QT dispersion in children with ventricular arrhythmia and a structurally normal heart

In adults, increased QT dispersion has been shown to predict arrhythmic risk as well as risk of sudden death in several clinical settings. It is not known whether or not QT dispersion is increased in children with idiopathic ventricular arrhythmia. We studied three groups of children: (1) 20 patients with idiopathic VT (aged 3-18 years; mean 11.2 years); (2) 30 patients with benign PVCs (aged 1-20 years; mean 10.5 years); and (3) 30 control subjects (aged 4-17 years; mean 12 years). Standard ECGs were reviewed and the dispersion of both QT and JT intervals was compared. No patient had structural heart disease or long QT syndrome. The QT and QTc dispersion (QT delta, QTc delta) among the three groups did not differ: QTc delta of the VT group was 70 ms +/- 30 ms, QTc delta of PVC patients was 60 ms +/- 30 ms, and the QTc delta of the control group was 65 ms +/- 30 ms. The JTc delta among the three groups did not differ as well: JTc delta of the VT group was 70 ms +/- 30 ms, the JTc delta of the PVC group was 60 msec +/- 25 msec, and the JTc delta of the control group was 70 ms +/- 30 ms. We conclude that QT and JT dispersion are not significantly altered in children with idiopathic VT or benign PVCs when compared to control subjects. QT dispersion is not a reliable marker for arrhythmic risk in children with idiopathic ventricular arrhythmias and structurally normal hearts.     

Prolonged QRS duration increases QT dispersion but does not relate to arrhythmias in survivors of acute myocardial infarction

QT dispersion has been suggested and disputed as a risk marker for ventricular arrhythmias after myocardial infarction. Delayed ventricular activation after myocardial infarction may affect arrhythmic risk and QT intervals. This study determined if delayed activation as assessed by (1) QRS duration in the 12-lead ECG and by (2) late potentials in the signal-averaged ECG affects QT dispersion and its ability to assess arrhythmic risk after myocardial infarction. QT duration, JT duration, QT dispersion, and JT dispersion were compared to QRS duration in the 12-lead ECG and to late potentials in the signal-averaged ECG recorded in 724 patients 2-3 weeks after myocardial infarction. Prolonged QRS duration (> 110 ms) and high QRS dispersion increased QT and JT dispersion by 12%-15% (P < 0.05). Presence of late potentials, in contrast, did not change QT dispersion. Only the presence of late potentials (n = 113) was related to arrhythmic events during 6-month follow-up. QT dispersion, JT dispersion, QRS duration, and QRS dispersion were equal in patients with (n = 29) and without arrhythmic events (QT disp 80 +/- 7 vs 78 +/- 1 ms, JT disp 80 +/- 6 vs 79 +/- 2 ms, mean +/- SEM, P > 0.2). In conclusion, prolonged QRS duration increases QT dispersion irrespective of arrhythmic events in survivors of myocardial infarction. Presence of late potentials, in contrast, relates to arrhythmic events but does not affect QT dispersion. Therefore, QT dispersion may not be an adequate parameter to assess arrhythmic risk in survivors of myocardial infarction.     

