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Background: Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with enhanced response to drug-induced QT interval lengthening. We determined the influence of HFpEF on drug-induced lengthening of dispersion of repolarization, a measure of proarrhythmic risk., Methods: We administered intravenous ibutilide 0.003 mg/kg to 10 patients with HFpEF and 10 age- and sex-matched controls without HF. Twelve‑lead electrocardiograms were obtained prior to ibutilide and serially for 8 h post-ibutilide. Tpeak-Tend, a measure of dispersion of ventricular repolarization, and heart rate-corrected J-Tpeak (J-Tpeakc), representing early repolarization, were measured by an investigator blinded to study groups., Results: Baseline (pre-ibutilide) Tpeak-Tend and J-Tpeakc were not significantly different in the HFpEF and control groups. Maximum Tpeak-Tend was longer in the HFpEF group than in the control group (85 ± 10 vs 73 ± 8 ms, p = 0.01). Additionally, % change from baseline in Tpeak-Tend was greater in the HFpEF group [median (IQR) 17 (11) vs 8 (3)%, p = 0.003]. The area under the effect curve from 0 to 8 hours following ibutilide (including the 10-minute infusion) (AUEC 0-8.17 ) for Tpeak-Tend was also larger in the HFpEF group (600 ± 42 vs. 543 ± 49 ms•hr, p = 0.03). Maximum J-Tpeakc, % change from baseline in J-Tpeakc and AUEC 0-8.17 for J-Tpeakc in the two groups were not significantly different., Conclusion: HFpEF is associated with enhanced response to drug-induced increases in dispersion of repolarization., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Long QT syndrome (LQTS) is an inherited arrhythmia disorder characterized by ventricular repolarization abnormalities and a risk of sudden cardiac death. The electrophysiological components generating the high risk of arrhythmias in LQTS are prolonged repolarization, increased dispersion of repolarization, and early afterdepolarizations, which are clinically estimated as QT interval, T-wave peak to T-wave end (TPE) interval, and T2/T1-wave amplitude ratio, respectively. In experimental LQTS type 2 (LQT2) models, β-blockers decrease dispersion of repolarization and prevent early afterdepolarizations. In clinical studies in patients with LQT2 , β-blockers are more effective against exercise-induced than arousal-induced cardiac events., Objectives: The aim of the study was to investigate the effects of β-blocker therapy on repolarization properties in LQT2., Methods: QT and TPE intervals and maximal T2/T1-wave amplitude ratios recorded by 24-hour electrocardiograms before and during β-blocker therapy were evaluated in 25 patients with LQT2., Results: β-Blocker therapy decreased the maximal T2/T1-wave amplitude ratio from 2.9 ± 1.1 to 1.8 ± 0.7 (P < .001), but did not change the pause-induced T2/T1-wave amplitude ratio. Under medication, abrupt maximal TPE intervals were shorter at heart rates of ≥75 beats/min and maximal QT intervals were shorter at a heart rate of 100 beats/min., Conclusion: β-Blockers stabilize ventricular repolarization in LQT2 by reducing electrocardiographic early afterdepolarizations and by reducing abrupt prolongation of electrocardiographic dispersion of repolarization and ventricular repolarization duration at elevated heart rates. The effect of β-blockers on pause-induced electrocardiographic early afterdepolarizations is weak. The findings provide electrocardiographic explanation for the protective effects of β-blockers against exercise-induced cardiac events in LQT2., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Congenital long QT syndrome (LQTS) predisposes affected individuals to ventricular tachycardia/fibrillation (VF/VF), potentially resulting in sudden cardiac death. The T peak -T end interval and the T peak -T end /QT ratio, electrocardiographic markers of dispersion of ventricular repolarization, were proposed for risk stratification but their predictive values in LQTS have been controversial. A systematic review and meta-analysis was conducted to examine the value of T peak -T end intervals and T peak -T end /QT ratios in predicting arrhythmic and mortality outcomes in congenital LQTS., Method: PubMed and Embase databases were searched until 9th May 2017, identifying 199 studies., Results: Five studies on long QT syndrome were included in the final meta-analysis. T peak -T end intervals were longer (mean difference [MD]: 13ms, standard error [SE]: 4ms, P=0.002; I 2 =34%) in congenital LQTS patients with adverse events [syncope, ventricular arrhythmias or sudden cardiac death] compared to LQTS patients without such events. By contrast, T peak -T end /QT ratios were not significantly