Q-onset and T-end delineation: assessment of the performance of an automated method with the use of a reference database

The aim of the study is to assess the performance of an automated method for Q-onset and T-end delineation, as well as QT measurement with the use of a 'gold standard' of a manually created reference database. The data to be used comprise 548 recordings of the PTB Diagnostic ECG Database. The ECG signals are preprocessed, suppressing power-line interference, electromyographic noise and baseline drift according to our previously published investigations, guaranteeing accurate Q-onset and T-end locality preservation. Our method for automatic detection of Q-onset and T-end is based on the minimum value of the angle between two segments having a common mid point and equal lengths of 10 ms. The minimum of the angle is searched in defined time intervals delimited separately for the Q-onset and T-end. All measurements are performed on lead II only. Mean +/- standard deviations are obtained for 95% of the recordings: -0.08 +/- 2.71 for Q-onset, 5.10 +/- 9.22 for T-end and 4.40 +/- 9.93 for QT interval, as well as for 100% of the recordings: 0.46 +/- 4.84 for Q-onset, 1.28 +/- 16.75 for T-end and 0.83 +/- 16.67 for QT interval.     

QT dispersion in 120 electrocardiographic leads in patients with structural heart disease

The clinical significance of QT dispersion (QTd) measured in 12-lead ECGs is controversial. The aim of this study was to clarify factors that determine the QTd and its measurement errors in different lead arrays in patients with structural heart disease. Two blinded observers measured QT intervals on a computer screen from 120-channel ECG recordings in a retrospective set of 257 patients, comprising a group of 121 myocardial infarction (MI) survivors without ventricular tachyarrhythmia during a 6-month follow-up and a group of 136 survivors of ventricular tachyarrhythmia/fibrillation. QTd did not differ in patients with and without ventricular tachyarrhythmia/fibrillation. Eleven ventricular tachyarrhythmia/fibrillation survivors without structural heart disease had the lowest QTd (P < or = 0.02). The strongest factor determining QTd and the magnitude of its measurement error was the lead array (P = 0.0001). Measurement errors had two components. The smallest relative errors were in the total body surface mapping array with one component related to interobserver reproducibility (9.1 +/- 7.6%), and the other component related to accuracy of measurement of the QT interval (36 +/- 16%). The authors estimated that a difference of QTd of at least 50 ms between study groups is required in a 12-lead ECG to draw any conclusions from the studies. In patients with structural heart disease, QTd from limited arrays of ECG leads was not a reliable measure. It correlated with the presence of structural heart disease, but not with arrhythmogenicity. An array consisting of ECG leads covering the entire chest allowed better reproducibility and measurement accuracy of QTd.     

Clinical assessment of drug-induced QT prolongation in association with heart rate changes

BACKGROUND: The formulas for heart rate (HR) correction of QT interval have been shown to overcorrect or undercorrect this interval with changes in HR. A Holter-monitoring method avoiding the need for any correction formulas is proposed as a means to assess drug-induced QT interval changes. METHODS: A thorough QT study included 2 single doses of the alpha1-adrenergic receptor blocker alfuzosin, placebo, and a QT-positive control arm (moxifloxacin) in 48 healthy subjects. Bazett, Fridericia, population-specific (QTcN), and subject-specific (QTcNi) correction formulas were applied to 12-lead electrocardio-graphic recording data. QT1000 (QT at RR = 1000 ms), QT largest bin (at the largest sample size bin), and QT average (average QT of all RR bins) were obtained from Holter recordings by use of custom software to perform rate-independent QT analysis. RESULTS: The 3 Holter end points provided similar results, as follows: Moxifloxacin-induced QT prolongation was 7.0 ms (95% confidence interval [CI], 4.4-9.6 ms) for QT1000, 6.9 ms (95% CI, 4.8-9.1 ms) for QT largest bin, and 6.6 ms (95% CI, 4.6-8.6 ms) for QT average. At the therapeutic dose (10 mg), alfuzosin did not induce significant change in the QT. The 40-mg dose of alfuzosin increased HR by 3.7 beats/min and induced a small QT1000 increase of 2.9 ms (95% CI, 0.3-5.5 ms) (QTcN, +4.6 ms [95% CI, 2.1-7.0 ms]; QTcNi, +4.7 ms [95% CI, 2.2-7.1 ms]). Data corrected by "universal" correction formulas still showed rate dependency and yielded larger QTc change estimations. The Holter method was able to show the drug-induced changes in QT rate dependence. CONCLUSIONS: The direct Holter-based QT interval measurement method provides an alternative approach to measure rate-independent estimates of QT interval changes during treatment.     

Systematic Comparisons of Electrocardiographic Morphology Increase the Precision of QT Interval Measurement

Decreased intrasubject variability of QTc values is needed to increase the power and reduce the size of the so-called thorough QT studies. One source of QTc variability is the lack of systematic measurements when electrocardiograms (ECG) with closely matching morphologies are not measured in an exactly corresponding way. The inaccuracy can be eliminated by postprocessing of QT measurements by ECG pattern matching. This study tested the effects of pattern matching in ECG measurements in two populations of healthy subjects (n = 48 + 56) and in a population of patients with advanced Parkinson's disease (n = 130) in whom both day-time and night-time data were available. Intrasubject QTc variability was measured by intrasubject standard deviations (SD) of QTc values obtained with manual measurements before and after pattern-matching measurement alignments. In each subject, QT values (n = 230–320) in one drug-free long-term ECG recording were evaluated. The pattern-matching adjustment of the QT measurement decreased the intrasubject QTc variability from 5.2 ± 1.0 to 4.5 ± 1.0 ms (P < 10⁻¹⁴) from 6.4 ± 1.7 to 5.5 ± 1.6 ms (P < 10⁻¹⁰) from 5.6 ± 1.5 to 4.6 ± 1.4 ms (P < 10⁻³⁴) and from 6.1 ± 1.9 to 5.0 ± 1.7 ms (P < 10⁻³³), in the two populations of healthy subjects and in the day-time and night-time recordings of Parkinson's disease patients, respectively. Hence, morphological pattern adjustment of QT interval measurements improves the quality of the QT data with substantial practical implications. Reductions in intrasubject QTc variability were reproducibly found in different populations and thus the technology might be recommended for every thorough QT/QTc study. Noticeable reductions of necessary study size are likely achievable in this way.     

Short-and Long-Term Reproducibility of QT, QTc, and QT Dispersion Measurement in Healthy Subjects

The study investigated interobserver and intrasubject reproducibility of QT interval duration and dispersion measured in standard 12-lead ECGs recorded at 25 mm/sec. Twenty-eight healthy volunteers were studied. Each undenvent four ECG recordings, which were performed 1, 7, and 30 days apart. Two independent observers analyzed each ECG record. In each lead with a distinguishable T wave pattern, the RR interval, Q-peak of T interval, and Q-end of T interval were measured using a digitizing board with a 0.1-mm resolution. From each recording the following measures were derived: the maximum, minimum, and mean QT interval; maximum, minimum, and mean heart rate corrected QT interval (QTc); QT and QTc dispersion (the difference between the maximum and minimum QT interval among the 12 leads); and adjusted QT and QTc dispersion (dispersion divided by the square root of the number of leads measured). The interobserver and short-term (1 day) and long-term (1 week and 1 month) reproducibility of individual indices was assessed by computing the relative errors and comparing them by a standard sign test. In addition, the distributions of maximum and minimum QTc values among electrocardiographicleads, and the differences between QT-end and QT-peak based measurements were investigated. The results showed that: (1) the measurement of the QT interval from standard ECG recordings is feasible and not operator dependent (interobserver relative error <4%); (2) the duration of the QT interval in healthy volunteers is stable and its short- and long-term reproducibility is high (intrasubject relative error < 6%); (3) parameters that characterize dispersion of the QT interval in the 12-lead ECG are highly nonreproducible, both between subsequent recording (relative error of 25%–35%) and between observers (relative errar 28%–33%), the reproducibility of QT dispersion is significantly lower than that of QT duration (P < 0.01); and (4) the duration of the entire QT interval correlates only weakly with the duration of the Q-peak of T interval.     

Hysteresis of electrocardiographic depolarization-repolarization intervals during dynamic physical exercise and subsequent recovery

The post-exercise electrocardiographic QT interval is shortened relative to that at similar heart rates during exercise or pre-exercise rest. This lag in QT adaptation to the recovering heart rate is described as "hysteresis". No previous studies have quantified the influence of ECG electrode placement on hysteresis following physical exercise. Six males and six females of similar age, mass and aerobic fitness undertook progressive sub-maximal bicycle exercise. A three-channel ECG was recorded continuously during pre-exercise, exercise and recovery. Beat-to-beat NN (cardiac interval) and QT(a) interval (Q wave onset to T wave apex) data were measured for each sinus heart beat. QT(a)-NN hysteresis was calculated as the difference in QT(a) magnitude at identical heart rates during the rest/exercise and post-exercise recovery periods. There were some significant (p < 0.05) between-channel and between-gender differences in calculated hysteresis values. Hysteresis was generally greatest during the second or third minute post-exercise; ranges of means for all channels were 10.9 +/- 11.7 ms to 25.5 +/- 16.8 ms (males) and 19.1 +/- 10.3 ms to 28.4 +/- 3.0 ms (females). For males only, hysteresis values calculated using channel 1 between 1 and 3 min post-exercise were generally significantly (p < 0.05) different to those between 4 and 10 min. Similar trends were observed in females. QT(a)-NN hysteresis is significantly affected by the locations of the ECG electrodes used to record the surface ECG. These results emphasize the need for standardization of ECG electrode placement in future investigations.     

QT dispersion from body surface ECG does not reflect the spatial dispersion of ventricular repolarization in sheep

The correlation between the QT dispersion on body surface ECG and the dispersion in ventricular repolarization from the cardiac surface was studied in six sheep anesthetized with pentobarbital. The standard 12-lead body surface ECG and multiple ventricular epicardial ECGs were simultaneously recorded. The activation-recovery interval (ARI) was measured from the unipolar epicardial ECGs. The pooled QT dispersion from the six animals was significantly smaller than the pooled ARI dispersion (22.7 +/- 2.6 vs 33.0 +/- 6.9 ms, P < 0.01). There was no correlation between the QT and ARI dispersion. The unipolar epicardial ECGs were then converted into bipolar ECGs and epicardial QT intervals were subsequently acquired from these ECGs. The average value of epicardial QT dispersion from the six animals was similar to that of body surface ECG, but was less than the ARI dispersion (27.5 +/- 6.8 vs 33.0 +/- 6.9, P < 0.01). A good correlation between the epicardial QT dispersion and ARI dispersion was identified (r = 0.84, P < 0.05). In addition, a prolongation in ventricular repolarization, induced by an increase in coronary flow, elicited a pooled ARI dispersion of 62.3 +/- 6.2 ms (n = 6), which was larger than the simultaneously recorded body surface QT dispersion (28.3 +/- 9.8 ms, n = 6, P < 0.01). No correlation between the ARI and QT dispersion was found in the presence of the prolonged ventricular repolarization. In conclusion, QT dispersion from a 12-lead body surface ECG seems to underestimate the spatial dispersion of ventricular repolarization acquired from sheep epicardium.     

Impact of electrocardiogram recording format on QT interval measurement and QT dispersion assessment

The aim of this study was to determine the effect of recording conditions on the operator dependent measures of QT dispersion in patients with known and/or suspected repolarization abnormalities. Among several methods for risk stratification, QT dispersion has been suggested as a simple estimate of repolarization abnormalities. In a cohort of high and low risk patients, different components of the repolarization process were assessed in the 12-lead ECG using three different paper speeds and amplifier gains. To assess measurement error and reproducibility, a straight line was repeatedly measured. The operator error was 0.675 +/- 0.02 mm and the repeatability of the measurement error was 31 +/- 6%. The QT interval was most frequently measurable in V2-V5. Depending on the lead selected for analysis, the incidence of visible U waves was greatest in the precordial leads with high amplifier gain and low paper speed, strongly affecting QT interval measurement. The timing of the onset of the QRS complex (QRS onset dispersion) or offset of the T wave was strongly dependent on the paper speed. Paper speed, but not amplifier gain, had a significant shortening effect on the measurement of the maximum QT interval. As QT interval measurement in each ECG lead incorporates QRS onset and T wave offset (depending on the number of visible U waves), the dispersion of each of these parameters significantly affected QT dispersion. Thus, QT dispersion appears to reflect merely the presence of more complex repolarization patterns in patients at risk of arrhythmias.     

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.     

Effect of epirubicin-based chemotherapy and dexrazoxane supplementation on QT dispersion in non-Hodgkin lymphoma patients

BACKGROUND AND OBJECTIVE: Aim of the present study was to assess the effect of epirubicin-based chemotherapy on QT interval dispersion in patients with aggressive non-Hodgkin lymphoma (NHL), and the effect of dexrazoxane supplementation. Prolongation of QT dispersion may not only represent a sensitive tool in identifying the first sign of anthracycline-induced cardiotoxicity, but it may serve also in identifying patients who are at risk of arrhythmic events. METHODS: Twenty untreated patients, 相似文献   

Dynamic Beat-to-Beat QT-RR Relationship During Physiotherapy Effort in Elderly Patients Without Primary Heart Disease

The ECGs from 18 patients hospitalized in a rehabilitation setting, following surgery for hip fracture, were examined to characterize the dynamic behavior of uncorrected QT interval in relation to changing RR interval during physiotherapy effort. ECG waveforms were analyzed to extract beat-to-beat QT and RR intervals using a computerized ECG Analyzer (CEA-1100). The method of defining the QT and RR intervals is based on performing multiple cross-correlations that enable rejection of artifacts from the analysis. The relationship between the RR and QT intervals was found using the following general formula QTi = cRRi-1b. Linear regression was performed on the logarithms of QT and RR measurements obtained to estimate the constant (a = log c) and the slope (b) values, reflecting the dynamic change of QT during physiotherapy effort. Having these two values, the dynamic QT extrapolated to a heart period of 1 second (QTcd) was calculated. The results were compared to the conventional corrected static QT according to the Bazzet formula (QTcs). The mean values of constants (a = log c) and slopes (b) over all patients were found to be 1.61 +/- 0.23 and 0.33 +/- 0.08, respectively, giving a QT (ms) heart-period (ms) dynamic relation of QTi = 41 x RR(i-1)0.33. The correlation between the dynamic QT and the static QT intervals was not significant. The mean values of the QTcd and QTcs intervals were significantly different (392 +/- 25 ms vs 434 +/- 28 ms; P < 0.0001). This dynamic measurement method of QT intervals may provide additional information on normal and abnormal cardiac repolarization in health and disease, helping in the diagnosis of cardiac disorders and arrhythmia risk.     

Measurement of high resolution ECG QT interval during controlled euglycaemia and hypoglycaemia

During hypoglycaemia, typically there is a change in the surface ECG characterized by a flattened and prolonged T wave, often accompanied by a fused U wave. The QT interval is a useful parameter for quantifying the ECG morphology. However, reliable measurement of QT is not straightforward, particularly for hypoglycaemic ECG morphology. The objective of this study was to compare the ability of two methods of QT measurement to distinguish between ECGs recorded during euglycaemia and hypoglycaemia. The first method involves manually setting the intersection of the isoelectric line and the T wave or, where this is not possible, the nadir between the T and U wave. The second method is semi-automatic and fits a tangent to the point of maximum gradient on the downward slope of the T wave. Two independent observers used both methods to measure the QT for high resolution ECG data recorded during a study of 17 non-diabetic subjects undergoing controlled euglycaemia and hypoglycaemia. Using the mean results of the two observers, the mean +/- SD increase in heart rate corrected QT, QTc, for ECGs recorded during euglycaemia and hypoglycaemia was 32 +/- 25 ms for the non-tangent method and 60 +/- 24 ms for the tangent method. Therefore, the tangent method provides greater distinction between ECGs recorded during euglycaemia and hypoglycaemia than the non-tangent method. A potential clinical application could be the non-invasive detection of impending hypoglycaemia at night, which would be of significant benefit to adults and young children with diabetes.     

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.     

Isoproterenol exacerbates a long QT phenotype in Kcnq1-deficient neonatal mice: possible roles for human-like Kcnq1 isoform 1 and slow delayed rectifier K+ current

To determine whether the neonatal mouse can serve as a useful model for studying the molecular pharmacological basis of Long QT Syndrome Type 1 (LQT1), which has been linked to mutations in the human KCNQ1 gene, we measured QT intervals from electrocardiogram (ECG) recordings of wild-type (WT) and Kcnq1 knockout (KO) neonates before and after injection with the beta-adrenergic receptor agonist, isoproterenol (0.17 mg/kg, i.p.). Modest but significant increases in JT, QT, and rate-corrected QT (QTc) intervals were found in KO neonates relative to WT siblings during baseline ECG assessments (QTc = 57 +/- 3 ms, n = 22 versus 49 +/- 2 ms, n = 28, respectively, p < 0.05). Moreover, JT, QT, and QTc intervals significantly increased following isoproterenol challenge in the KO (p < 0.01) but not the WT group (p = 0.57). Furthermore, whole-cell patch-clamp recordings show that the slow delayed rectifier K+ current (IKs) was absent in KO but present in WT myocytes, where it was strongly enhanced by isoproterenol. This finding was confirmed by showing that the selective IKs inhibitor, L-735,821, blocked IKs and prolonged action potential duration in WT but not KO hearts. These data demonstrate that disruption of the Kcnq1 gene leads to loss of IKs, resulting in a long QT phenotype that is exacerbated by beta-adrenergic stimulation. This phenotype closely reflects that observed in human LQT1 patients, suggesting that the neonatal mouse serves as a valid model for this condition. This idea is further supported by new RNA data showing that there is a high degree of homology (>88% amino acid identity) between the predominant human and mouse cardiac Kcnq1 isoforms.     

New Insight into Repolarization Abnormalities in Patients with Congenital Long QT Syndrome: the Increased Transmural Dispersion of Repoiarization

There is evidence from experimental studies that the time interval from the peak to the end of T-wave reflects the transmural dispersion in repolarization (electrical gradient) between myocardial "layers" (epicardial, M-cells, endocardial). Since Congenital Long QT Syndrome (LQTS) is considered to be classical disease or repolarisation abnormalities, we performed the present study to assess the transmtiral dispersion of repolarization in LQTS patients. The study group consisted of 17 patients: 7 LQTS pts and 10 pts from the control group. In each patient the 24-hour ECG recording was performed on magnetic tape. The interval from the peak to the end of the T-wave (TpTo) was automatically measured by Holter system during every hour as a measure of transmural dispersion of repolarisation. Thereafter the mean TpTo from 24-hours was calculated. In addition the spatial QT dispersion was measured from 12 lead ECG and 3 channel Holter tape as a difference between the shortest and the longest QT interval between leads. The values were compared between groups using the Anova test.
TpTo was 79,6±9,6 ms (72–92 ms) in LQTS group and 62,4±7,5 ms (51–70) in the control group (p< 0.001). In LQTS group TpTo was significantly longer at night hours 72,5±2 when compared to day hours 87,4±8 (p<0.01). The spatial QT dispersion was significantly higher in LQTS patients when compared to control, both in 12-lead standard and Holter ECG.
Congenital long QT syndrome is associated with increase in both transmural and spatial dispersion of repolarization. The extent of prolongation of the terminal portion of QT in patients with congenital long QT syndrome is greater at night sleep hours compared to daily activity.     

Difference in QT Interval Measurement on Ambulatory ECG Compared with Standard ECG

Measurement of the QT interval on standard ECG has diagnostic importance in the congenital long QT syndrome, in pharmacological therapy of arrhythmias, as well as in ischemic heart disease. It has been suggested that QT prolongation on ambulatory ECG (Holter) may have similar importance. To assess agreement between methods, QT interval measurement on standard ECG was compared to that on Holter. Simultaneously obtained ECG and Holter tracings (25 mm/s) of the same complexes in leads V₁ and V₅ were studied in 14 patients (age range 4–36 years). ECG pairs (n = 100, 49 V₁ and 51 V₅) were compared over a range of QT interval from 300–620 ms, as determined with the use of calipers by two observers blinded to pairing relationship. Correlation between methods was high for both observers (observer 1: r[V₁] = 0.872, r[V₅] = 0.973; observer 2: r[V₁] = 0.972, r[V₅] = 0.988), and interobserver variability was small (> 85% of measurements within 20 ms). As compared to ECG, Holter underestimated QT interval in V₁ mean difference (QT [Holter]—QT [ECG]) observer 1 (-23 ms, P < 0.001), observer 2 (-7 ms, P < 0.05), and overestimated QT in V5, mean difference observer 1 (+ 13 ms, P < 0.001), observer 2 (+13 ms, P < 0.001). However, individual variation between methods was wide, as expressed by the difference between individual measurements (95% confidence interval [V₁]: observer 1 [-99 to +53 ms] observer 2 [-47 to +33 ms]; [V₅]: observer 1 [-33 to +59 ms] observer 2 [-17 to +43 ms]). Furthermore, when using the QTA (interval from onset of Q wave to apex of T wave) similar variability was observed. In the assessment of QT interval, potential sources of error of this magnitude could limit the clinical utility of ambulatory monitoring in detecting prolongation of the QT interval for diagnostic purposes.     

Nicotine induces a long QT phenotype in Kcnq1-deficient mouse hearts

We have previously shown that targeted disruption of the mouse Kcnq1 gene produces a long QT phenotype in vivo that requires extracardiac factors for manifestation (Casimiro et al., 2001). In the present study, we explore the hypothesis that autonomic neuroeffector transmission represents the "extra cardiac" stimulus that induces a long QT phenotype in mouse hearts lacking Kcnq1. Using the isolated perfused (Langendorff) mouse heart preparation, we challenged wild-type (Kcnq1+/+) and mutant (Kcnq1-/-) mouse hearts with nicotine, an autonomic stimulant. ECGs were recorded continuously, and QT intervals were compared at baseline and peak nicotine-induced heart rates. No significant differences in QT or any other ECG parameters were observed in Kcnq1+/+ versus Kcnq1-/- hearts at baseline. In the presence of nicotine, however, the JT, QT, and rate-corrected QT (QTc) intervals were significantly prolonged in Kcnq1-/- hearts relative to Kcnq1+/+ hearts (e.g., QTc = 92 +/- 11 ms versus 66 +/- 2 ms, respectively, p < 0.01). Similar findings were obtained when the hearts were challenged with either epinephrine or isoproterenol (0.1 microM each), thereby suggesting that sympathetic stimulation drives the long QT phenotype in Kcnq1-deficient hearts. This idea is supported by in vivo ECG data obtained from unrestrained conscious mice using radiotelemetry recording techniques. Again, no significant ECG differences were observed in Kcnq1-/- versus Kcnq1+/+ mice at baseline, but handling/injection stress led to significant QTc increases in Kcnq1-/- mice relative to wild-type controls (11 +/- 3 versus -1 +/- 1%, respectively, p < 0.05). These data suggest that sympathetic stimulation induces a long QT phenotype in Kcnq1-deficient mouse hearts.     

Effect of a single oral dose of moxifloxacin (400 mg and 800 mg) on ventricular repolarization in healthy subjects

BACKGROUND: Moxifloxacin is a new fluoroquinolone. In vitro studies have suggested that it could prolong ventricular repolarization. The main objective of this study was to measure the actual effect of single oral doses of moxifloxacin on QT interval duration in healthy volunteers. METHODS: Nine men and 9 women participated in a double-blind, randomized, placebo-controlled, crossover study. Each participant received single oral doses (400 mg and 800 mg) of moxifloxacin or placebo. At the time of expected moxifloxacin maximum concentration, several electrocardiographic recordings were obtained at rest and during the course of a submaximal exercise test. QT interval and the corresponding RR interval value were measured within a wide range of RR intervals in each subject. RESULTS: ANOVA showed that both moxifloxacin doses increased mean QT intervals compared with placebo. The mean QT interval duration at RR = 1000 ms was 379 +/- 24 ms during placebo, 394 +/- 33 ms during moxifloxacin 400 mg (P < .05), and 396 +/- 28 ms during moxifloxacin 800 mg (P < .05). Moxifloxacin-induced QT interval prolongation remained significant at all tested heart rates. The increase in QT interval duration relative to placebo remained between 2.3% +/- 2.8% and 4.5% + 3.8% across the range of RR intervals tested. CONCLUSION: Moxifloxacin prolongs QT interval duration. The amplitude of this effect is small, and the risk of moxifloxacin-induced torsades de pointes is expected to be minimal when the drug is administered at the recommended dose of 400 mg/d. However, moxifloxacin should not be used in patients with predisposing factors of torsades de pointes such as electrolyte disturbances and bradycardia or during coadministration of proarrhythmic drugs.     

Digital Holter measurement of QT prolongation in ziprasidone overdose

Objective. QT prolongation is an important complication in drug overdose, particularly with some antidepressants and antipsychotics. There are problems with the accurate measurement of the QT interval and determining for what QT interval patients should be monitored, because of the risk of torsades des pointes (TdP). We report a case of ziprasidone overdose with QT prolongation, demonstrating different methods of measuring the QT interval. Case report. A 47-year-old female presented after taking 1.2 g of ziprasidone and 250 mg of diazepam. She was taking propranolol and venlafaxine therapeutically. She developed bradycardia and QT prolongation (540 msec). She was transferred to a telemetry bed and observed for 48 h until her QT interval returned to normal (460 msec). QT intervals were extracted from (1) 12-lead digital Holter recordings (gold standard); (2) automated measurements on standard electrocardiograms (ECGs); and (3) manual measurements on standard ECGs, and compared on a QT versus time plot. An abnormal QT was determined based on the QT nomogram. Manual QT measurements showed a clear temporal association between ziprasidone overdose and a long QT, consistent with accurate QT measurements using continuous 12-lead Holter recordings with automatic QT measurements. However, standard automated measurements did not indicate an abnormal QT. Conclusions. Manual measurement of the QT interval appeared to be similar to the more accurate measurement of the QT by automated digital Holter recordings and better than standard automated measurements. Manual QT measurements would be more appropriate in clinical assessment of patients.     

Cumulative effect of preceding pacing cycle length on ventricular repolarization after a pause

This study was designed to investigate if the components of the QT interval after a pause are influenced by the preceding pacing cycle length. Ten patients (seven women and three men; age 79 +/- 9 years, means +/- SD) with complete atrioventricular block or sick sinus syndrome whose own heart rate was < 40 beats/min were examined. All patients had already undergone implantation of a permanent pacemaker. Ventricular pacing protocol was performed with simultaneous recording of a 12-lead electrocardiogram. One set of regular stimuli for 30 seconds (S1) with a variable cycle length (1,000, 700, and 400 ms) was followed by a single stimulus (S2) with a fixed coupling interval of 1,500 ms. QT intervals in response to the last S1 (S1-QT) and S2 (S2-QT) were measured. The QT interval was divided into two components, the interval from start of Q wave to the peak of T wave (QaT) and that from the peak to end of T wave (Tae). The S2-QT and S1-QT interval shortened in association with a decrease in the S1S1 interval. The abbreviation of S2-QT interval was not associated with a significant change in the Tae interval. The results demonstrated that the QT interval after a pause shortened by reducing the preceding pacing cycle length. This shortening is probably due to a homogenous abbreviation of action potential duration across the ventricular wall.