Greater quinidine-induced QTc interval prolongation in women

BACKGROUND: Prolongation of the electrocardiographic QT interval by drugs is associated with the occurrence of a potentially lethal form of polymorphic ventricular tachycardia termed torsades de pointes. Women are at greater risk than men for development of this adverse event when taking drugs that prolong the QT interval. To determine whether this may be the result of gender-specific differences in the effect of quinidine on cardiac repolarization, we compared the degree of quinidine-induced QT interval lengthening in healthy young men and women. METHODS: Twelve women and 12 men received a single intravenous dose of quinidine (4 mg/kg) or placebo in a single-blind, randomized crossover trial. Total plasma and protein-free concentrations of quinidine and 3-hydroxyquinidine were measured in serum. QT intervals were determined and corrected for differences in heart rate with use of the method of Bazett (QTc = QT/RR1/2). RESULTS: As expected, the mean QTc interval at baseline was longer for women than for men (mean +/- SD; 407 +/- 7 versus 395 +/- 9 ms, P < .05). The slope of the relationship between change in the QTc interval (delta QTc) from baseline to the serum concentration of quinidine was 44% greater for women than for men (mean +/- SE; 42.2 +/- 3.4 versus 29.3 +/- 2.6 ms/microg per mL, P < .001). These results were not influenced by analysis of 3-hydroxyquinidine, free concentrations of quinidine and 3-hydroxyquinidine, or the JT interval. CONCLUSIONS: Quinidine causes greater QT prolongation in women than in men at equivalent serum concentrations. This difference may contribute to the greater incidence of drug-induced torsades de pointes observed in women taking quinidine and has implications for other cardiac and noncardiac drugs that prolong the QTc interval. Adjustment of dosages based on body size alone are unlikely to substantially reduce the increased risk of torsades de pointes in women.     

Magnetocardiographic QT Interval Dispersion in Postmyocardial Infarction Patients with Sustained Ventricular Tachycardia: Validation of Automated QT Measurements

T dispersion is a measure of heterogeneity in ventricular repolarization. Increased ECG QT dispersion is associated with life-threatening ventricular arrhythmias. We studied if magnetocardiographic (MCG) measures of QT dispersion can separate postmyocardial infarction patients with and without susceptibility to sustained VT. Manual dispersion measurements were compared to a newly adapted automatic QT interval analysis method. Ten patients with a history of sustained VT (VT group) and eight patients without ventricular arrhythmias (Controls) were studied after a remote myocardial infarction. Single-channel MCGs were recorded from 42 locations over the frontal chest area and the signals were averaged. QT dispersion was defined as maximum — minimum or standard deviation of measured QT intervals. VT group showed significantly more QT and JT dispersion than Controls. QT_apex dispersions were 127 ± 26 versus 83 ± 21 ms (P = 0.004) and QT_end dispersions 130 ± 37 versus 82 ± 37 ms (P = 0.013), respectively. Automatic method gave comparable values. Their relative differences were 9% for QT_apex and 27% for QT_end dispersion on average. In conclusion, increased MCG QT interval dispersion seems to be associated with a susceptibility to VT in postmyocardial infarction patients. MCG mapping with automated QT interval analysis may provide a user independent method to detect nonhomogeneity in ventricular repolarization.     

Influence of electrolyte abnormalities on interlead variability of ventricular repolarization times in 12-lead electrocardiography

Increased QT dispersion (QT(d)) has been associated with increased risk for ventricular arrhythmias. Pathologic extracellular electrolyte concentrations may result in ventricular arrhythmias. The aim of this study was to evaluate the effect of electrolyte abnormalities on QT(d). Ten consecutive patients with isolated electrolyte abnormalities were selected for each of the following groups: hypokalemia, hyperkalemia, hypercalcemia, hypocalcemia, hypomagnesemia, and normal controls. Standard 12-lead electrocardiography was performed for each patient and average QT, JT, and RR intervals were calculated for each lead. Dispersion of QT, JT (JT(d)), and QTc (QTc(d)) intervals were calculated as the range between the longest and shortest measurements. Compared with controls, only patients with hypokalemia had a greater QT(d) (115 +/- 31 vs. 49 +/- 15 ms), JT(d) (116 +/- 34 vs. 52 +/- 12 ms), and QTc(d) (141 +/- 40 vs. 58 +/- 1 ms), (P < 0.05). In an experimental substudy, seven rats were maintained on K(+) and seven on Mg(2+)-free diet followed by normal diet. Experimental hypokalemia significantly increased QT(d) (10 +/- 4 to 37 +/- 7 ms), and QTc(d) (32 +/- 6 to 79 +/- 27 ms) (P < 0.05), whereas hypomagnesemia did not. Restoration of serum potassium resulted in normalization of dispersion (QT(d), 14 +/- 2; QTc(d), 34 +/- 6 ms). Hypokalemia increases the dispersion of ventricular repolarization that may be responsible for arrhythmias. Even though hyperkalemia, hypocalcemia, and hypercalcemia are known to affect ventricular repolarization, our study shows that they are not associated with increased dispersion.     