different between the two groups (MD: 0.02, SE: 0.02, P=0.26; I 2 =0%)., Conclusion: This meta-analysis showed that T peak -T end interval is significant higher in individuals who are at elevated risk of adverse events in congenital LQTS, offering incremental value for risk stratification., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The aim of the study was to differentiate the effect of dispersion of repolarization (DOR) and action potential duration (APD) on T-wave parameters being considered as indices of DOR, namely, Tpeak-Tend interval, T-wave amplitude and T-wave area., Methods: T-wave was simulated in a wide physiological range of DOR and APD using a realistic rabbit model based on experimental data. A simplified mathematical formulation of T-wave formation was conducted., Results: Both the simulations and the mathematical formulation showed that Tpeak-Tend interval and T-wave area are linearly proportional to DOR irrespectively of APD range, while T-wave amplitude is non-linearly proportional to DOR and inversely proportional to the minimal repolarization time, or minimal APD value., Conclusion: Tpeak-Tend interval and T-wave area are the most accurate DOR indices independent of APD. T-wave amplitude can be considered as an index of DOR when the level of APD is taken into account., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The T peak - T end interval (the interval from the peak to the end of the T wave), an electrocardiographic marker reflecting transmural dispersion of repolarization, has been used to predict ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac death in different clinical settings., Objective: This systematic review and meta-analysis evaluated the significance of the T peak - T end interval in predicting arrhythmic and/or mortality end points., Methods: PubMed, Embase, Cochrane Library, and CINAHL Plus databases were searched through November 30, 2016., Results: Of the 854 studies identified initially, 33 observational studies involving 155,856 patients were included in our meta-analysis. T peak - T end interval prolongation (mean cutoff value 103.3 ± 17.4 ms) was a significant predictor of the arrhythmic or mortality outcomes (odds ratio [OR] 1.14; 95% confidence interval [CI] 1.11-1.17; P < .001). When different end points were analyzed, the ORs were as follows: VT/VF, 1.10 (95% CI 1.06-1.13; P < .0001); sudden cardiac death, 1.27 (95% CI 1.17-1.39; P < .0001); cardiovascular death, 1.40 (95% CI 1.19-1.64; P < .0001); and all-cause mortality, 4.56 (95% CI 0.62-33.68; P < .0001). Subgroup analysis for each disease revealed that the risk of VT/VF or death was highest for Brugada syndrome (OR 5.68; 95% CI 1.57-20.53; P < .01), followed by hypertension (OR 1.52; 95% CI 1.26-1.85; P < .0001), heart failure (OR 1.07; 95% CI 1.04-1.11; P < .0001), and ischemic heart disease (OR 1.06; 95% CI 1.02-1.10; P = 0.001)., Conclusion: The T peak - T end interval is a useful risk stratification tool in different diseases and in the general population., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Patients with chronic heart failure are at high risk of sudden cardiac death (SCD). Increased dispersion of repolarization restitution has been associated with SCD, and we hypothesize that this should be reflected in the morphology of the T-wave and its variations with heart rate. The aim of this study is to propose an electrocardiogram (ECG)-based index characterizing T-wave morphology restitution (TMR), and to assess its association with SCD risk in a population of chronic heart failure patients., Methods and Results: Holter ECGs from 651 ambulatory patients with chronic heart failure from the MUSIC (MUerte Súbita en Insuficiencia Cardiaca) study were available for the analysis. TMR was quantified by measuring the morphological variation of the T-wave per RR increment using time-warping metrics, and its predictive power was compared to that of clinical variables such as the left ventricular ejection fraction and other ECG-derived indices, such as T-wave alternans and heart rate variability. TMR was significantly higher in SCD victims than in the rest of patients (median 0.046 versus 0.039, P <0.001). When TMR was dichotomized at TMR=0.040, the SCD rate was significantly higher in the TMR≥0.040 group ( P <0.001). Cox analysis revealed that TMR≥0.040 was strongly associated with SCD, with a hazard ratio of 3.27 ( P <0.001), independently of clinical and ECG-derived variables. No association was found between TMR and pump failure death., Conclusions: This study shows that TMR is specifically associated with SCD in a population of chronic heart failure patients, and it is a better