Assessment of the effect of a single oral dose of telithromycin on sotalol-induced qt interval prolongation in healthy women

AIMS: Telithromycin belongs to ketolides, a new class of macrolide antibiotics. Macrolides are known to have the potential to prolong QT interval duration. Previous studies have shown that telithromycin did not induce significant QT interval prolongation in healthy subjects compared with placebo. The main objective of this study was to demonstrate the absence of amplification of QT interval prolongation induced by sotalol, when telithromycin and sotalol were co-administered. The secondary objective was to correlate the QT interval changes induced by the study drugs to plasma concentrations during the elimination phase. METHODS: Twenty-four women received sotalol (160 mg) together with placebo or telithromycin (800 mg) in a two-period, double-blind, randomized study. Electrocardiograms were recorded at rest. Comparison of maximal corrected QT interval (QTc(max)) with sotalol in the presence or absence of telithromycin was performed. The relation between sotalol concentration and QTc was studied using linear regression. RESULTS: Mean difference (95% CI) between QTc(max) with sotalol-placebo and QTc(max) with sotalol-telithromycin was -15.5 ms (-27.7 to -3.2 ms). QTc(max) interval prolongation was lower (P < 0.05) with sotalol-telithromycin than with sotalol-placebo, in relation to decreased sotalol plasma concentrations. Regression analysis showed that the relationship between sotalol plasma concentration and QTc interval duration was not modified by telithromycin co-administration. CONCLUSION: Our results do not support a potential synergistic effect on QT interval prolongation between sotalol and telithromycin. The decrease of mean QTc interval in subjects taking telithromycin and sotalol may be explained by a decrease of sotalol concentration.     

冠心病合并2型糖尿病患者Tp-e间期与Tp-e/QT比值的研究

目的探讨2型糖尿病合并冠心病患者QT间期、Tp-e间期和Tp-e/QT检测的临床价值。方法随机选取冠心病合并2型糖尿病50例,分别与年龄、性别与之匹配的体检组、2型糖尿病、冠心病患者各50例进行比较,分别测量四组V4导联QT间期、Tp-e间期、计算Tp-e/QT。结果 (1)冠心病合并2型糖尿病组与体检组对比QT间期、Tp-e间期和Tp-e/QT比值差异有统计学意义(P0.05)。(2)冠心病合并2型糖尿病组与2型糖尿病组、冠心病组对比,Tp-e间期和Tp-e/QT比值均显著高,差异有统计学意义(P0.05)。(3)冠心病合并2型糖尿病组与冠心病组、2型糖尿病组比较,QT间期差异无统计学意义(P0.05)。结论 Tp-e间期与Tp-e/QT比值比QT间期在预测室性心律失常更有价值;Tp-e间期和Tp-e/QT可作为冠心病合并2型糖尿病患者发生恶性心律失常的预测指标。     

Effet d’un effort intermittent d’intensité variable sur la variation du QT et du risque de mort subite chez des élèves camerounais

IntroductionSeveral cases of sudden deaths are observed among students practicing sport and physical activity (SPA). Just few studies have been carried out on the variation of the QT (interval) and risk of sudden death during sporting exercises.AimTo determine the effect of variable intermittent stress intensity on the variation of QT and the risk of sudden cardiac death.Patients and methodsForm 4, lower sixth and upper sixth students were recruited from a high school in Douala (Cameroon). Each subject was tested; starting with a 2-km walk followed by a sprint race or an endurance race, protocol I (P1) or the reverse; protocol II (P2). Two electrocardiograms were recorded; prior to the beginning of the SPA and 5 minutes after the last race. QT was corrected using four formulas.ResultsForty-one subjects (21 women and 20 men), mean age 18 ± 2 years were recruited. At the end of the exercise, corrected QT increased with Bazzet's formula and decreased with Frahmingam's formula. The difference was not significant with Fridericia and Hodges formulas. The frequency of long QT was higher at the end of the exercise with Bazzet's formula (12.2% vs. 24.4%, P = 0.009) while the difference was not significant for the other formulas.ConclusionThe risk of sudden cardiac death increases significantly after SPA. More studies on large samples are needed.     

生草乌及配伍诃子的整合TK-TD模型研究

目的:应用整合的毒物代谢动力学(TK)-毒物效应动力学(TD)模型作为一种新的定量框架来评估生草乌引起的异常心率(HR)合并QT间期变化.初步应用于探讨草乌诃子1∶1、1∶3、3∶1配伍后的TK-TD拟合,进一步研究诃子草乌配伍减毒存效可能的机制.方法:建立TK-TD结构模型和原假设H0:Σ=S,采用Amos 24...     

Computer‐Based Analysis of Dynamic QT Changes: Toward High Precision and Individual Rate Correction

Background: New strategies are needed to improve the results of automatic measurement of the various parts of the ECG signal and their dynamic changes. Methods: The EClysis software processes digitally‐recorded ECGs from up to 12 leads at 500 Hz, using strictly defined algorithms to detect the PQRSTU points and to measure ECG intervals and amplitudes. Calculations are made on the averaged curve of each sampling period (beat group) or as means ± SD for beat groups, after being analyzed at the individual beat level in each lead. Resulting data sets can be exported for further statistical analyses. Using QT and R‐R measured on beat level, an individual correction for the R‐R dependence can be performed. Results: EClysis assigns PQRSTU points and intervals in a sensitive and highly reproducible manner, with coefficients of variation in ECG intervals corresponding to ca. 2 ms in the simulated ECG. In the normal ECG, the CVs are 2% for QRS, 0.8% for QT, and almost 6% for PQ intervals. EClysis highlights the increase in QT intervals and the decrease of T‐wave amplitudes during almokalant infusion versus placebo. Using the observed linear or exponential relationships to adjust QT for R‐R dependence in healthy subjects, one can eliminate this dependence almost completely by individualized correction. Conclusions: The EClysis system provides a precise and reproducible method to analyze ECGs. A.N.E. 2002;7(4):289–301     

A survey of health care practitioners’ knowledge of the QT interval

OBJECTIVE: To assess health care practitioners' ability to correctly measure the QT interval, and to identify factors and medications that may increase the risk of QT-interval prolongation and torsades de pointes. DESIGN: A cross-sectional analysis of a survey administered between April 2002 and March 2003. PARTICIPANTS AND SETTING: Health care practitioners attending Grand Rounds Conferences at 6 academic institutions in the United States in internal medicine and psychiatry and at 6 community hospitals in the same geographical areas as the academic institutions. INTERVENTION: Anonymous, self-administered questionnaire that included 20 questions on the QT interval. MEASUREMENTS AND MAIN RESULTS: Of approximately 826 attendees, 517 (63%) completed the survey. Of about 608 attendees of internal medicine conferences, 371 (61%) responded, and of about 208 attendees of psychiatry conferences, 146 (67%) responded. Of a total number of 20 questions, the median number of correct answers for the whole group was 10 (interquartile range 7-13). The median number of correct answers for internists was 12 (interquartile range 9-13), for psychiatrists 10 (interquartile range 7-13), and for other specialists 10 (interquartile range 5-13). Respondents who graduated between 1990 and 1999 and academicians performed significantly better overall than other respondents. Of the 517 respondents, 224 (43%) measured the QT interval correctly. Physicians in training and academicians were more likely to measure the QT interval correctly. CONCLUSION: The majority of health care practitioners cannot correctly measure the QT interval and cannot correctly identify factors and medications that can prolong the QT interval. Our findings suggest that greater attention to the QT interval is warranted to ensure safer use of QT prolonging medications.     

Drug-induced torsades de pointes and implications for drug development

Torsades de pointes is a potentially lethal arrhythmia that occasionally appears as an adverse effect of pharmacotherapy. Recently developed understanding of the underlying electrophysiology allows better estimation of the drug-induced risks and explains the failures of older approaches through the surface ECG. This article expresses a consensus reached by an independent academic task force on the physiologic understanding of drug-induced repolarization changes, their preclinical and clinical evaluation, and the risk-to-benefit interpretation of drug-induced torsades de pointes. The consensus of the task force includes suggestions on how to evaluate the risk of torsades within drug development programs. Individual sections of the text discuss the techniques and limitations of methods directed at drug-related ion channel phenomena, investigations aimed at action potentials changes, preclinical studies of phenomena seen only in the whole (or nearly whole) heart, and interpretation of human ECGs obtained in clinical studies. The final section of the text discusses drug-induced torsades within the larger evaluation of drug-related risks and benefits.