JT Dispersion in Wolff-Parkinson-White Syndrome: Effect of Eccentric Ventricular Depolarization on the Dispersion of Repolarization

There is much interest in QT dispersion for noninvasive risk stratification of patients at risk of arrhythmias. However, little is known about the genesis of abnormal QT dispersion. In particular, whether eccentric ventricular depolarization, as seen in preexcitation, can lead to abnormal dispersion of repolarization is unknown. We studied 24 children aged 1–19 years (mean ± SD, 11 ± 5 years) with manifest preexcitation due to Wolff-Parkinson-White syndrome who had successful catheter ablation. Standard ECGs done preablation, early postablation (< 1 week), mid postablation (> 1 week, < 2 months), and late postablation (> 2 months) were reviewed. The QRS duration prior to ablation ranged from 90–160 ms (mean ± SD, 123 ±21 ms). On the preablation ECG, the JT and JTc dispersions showed no relationship to the QRS duration (r = 0.04 and 0.07, respectively). There was no change in JT dispersion when the preablation (42 ±15 ms) ECG was compared to early (43 ±15 ms), mid (44 ±13 ms), and late postablation (48 ± 19 ms) ECGs. There was no significant change in JTc dispersion as well. Thus, JT dispersion is unrelated to QRS duration and unaffected by catheter ablation in patients with Wolff-Parkinson-White syndrome. Eccentric ventricular depolarization does not lead to abnormal dispersion of repolarization.     

Ambulatory Assessment of the QT Interval in Patients with Hypertrophic Cardiomyopathy: Risk Stratification and Effect of Low Dose Amiodarone

This study aims to assess the dynamics of the QT interval in patients with hypertrophic cardiomyopathy (HCM). Three consecutive QT intervals and the preceding RR intervals were measured on 24-hour ambulatory electrocardiograms at 30-minute intervals in ten high risk patients with HCM (sudden cardiac death [SCD] and/or documented ventricular fibrillation), aged 29 ± 17 years, compared with ten age and sex matched low risk patients with HCM (no syncope, no adverse family history, and no ventricular tachycardia on Holter monitoring), and ten normal subjects. Another ten patients who were on amiodarone therapy (200-mg daily) were also studied. Patients witb intraventricular conduction defects were excluded. There were 4,424 pairs of QT intervals and their preceding RR intervals were measured in this study. A nonsignificant prolongation in the QT interval and a significant prolongation in QT_c values (Bazett's and Fridericia's formulas) were demonstrated in patients with HCM compared with normals. There were no significant differences in the QT and QT_c between high and low risk patients. The slope of regression line for the QT against RR interval was significantly different between normals and HCM (0.1583 ± 0.040 vs 0.2017 ± 0.043. P < 0.05), but not between high and low risk patients. Amiodarone significantly prolonged the QT and QT_c without significantly altering the slope of the regression line (0.2017 ± 0.043 vs 0.2099 ± 0.037, NS). Our findings support the observations that there is a prolonged QT interval in patients with HCM and that there is no significant use dependent effect of amiodarone on ventricular repolarization. In conclusion, ambulatory assessment of the QT interval provides an alternative method for the assessment of ventricular repolarization and for the assessment of use dependent effects of anti arrhythmic drugs on ventricular repolarization during normal daily activities. However, this method does not help in the identification of patients at high risk of SCD in HCM.     

