the possibility of overor under-correction. The interindividual QT c changes from baseline varied significantly depending on the method of correction used.

The effect of bolus administration of remifentanil on QTc interval during induction of sevoflurane anaesthesia

“…The average QTc interval using Bazett's formula was 445.1 ms, with 60% of the patients showing a QTc prolongation above 440 ms, which was about 28 ms longer than that of Hodges' formula, when the HR was up to 100 beats.min )1 immediately after intubation in the saline group (data not shown). Unfortunately there is no general consensus on the best formulas, including those of Fridericia, Framingham, or Hodges, for use in clinical practice [15,[26][27][28]. Hodges' formula, which may be one of least correlated with HR [15], was used rather than Bazett's formula in our study.…”

Effects of fentanyl pretreatment on the QTc interval during propofol induction

“…Because the QTc interval varies with heart rate (lengthening with bradycardia and shortening with tachycardia) in the absence of modifying factors, it is common to derive a heart rate-corrected (QTc) interval, and this is most frequently used when evaluating the effect of an intervention [30]. Although the Bazett correction is most commonly employed in clinical ECG algorithms and practice, it is considered the most inaccurate, especially with an increased heart rate [31]. The fixed exponent Fridericia correction is considered a much better approach, although there is no standard method of heart rate correction in the QTc interval [32].…”

Utility of hERG Assays as Surrogate Markers of Delayed Cardiac Repolarization and QT Safety

“…However, this approach has limitations related to the confounding effect of heart rate on the QT interval, the accurate measurement of the end of the interval, and the ability to reliably detect small changes in the QT interval (<5% of the interval) (Malik, 2002;Desai et al, 2003). In addition, while a link has been established between druginduced QT prolongation and proarrhythmia (see later), the exact nature of that relationship is uncertain and likely varies with different drugs.…”