Comparing Methods of Measurement for Detecting Drug‐Induced Changes in the QT Interval: Implications for Thoroughly Conducted ECG Studies

Background: The aim of this study was to compare the reproducibility and sensitivity of four commonly used methods for QT interval assessment when applied to ECG data obtained after infusion of ibutilide. Methods: Four methods were compared: (1) 12‐lead simultaneous ECG (12‐SIM), (2) lead II ECG (LEAD II), both measured on a digitizing board, (3) 3‐LEAD ECG using a manual tangential method, and (4) a computer‐based, proprietary algorithm, 12SL? ECG Analysis software (AUT). QT intervals were measured in 10 healthy volunteers at multiple time points during 24 hours at baseline and after single intravenous doses of ibutilide 0.25 and 0.5 mg. Changes in QT interval from baseline were calculated and compared across ECG methods, using Bland–Altman plots. Variability was studied using a mixed linear model. Results: Baseline QT values differed between methods (range 376–395 ms), mainly based on the number of leads incorporated into the measurement, with LEAD II and 3‐LEAD providing the shortest intervals. The 3‐LEAD generated the largest QT change from baseline, whereas LEAD II and 12‐SIM generated essentially identical result within narrow limits of agreement (0.4 ms mean difference, 95% confidence interval ± 20.5 ms). Variability with AUT (standard deviation 15.8 ms for within‐subject values) was clearly larger than with 3‐LEAD, LEAD II, and 12‐SIM (9.6, 10.0, and 11.3 ms). Conclusion: This study demonstrated significant differences among four commonly used methods for QT interval measurement after pharmacological prolongation of cardiac repolarization. Observed large differences in variability of measurements will have a substantial impact on the sample size required to detect QT prolongation in the range that is currently advised in regulatory guidance.     

The Time Course of New T‐Wave ECG Descriptors Following Single‐ and Double‐Dose Administration of Sotalol in Healthy Subjects

Introduction: The aim of the study was to assess the time course effect of IKr blockade on ECG biomarkers of ventricular repolarization and to evaluate the accuracy of a fully automatic approach for QT duration evaluation. Methods: Twelve‐lead digital ECG Holter was recorded in 38 healthy subjects (27 males, mean age = 27.4 ± 8.0 years) on baseline conditions (day 0) and after administration of 160 mg (day 1) and 320 mg (day 2) of d‐l sotalol. For each 24‐hour period and each subject, ECGs were extracted every 10 minutes during the 4‐hour period following drug dosage. Ventricular repolarization was characterized using three biomarker categories: conventional ECG time intervals, principal component analysis (PCA) analysis on the T wave, and fully automatic biomarkers computed from a mathematical model of the T wave. Results: QT interval was significantly prolonged starting 1 hour 20 minutes after drug dosing with 160 mg and 1 hour 10 minutes after drug dosing with 320 mg. PCA ventricular repolarization parameters sotalol‐induced changes were delayed (>3 hours). After sotalol dosing, the early phase of the T wave changed earlier than the late phase prolongation. Globally, the modeled surrogate QT paralleled manual QT changes. The duration of manual QT and automatic surrogate QT were strongly correlated (R²= 0.92, P < 0.001). The Bland and Altman plot revealed a nonstationary systematic bias (bias = 26.5 ms ± 1.96*SD = 16 ms). Conclusions: Changes in different ECG biomarkers of ventricular repolarization display different kinetics after administration of a potent potassium channel blocker. These differences need to be taken into account when designing ventricular repolarization ECG studies. Ann Noninvasive Electrocardiol 2010;15(1):26–35     

Electrocardiographic Identification of Drug‐Induced QT Prolongation: Assessment by Different Recording and Measurement Methods