Effects of Sotalol on the Circadian Rhythmicity of Heart Rate and QT Intervals With a Noninvasive Index of Reverse-Use Dependency

BACKGROUND: The effects of sotalol on the 24-hour profile of the QT interval relative to that of the heart rate (HR) may be helpful in determining the time course of the drug's action in controlling cardiac arhythmias. This has not been previously determined. Thus, the objective of the current study was to evaluate the influence of the drug on the circadian rhythmicity of HR and QT intervals from Holter recordings in ambulatory patients. Reverse-use dependency (RUD) of sotalol was also studied noninvasively from Holter recordings. METHODS AND RESULTS: Holter recordings of 18 patients with ventricular arrhythmias were analyzed before and after 3-7 days of treatment with sotalol. We developed and used a signal processing system. A new noninvasive index to evaluate RUD was defined and applied to sotalol as a test agent. Sotalol significantly reduced HR from 76.9 +/- 3.2 to 60.0 +/- 1.1 (P <.001). The mean QT interval increased from 393 +/- 11 ms to 489 +/- 9 ms, whereas the mean normalized QT (QTc) interval increased from 415 +/- 5 ms to 487 +/- 5 ms (P <.001) during the drug treatment. Circadian rhythmicity of RR interval was abolished, but the circadian rhythms of the QT and QTc intervals were maintained during continuous treatment with sotalol. This finding is in contrast to amiodarone, which abolished the circadian rhythmicity of QTc interval while maintaining that of RR interval. RUD index was increased from 0.13 +/- 0.08 to 0.24 +/- 0.10 (P <.001) after sotalol, consistent with increased RUD with sotalol. CONCLUSIONS: The effects of sotalol on the circadian rhythmicity of HR and QTc interval are dissociated. They are in direct contrast to those reported for amiodarone, a difference that may be of clinical significance. The RUD index introduced here provides a noninvasive parameter for comparing short-term as well as long-term effects of class III antiarrhythmic drugs on RUD.     

Dispersion in ventricular repolarization in patients with severe intraventricular conduction disturbances

Increased dispersion of repolarization, measured invasively or by QT interval measurements, is associated with an increased risk for ventricular arrhythmias and sudden death. Most studies on this issue have included patients with normal intraventricular conduction, and it is not known if this finding has a predictive value also in patients with intraventricular conduction disorders. An invasive electrophysiological study, including programmed ventricular stimulation and assessment of effective refractory periods at two RV sites, was performed in 103 patients with bifascicular block (mean age 67 +/- 12 years). QT dispersion was measured from standard 12-lead ECGs. In patients with inducible sustained polymorphic VT or VF the dispersion in refractoriness between the two RV sites was significantly greater (46 +/- 11 ms, n = 13) than in noninducible patients (14 +/- 14 ms, n = 84) and in patients with inducible sustained monomorphic VT (16 +/- 5 ms, n = 6) (P < 0.01). Similarly, QT dispersion was 104 +/- 46 ms, 66 +/- 31 ms, and 77 +/- 33 ms, respectively, in the three groups (P < 0.05). Dispersion in repolarization, neither measured invasively nor by QT interval measurements, predicted sudden death, all cause mortality, or ventricular arrhythmia during a mean follow-up period of 3 years. In patients with bifascicular block, there is a relation between the degree of dispersion of ventricular repolarization and the inducibility of polymorphic ventricular arrhythmia, but this outcome did not occur during follow-up.     

