Exponential correction of QT interval to minimize the effect of the heart rate in children.

Yoshinaga, Masao; Tomari, Tsutomu; Aihoshi, Sogo; Kawashita, Tomoko; Nishi, Junichiro; Tanaka, Yuji; Takezaki, Tomoko; Kono, Yukiharu; Yuasa, Y.; Nakamura, Makoto; Nomura, Yoshio; Oku, Shozo; Haraguchi, Tsutomu; Miyata, Koichiro

doi:10.1253/jcj.57.102

Cited by 19 publications

(5 citation statements)

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“…Fridericia's study 20 evaluated 50 ECGs of 28 men and boys and 22 women and girls and concluded that the optimum parameter α = 0.3558 for this data set may be approximated by α = %. In a study of 200 "quite healthy" Japanese subjects (135 men) aged 18-64 years, Mayeda 21 found that α = 0.604 and in 12 543 ECGs of Japanese children and adolescents, Yoshinaga and colleagues 22 found α = 0.31 ranging from 0.305 in 6 year old girls to 0.319 in 12 year old boys. Simonson and associates 23 investigated ECGs of 649 men and 311 women and concluded that α = 0.32 in addition to an age correction factor (increase of QT by about 3 ms every 10 years).…”

Section: Discussionmentioning

confidence: 98%

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

Malík

Färbom²,

Batchvarov³

et al. 2002

Heart

397

357

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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...

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Section: Discussionmentioning

confidence: 98%

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

Malík

Färbom²,

Batchvarov³

et al. 2002

Heart

397

357

View full text Add to dashboard Cite

show abstract

“…Interval measurements were performed across three consecutive cardiac cycles from the optimum technical portion of the Lead II tracing. QT was corrected for heart rate (QTc) using the parabolic log/log formula where a = 0.25 for Kawataki [14], 0.31 for Yoshinaga [15], 0.32 for Simonson [16], 0.33 for Fridericia [8], 0.38 for Hodges [17], 0.398 for Boudolas [18], 0.5 for Bazett [6] and 0.603 for Mayeda [19], but using individualized avalues derived from individual off-drug QT/RR relationships for each subject as previously described [9,10]. This avoids the problem of using formulae based on populations other than the one under study, and allows for the considerable interindividual variability in the QT/RR relationships [20], but low intraindividual variability over time [21].…”

Section: Ecg Parametersmentioning

confidence: 99%

Co‐administration of ketoconazole with H₁‐antagonists ebastine and loratadine in healthy subjects: pharmacokinetic and pharmacodynamic effects

Chaikin¹,

Gillen

Malik

et al. 2005

Brit J Clinical Pharma

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AimsTwo studies were conducted to evaluate the effects of coadministration of ketoconazole with two nonsedating antihistamines, ebastine and loratadine, on the QTc interval and on the pharmacokinetics of the antihistamines. MethodsIn both studies healthy male subjects (55 in one study and 62 in the other) were assigned to receive 5 days of antihistamine (ebastine 20 mg qd in one study, and loratadine 10 mg qd in the other) or placebo alone using a predetermined randomization schedule, followed by 8 days of concomitant ketoconazole 450 mg qd/ antihistamine or ketoconazole 400 mg qd/placebo. Serial ECGs and blood sampling for drug analysis were performed at baseline and on study days 5 (at the end of monotherapy) and 13 (at the end of combination therapy). QT intervals were corrected for heart rate using the formula QTc = QT/RR a with special emphasis on individualized a values derived from each subject's own QT/RR relationship at baseline. ResultsNo significant changes in QTc interval from baseline were observed after 5 days administration of ebastine, loratadine or placebo. Ketoconazole/placebo increased the mean QTc (95% CI) by 6.96 (3.31-10.62) ms in the ebastine study and by 7.52 (4.15-10.89) ms in the loratadine study. Mean QTc was statistically significantly increased during both ebastine/ketoconazole administration (12.21 ms; 7.39-17.03 ms) and loratadine/ketoconazole administration (10.68 ms; 6.15-15.21 ms) but these changes were not statistically significantly different from the increases seen with placebo/ketoconazole (6.96 ms; 3.31-10.62 ms), P = 0.08 ebastine study, (7.52 ms; 4.15-10.89 ms), P = 0.26 loratadine study). After the addition of ketoconazole, the mean area under the plasma concentration-time curve (AUC) for ebastine increased by 42.5 fold, and that of its metabolite carebastine by 1.4 fold. The mean AUC for loratadine increased by 4.5 fold and that of its metabolite desloratadine by 1.9 fold following administration of ketoconazole. No subjects were withdrawn because of ECG changes or drug-related adverse events. ConclusionsKetoconazole altered the pharmacokinetic profiles of both ebastine and loratadine although the effect was greater for the former drug. The coadministration of ebastine with ketoconazole resulted in a non significant mean increase of 5.25 ms ( -0.65 to Co-administration of ketoconazole with H1-antagonists ebastine and loratadine Br J Clin Pharmacol 59 :3 347

