The effect of antihistamine cetirizine on ventricular repolarization in congenital long QT syndrome

Introduction: Many drugs are known to block cardiac potassium channels, thus prolonging QT interval and predisposing to malignant arrhythmias. Patients with congenital long QT syndrome are particularly vulnerable, but usually electrophysiological effects of drugs have not been assessed in these patients at risk.
Methods: Fifteen asymptomatic patients with type 1 (LQT1), 15 patients with type 2 (LQT2) long QT syndrome, and 15 healthy volunteers took a placebo and cetirizine 10 mg. In addition, healthy volunteers took cetirizine 50 mg. The study was single-blinded and randomized. Exercise tests were performed during stable plasma concentrations. The electrocardiogram was recorded with a body surface potential mapping system (BSPM). Data were analyzed with an automated analyze program. QT intervals to the T wave apex and T wave end and their difference (Tp-e) were determined at rest and at specified heart rates during and after exercise.
Results: Cetirizine did not lengthen the QT intervals at rest or during exercise and recovery in any group. It shortened Tp-e at rest in LQT1 and LQT2 patients and during exercise test in LQT1 patients, thus slightly decreasing electrocardiographic transmural dispersion of repolarization.
Conclusions: Cetirizine does not adversely modify ventricular repolarization in types 1 and 2 long QT syndrome, suggesting that it might be used safely in these long QT syndrome patients.     

Repolarization Dynamics During Exercise Discriminate Between LQT1 and LQT2 Genotypes

Genotype and Exercise in LQTS . Background: Repolarization dynamics during exercise in patients with long‐QT Syndrome (LQTS) may be influenced by various factors such as a patient's genotype. We sought to systematically characterize the repolarization dynamics during exercise in patients with LQTS with a particular focus on the influence of genotype. Methods: Three groups of patients were studied on the basis of clinical status and genotype: LQT1, LQT2, and normal controls. Twenty‐five age‐ and gender‐matched patients were selected for each group. The QTc was measured during bicycle exercise testing and its dynamics were compared between the 3 groups. Results: The degree of QTc prolongation during exercise was greater in LQTS patients (LQT1 80 ± 47 ms, LQT2 64 ± 41 ms, Control 46 ± 20 ms, P = 0.02), with significant differences between LQT1 and LQT2 patients observed at heart rates ≥60% of the predicted maximum (P < 0.05). LQT1 patients demonstrated progressive or persistent QTc prolongation at higher heart rates, whereas LQT2 patients demonstrated maximum QTc prolongation at submaximal heart rates (～50% of the predicted maximum) with subsequent QTc correction toward baseline values at higher heart rates. Importantly, these observations were consistent regardless of age, gender, or exercise type in subgroup analyses. Conclusions: Reduced repolarization reserve in LQTS is genotype and heart rate specific. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1242‐1246, November 2010)     

The Measurement of the QT Interval

The evaluation of every electrocardiogram should also include an effort to interpret the QT interval to assess the risk of malignant arrhythmias and sudden death associated with an aberrant QT interval. The QT interval is measured from the beginning of the QRS complex to the end of the T-wave, and should be corrected for heart rate to enable comparison with reference values. However, the correct determination of the QT interval, and its value, appears to be a daunting task. Although computerized analysis and interpretation of the QT interval are widely available, these might well over- or underestimate the QT interval and may thus either result in unnecessary treatment or preclude appropriate measures to be taken. This is particularly evident with difficult T-wave morphologies and technically suboptimal ECGs. Similarly, also accurate manual assessment of the QT interval appears to be difficult for many physicians worldwide. In this review we delineate the history of the measurement of the QT interval, its underlying pathophysiological mechanisms and the current standards of the measurement of the QT interval, we provide a glimpse into the future and we discuss several issues troubling accurate measurement of the QT interval. These issues include the lead choice, U-waves, determination of the end of the T-wave, different heart rate correction formulas, arrhythmias and the definition of normal and aberrant QT intervals. Furthermore, we provide recommendations that may serve as guidance to address these complexities and which support accurate assessment of the QT interval and its interpretation.     

Will QT Dispersion Play a Role in Clinical Decision-Making?

