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.     

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.     

Dynamic Relationship Between the Q-aT Interval and Heart Rate in Patients with Long QT Syndrome During 24-Hour Holter ECG Monitoring

The purpose of this study was to investigate the dynamic relationship between heart rate and the Q-aT interval (the interval from the Q wave to the T wave apex) in patients with long QT syndrome. The QT to heart rate relation is useful for evaluating abnormalities of the ventricular repolarization, but its clinical application to the long QT syndrome requires accurate computer aided measurement of the QT interval and the sampling of a large number of beats. Therefore, the Q-aT interval was used on the basis of some reports that the heart rate dependency of the QT interval was concentrated in the Q-aT interval. Recent advances in the computer technology have allowed analysis of the relationship between the Q-aT and RR intervals on Holter ECG recordings. However, in addition to a prolonged QT interval, most patients with long QT syndrome have bizarre and variable T waves and the influence of this T wave morphology on the Q-aT to heart rate relation has not been clarified. We investigated the dynamic relationship between the Q-aT interval and heart rate in 10 patients with long QT syndrome and 11 control subjects using our original computer algorithm for the analysis of 24-hour Holter ECG recordings. The patients showed morphological T wave changes associated with heart rate changes during Holter recordings and these affected the Q-aT interval. The patients showed the following characteristics in the relationship between the major T wave peak and the RR interval: (1) a modestly decreased correlation between Q-aT and RR than in the control subjects (a median r value of 0.87 vs 0.93; P = 0.001); and (2) a steeper Q-aT/RR slope than in controls (a median slope of 0.24 vs 0.16; P < 0.05). Abnormal and variable T wave morphology in the long QT patients was closely related to a modestly decreased correlation between Q-aT and RR than in the control subjects. The steep Q-aT/RR slope might reflect unstable repolarization of the ventricle, which could act as a substrate for ventricular tachyarrhythmias.     

Inter- and Intraday Variability in Major Electrocardiogram Intervals and Amplitudes in Healthy Men and Women

DOTA, C.D., et al. : Inter- and Intraday Variability in Major Electrocardiogram Intervals and Amplitudes in Healthy Men and Women. The ECG may vary during the day (intra-day), and between days (interday), for the same subject. Variability in ECG characteristic measurements between different investigators is well documented and is often large. During days 1–6 of each placebo period of a two-way crossover Phase I study, digital ECGs were recorded at about 8 and 12 am in 16 healthy volunteers (8 men, 8 women). Two observers independently analyzed leads V₂ and V₆ using EClysis software. The durations and amplitudes of major ECG waves and the intervals between major electrocardiographic events were analyzed in a mixed model ANOVA, in which subject, observer, time, and day were treated as random factors. The influence of various corrections for heart rate on the variability of QT intervals was investigated. The difference among subjects explained between 44–81% of the total variability in ECG intervals and amplitudes. Overall, inter- and intraday variability was not statistically significant for any variable. The individualized exponential correction of the QT interval for heart rate eliminated the QT interval dependence on the RR interval in all subjects. Changes in T wave morphology and shortening of the QT interval from morning to noon were observed in ten subjects. The interobserver variability was close to zero   (SD < 0.005 ms)   for all variables except the PQ interval (SD 1.4 ms). The various sources of variability in determinations of ECG wave characteristics should be considered in the design of clinical studies. The use of EClysis software for ECG measurements in this study made the results highly observer independent. (PACE 2003; 26[Pt. II]:361–366)     