Serum quinidine concentrations and effect on QT dispersion and interval

OBJECTIVE: To establish a relationship between serum quinidine concentrations (SQCs) and QT interval dispersion, compared with corresponding QT intervals, in order to identify a reason why many reports describe torsade de pointes as occurring at subtherapeutic concentrations. DESIGN: Retrospective study. SETTING: University teaching hospital. PARTICIPANTS: Eleven patients with atrial arrhythmias managed with quinidine therapy. MAIN OUTCOME MEASURES: Patients with subtherapeutic (<2 microg/mL) and therapeutic (2-5 microg/mL) SQCs with corresponding 12-lead electrocardiograms (ECGs) (25 mm/sec) and baseline ECG were evaluated for QT interval dispersion, calculated as the maximum minus the minimum QT interval on the 12-lead ECG. RESULTS: Mean +/- SD subtherapeutic and therapeutic SQCs were 1.48 +/- 0.39 microg/mL and 3.78 +/- 0.88 microg/mL (p < 0.001). Baseline values for QT/QTc intervals were 376.4 +/- 59.2/429.5 +/- 57.3 msec. At subtherapeutic and therapeutic SQCs, mean QT/QTc intervals were 403.6 +/- 59.9/450.5 +/- 38.5 msec and 439.1 +/- 48.9/472.4 +/- 44.6 msec, respectively. Mean QT dispersion was 47 +/- 16.2 msec at baseline, 98.2 +/- 27.5 msec at subtherapeutic SQC, and 70.9 +/- 33.9 msec at therapeutic SQCs (p = 0.001 for overall analysis; p < 0.001 for baseline vs. subtherapeutic concentrations; p = NS for therapeutic vs. subtherapeutic in post hoc comparison). CONCLUSIONS: Despite QT interval lengthening with increasing SQCs, QT dispersion was numerically greatest at subtherapeutic SQCs. Further study is required to determine the value of QT dispersion as a tool for identifying proarrhythmic risk with drugs that prolong the QT interval.     

Amiodarone-induced postrepolarization refractoriness suppresses induction of ventricular fibrillation

It is still incompletely understood why amiodarone is such a potent antiarrhythmic drug. We hypothesized that chronic amiodarone treatment produces postrepolarization refractoriness (PRR) without conduction slowing and that PRR modifies the induction of ventricular arrhythmias. In this study, the hearts of 15 amiodarone-pretreated (50 mg/kg p.o. for 6 weeks) rabbits and 13 controls were isolated and eight monophasic action potentials were simultaneously recorded from the epicardium and endocardium of both ventricles. Steady-state action potential duration (APD), conduction times, refractory periods, and dispersion of action potential durations were determined during programmed stimulation and during 50-Hz burst stimuli, and related to arrhythmia inducibility. Amiodarone prolonged APD by 12 to 15 ms at pacing cycle lengths of 300 to 600 ms (p < 0.05) but did not significantly increase conduction times or dispersion of APD. Amiodarone prolonged refractoriness more than action potential duration, resulting in PRR (refractory period - APD at 90% repolarization, 14 +/- 10 ms, p < 0.05 versus controls). PRR curtailed the initial sloped part of the APD restitution curve by 20%. During burst stimulation, pronounced amiodarone-induced PRR (40 +/- 15 ms, p < 0.05 versus controls) reduced the inducibility of ventricular arrhythmias (p < 0.05 versus controls). Furthermore, in 35% of bursts only monomorphic ventricular tachycardias and no longer ventricular fibrillation were inducible in amiodarone-treated hearts (p < 0.05 versus controls). Chronic amiodarone treatment prevents ventricular tachycardias by inducing PRR without much conduction slowing, thereby curtailing the initial part of APD restitution. PRR without conduction slowing is a desirable feature of drugs designed to prevent ventricular arrhythmias.     

Amiodarone Induced Torsades de Pointes with Excessive QT Dispersion Following Quinidine Induced Polymorphic Ventricular Tachycardia

We report a case of amiodarone induced torsades de pointes (TdP) associated with increase QT dispersion in a patient with a history of quinidine induced TdP. An increase in QT dispersion of > 100% was noted on the 12 lead surface ECG postamiodarone therapy. In summary, amiodarone has a potential to induce TdP in patients with a previous history of quinidine induced TdP. QT dispersion could be a potential marker of TdP in these patients.     