Role of QT Dispersion, (1) Dispersion of QT intervals is the difference between the longest and the shortest QT interval in the ECG. Owing to the relative ease of measurement and the perceived need for new markers of arrhythmogenicity, the method has attracted the interest of clinical investigators hut has not reached the level of practical utility. (2) It is postulated that to pass the test of practical utility, the method must meet the following criteria: (a) standardization; (b) establishment of normal values; (c) established sensitivity and/or specificity for diagnosis and/or prognosis; and (d) uniqueness of relevant information. (3) Analysis of the data from the literature suggests that standardization of the method and the range of normal values have not been established, and that the method lacks specificity for separating healthy persons from patients with heart disease. (4) Large values, such as average QT dispersion > 65 msec, have been found predominantly in patients with serious, life-threatening ventricular tachyarrhythmias, and the largest values, i.e., > 110 msec in patients with congenital long QT syndrome. (5) The prognostic value of QT dispersion has been disputed, and the uniqueness of the relevant information has not been tested. (6) It is concluded that the acceptance of QT dispersion as a useful test in practice faces manifold and serious obstacles. It remains to be established whether these obstacles are insurmountable.     

Continuous QT Interval Measurements from 24-Hour Electrocardiography and Risk after Myocardial Infarction

Objectives: The aim of this study was to examine the clinical value of QT analysis from Holter recordings in patients after myocardial infarction (Ml). Background: Prolongation and dispersion of QT intervals in the 12-lead standard ECG have been proposed as indicators of risk for arrhythmic events. However, the value of QT and T wave measurements from Holter recordings has yet to be established. Methods: Intervals from Q to the peak and to the end of T were determined every 30 seconds from 24-hour Holter recordings and corrected for cycle length (QTc). The duration of late repolarization was calculated as QT end minus QT peak. 24-hour QT variability was determined as the standard error of estimate from the linear regression analysis of QT and RR intervals. In a case control design, 51 post-MI patients suffering from subsequent cardiac death within 1 year were compared to 51 post-MI patients with an uncomplicated follow-up. Results: QTc intervals as well as 24-hour QT variability did not differ between post-MI patients with favorable and unfavorable clinical outcome. However, there was a prolonged interval from the peak to the end of the T wave in cardiac death victims (mean ± SE: 110 ± 4 ms) as compared to controls (95 ± 3ms, P < 0.001). Conclusions: Prolongation of the late repolarization phase seems to be associated with an increased risk of cardiac death after Ml. Standard QT measurements from ambulatory ECG recordings have no predictive value in post-MI patients.     

Repolarization dynamics in patients with long QT syndrome

INTRODUCTION: Dynamics of ventricular repolarization may contribute to cardiac arrhythmias in subjects with the long QT syndrome (LQTS). The aim of the present study was to assess the dynamics of repolarization duration and the dynamics of repolarization complexity in LQTS patients and their unaffected family members. METHODS AND RESULTS: Twelve-lead 24-hour ambulatory ECG recordings were obtained from LQTS patients (n = 38) and unaffected family members (n = 20). The 24-hour dynamics of the QT interval, T wave complexity (TWC) index measured by principal component analysis, and the RR interval were analyzed using standard deviation (SD) and square root of the mean squared differences of successive values of the parameters (RMSSD). QT variability, mean TWC, and TWC variability were increased in the LQTS patients compared with unaffected family members (QT-SD: 38 +/- 20 msec vs 19 +/- 7 msec, P = 0.0001; QT-RMSSD: 36 +/- 20 msec vs 14 +/- 8 msec, P = 0.0001; TWC: 27.7% +/- 11.1% vs 20.4% +/- 6.7%, P = 0.003; TWC-SD: 6.7% +/- 2.8% vs 4.6% +/- 1.8%, P = 0.003; TWC-RMSSD: 5.3% +/- 2.8% vs 3.7% +/- 1.2%, P = 0.004, respectively). At the same time, the measures of heart rate variability were similar between the affected and unaffected LQTS subjects (SD of normal-to-normal RR intervals [SDNN]: 94 +/- 25 msec vs 89 +/- 37 ms, P = 0.56; RMSSD: 49 +/- 26 msec vs 49 +/- 34 ms, P = 0.97, respectively). CONCLUSION: Despite similar heart rate variability, QT variability and the variability of TWC are significantly increased in LQTS patients compared with unaffected family members, suggesting that disturbances in temporal dynamics of repolarization and repolarization complexity in LQTS patients possibly increase vulnerability to arrhythmias.     