Background: Careful assessment of QT interval prolongation is required before novel drugs are approved by regulatory authorities. The choice of the most appropriate method of electrocardiogram (ECG) acquisition and QT/RR interval measurement in clinical trials requires better understanding of the differences among currently available approaches. This study compared standard and Holter‐derived 12‐lead ECGs for utility in detecting sotalol‐induced QT/QTc and RR changes. Manual methods (digitizing pad and digital on‐screen calipers) were compared for precision of QT and RR interval measurement. Methods and Results: Sixteen hundred pairs of serial 12‐lead digital ECGs were recorded simultaneously by standard resting ECG device and by continuous 12‐lead digital Holter over 3 days in 39 healthy male and female volunteers. No therapy was given on the 1st day followed by 160 mg and 320 mg of sotalol on the 2nd and 3rd day, respectively. Holter‐derived and standard ECGs produced nearly identical sotalol‐induced QT/QTc and RR changes from baseline, as did the manual digipad and on‐screen caliper measurements. The variability of on‐screen QT measurement in this study was greater than that of digipad. Conclusions: Digital 12‐lead Holter and standard 12‐lead ECG recorders, as well as the manual digitizing pad and digital on‐screen calipers, are of equal utility for the assessment of drug‐induced change from baseline in QT and RR interval, although the variability of the on‐screen method in this study was greater than of the digipad.     

Changes of the T-wave amplitude and angle: an early marker of altered ventricular repolarization in hypertension

BACKGROUND: The heterogeneity of ventricular repolarization is an important proarrhythmic factor. QT dispersion has been proposed to reflect the inhomogeneity of ventricular repolarization, but a poor reproducibility limits its clinical applicability. Reliable noninvasive methods to quantify abnormalities in ventricular repolarization are still lacking. The T-loop morphology analysis is a novel method aimed at quantifying ventricular repolarization. HYPOTHESIS: To test the ability of the T-loop morphology analysis to discriminate between hypertensive patients and healthy subjects, 105 hypertensive patients (mean age 63.6 +/- 12.3 years) and 110 healthy controls (mean age 49.7 +/- 14.3 years) were evaluated. METHODS: The maximum QT interval (QT maximum), the minimum QT interval (QT minimum), and their difference (QT dispersion) were calculated from a digitally recorded 12-lead electrocardiogram (ECG) in both study groups. X, Y, and Z leads were reconstructed from the 12-lead ECG, and the amplitude of the maximum T vector (T amplitude) and the angle between the maximum T vector and X axis (T angle) were calculated from the projection of the T loop in the frontal plane. RESULTS: T amplitude (p < 0.001), T angle (p = 0.05), and QT dispersion (p = 0.04) were significantly different between hypertensive patients and controls, while QT maximum (p = 0.14) and QT minimum (p = 0.35) did not differ between the groups. T amplitude was the only marker which differed between hypertensive patients without ECG criteria for left ventricular hypertrophy and controls (p = 0.002). CONCLUSIONS: T-loop features and particularly T amplitude are significantly different between hypertensive patients and healthy controls and may serve as early markers of repolarization abnormalities in a hypertensive population.     

Dynamics of Ventricular Repolarization in Patients with Dilated Cardiomyopathy Versus Healthy Subjects

Background: Patients with impaired left ventricular function have a high risk of developing ventricular arrhythmias and sudden death. Among different markers of risk, the prolongation and regional heterogeneity of repolarization are of increasing interest. However, there are limited data regarding feasibility of analyzing repolarization parameters and their dynamics in 24‐hour Holter ECG recordings. Methods: Dynamic behavior of repolarization parameters was studied with a new automatic algorithm in digital 24‐hour Holter recordings of 60 healthy subjects and 55 patients with idiopathic dilated cardiomyopathy (IDC). Repolarization parameters included the mean value of QT and QTc durations, QT dispersion, and peaks of QT duration and QT dispersion above prespecified thresholds. Results: In comparison to healthy subjects, patients with IDC had lower heart rate variability, longer mean QT and QTc durations, higher content of QTc peaks >500 ms, longer QT dispersion and its standard deviation, and a higher content of peaks >100 ms of QT dispersion (P < 0.01 for all comparisons). These repolarization parameters were significantly higher in IDC patients after adjustment for age, sex, and heart rate variability. The parameters of repolarization dynamics correlated with SDNN in healthy subjects but not in dilated cardiomyopathy patients. Conclusions: The automatic assessment of repolarization parameters in 24‐hour digital ECG recordings is feasible and differentiates dilated cardiomyopathy patients from healthy subjects. Patients with dilated cardiomyopathy have increased QT duration, QT dispersion, and increased variability of QT dispersion reflecting variations in T‐wave morphology, the factors which might predispose them to the development of arrhythmic events.     

