Relation between QT and RR intervals is highly individual among healthy subjects: implications for heart rate correction of the QT interval

Abstract

Objective: To compare the QT/RR relation in healthy subjects in order to investigate the differences in optimum heart rate correction of the QT interval. Methods: 50 healthy volunteers (25 women, mean age 33.6 (9.5) years, range 19-59 years) took part. Each subject underwent serial 12 lead electrocardiographic monitoring over 24 hours with a 10 second ECG obtained every two minutes. QT intervals and heart rates were measured automatically. In each subject, the QT/RR relation was modelled using six generic regressions, including a linear model (QT = β + α × RR), a hyperbolic model (QT = β + α/RR), and a parabolic model (QT = β × RR α ). For each model, the parallelism and identity of the regression lines in separate subjects were statistically tested. Results: The patterns of the QT/RR relation were very different among subjects. Regardless of the generic form of the regression model, highly significant differences were found not only between the regression lines but also between their slopes. For instance, with the linear model, the individual slope (parameter α) of any subject differed highly significantly (p < 0.000001) from the linear slope of no fewer than 21 (median 32) other subjects. The linear regression line of 20 subjects differed significantly (p < 0.000001) from the linear regression lines of each other subject. Conversion of the QT/RR regressions to QTc heart rate correction also showed substantial intersubject differences. Optimisation of the formula QTc = QT/RR α led to individual values of α ranging from 0.234 to 0.486. Conclusion: The QT/RR relation exhibits a very substantial intersubject variability in healthy volunteers. The hypothesis underlying each prospective heart rate correction formula that a "physiological" QT/RR relation exists that can be mathematically described and applied to all people is incorrect. Any general heart rate correction formula can be used only for very approximate clinical assessment of the QTc interval over a narrow window of resting heart rates. For detailed precise studies of the QTc interval (for example, drug induced QT interval prolongation), the individual QT/RR relation has to be taken into account.T he QT interval adapts to changes in heart rate, which makes it difficult to compare the QT interval recorded at different heart rates. To allow such a comparison, the concept of the heart rate corrected QTc interval was developed and many formulas have been proposed to describe the QT interval heart rate adaptation. Bazett's formula 1 is both the most frequently used and the most criticised. 2-4In principle, every heart rate correction formula assumes that a mathematical form exists to describe the physiological QT/RR relation. Such a form may be converted into a formula that normalises a measured QT interval to that which would be associated with a "standard" heart rate, for example, of 60 beats/min. Most studies that have proposed a heart rate correction formula relied on QT and RR interval data obtained from healthy volunteers, different groups of patients, o...

Longitudinal changes in QT interval variability and rate adaptation in pregnancies with normal and abnormal uterine perfusion

“…The method proposed by Malik et al 14,15 was applied. Briefly, a set of different regression models was employed to describe the relationship between QT interval and heart rate individually for each subject.…”

Control of rapid heart rate changes for electrocardiographic analysis: implications for thorough QT studies

“…The so-called "universal-correction" formulae have been shown to over-or undercorrect the QT interval potentially when HR changes. 6,7 New techniques have been proposed, such as population-specific formula, 8 subject-specific correction formula, 9 as well as the "bin" method avoiding the need for any QTcorrection formulae. 10 -13 Less attention has been paid so far to the hysteresis phenomenon.…”

How to Assess QT Prolongation in Clinical Studies-Implications of the ICH E14 Guidance Document

“…Which one to use, if any, is an area of intense debate and considerable controversy. Historically, Bazett's correction formula (QTcB) 43) has often been used, even though it clearly generates longer QTc intervals than other formulas as the heart rates increases 39,44,45). Despite this acknowledged limitation, QTcB should be re ported to allow for comparison with data on file with regulatory authorities, along with uncorrected QT, RR and QTcF.…”

“…Most spon sors avoid the use of QTcB in the primary analysis, and instead apply a population-based (e.g. Framingham correction formula or Fridericia), or a subject-or study-derived correction formula 45,46).…”