Precision of QT interval measurement by advanced electrocardiographic equipment

The costs of clinical investigations of drug-induced QT interval prolongation are mainly related to manual processing of electrocardiographic (ECG) recordings. Potentially, however, these costs can be decreased by automatic ECG measurement. To investigate the improvements in measurement accuracy of the modern ECG equipment, this study investigated QT interval measurement by the "old" and "new" versions of the 12SL ECG algorithm by GE Healthcare (Milwaukee, WI, USA) and compared the results to carefully validated and reconciled manual measurements. The investigation used two sets (A and B) of ECG recordings that originated from large clinical studies. Sets A and B consisted of 15,194, and 29,866 10-second ECG recordings, respectively. All the recordings were obtained with GE Healthcare recorders and were available in digital format compatible with ECG processing software by GE Healthcare. The two sets of recordings differed significantly in ECG quality with set B being substantially more noise polluted. Compared to careful manual QT interval readings in recording set A, the errors of the automatic QT interval measurement were (mean +/- SD) +3.95 +/- 5.50 ms, and +0.51 +/- 12.41 ms for the "new" and "old" 12SL algorithm, respectively. In recording set B, these numbers were +2.41 +/- 9.47 ms, and -0.17 +/- 14.89 ms, respectively (both differences were highly statistically significant, P < 0.000001). In recording set A, 95.9% and 76.6% of ECGs were measured automatically within 10 ms of the manual measurement by the "new" and "old" versions of the 12SL algorithm, In recording set B, these numbers were 83.9% and 59.5%. The errors made by the "new" and "old" version of 12SL algorithm were practically independent each of the other (correlation coefficients of 0.031 and 0.281 in recording sets A and B, respectively). The study shows that (a) compared to the "old" version of the 12SL algorithm, the QT interval measurement by the "new" version implemented in the most recent ECG equipment by GE Healthcare is significantly better, and (b) the precision of automatic measurement by the 12SL algorithm is substantially dependent on the quality of processed ECG recordings. The improved accuracy of the "new" 12SL algorithm makes it feasible to use modern ECG equipment without any manual intervention in selected parts of drug-development program.     

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.     

Effects of adrenaline and potassium on QTc interval and QT dispersion in man

BACKGROUND: Hypoglycaemia alters cardiac repolarization acutely, with increases in rate-corrected QT (QTc) interval and QT dispersion (QTd) on the electrocardiogram (ECG); such changes are related to the counterregulatory sympatho-adrenal response. Adrenaline produces both QTc lengthening and a fall in plasma potassium (K+) when infused into healthy volunteers. Hypokalaemia prolongs cardiac repolarization independently however, and therefore our aim was to determine whether adrenaline-induced repolarization changes are mediated directly or through lowered plasma K+. MATERIALS AND METHODS: Ten healthy males were studied on two occasions. At both visits they received similar l-adrenaline infusions but on one occasion potassium was also administered; infusion rates were adjusted to maintain circulating K+ at baseline. The QTc interval, QTd, peripheral physiological responses and plasma adrenaline and potassium concentrations were measured during both visits. RESULTS: The QTc interval and QTd increased both with and without potassium clamping. Without K+ replacement, mean (SE) QTc lengthened from 378 (5) ms to a final maximum value of 433 (10) ms, and QTd increased from 36 (5) ms to 69 (8) ms (both P < 0.001). During K+ replacement, QTc duration at baseline and study end was 385 (7) ms and 423 (11) ms, respectively (P < 0.001), and QTd 38 was (4) ms and 63 (5) ms (P = 0.001). CONCLUSIONS: These data suggest that disturbed cardiac repolarization as a result of increases in circulating adrenaline occurs independently of extracellular potassium. A direct effect of adrenaline upon the myocardium appears the most likely mechanism.     

Arrhythmic risk stratification after myocardial infarction using ambulatory electrocardiography signal averaging

Ambulatory ECG had been proposed to examine the amplified high resolution signal-averaged electrocardiogram (SAECG). Clinical investigations are required to confirm the predictive value of such a high resolution technique in arrhythmic risk stratification. The prognostic value of ambulatory Holter SAECG was evaluated in 108 postinfarction patients for the purpose of predicting the occurrence of serious arrhythmic (SARR) events (sudden cardiac death [SCD], VT, or VF) in comparison with classical real-time SAECG. During the 42+/-8 months of follow-up, the sudden cardiac death mortality was 4.6% (five deaths), six (5.6%) patients had VT, and one (0.9%) VF. QRSd was found to be the most predictive parameter using ROC curves analysis for SAAR + outcome (W = 0.833 and W = 0.803 for 25-250 Hz and 40-250 Hz filters, respectively) followed by RMS (W = 0.766 and W = 0.721) and LAS (W = 0.759, W = 0.709) (all P < 0.01). Abnormal Holter SAECG for 25 and 40-Hz LP filter were significant predictors of SARR+ by log-rank test (P < 0.01, P < 0.05, respectively). This study confirms that valuable prognostic information can be obtained from the ambulatory high resolution ECG technique and that Holter SAECG may predict arrhythmic risk in a postinfarction population.     

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.     

Influence of long‐term oxygen therapy on heart rate and QT time‐series in hypoxic patients with chronic obstructive pulmonary disease

Background: There is increasing interest in the cardiovascular pathology independently associated with chronic obstructive pulmonary disease (COPD). We examined the influence of long‐term oxygen therapy (LTOT) on heart rate (RR) and QT time‐series in COPD. Methods: Ten hypoxic stable COPD patients underwent Holter ECG monitoring for 24 h and physical activity/energy expenditure monitoring for 5 days before and after LTOT. Variability of RR and QT time‐series was quantified using standard statistics and their structural (correlation/scaling) properties were assessed using multifractal analysis. Pre‐ and post‐LTOT cardiac/activity parameters were compared to examine the influence of oxygen therapy and circadian variation. Results: PaO₂ increased (P = 0·0004) whilst PaCO₂ was unchanged (P = 0·56) following LTOT. Activity/energy expenditure estimates were also unchanged following LTOT (P = 0·64–0·99), but RR variability was increased during the morning (P < 0·05) and night (P < 0·1, trend only). Multifractality of RR and QT time‐series was not significantly changed following LTOT, although QT multifractality showed some time‐dependent fluctuations. Trends in RR and QT time‐series over 24‐h were similar pre‐ and post‐LTOT, indicating a generally normal circadian response. Conclusions: An increase in HRV following LTOT (but notably in the absence of altered activity levels) provides tentative evidence that LTOT has a direct effect on heart rate control in COPD. This beneficial influence was expressed mainly during the morning, and the relevance of this diurnal variation in response requires further investigation. It was also confirmed that both RR and (to a lesser degree) QT time‐series in COPD have a multifractal structure, and this is not affected appreciably by LTOT.     

Normal values for QT intervals in ECG during ramp exercise on bicycle

Summary. The relation between QT interval and heart rate during ramp exercise tests on a bicycle was investigated in 37 healthy individuals (21 women) without regular medication and with a normal thallium-201 exercise scintigram (mean age 52–9 ± 8–3, range 38–68). The test started at 20 W and the load increased by 10 W min^-1. A 12-lead ECG was recorded twice every min and mean complexes (during a 15 s period) were calculated by computer. At rest the QT interval (in s) corrected for heart rate (QT_C) for women and men was 0–408 ± 0–004 and 0–399 ± 0–005, respectively, P > 0–05). During exercise there was no difference in QT interval between women and men or between younger (<50 years) and older (> 50 years) individuals. A straight line was used to describe the relation between QT interval and heart rate (beats min^-1; QT = 0–459–12–3xlO^-4*HR). A 95% prediction interval around the regression line was determined using a non-parametric statistical method. When QT_C was calculated using Bazett's formula with a cut-off value of QT_c= 0–46, 19 individuals (11 women) had a prolonged QT interval during exercise. It is concluded that the relation between QT interval and heart rate can during exercise be described by a straight line for normal individuals. It is not valid to use Bazett's formula for correction of QT intervals during ramp exercise tests.     

Literature review and pilot studies of the effect of QT correction formulas on reported beta2-agonist-induced QTc prolongation

BACKGROUND: Drugs that stimulate the beta2-adrenergic receptor have been reported to prolong the QT interval corrected for heart rate (QTc interval), a potential mechanism for cardiac toxicity. OBJECTIVE: This study evaluated whether beta2-adrenergic agonist drugs prolong the QTc interval when different correction formulas for the effect of heart rate are used. METHODS: Healthy subjects of both sexes aged 19 to 33 years were recruited with advertisements. In pilot studies, subjects took a preparation containing the beta2-agonist ephedrine, or they participated in a postural study of the effect of endogenous beta-agonists. The study-drug group took 3 pills of the ephedra preparation per day for 2 days and then 6 pills per day for the next 2 days. Electrocardiograms (ECGs) were recorded before and at 1, 3, and 82 hours after the first study-drug dose and both before and after standing in the standing-up group. QT intervals obtained by automatic measurement were corrected for heart rate with 3 formulas: Bazett (QTc[B]), Framingham (QTc[F]), and Fridericia (QTc[Fr]). For the literature review, PubMed was searched using the search terms beta2-agonist drugs, QT, QTc, EKG, ECG, or electrocardiogram for studies that reported prolongation of the QTc by beta2-agonist drugs. We analyzed the method by which 11 different studies corrected QT interval for heart rate after the use of formoterol, salmeterol, terbutaline, salbutamol, and fenoterol. RESULTS: The ephedra study included 20 healthy subjects (35% men; mean [SD] age, 25 [4] years). Two hours after the last dose, QTc[B] had increased significantly from baseline by 19 ms (P=0.02). QTc[F] and QTc[Fr] did not change significantly. In the postural study, 19 healthy subjects (68% men; mean [SD] age, 32 [8] years) stood up and QTc[B] increased by a mean (SD) of 8 (15) ms (P=0.03). In these subjects, the QTc[B]/RR regression slope was significantly different from 0 (r=0.60, P=0.002), and the Bazett formula did not eliminate the dependence of QTc on heart rate. However, QTc[F] and QTc[Fr] did not change significantly, meaning that these formulas eliminated the dependence of QTc on heart rate. Eleven publications reported prolongation of QTc[B] by 5 beta2-adrenergic agonists for asthma. The change in QTc[B] interval from these publications was still dependent on the change in heart rate (r=0.63, P=0.004), but this dependence was eliminated after using QTc[F] and QTc[Fr]. The increase in QTc[B] would have been up to 30 ms less if QTc[F] or QTc[Fr] had been reported instead. CONCLUSIONS: The Bazett correction is the one typically reported by computerized ECG machines and the medical literature. This review suggests that QTc[B] may overestimate QTc when heart rate increases. Because the beta2-adrenergic agonist drugs increase heart rate, a systematic bias may have implicated these drugs in prolongation of cardiac repolarization. Prospective, large studies with a placebo and active control group are needed to evaluate the effect of beta2 agonists on QTc using formulas other than Bazett.     

Severe QTc prolongation under mild hypothermia treatment and incidence of arrhythmias after cardiac arrest--a prospective study in 34 survivors with continuous Holter ECG

Background

Mild hypothermia treatment (32-34 °C) in survivors after cardiac arrest (CA) is clearly recommended by the current guidelines. The effects of cooling procedure towards QT interval have not been evaluated so far outside of case series. In a prospective study 34 consecutive survivors after cardiac arrest were continuously monitored with Holter ECG over the first 48 h.

Patients and methods

A total of 34 patients were analysed and received mild therapeutic hypothermia treatment (MTH) according to the current guidelines and irrespective of the initial rhythm. At admission to hospital and in the field in case of OHCA, a 12-lead ECG was performed in all patients.

Results

During cooling the incidence of ventricular tachycardia was low (8.8%) and in none of the patients Torsade de pointes occurred. The QTc interval was within normal range at first patient contact with EMS in the field (440.00 ms; IQR 424.25-476.75; n = 17) but during hypothermia treatment the QTc interval was significantly prolonged at 33 °C after 24 h of cooling (564.47 ms; IQR 512.41-590.00; p = 0.0001; n = 34) and decreased after end of hypothermia to baseline levels (476.74 ms; 448.71-494.97; p = 0.15).

Conclusion

The QTc interval was found to be significantly prolonged during MTH treatment, and some severe prolongations >670 ms were observed, without a higher incidence of life-threatening arrhythmias, especially no Torsade des pointes were detected. However, routine and frequent ECG recording with respect to the QTc interval should become part of any hypothermia standard operation protocol and should be recommended by official guidelines.     

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.     

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.     

Reverse Electrical Remodeling of the Ventricles Following Successful Restoration of Sinus Rhythm in Patients with Persistent Atrial Fibrillation

Background: Atrial fibrillation (AF) has been shown to be associated with reduced survival and increased ventricular arrhythmogenesis. The purpose of this study was to assess the effects of AF with adequate rate control on the electrophysiologic properties of the ventricles. We hypothesized that AF results in increased ventricular arrhythmogenic risk and that reverse remodeling occurs postsuccessful cardioversion. Methods: In nine patients with persistent AF, we recorded 12‐lead electrocardiograms (ECGs) and 1‐hour high‐resolution Holter ECGs (H12+, Mortara Instrument, Inc. Milwaukee, WI, USA; recorders [1000 sps] immediately following cardioversion (Day 1) and after 30 days of maintaining sinus rhythm (Day 30). We measured QTc, QT dispersion, and calculated estimates of mean ventricular action potential duration (RT), diastolic interval (DI), T‐wave width (TW), T‐wave peak‐to‐end, and their respective scatter on Day 1 and Day 30. Maintenance of normal sinus rhythm was confirmed with a weekly trans‐telephonic ECG transmission. Results: The average QTc interval decreased from 449 ± 28 ms on Day 1 to 422 ± 36 ms on Day 30 (P = 0.04). There was no significant difference in the average QT dispersion. A significant decrease was also noted in DI and TW scatter at Day 30 when compared with Day 1 (P = 0.03 and 0.04, respectively). A decrease in RT scatter was also noted albeit not statistically significant (P = 0.07). Conclusion: Our results suggest a greater propensity to ventricular arrhythmogenesis in the immediate period following restoration of sinus rhythm and reverse electrical remodeling of the ventricles during the first month after successful maintenance of sinus rhythm. (PACE 2010; 33:1198–1202)     

Examination of ECG characteristics of patients admitted to emergency department with conversive attack

ObjectiveConversion disorder is defined as a disorder with one or more neurological symptoms that accompany psychological conflict, suggesting a physical disorder. It has been shown that patients with conversion disorder have an imbalance in the autonomic nervous system. There are only a limited number of studies that have examined how conversion disorder is related with surface ECG parameters. The present study aimed to investigate the effects of conversion disorder on the surface ECG parameters of patients with conversion disorder admitted to the emergency department.MethodsThis cross-sectional case-control study included 98 patients who were admitted to the emergency department and diagnosed with conversion disorder and 56 healthy volunteers. All patients underwent 12-derivation ECG. PR interval, P wave dispersion, duration of QRS complex, QT interval, QTc interval, frontal QRS-T angle values were calculated for all individuals.ResultsWhen compared with the control group, the conversion disorder group revealed a significant difference in terms of PWD [60 (40–80) vs. 40 (40–60) P = 0.01], QT [385 (364–410) vs. 378 (354–394), P = 0.048], QTc [420 (405–430) vs. 406 (397–429), P = 0.039], and frontal QRS-T angle [25 (15–33) vs. 20 (8–35), P = 0.018]. In the multivariate linear regression analysis, conversion disorder was found to be an independent predictor for both PWD (β = 0.196, P = 0.014) and frontal QRS-T angle (β = 0.258, P = 0.011).ConclusionThis study is the first to show that conversion disorder significantly increases QT, QTc, P wave dispersion, and frontal QRS-T angle.     