Interlead Difference in QT Interval Rate Adaptation During Exercise in Coronary Artery Disease Patients Susceptible to Ventricular Fibrillation

Background: Nonhomogeneity in ventricular repolarization predisposes to ventricular tachyarrhythmias. Rate adaptation of the QT interval parallels rate adaptation of the action potential, both of which reflect the repolarization phase in ventricular myocardium. The aim of this study was to examine in patients with coronary artery disease (CAD) the relation of interlead differences in QT interval rate‐adaptation to arrhythmia vulnerability. Methods: We studied 29 CAD patients with a history of ventricular fibrillation (VF) not associated with acute myocardial infarction (VF group), and their 29 individually matched CAD controls without arrhythmic events (controls). Rate adaptation of the QT intervals in the 12 leads of the electrocardiogram were determined from QT intervals measured at rest and at the end of each 3 minute load step during exercise test. The relation between heart rate (HR) and QT interval (QT/HR slope) was calculated separately in each lead by the linear regression equation. The slopes of these equations were used to characterize spatial QT interval rate adaptation. Results: The steepest QT_apex/ HR slopes in any lead were (mean ±mD SD) ?2.45 ± 0.63 in the VF group and ‐1.97 ± 0.45 in controls (P = 0.008), whereas the smallest slopes showed no difference (P = NS). The standard deviations of QT_apex/ HR slopes were 0.48 ± 0.23 in the VF group and 0.33 ± 0.12 in controls (P = 0.012). Conclusions: Rate adaptation of the QT_apex interval is locally exaggerated, resulting in nonhomogenous exercise response of the QT_apex intervals in CAD patients susceptible to life‐threatening ventricular arrhythmias. A.N.E. 2000;5(4):346–353     

Electrocardiographic Transmural Dispersion of Repolarization in Patients with Inherited Short QT Syndrome

Background : Short QT syndrome (SQTS) carries an increased risk for sudden cardiac death. However, only a short QT interval does not express the risk of ventricular arrhythmias. Thus, additional evaluation of the repolarization abnormality in SQTS patients is essential. In experimental models of SQTS, increased transmural dispersion of repolarization (TDR) and its electrocardiographic counterpart T‐wave peak to T‐wave end interval (TPE) appeared critical for induction of polymorphic ventricular tachycardia (PMVT). In a clinical study with acquired long QT syndrome patients, TPE/QT ratio > 0.28 indicated arrhythmia risk. We hypothesized that the TPE/QT ratio would be greater in SQTS patients than in control subjects. Methods and Results : We compared the behavior of the electrocardiographic TDR in three seriously symptomatic SQTS patients of unknown genotype presenting baseline QTc values <320 ms and in nine healthy age‐matched control subjects. We determined QT and TPE intervals as well as TPE/QT ratio from 24‐hour ECG recordings using a computer‐assisted program. Diurnal average of TPE/QT ratio was 0.28 ± 0.03 in SQTS patients and 0.21 ± 0.02 in control subjects (P = 0.01). SQTS patients had also lesser capacity to change TPE intervals from steady‐state conditions to abrupt maximal values than control subjects. Conclusion : SQTS patients have increased and autonomically uncontrolled electrocardiographic TDR. According to experimental SQTS models, the present results may in part explain increased vulnerability of SQTS patients to ventricular arrhythmias.     

QT Dynamics and Variability

Repolarization dynamics and variability are of increasing interest as Holter‐derived parameters reflecting changes in myocardial vulnerability and contributing to increased risk of arrhythmic events and sudden death. Repolarization dynamics is usually defined as phenomenon describing and quantifying QT adaptation to changing heart rate. The analysis of QT–R‐R slopes in long ECG recordings is one of the ways to evaluate repolarization dynamics. Increased QT–R‐R slopes are frequently observed in patients at risk for cardiac death and arrhythmic events: postinfarction patients, long QT syndrome patients, patients with nonischemic cardiomyopathy as well as in patients taking drugs affecting repolarization. QT variability reflects beat‐to‐beat changes in repolarization duration and morphology and such changes can be quantified using a number of algorithms currently in various phases of development and validation. Increased QT variability is observed in several conditions with increased risk of arrhythmias. Recent data from MADIT II indicate that increased QT variability is a powerful predictor of arrhythmic events in postinfarction patients with left ventricular dysfunction. More studies are needed to determine further the potential clinical usefulness for diagnosing patients and for risk stratification purposes using both QT dynamics and QT variability methods, and compare these methods with exercise‐induced T wave alternans.     

Reduction of dispersion of repolarization and prolongation of postrepolarization refractoriness explain the antiarrhythmic effects of quinidine in a model of short QT syndrome

Background: Short QT syndrome (SQTS) is a newly described ion channelopathy, characterized by a short QT interval resulting from an accelerated cardiac repolarization, associated with syncope, atrial fibrillation, and sudden cardiac death due to ventricular fibrillation. As therapeutic options in SQTS are still controversial, we examined antiarrhythmic mechanisms in an experimental model of SQTS. Methods and Results: Pinacidil, an I_K‐ATP channel opener, was administered in increasing concentrations (50–100 μM) in 48 Langendorff‐perfused rabbit hearts and led to a significant reduction of action potential duration and QT interval, thereby mimicking SQTS. Eight simultaneously recorded monophasic action potentials demonstrated an increase in dispersion of repolarization, especially between the left and the right ventricle. During programmed ventricular stimulation with up to two extrastimuli, pinacidil significantly increased the inducibility of ventricular fibrillation (1 heart under baseline conditions, 29 hearts during pinacidil administration; P = 0.0001). Additional treatment with the I_Kr blocker sotalol (100 μM) and the class I antiarrhythmic drugs flecainide (2 μM) and quinidine (0.5 μM) randomly assigned to three groups of 16 hearts led to prolongation of repolarization as well as refractory period. Sotalol or flecainide did not reduce the rate of inducibility of ventricular fibrillation significantly (P = 0.63; P = 0.219). However, quinidine reduced the inducibility of ventricular fibrillation by 73% (P = 0.008). The antiarrhythmic potential of quinidine was associated with a significantly greater prolongation of MAP duration, refractoriness, and postrepolarization refractoriness (PRR) as compared with sotalol and flecainide. Moreover, quinidine, in contrast to sotalol and flecainide, reduced dispersion of repolarization. Conclusion: Pinacidil mimics SQTS via increasing potassium outward currents, thereby facilitating inducibility of ventricular fibrillation. Quinidine demonstrates superior antiarrhythmic properties in the treatment of ventricular fibrillation in this model as compared with sotalol and flecainide because of its effects on refractoriness, PRR, and by reducing dispersion of repolarization.     

Reproducibility of Computerized Measurements of QT Interval from Multiple Leads at Rest and During Exercise

Background: Accurate measurement of the QT interval is important for diagnosing long QT syndrome (LQTS), and in research on determinants of ventricular repolarization time. We tested automatic analysis of QT intervals from multiple ECG leads on chest. Methods: Eleven healthy volunteers and 10 genotyped LQTS patients were tested at rest and during exercise with a bicycle ergometer twice 1–31 months apart. Electrocardiograms were recorded with the body surface potential mapping system, and 12 precordial channels were selected for analysis. Averaged QT peak and QT end intervals were determined with an automated algorithm, and the difference QT end minus QT peak (Tp‐e) was calculated. Repeatability was assessed by coefficient of variation (CV) between measurements. Results: Within one test at rest the QT end intervals were highly repeatable with CV 0.6%. In repeated tests CV was 4.4% for QT end interval and 3.5% when the QT interval was corrected for heart rate. In exercise test at specified heart rates, mean CV was 3.0% for QT end and 2.9% for QT peak interval. The CV of Tp‐e interval was 10.2% at rest, and 9.3% in exercise test. Reproducibility was comparable between healthy subjects and LQTS patients. Conclusions: The BSPM system with automated analysis produced accurate and highly repeatable QT interval measurements. Reproducibility was adequate also over prolonged time periods both at rest and in exercise stress test. The method can be applied in studying duration of ventricular repolarization time in different physiologic and pharmacologic interventions.     

Arrhythmogenesis of T wave alternans associated with surface QRS complex alternans and the role of ventricular prematurity: observations from a canine model of LQT3 syndrome

INTRODUCTION: T wave alternans (TWA) is characterized by cycle-to-cycle changes in the QT interval and/or T wave morphology. It is believed to amplify the underlying dispersion of ventricular repolarization. The aim of this study was to examine the mechanisms and arrhythmogenesis of TWA accompanied by QRS complex and/or blood pressure (BP) waveform alternans, using transmural ventricular electrogram recordings in an anthopleurin-A model of long QT syndrome. METHODS AND RESULTS: The cardiac cycle length was gradually shortened by interruption of vagal stimulation, and TWA was induced in six canine hearts. Transmural unipolar electrograms were recorded with plunge needle electrodes from endocardial (Endo), mid-myocardial (Mid), and epicardial (Epi) sites, along with the surface ECG and BP. The activation-recovery interval (ARI) was measured to estimate local refractoriness. During TWA, ARI alternans was greater at the Mid than the Epi/Endo sites, and it was associated with the development of marked spatial dispersion of ventricular repolarization. As TWA increased, ventricular activation of the cycles associated with shorter QT intervals displayed delayed conduction at the Mid sites as a result of a critically longer ARI of the preceding cycle and longer QT interval, while normal conduction was preserved at the Epi site. Delayed conduction at the Mid sites manifested as surface ECG QRS and BP waveform alternans, and spontaneous ventricular tachyarrhythmias developed in absence of ventricular prematurity. In other instances, in absence of delayed conduction during TWA, ventricular premature complexes infringed on a prominent spatial dispersion of ventricular repolarization of cycles with long QT intervals and initiated ventricular tachyarrhythmia. CONCLUSION: TWA accompanied by QRS alternans may signal a greater ventricular electrical instability, since it is associated with intramural delayed conduction, which can initiate ventricular tachyarrhythmia without ventricular premature complexes.     

QT dispersion ratio in patients with unstable angina pectoris (A new risk factor?)

Background: QT dispersion has been shown to be associated with fatal arrhythmias and sudden death in coronary artery disease. A recent study indicated that marked QT dispersion in electrocardiograms (ECGs) obtained during acute ischemia demonstrated a significant correlation with ventricular fibrillation. Hypothesis: This study investigated the ECG parameters for repolarization (QT dispersion, corrected QT, corrected QT dispersion, and QT dispersion ratio) and their interrelation with acute ischemia. Methods: QT parameters as well as a newly developed repolarization index, QT dispersion ratio l(QT dispersion/RR interval) × 100] were calculated digitally during rest and ischemia in 32 patients with coronary artery disease (rest angina, Braunwald class III). Results were correlated with clinical consequences, mainly arrhythmias, within a follow-up period of 5±2days. Results: While most patients had an increase in all four parameters, only the QT dispersion ratio showed a significant difference when correlated with ventricular arrhythmias (p < 0.001, F ratio = 38). Conclusion: QT dispersion ratio appears to be a new and promising parameter in predicting ventricular arrhythmias in patients with acute ischemia.     