QT Variability during Rest and Exercise in Patients with Implantable Cardioverter Defibrillators and Healthy Controls

Background: Increased QT Variability (QTVI) is predictive of life threatening arrhythmias in vulnerable patients. The predictive value of QTVI is based on resting ECGs, and little is known about the effect of acute exercise on QTVI. The relation between QTVI and arrhythmic vulnerability markers such as T‐wave alternans (TWA) has also not been studied. This study examined the effects of exercise on QTVI and TWA in patients with arrhythmic vulnerability. Methods: Digitized ECGs were obtained from 47 ICD patients (43 males; age 60.9 ± 10.1) and 23 healthy controls (18 males; age 59.7 ± 9.5) during rest and bicycle exercise. QTVI was assessed using a previously validated algorithm and TWA was measured as both a continuous and a categorical variable based on a priori diagnostic criteria. Results: QTVI increased with exercise in ICD patients (?0.79 ± 0.11 to 0.36 ± 0.08, P < 0.001) and controls (?1.50 ± 0.07 to ?0.19 ± 0.12, P < 0.001), and QTVI levels were consistently higher in ICD patients than controls during rest and exercise (P < 0.001). The magnitude of QTVI increase from baseline levels was not larger among ICD patients versus controls (P > 0.20). Among ICD patients, elevated exercise QTVI was related to lower LV ejection fraction and inducibility of ischemia (P < 0.05). QTVI at rest correlated with exercise TWA (r = 0.54, P = 0.0004). Conclusions: QT variability increases significantly with exercise, and exercise QTVI is related to other well‐documented markers of arrhythmic vulnerability, including low ejection fraction, inducible ischemia, and TWA. Resting QTVI may be useful in the risk stratification of individuals incapable of performing standard exercise protocols.     

Evaluation of QT Interval Dispersion in a Multiple Electrodes Recording System versus 12‐Lead Standard ECG in an In Vitro Model

Background: QT interval dispersion (QTID) as assessed on conventional surface electrocardiogram (ECG) has been used as a clinical tool to identify patients at high risk of ventricular arrhythmia. However, the results obtained have been controversial. The main purpose of this study was to compare QTID measured from an array of 5 × 6 electrodes homogeneously distributed against the values found when the 12‐lead standard ECG was used. Methods: QTID was calculated in a modified Langendorff‐perfused rabbit heart model immersed in a cylindrical chamber. Dispersion in ventricular repolarization was artificially increased by d‐sotalol (60 μ;m) perfusion. Results: All the duration variables measured from any of the lead systems used were significantly increased after d‐sotalol perfusion. The most commonly used variables in clinical studies, such as QTID (maximum ‐ minimum), do not reach a level of statistical significance, except when measured from the 30‐electrodes array or 15 electrodes covering the left or right side of the heart. The standard deviation of the QT interval (QTI) hardly reached a significant level (P = 0.0499) when calculated from the 12‐lead standard ECG. QTID measured at the peak of the T wave exhibited the highest level of significance when calculated from any of the lead systems used. Conclusion: Thirty electrodes homogeneously distributed on the body surface can better discriminate changes in heterogeneity of repolarization. These data further support the importance of multiple recording systems for the evaluation of QTID and may help to provide an understanding of the discrepancies found in clinical applications.     

Interobserver Reproducibility of QT Interval Measurement and QT Dispersion in Patients After Acute Myocardial Infarction