predictor than clinical and ECG-derived variables., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Introduction: In experimental models, spatial dispersion of repolarization (DOR) due to discordant cellular alternans predisposes to ventricular fibrillation. To test the hypothesis that microvolt T-wave alternans (MTWA) in humans causes spatial DOR, we measured Tpeak-Tend interval (Tpe) and Tpe/QT ratio, electrocardiographic indices of spatial DOR., Methods: Mean Tpe and Tpe/QT were compared in ischemic cardiomyopathy patients with positive and negative MTWA studies., Results: MTWA was positive in 12 and negative in 24 patients. Tpe and Tpe/QT were higher in MTWA+ subjects compared to MTWA- subjects during exercise (64.5±6.8 vs. 54.9±8.7ms, p=0.001 and 0.218±0.03 vs. 0.177±0.02, p=0.001) but not at rest., Conclusion: Ischemic cardiomyopathy patients have increased Tpe and Tpe/QT when MTWA is induced during exercise, suggesting that MTWA causes increased spatial DOR in humans. Future studies are needed to determine if Tpe and Tpe/QT during exercise might predict increased risk of SCD alone or in combination with measurement of MTWA., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Objective: Droperidol and ondansetron prolong QT interval, a circumstance that has raised some concerns regarding the possibility of inducing torsades de pointes (TdP). However drug-induced spatial dispersion of ventricular repolarization has been shown to be the principal arrhythmogenic substrate for TdP. The aim of this study is to explore the effects of droperidol and ondansetron on the dispersion of repolarization, measured using the T peak-to-end interval (Tp-e) and Tp-e/QT and Tp-e/RR(1/2) ratios in surgical anesthetized patients., Methods: A randomized, double-blind study carried out on sixty-three adult patients without cardiac disease or factors favoring QT prolongation and undergoing non-cardiac surgery were randomly assigned to the droperidol or ondansetron group. Under propofol anesthesia, a 12-lead EKG was obtained, and 1.25mg droperidol or 4mg ondansetron was injected. Five minutes later, a new 12-lead EKG was recorded. EKG analyses were independently performed by two cardiologists blinded to the state of the traces or group allocation. QT, RR and Tp-e intervals were measured by averaging five successive beats in leadII (QT) or V5 (Tp-e). The mean value for each measurement was calculated for statistical analysis., Results: Thirty-two patients (19 women) received droperidol, and 31 (22 women) ondansetron. Droperidol and ondansetron prolonged the QTcF interval (Fridericia formula) by 6.8 and 7.2ms (mean values) respectively, but neither droperidol nor ondansetron increased the Tp-e interval or Tp-e/QT and Tp-e/RR(1/2) ratios., Conclusion: At antiemetic doses, neither ondansetron (4mg) nor droperidol (1.25mg) increases the dispersion of ventricular repolarization in healthy adult patients anesthetized with propofol., (Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Acquired QT interval prolongation has been linked with malignant ventricular arrhythmias, such as torsade de pointes , in turn predisposing to sudden cardiac death. Increased dispersion of repolarization has been identified as a pro-arrhythmic factor and can be observed as longer Tpeak – Tend interval and higher Tpeak – Tend/QT ratio on the electrocardiogram. However, the values of these repolarization indices for predicting adverse outcomes in this context have not been systematically evaluated. Method: PubMed, Embase and Cochrane Library databases were searched until 14th February 2018, identifying 232 studies. Results: Five studies on acquired QT prolongation met the inclusion criteria and 308 subjects with drug-induced LQTS patients (mean age: 66 ± 18 years old; 46% male) were included in this meta-analysis. Tpeak – Tend intervals were longer [mean difference [MD]: 76 ms, standard error [SE]: 26 ms, P = 0.003; I2 = 98%] and Tpeak – Tend/QT ratios were higher (MD: 0.14, SE: 0.03, P = 0.000; I2 = 29%) in patients with torsade de pointes compared to those without these events. Conclusion: Tpeak – Tend interval and Tpeak – Tend/QT ratio were higher in patients with acquired QT prolongation suffering from torsade de pointes compared to those who did not. These repolarization indices may provide additional predictive value for identifying high-risk individuals. [ABSTRACT FROM AUTHOR]

In the present study we investigated the contribution of ventricular repolarization time (RT) dispersion (the maximal difference in RT) and RT gradients (the differences in RT in apicobasal, anteroposterior and interventricular directions) to T-wave flattening in a setting of experimental diabetes mellitus. In 9 healthy and 11 diabetic (alloxan model) open-chest rabbits, we measured RT in ventricular epicardial electrograms. To specify the contributions of apicobasal, interventricular and anteroposterior RT gradients and RT dispersion to the body surface potentials we determined T-wave voltage differences between modified upper- and lower-chest precordial leads (T-wave amplitude dispersions, TWAD). Expression of RT gradients and RT dispersion in the correspondent TWAD parameters was studied by computer simulations. Diabetic rabbits demonstrated flattened T-waves in precordial leads associated with increased anteroposterior and decreased apicobasal RT gradients (P<0.05) due to RT prolongation at the apex. For diabetics, simulations predicted the preserved T-vector length and altered sagittal and longitudinal TWAD proven by experimental measurements. T-wave flattening in the diabetic rabbits was not due to changes in RT dispersion, but reflected the redistributed ventricular repolarization pattern with prolonged apical repolarization resulting in increased anteroposterior and decreased apicobasal RT gradients. [ABSTRACT FROM AUTHOR]

Background Sudden cardiac death is prevalent in chronic hemodialysis (HD) patients while the dialysis process may have arrhythmogenic potential. We sought to examine the effect of HD on conventional electrocardiographic parameters as well as on novel indexes of repolarization, given that increased spatial dispersion of repolarization is related to ventricular arrhythmias. Methods We recorded clinical, echocardiographic, and laboratory parameters as well as electrocardiographic indexes before and after a single HD session. Specifically, we calculated the QTc interval, the QRS duration, the T peak-to-end (Tpe) interval, and the Tpe/QT ratio. Results The study population consisted of 66 chronic HD patients (mean age: 68.9 ± 11.8 years, 40 males). Heart rate, blood pressure, QRS duration, QTc interval, and QT dispersion did not change significantly after the HD session. However, the Tpe interval and the Tpe/QT ratio increased significantly (80 [65-90] ms vs 85 [77.5-100] ms; P = 0.04, and 0.21 [0.18-0.24] vs 0.25 [0.21-0.28]; P = 0.05, respectively). Correlation analysis and multiple regression analysis failed to show significant associations between the baseline parameters and the baseline values of Tpe and Tpe/QT or between the change of the laboratory parameters during HD and the corresponding change of the Tpe and the Tpe/QT values. No significant arrhythmias were observed during the HD sessions. Conclusions HD induces an increase in novel markers of spatial dispersion of ventricular repolarization. Whether the assessment of these indexes of heterogeneity of repolarization at baseline or their change during HD has a prognostic value with regard to future untoward events, remains to be elucidated. [ABSTRACT FROM AUTHOR]

Cardiac repolarization is prolonged in diabetes mellitus (DM), however the distribution of repolarization durations in diabetic hearts is unknown. We estimated the ventricular repolarization pattern and its relation to the ECG phenomena in diabetic mice. Potential mapping was performed on the anterior ventricular surface in healthy (n=18) and alloxan-induced diabetic (n=12) mice with the 64-electrode array. Activation times, end of repolarization times, and activation-recovery intervals (ARIs) were recorded along with limb lead ECGs. ARIs were shorter in the left as compared to right ventricular leads (P<0.05). The global dispersion of repolarization, interventricular and apicobasal repolarization gradients were greater in DM than in healthy animals (P<0.03). The increased dispersion of repolarization and apicobasal repolarization gradient in DM correlated with the prolonged QTc and Tpeak-Tend intervals, respectively. The increased ventricular repolarization heterogeneity corresponded to the electrocardiographic markers was demonstrated in DM. [ABSTRACT FROM AUTHOR]

Aims Life-threatening arrhythmias are a major problem in chronic heart failure (CHF). The aim of the present study was to investigate the mechanism underlying the low proarrhythmic potential of amiodarone in a model of pacing-induced heart failure. Methods and results Heart failure was induced in 35 female rabbits by rapid ventricular pacing, resulting in a significant decrease of ejection fraction. Thirty-four rabbits were sham-operated. In 17 of 35 CHF-rabbits and 20 of 34 ‘sham’-rabbits, amiodarone (50 mg/kg/day) was fed for 6 weeks. Eight monophasic action potentials and a simultaneously recorded 12-lead electrocardiogram showed prolongation of QT-interval and action potential duration (APD90) in all failing hearts (P< 0.05). Amiodarone pre-treatment led to a prolongation of APD90 (+19 ms) as compared with sham-controlled hearts but showed only a marginal effect on APD90 in failing hearts. Infusion of sotalol (50–100 µM) led to a significant prolongation of APD90 in sham and a further prolongation of APD90 in failing hearts [+55 ms (50 µM); +70 ms (100 µM); P< 0.01 as compared with sham hearts]. Sotalol led to a triangular action potential configuration in sham and failing hearts, whereas amiodarone did not cause triangularization but caused a rapid phase-III repolarization. Moreover, amiodarone did not increase dispersion of repolarization either in sham or in failing hearts. Infusion of sotalol led to a significant increase in dispersion of repolarization in sham (+29 ms) and a further increase in failing hearts (+67 ms; P< 0.05). Conclusion Chronic amiodarone results in a rapid phase-III-repolarization and does not increase dispersion of repolarization. These electrophysiological findings are present in healthy hearts and are preserved in heart failure. This contributes to the low proarrhythmic potential of amiodarone in heart failure. [ABSTRACT FROM AUTHOR]

Background: Cardiac resynchronization therapy (CRT) may be proarrhythmic in some patients. This may be due to the effect of left ventricular (LV) epicardial pacing on ventricular repolarization. The purpose of this study was to evaluate the effect of endocardial versus epicardial LV biventricular pacing on surface electrocardiogram (ECG) parameters that are known markers of arrhythmogenic repolarization. Methods: ECG markers of repolarization (QT dispersion, QTD; T peak to end, Tpeak-end; Tpeak-end dispersion, Tpeak-endD; QTc) were retrospectively measured before and after CRT in seven patients with transseptal LV endocardial leads (TS group), 28 matched patients with coronary sinus (CS) LV leads (CS group), and eight patients with surgical LV epicardial leads (SUR group). All ECGs were scanned and analyzed using digital callipers. Results: Compared to the CS group, the TS group CRT was associated with a significant postpacing reduction in QTD (−45.2 ± 35.6 vs −4.3 ± 43.6 ms, P = 0.03) and Tpeak-end (−24.2 ± 22.1 vs 3.4 ± 26.7 ms, P = 0.02). There was a nonsignificant post-CRT reduction in both Tpeak-endD (−11.3 ± 31.0 vs 2.4 ± 28.9 ms, P = 0.27) and QTc (−50.0 ± 46.4 vs 4.4 ± 70.2 ms, P = 0.06) in the TS versus the CS group. In contrast, there were no differences between the SUR and CS groups in terms of the effect of CRT on these repolarization parameters. Conclusions: CRT with (atrial transseptal) endocardial LV lead placement is associated with repolarization characteristics that are considered to be less arrhythmogenic than those generated by CS (epicardial) LV lead placement. Further work is needed to determine whether these changes translate to a reduction in proarrhythmia. (PACE 2011; 34:1258-1266) [ABSTRACT FROM AUTHOR]

Objectives: We tested the hypothesis that exposure to concentrated ambient particles (CAP) and/or ozone (O3) would increase dispersion of ventricular repolarization. Background: Elevated levels of air pollution are associated with cardiac arrhythmias through mechanisms yet to be elucidated. Methods: Each of 25 volunteers (18 to 50 years of age) had four 2-h exposures to 150 μg/m3 CAP; 120 parts per billion O3; CAP + O3; and filtered air (FA). Exposure-induced changes (Δ = 5-min epochs at end-start) in spatial dispersion of repolarization were determined from continuous 12-lead electrocardiographic recording. Results: Spatial dispersion of repolarization assessed by corrected ΔT-wave peak to T-wave end interval increased significantly for CAP + O3 (0.17 ± 0.03, p < 0.0001) exposure only, remaining significant when factoring FA (CAP + O3 − FA) as control (0.11 ± 0.04, p = 0.013). The influence on repolarization was further verified by a significant increase in ΔQT dispersion (for CAP + O3 compared with FA (5.7 ± 1.4, p = 0.0002). When the low-frequency to high-frequency ratio of heart rate variability (a conventional representation of sympathetic-parasympathetic balances) was included as a covariate, the effect estimate was positive for both corrected ΔT-wave peak to T-wave end interval (p = 0.002) and ΔQT dispersion (p = 0.038). When the high-frequency component (parasympathetic heart rate modulation) was included as a covariate with corrected ΔT-wave peak to T-wave end interval, the effect estimate for high frequency was inverse (p = 0.02). Conclusions: CAP + O3 exposure alters dispersion of ventricular repolarization in part by increasing sympathetic and decreasing parasympathetic heart rate modulation. