Corrected QT interval

The determinant that mostly influences the QT interval duration is cycle length (RR interval) the longer the RR interval, the longer the QT interval and vice versa. Therefore, a number of formulas (see [94] for a list) are used to normalize the QT interval for heart rate and obtain a corrected QT interval (QTc), a key issue especially... 

Zipes, D.P. (2007) Heart rate-corrected QT interval in men increases during winter months. Heart Rhythm, 4, 277-281. 

Funck-Brentano, C. and Jaillon, P. (1993) Rate-corrected QT interval techniques and limitations. The American Journal of Cardiology, 72, 17B—22B. 

Spence, S., Soper, K., Hoe, C.M. and Coleman, J. (1998) The heart rate-corrected QT interval of conscious beagle dogs a formula based on analysis of covariance. Toxicological Sciences, 45, 247-258. 

Schematic illustration of an integrated risk assessment aimed at assessing the liability for an NCE to prolong the QT interval in man. APD = Action Potential Duration NCE = New Chemical Entity QTCV = Van de Water corrected QT interval duration.

Despite concerns regarding safety and side effects, TCAs are appropriate for some patients. When starting a TCA, a baseline EKG is required. If the EKG reveals a second-degree or higher heart block, a bundle branch block, or a corrected QT interval exceeding 440 milliseconds, then a TCA should not be started. The initial doses should be low, especially in older patients or those with anxiety who are particularly sensitive to side effects. Over the first 7-14 days, the dose should be increased gradually to the lower end of the expected therapeutic range. After an additional 2-3 weeks, the dose may be increased further if necessary. 

QTprolongation In a multicenter, randomized, double-blind trial that enrolled 198 patients with COPD, the number of subjects with changes from baseline-corrected QT interval of 30 to 60 msec was higher in the tiotropium group as compared with placebo. No patients in either group had QT of more than 500 msec. 

Administration of sotalol is associated with dose- and concentration-dependent slowing of the heart rate and prolongation of the PR interval. The QRS duration is not affected with plasma concentrations within the therapeutic range. The corrected QT interval is prolonged as a result of the increase in the ERP of ventricular myocardium. 

Note. EPS=extrapyramidal symptoms QTc=corrected QT interval on the electrocardiogram. Lower dosages and slower titrations are indicated for the elderly. 

Inhibitors of the renal cation secretion mechanism, eg, cimetidine, prolong the half-life of dofetilide. Since the QT-prolonging effects and risks of ventricular proarrhythmia are directly related to plasma concentration, dofetilide dosage must be based on the estimated creatinine clearance. Treatment with dofetilide should be initiated in hospital after baseline measurement of the rate-corrected QT interval (QTC) and serum electrolytes. A baseline QTC of > 450 ms (500 ms in the presence of an intraventricular conduction delay), bradycardia of < 50 bpm and hypokalemia are relative contraindications to its use. 

Dose- and concentration-related increase in the uncorrected and rate-corrected QT interval... 

In two studies lithium treatment was associated with prolongation of the corrected QT interval (QTC). A retrospective analysis of the records of 76 patients taking... 

Douglas PH, Block PC. Corrected QT interval prolongation associated with intravenous haloperidol in acute coronary syndromes. Catheter Cardiovasc Interv 2000 50(3) 352-5. 

Women appear to be at an increased risk of torsades de pointes because the baseline heart rate-corrected QT interval in women is, on average, longer than it is in men (103). The length of the QT interval is similar in males and females at birth, but shortens in males at puberty. The risk of this arrhythmia shows no sex difference before adolescence, and women have an increased incidence of torsades de pointes only after puberty. These observations are consistent with the fact that sex hormones affect potassium channel activity. Thus, estrogens have a down-regulating effect on potassium channel activity and androgens may be responsible for the QT interval shortening that is seen in postpubertal males (95, 96, 104). 

Schwartz CL, Hobbie WL, Truesdell S, Constine LC, Clark EB. Corrected QT interval prolongation in anthra-cycline-treated survivors of childhood cancer. J Clin Oncol 1993 11(10) 1906-10. 

Ferrari S, Figus E, Cagnano R, lantomo D, Bacci G. The role of corrected QT interval in the cardiologic foUow-up of young patients treated with Adriamycin. J Chemother 1996 8(3) 232-6. 

The pharmacokinetics of cisapride have been studied in eight elderly patients (mean age 85 years) (27). There were no adverse effects, apart from a slight increase in stool freqnency. There were no changes in the corrected QT interval. However, plasma cisapride concentrations were higher than expected. Thus, in extremely elderly patients cisapride should be given once or twice a day rather than three times. 

Cools F, Benatar A, Bougatef A, Vandenplas Y. The effect of cisapride on the corrected QT interval and QT dispersion in premature infants. J Pediatr Gastroenterol Nutr 2001 33(2) 178-81. 

Benatar A, Feenstra A, Decraene T, Vandenplas Y. Cisapride plasma levels and corrected QT interval in infants undergoing routine polysomnography. J Pediatr Gastroenterol Nutr 2001 33(l) 41-6. 

Bertino JS Jr, Owens RC. Jr., Carnes TD, lannini PB. Gatifloxacin-associated corrected QT interval prolongation, torsades de pointes, and ventricular fibrillation in patients with known risk factors. Clin Infect Dis 2002 34(6) 861-3. 

White CM, Grant EM, Quinthiani R. Moxifloxacin does increase the corrected QT interval. Chn Infect Dis 2001 33(8) 1441-4. 

The QT interval has an inverse relationship to the heart rate, so as the heart rate increases, QT interval decreases. The changes are not proportional to the change in heart rate, so QT measurements are often standardized by various formulas to the corrected QT interval, or QTc interval. Unfortunately, there is no standard formula that is used for the correction. Over thirty corrections have been proposed and several, including Bazette s, Fridericia s, and Van de Water s are in common use. In an EGG, both the QT interval and the QTc interval are usually examined for abnormalities. 

Homs E, Marti V, Guindo J et al. Automatic measurement of corrected QT interval in Holter recordings comparison of its dynamic behavior in patients after myocardial infarction with and without life-threatening arrhythmias. Am Heart J 1997 134 181. 

Biomarkers need to be identified and investigated in preclinical studies, especially those that may predict future safety problems. Sometimes the lowering of blood pressure or the prolongation of the corrected QT interval may give one a heads up to potential toxicities or dose-related toxicities that may occur during clinical development. When a thorough job is done during preclinical development, then transition to clinical development can be done efficiently and with confidence. 

The objective of correcting the QT interval for HR or RR is to obtain a corrected QT interval that is statistically independent of the HR or RR interval. Figure 40.2 shows the dependence of QT on HR. In order to eliminate the dependence of QT on heart rate, numerous HR or RR correction formulas have been proposed in the ECG literature, reflecting the variety of statistical models that have been ht to the data. The reader should be aware that there is no best QT interval correction method for heart rate, but there are some practical methods. The most popular corrections are the Bazett (3) and Fridericia (4) formulas. Both are based on the simple power model QTc = QT/RR that is, calculation of the QTc is equal to the observed QT in milliseconds divided by the term of a root of the RR interval in milliseconds. 

Omeprazole 40 mg daily for one week had no effect on the pharmacokinetics of a single 400-mg dose of quinidine sulfate in 8 healthy subjects. In addition, the corrected QT interval was not significantly changed. There would not appear to be the need for any special precautions during concurrent use. 

Quantitative structure-activity relationship Interval between beginning of Q wave and end of T wave in the heart s electrical cycle Corrected QT interval... 

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