Effects of Postmyocardial Infarction Scar Size, Cardiac Function, and Severity of Coronary Artery Disease on QT Interval Dispersion as a Risk Factor for Complex Ventricular Arrhythmia

The aim of the study was to determine the relation between QT dispersion and ventricular arrhythmia after myocardial infarction, as well as the effects of postinfarction scar size, cardiac function, and severity of coronary artery disease on QT dispersion. Three hundred three patients, 3 months after myocardial infarction, and a group of 21 healthy subjects were evaluated. QT dispersion was the difference between maximal and minimal QT interval in 12-ECG leads. Postinfarction scar size was determined by Selvester's QRS scoring system. Cardiac function was evaluated by echocardiography and exercise stress test, and the severity of coronary artery disease by the number and degree of coronary artery stenoses. QT dispersion increased significantly in relation to the severity of arrhythmia (< 50 premature ventricular complexes vs ventricular tachycardia; 61.6 [± 12.3] vs 84.8 [± 16.4] ms, P < 0. 001). QT dispersion > 80 ms was associated with ventricular tachycardia with the sensitivity of 68% and specificity of 88%. QT dispersion also increased significantly, dependent on the postinfarction scar size (0% vs ± 33% of left ventricular myocardium; 61.8 [± 16.4] vs 74.7 [± 16] ms, P < 0. 001), as well as in the case of significantly impaired cardiac function. Although QT dispersion increased with the number of diseased vessels and the degree of stenoses, the differences were not significant (P > 0. 05). In conclusion, QT dispersion is a risk marker of complex ventricular arrhythmia in the chronic stage of myocardial infarction. Multiple regression analysis indicates that only the postinfarction scar size has an independent effect on QT dispersion (R²= 0. 39, P < 0. 05).     

索他洛尔与胺碘酮对运动心电和运动生理的作用比较

目的 比较索他洛尔与胺碘酮对运动心电图和血流动力学的影响。方法 采用单盲、自身前后对照研究索他洛尔与胺碘酮对3l例无器质性心脏病患者运动心电图、运动血压及心率一收缩压乘积的影响。结果 与胺碘酮比较，索他洛尔显著降低运动心率、收缩压及心率一收缩压乘积，不影响心率储备、运动时间和运动当量；与用药前比较，索他洛尔与胺碘酮均显著延长静态和运动各级爪间期，但是在运动过程中，与用药前及胺碘酮比较，索他洛尔致爪间期加速缩短并与心率呈正相关。结论 索他洛尔可显著降低运动氧耗量，有抗心肌缺血作用；和胺碘酮比较，索他洛尔延长运动JTc的作用表现为加速缩短(逆频率依赖现象)，提示其在运动中抗心律失常作用减弱。     

Dispersion of Ventricular Repolarization in the Voltage Domain

Dispersion of ventricular repolarization, assessed as QT dispersion in the ECG or by multiple monophasic action potential (MAP) recordings, is defined as the difference between the earliest and latest repolarization. It is thus measured in the time domain. However, myocardial refractoriness is primarily a function of the membrane potential during phase 3 repolarization. The purpose of this study, therefore, was to measure dispersion of ventricular repolarization in the voltage domain and to study its relation to VF inducibility. To further validate this concept, the effects of chronic amiodarone treatment on the voltage dispersion were assessed. MAPs were recorded simultaneously at 10 epicardial and endocardial sites in isolated rabbit hearts, both under baseline conditions (n = 8) and after chronic amiodarone treatment (n = 8). Repolarization dispersion in the voltage domain was calculated as the difference between the highest and lowest repolarization level of all 10 MAPs at 10-ms steps, starting from the MAP plateau level to complete repolarization. Plotting these voltage differences along the time axis resulted in a dispersion curve, which rose during early repolarization, reached a peak during phase 3 repolarization, and thereafter declined toward zero. There was a close correlation between VF vulnerability in response to electrical field stimuli and the time during which voltage dispersion was maximal (r = 0.828, P < 0.0001). Amiodarone caused a right-ward shift of both the dispersion curve (P = 0.007) and VF vulnerability (P = 0.025), but did not change the magnitude nor the shape of the voltage dispersion curve and its relation to VF vulnerability. Repolarization dispersion in the voltage domain describes an alternate approach for evaluating the heterogeneity of ventricular repolarization and may help to characterize arrhythmia susceptibility under experimental conditions.     