QT dispersion failed to estimate the global dispersion of ventricular repolarization measured using monophasic action potential mapping technique in swine and patients

The aim of this study was to evaluate whether the QT dispersion measured from 12-lead electrocardiogram (ECG) can estimate the global dispersion of ventricular repolarization (DVR) measured using a monophasic action potential (MAP) mapping technique. Monophasic action potentials were recorded from 75 +/- 12 left ventricular sites in 10 pigs and from 48 +/- 16 left or right ventricular sites in 15 patients using the CARTO mapping system. The maximum DVRs in both end-of-repolarization and MAP duration among all the mapped sites were calculated and termed as global DVR for each measurement. QT intervals, QT peak and QT end , were measured from the 12-lead ECG, and QT dispersions; namely the differences between the maximum and the minimum of the QT peak and QT end were calculated. We found that QT dispersions were significantly smaller than (P < .05) and poorly correlated with the global DVRs both in pigs and patients. Bland-Altman agreement analysis demonstrated a marked variation of the differences and an obvious lack of agreement between the results obtained using the ECG and the MAP methods. In our patients, the global DVR increased markedly during ventricular tachycardia as compared with that during sinus rhythm (P < .05), whereas there was no significant difference in QT dispersion between these 2 subgroups. In conclusion, QT dispersion on the surface ECG could not estimate the global DVR measured using the MAP mapping technique. These findings are not consistent with some previously reported observations, suggesting the need for reappraisal of the electrophysiological implications of QT dispersion.     

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。     

Predictive Value of QT Dispersion for Ventricular Tachyarrhythmias in Patients with Implantable Cardioverter Defibrillator

Background: QT dispersion, measured as interlead variability of QT intervals in the surface electrocardiogram, has been demonstrated to provide an indirect measurement of the inhomogeneity of myocardial repolarization as a potential substrate for ventricular arrhythmias. Methods: QT dispersion was measured in the standard 12-lead ECG in 51 patients at the time of implantation of a third generation implantable cardioverter defibrillator (ICD) with automatic electrogram storage capability for electrical events triggering device therapy. In addition, QT dispersion was measured in 100 age- and sex-matched healthy controls. All 5 1 study patients with ICD were prospectively followed to determine possible associations between QT dispersion at implant and subsequent spontaneous ICD shocks for ventricular tachyarrhythmias (VT). Results: Rate-corrected QT dispersion and adjusted QTc dispersion, which takes account of the number of leads measured, were significantly greater in ICD patients compared to controls (76 ± 25 ms vs 46 ± 11 ms, and 24 ± 7 ms vs 14 ± 3 ms respectively, P < 0.0 1). During 15 ± 8 months follow-up, ventricular tachyarrhythmias occurred in 23 (45%) of 51 ICD patients. QTc dispersion and adjusted QTc dispersion were not significantly different between ICD patients with ventricular tachyarrhythmias and ICD patients without ventricular tachyarrhythmias during follow-up (74 ± 19 ms versus 77 ± 29 ms, and 23 ± 6 ms vs 25 ± 8 ms respectively). Conclusion: Increased QT dispersion measured in the 12-lead standard ECG does not appear to be a useful marker for future arrhythmic events in a mixed patient population with ICD.     