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“…9 Screening for prolongation of the QT interval was based on the heart rate dependent criterions already described. 10,11 Electrocardiograms judged as abnormal by the Committee members were later reviewed by the two experienced observers (KN, pediatric cardiologist and YS, board certified adult cardiologist). The final diagnosis was derived after establishing consensus between the two.…”

Section: Cardiac Screening Testmentioning

confidence: 99%

Prevalence of arrhythmias and conduction disturbances in large population-based samples of children

et al. 2004

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The aim of our study is to provide data on the prevalence of disturbances of rhythm in the general population of children. Accurate estimates of true prevalence of such disturbances of rhythm from large samples are mandatory if we are to interpret properly electrocardiographic abnormalities. We analysed prevalence of disturbances of rhythm in a population of 152,322, comprised of 71,855 elementary school students, 36,692 males and 35,163 females, aged from 5 to 6 years, and 80,467 students of junior high school, 41,842 males and 38,625 females, aged from 12 to 13 years. We analysed the prevalence of premature atrial and ventricular contractions, first, second and third degree atrioventricular block, incomplete and complete right bundle branch block, Wolff-Parkinson-White syndrome, and prolongation of the QT interval. The prevalence of disturbances of rhythm in total rose with age, being found in 1.25% of elementary school students and 2.32% of junior high school students, and was higher in males than females, at 2.00% as opposed to 1.38%, both values being statistically significant at a level of less than 0.0001. Prevalences of all types of rhythmic disturbances were higher in junior high school students than elementary school students (p < 0.0001). Premature atrial and ventricular contractions and prolongation of the QT interval were higher in female than male students, at percentages of 0.089, 0.497, and 0.02 for males, and 0.123, 0.534 and 0.027 in females (p < 0.0001). In contrast, incomplete and complete right bundle branch blocks were higher in males than females, at 0.983% and 0.083% in males versus 0.410% and 0.161% in females (p < 0.0001). Disturbances of rhythm increased with age, and conduction disturbances were higher in male students than female, although premature atrial and ventricular contractions and prolongation of the QT interval were more frequent in female. These data may be useful for future comparative studies of disturbance of rhythm in children.

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Exponential correction of QT interval to minimize the effect of the heart rate in children.

Cited by 19 publications

References 10 publications

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

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

Co‐administration of ketoconazole with H₁‐antagonists ebastine and loratadine in healthy subjects: pharmacokinetic and pharmacodynamic effects

Prevalence of arrhythmias and conduction disturbances in large population-based samples of children

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Exponential correction of QT interval to minimize the effect of the heart rate in children.

Cited by 19 publications

References 10 publications

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

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

Co‐administration of ketoconazole with H1‐antagonists ebastine and loratadine in healthy subjects: pharmacokinetic and pharmacodynamic effects

Prevalence of arrhythmias and conduction disturbances in large population-based samples of children

Contact Info

Product

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About

Co‐administration of ketoconazole with H₁‐antagonists ebastine and loratadine in healthy subjects: pharmacokinetic and pharmacodynamic effects