Background: The study evaluated interobserver differences in the classification of the T-U wave repolarization pattern, and their influence on the numerical values of manual measurements of QT interval duration and dispersion in standard predischarge 12-lead ECGs recorded in survivors after acute myocardial infarction. Methods: Thirty ECGs recorded at 25 mm/s were measured by six independent observers. The observers used an adopted scheme to classify the repolarization pattern into 1 of 7 categories, based on the appearance of the T wave, and/or the presence of the U wave, and the various extent of fusion between these. In each lead with measurable QRST(U) pattern, the RR, QJ, QT-end, QT-nadir (i.e., interval between Q onset and the nadir or transition between T and U wave) and QU interval were measured, when applicable. Based on these measurements, the mean RR interval, the maximum, minimum, and mean QJ interval, QT-end and/or QT-nadir interval, and QU interval, the difference between the maximum and minimum QT interval (QT dispersion [QTD]), and the coefficient of variation of QT intervals was derived for each recording. The agreement of an individual observer with other observers in the selection of a given repolarization pattern were investigated by an agreement index, and the general reproducibility of repolarization pattern classification was evaluated by the reproducibility index. The interobserver agreement of numerical measurements was assessed by relative errors. To assess the general interobserver reproducibility of a given numerical measurement, the coefficient of variance of the values provided by all observers was computed for each ECG. Statistical comparison of these coefficients was performed using a standard sign test. Results: The results demonstrated the existence of remarkable differences in the selection of classification patterns of repolarization among the observers. More importantly, these differences were mainly related to the presence of more complex patterns of repolarization and contributed to poor interobserver reproducibility of QTD parameters in all 12 leads and in the precordial leads (relative error of 31%–35% and 34%–43%, respectively) as compared with the interobserver reproducibility of both QT and QU interval duration measurements (relative error of 3%–6%, P < 0.01). This observation was not explained by differences in the numerical order between QT interval duration and QTD, as the reproducibility of the QJ interval (i.e., interval of the same numerical order as QTD was significantly better (relative error of 7.5%–13%, P < 0.01) than that of QTD. Conclusions: Poor interobserver reproducibility of QT dispersion related to the presence of complex repolarization patterns may explain, to some extent, a spectrum of QT dispersion values reported in different clinical studies and may limit the clinical utility in this parameter.     

健康人不同导联QT变异及QT变异指数

探讨健康人不同导联的QT变异(QTV)及QT变异指数(QTVI)。55例健康人在保持日常工作和生活起居的情况下佩戴12导联动态心电图监测仪,计算机辅助下自动测量12导联QT间期,计算每个导联每小时、24h、白天(6:00～22:00)和夜间(22:00～6:00)QT间期均值及其标准差、HR间期均值及其标准差,它们分别代表相应时间段的QT间期均值(QTm)、QTV、HR间期均值(HRm)和HR间期变异(HRV)。计算QTVI。同时运用心率变异时域指标SDNN观察自主神经活性。结果:不同导联间的QTV、QTVI比较具有显著性差异,P<0.05。不同导联24hQTV、QTVI与SDNN均存在负相关,P<0.05。结论:在使用QTV、QTVI来评价不同人群的心室复极离散时,要考虑到不同导联之间的可比性和一致性。QTVI是一种能更直接地反映心室复极逐波变化的新指标。     

Relation between Beat‐to‐Beat QT Interval Variability and T‐Wave Amplitude in Healthy Subjects

Objectives: Elevated beat‐to‐beat QT interval variability (QTV) has been associated with increased cardiovascular morbidity and mortality.The aim of this study was to investigate interlead differences in beat‐to‐beat QTV of 12‐lead ECG and its relationship with the T wave amplitude. Methods: Short‐term 12‐lead ECGs of 72 healthy subjects (17 f, 38 ± 14 years; 55 m, 39 ± 13 years) were studied. Beat‐to‐beat QT intervals were extracted separately for each lead using a template matching algorithm. We calculated the standard deviation of beat‐to‐beat QT intervals as a marker of QTV as well as interlead correlation coefficients. In addition, we measured the median T‐wave amplitude in each lead. Results: There was a significant difference in the standard deviation of beat‐to‐beat QT intervals between leads (minimum: lead V₃ (2.58 ± 1.36 ms), maximum: lead III (7.2 ± 6.4 ms), ANOVA: P < 0.0001). Single measure intraclass correlation coefficients of beat‐to‐beat QT intervals were 0.27 ± 0.18. Interlead correlation coefficients varied between 0.08 ± 0.33 for lead III and lead V₁ and 0.88 ± 0.09 for lead II and lead aVR. QTV was negatively correlated with the T‐wave amplitude (r =–0.62, P < 0.0001). There was no significant affect of mean heart rate, age or gender on QT variability (ANOVA: P > 0.05). Conclusions: QTV varies considerably between leads in magnitude as well as temporal patterns. QTV is increased when the T wave is small.     