Effect of amiodarone on qt dispersion in the 12-lead standard electrocardiogram and its significance for subsequent arrhythmic events

Background and hypothesis: QT dispersion, measured as interlead variability of QT intervals in the surface electrocardiogram, has been demonstrated to provide an indirect measurement of the inhomogeneity of myocardial repolarization. The purpose of the present study was twofold: (1) to analyze the effect of amiodarone on QT dispersion measured in the 12-lead standard ECG, and (2) to examine the association between QT dispersion on amiodarone and subsequent arrhythmic events. Methods: To determine the effect of amiodarone on QT dispersion and its clinical significance for subsequent arrhythmic events, QT dispersion was measured in the 12-lead standard electrocardiogram (ECG) in 52 patients before and after administration of empiric amiodarone for ventricular tachyarrhythmias. Results: QT intervals increased from 401 ± 44 ms before amiodarone to 442 ± 53 ms after amiodarone therapy, and rate corrected QT intervals (QTc) increased from 452 ± 43 ms to 477 ± 37 ms, respectively (p<0.01). QT dispersion, QTc dispersion, and adjusted QTc dispersion, which take account of the number of leads measured, were not significantly different before and after initiation of amiodarone therapy (58 ± 24 ms vs. 61 ± 26 ms, 68 ± 29 vs. 66 ± 26 ms, and 22 ± 8 vs. 22 ± 8 ms, respectively, p = NS). During 31 ± 25 months follow-up after initiation of amiodarone therapy, arrhythmic events defined as sustained ventricular tachycardia, ventricular fibrillation, or sudden death occurred in 11 of 52 study patients (21%). QT dispersion, QTc dispersion, and adjusted QTc dispersion on amiodarone were not different between patients with and without arrhythmic events during follow-up (65 ± 14 vs. 59 ± 29 ms, 73 ± 15 vs. 64 ± 28 ms, and 25 ± 6 vs. 21 ± 8 ms, respectively, p=NS). Conclusions: We conclude that (1) amiodarone increases QT intervals and QTc intervals during sinus rhythm but does not significantly change measures of QT dispersion; and (2) QT dispersion measured in the 12-lead standard ECG after initiation of amiodarone therapy does not appear to be a useful marker for subsequent arrhythmic events.     

Beat-to-Beat Repolarization Lability Identifies Patients at Risk for Sudden Cardiac Death

QT Interval Variability and Sudden Death. Introduction : Recent studies have implicated repolarization lability in the genesis of malignant ventricular arrhythmias. However, few data exist on assessment of temporal QT interval variability and its relation to arrhythmogenesis. We tested the ability of the QT variability index (QTVI), a measure of beat-to-beat QT interval fluctuations measured on a single ECG lead, to identify patients presenting with malignant ventricular arrhythmias and predict their subsequent occurrences.
Methods and Results : We measured the QTVI in 95 patients presenting for electrophysiologic study (EPS). The ability of the QTVI to identify patients with sudden cardiac death (SCD) or sustained monomorphic ventricular tachycardia (MVT) on presentation and during follow-up of 23.7 ± 14.3 months was compared with spatial QT dispersion, T wave alternans ratio during atrial pacing, MVT inducibility at EPS, signal-averaged ECG, heart rate variability, and ejection fraction. The QTVI was higher in patients with heart disease than in controls (-0.7 ± 0.7 vs −1.1 ± 0.5, P < 0.05), and higher in patients presenting with SCD than in other patients with heart disease (0.0 ± 0.6 vs −0.8 ± 0.5, P < 0.05). The QTVI was the only clinical variable that identified patients who presented with SCD ( P = 0.004, odds ratio = 12.5) on stepwise, logistic multiple regression. Fourteen patients had arrhythmic events during follow-up. In a Kaplan-Meier analysis of arrhythmic events, QTVI ≥ 0.1 was a discriminator for higher risk of arrhythmic events ( P < 0.05).
Conclusions : (1) This noninvasive measure of temporal repolarization lability identified patients with SCD and predicted arrhythmia-free survival. (2) Further studies are needed to determine the mechanisms that mediate beat-to-beat QT interval variability.     

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.     

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.