Late potentials and QT dispersion after high‐dose chemotherapy in patients with non‐Hodgkin lymphoma

The most common cardiotoxic effects of high‐dose cyclophosphamide (CY) are electrocardiographic changes and transient arrhythmias. Therefore, we prospectively assessed serial electrocardiogram (ECG) and signal‐averaged electrocardiogram (SAECG) recordings in 30 adult patients with non‐Hodgkin lymphoma (NHL) receiving high‐dose CY as part of high‐dose chemotherapy (HDT) regimen. All patients were treated with anthracyclines earlier. Heart‐rate‐corrected QT interval and QT dispersion (QTc and QTc dispersion) were measured from ECG. QRS duration and late potentials (LPs) were analysed from SAECG. Both ECG and SAECG were recorded 1 day (d) prior to HDT (d?7) at baseline, and 1 day (d?2), 7 days (d+7), 12 days (+12) and 3 months (m+3) after HDT. Stem cells were infused on day 0 (d0). Cardiac systolic and diastolic function were assessed on (d?7), (d+12) and (m+3) by radionuclide ventriculography. At baseline, four patients presented with LPs. Cardiac systolic function decreased significantly (53 ± 2; 49 ± 2%, P = 0·009 versus baseline), whilst no patient developed acute heart failure. QRS duration prolonged and RMS₄₀ reduced significantly versus baseline (104 ± 3; 107 ± 3 ms, P = 0·003; 41 ± 4; 38 ± 3 μV, P = 0·03), and six patients (21%) presented with LPs after CY treatment. Both QTc interval and QTc dispersion increased versus baseline (402 ± 5; 423 ± 5 ms, P<0·001; 32 ± 2; 44 ± 3 ms, P = 0·012), and six patients (20%) developed abnormal QT dispersion. In conclusion, high‐dose CY causes subclinical and transient electrical instability reflected by occurrence of LPs as well as increased QTc interval and QT dispersion. Thus, longer follow‐up is required to confirm the meaning of these adverse effects on cardiac function and quality of life.     

Holter monitoring in the evaluation of congenital long QT syndrome

Background: Long QT syndrome (LQTS) is a potentially lethal cardiac channelopathy that affects one in 2,000 persons; causes syncope, seizures, and sudden death; and is both under‐ and overdiagnosed. LQTS diagnostic miscues have stemmed from assessment of ambulatory electrocardiographic monitoring (Holter) results. Objective: We sought to determine the prevalence of positive Holter monitor tests and its diagnostic significance in evaluating LQTS. Methods: We performed an institutional review board‐approved review of patients evaluated in our LQTS clinic from 2000 to 2009 who had Holter testing during their evaluation. Included patients (N = 473) were diagnosed with LQTS or dismissed as otherwise normal. Holters classified as positive had an episode of nonsustained ventricular tachycardia, supraventricular tachycardia, ≥4 couplets/day, ≥10 premature ventricular contractions/hour, or >5‐second sinus pause. Results: Among 209 patients dismissed as normal (128 females, average age 21 ± 15 years, average QTc 424 ± 39 ms), 27 (12.9%) had a positive Holter, while among 264 patients with LQTS (149 females, average age 22 ± 16 years, average QTc 472 ± 41 ms), 30 (11.3%) had a positive Holter (P = NS). Patients with LQT3 (5/23, 21%) and genotype‐negative LQTS (5/19, 26%) had a higher rate of positive Holter testing compared to LQT1 patients (7/124, 6%, P < 0.03). Among the 473 Holters, only one (0.2%) impacted clinical decision making. Conclusion: Routine Holter monitoring appears to be of minimal clinical utility from a diagnostic and prognostic perspective in evaluating LQTS, and may not be cost effective. Whether Holter monitoring aids in therapeutic decisions such as dosing or whether ambulatory QTc measurements, provided by some newer devices, might help in the diagnostic evaluation warrants further scrutiny. (PACE 2011; 34:1100–1104)     

Sudden cardiac death with left main coronary artery occlusion in a patient whose presenting ECG suggested Brugada syndrome

This article describes a patient who died suddenly during Holter ECG monitoring. A ventricular premature systole with an extremely short coupling interval of 240 ms was immediately followed by torsades de pointes, soon degenerating into ventricular fibrillation. Retrospective survey of the patient's medical records revealed an incomplete right bundle branch block (iRBBB) configuration with fluctuating saddle back-type ST elevation in leads V1 and V2, these suggesting Brugada syndrome. Autopsy showed complete thrombotic occlusion of the left main coronary artery.