Effects of Head‐Up Tilt‐Table Test on the QT Interval

Background. The QT interval shortens in response to sympathetic stimulation and its response to epinephrine infusion (in healthy individuals and patients with long QT syndrome) has been thoroughly studied. Head‐up tilt‐table (HUT) testing is an easy way to achieve brisk sympathetic stimulation. Yet, little is known about the response of the QT interval to HUT. Methods. We reviewed the electrocardiograms of HUT tests performed at our institution and compare the heart rate, QT, and QTc obtained immediately after HUT with the rest values. Results. The study group consisted of 41 patients (27 females and 14 males) aged 23.9 ± 8.4 years. Head‐up tilting led to a significant shortening of the RR interval (from 825 ± 128 msec at rest phase to 712 ± 130 msec in the upward tilt phase, P < 0.001) but only to a moderate shortening of the QT interval (from 363.7 ± 27.9 msec during rest to 355 ± 30.3 msec during upward tilt, P = 0.001). Since the RR interval shortened more than the QT interval, the QTc actually increased (from 403 ± 21.5 msec during rest phase to 423.2 ± 27.4 msec during upward tilt, P < 0.001). The QTc value measured for the upward tilt position was longer than the resting QTc value in 33 of 41 patients. Of those, 4 male patients and 2 female patients developed upward‐tilt QTc values above what would be considered abnormal at rest. Conclusions. During HUT the QT shortens less than the RR interval. Consequently, the QTc increases during head‐up tilt. Ann Noninvasive Electrocardiol 2010;15(3):245–249     

The Effects of Unilateral Stellate Ganglion Blockade on Human Cardiac Function During Rest and Exercise

Unilateral Stellate Block. Introduction: Left sided stellate ganglion predominance has been proposed as a mechanism responsible for lethal ventricular arrhythmias, due to hetaerae nouns ventricular repolarization. To determine the cardiovascular effects of such asymmetric sympathetic ganglion innervations in man, studies were performed in 15 patients undergoing unilateral stellate ganglion blockade for the management of chronic arm pain.
Methods and Results: Standard 12-lead ECGs, systemic blood pressure, body surface potential mapping, and radionuclide angiography were performed during rest and graded exercise before and after blockade. Successful unilateral blockade was accomplished in 13 of the patients, 11 of whom had right-sided blockade and two left-sided blockade. No significant changes due to blockade of stellate ganglia, including QT intervals, were detected during rest or graded exercise in standard ECGs. No cardiac rhythm disturbances occurred in these states, Body surface potential maps and arterial blood pressure were similar during resting supine and upright positions, as well as immediately after exercise before and after blockade. Unilateral ganglion blockade did not modify resting or exercise cardiac ejection fractions.
Conclusion: Unilateral stellate blockade in man does not induce untoward cardiovascular effects during rest or exercise.     

QT and JT Dispersion in Children with Long QT Syndrome

QT and JT Dispersion in Long QT Syndrome. Introduction: Abnormalities of ventricular repolarization leading to ventricular arrhythmias place children with long QT syndrome at high risk for sudden death. Dispersion of the QT (QTd) and JT (JTd) intervals, as markers of cardiac electrical heterogeneity, may be helpful in evaluating children with long QT syndrome and identifying a subset of patients at high risk for development of critical ventricular arrhythmias (ventricular tachycardia, torsades de pointes, and/or cardiac arrest). Methods and Results: The QTd and JTd intervals in 39 children with long QT syndrome were compared to those of 50 normal age-matched children. In the long QT syndrome group, QTd measured 81 ± 70 msec compared to 28 ± 14 msec in the control group (P < 0.05), and JTd in the long QT syndrome group was 80 ± 69 msec compared to 25 ± 15 msec in the control group (P < 0.05). Conclusion: Children with long QT syndrome have an increased QTd and JTd when compared to normal controls. A QTd or JTd ≥ 55 msec correlates with the presence of critical ventricular arrhythmias. These ECG measures of dispersion can be useful in stratifying children with the long QT syndrome who are at higher risk for developing critical ventricular arrhythmias.