New antiarrhythmic drugs: tocainide, mexiletine, flecainide, encainide, and amiodarone

Tocainide, mexiletine, flecainide, encainide, and amiodarone are antiarrhythmic agents that have recently been approved by the Food and Drug Administration for general use in the treatment of ventricular arrhythmias. All five agents are effective in the treatment of patients with ventricular arrhythmias, whereas encainide, flecainide, and amiodarone are also useful in patients with supraventricular arrhythmias and the Wolff-Parkinson-White syndrome (although not yet approved for these indications). Tocainide and mexiletine are similar to lidocaine and are as effective as quinidine in patients with ventricular arrhythmias. Encainide and flecainide are superior to quinidine for the control of ventricular ectopic beats and as effective as quinidine for patients with ventricular tachycardia. Amiodarone is the most effective agent available for treating patients with ventricular tachycardia, but it is also the most toxic antiarrhythmic agent and should be used only when other antiarrhythmic drugs have not been effective or tolerated.     

Comparative Reproducibility of QT, QT Peak, and T Peak-T End Intervals and Dispersion in Normal Subjects, Patients with Myocardial Infarction, and Patients with Hypertrophic Cardiomyopathy

Abnormal repolarizaiion is associated with arrhythmogenesis. Because of controversies in existing methodology, new computerized methods may provide more reliable tools for the noninvasive assessment of myocardial repolarization from the surface electrocardiogram (ECC). Measurement of the interval between the peak and the end of the T wave (TpTe interval) has been suggested for the detection of repolarization abnormalities, but its clinical value has not been fully studied. The intrasubject reproducibility and reliability of automatic measurements of QT, QT peak, and TpTe interval and dispersion were assessed in 70 normal subjects, 49 patients with acute myocardial infarction (5th day; MI), and 37 patients with hypertrophic cardiomyopathy (HC). Measurements were performed automatically in a set of 10 ECCs obtained from each subject using a commercial software package (Marquette Medical Systems, Milwaukee, WI, U.S.A.). Compared to normal subjects, all intervals were significantly longer in HC patients (P < 0.001 for QT and QTp; p < 0.05 for TpTe); in MI patients, this difference was only significant for the maximum QT and QTp intervals (P < 0.05). In both patient groups, the QT and QTp dispersion was significantly greater compared to normal subjects (P < 0.05) but no consistent difference was observed in the TpTe dispersion among all three groups. In all subjects, the reproducibility of automatic measurement of QT and QTp intervals was high (coefficient of variation, CV, 1%-2%) and slightly lower for that of TpTe interval (2%–5%; p < 0.05). The reproducibility of QT, QTp, and TpTe dispersion was lower (12%–24%, 18%–28%, 16%–23% in normal subjects, MI and HC patients, respectively). The reliability of automatic measurement of QT, QTp, and TpTe intervals is high but the reproducibility of the repeated measurements of QT, QTp and TpTe dispersion is comparatively low.     

QT Duration and Dispersion in Patients with Anomalous Origins of Coronary Arteries

Background: Coronary artery anomalies have been reported to show various symptoms ranging from chest pain and dyspnea to cardio-respiratory arrest and sudden death. In this study, we attempted to assess the changes in QT interval duration and dispersion in anomalous origins of coronary arteries (AOCA).
Methods: Nineteen AOCA patients (mean age: 52 ± 11 years) and 30 healthy control subjects (mean age: 50 ± 12 years) were included in the study. Minimum and maximum corrected QT intervals, and corrected QT dispersion were calculated. The two groups were compared in terms of QT dispersion and QT duration.
Results: There was no difference between the two groups in terms of baseline demographic characteristics. Maximum corrected QT intervals (QTc max), minimum corrected QT intervals (QTc min), and corrected QT dispersion were higher in AOCA patients than controls (452 ± 38 vs 411 ± 25 ms [P = 0.0001], 402 ± 31 vs 383 ± 28 ms [P = 0.048], and 51 ± 30 vs 28 ± 12 ms [P = 0.001], respectively).
Conclusion: In the patients with anomalous origins of coronary arteries, QT dispersion that is an indicator of sudden cardiac death and arrhythmias frequency increased. QTc max, QTc min, and corrected QT dispersion are higher in patients with anomalous origin of the coronary artery than in control subjects.     

Proarrhythmic effects of a quinidine analog in dogs with chronic A-V block

Summary— The proarrhythmic effects of 3-hydroxy-hydroquinidine (3-OH-HQ) and quinidine were compared in a canine model of QT-dependent ventricular arrhythmias. Eight hypokalemic ([K+] ≤ 3.2 mmol/l) dogs with AV block (around 45 bpm) were given either drug in a randomized order at 2-day intervals. Each drug was given as two 1 hour doses, with a bolus (low dose: 5 mg/kg or high dose: 10 mg/kg) plus infusion (25 or 50 μg/kg/min) protocol. Propranolol infusion was combined with a third hour of the high dose infusion. Electrophysiologic measurements were performed at baseline and 30 minutes after the beginning of each dose and propranolol infusion, and proarrhythmic events were recorded 30 minutes before and during the experiment. Neither drugs altered the ventricular cycle length. Quinidine and 3-OH-HQ prolonged the QT interval similarly and significantly when paced at 60 bpm after the low dose (+ 39 ± 18 and + 28 ± 22 msec, respectively) and after the high dose (+ 51 ± 29 and + 50 ± 22 msec). Quinidine was more arrhythmogenic than 3-OH-HQ: 7/8 dogs (p ≤ 0.05) developed ventricular arrhythmias (isolated, repetitive ventricular beats, or polymorphic ventricular tachycardias) during quinidine infusion (low dose: 4 dogs) compared to 3/8 dogs (NS) during 3-OH-HQ infusion (low dose: 1 dog). Addition of propranolol-induced bradycardia (around 30 bpm) caused torsades de pointes (wave burst arrhythmias) or polymorphic ventricular tachycardias after both drugs (in 3 dogs after quinidine and in 2 dogs after 3-OH-HQ). Thus 3-OH-HQ was slightly less arrhythmogenic than quinidine in this model of torsades de pointes, but the addition of an extra favouring factor (bradycardia) reduced that difference.     

Evidences of the gender-related differences in cardiac repolarization and the underlying mechanisms in different animal species and human

Clinical and experimental studies have shown that gender differences exist in cardiac repolarization in various animal species and human, as is evidenced by significantly longer QT, JT intervals and action potential duration in females than in males due to a reduced repolarization reserve in females. The latter is shown by the relatively greater increase in ventricular repolarization and higher incidence of torsades de pointes (TdP) in preparations from females by drugs blocking repolarizing K(+) currents. These results can be modulated by gonadectomy, suggesting that gonadal steroids are important determinants of gender difference in repolarization. In human subjects, QT and JT intervals are longer in women, whereas QT dispersion and Tp-e interval (the interval from the peak to the end of T wave) are longer in men. At slow heart rates greater prolongation in QT and increase in transmural repolarization heterogeneity (i.e. increase in Tp-e) may predispose to TdP tachycardias in women. In healthy postmenopausal women, hormone replacement therapy with estrogen alone usually produced a prolongation of QT interval, while estrogen plus progesterone had no significant effects on QT interval but reduced QT dispersion. Along with these, there are still conflicting data reported. Further work is needed before the elucidation of the basis of gender differences in ventricular repolarization.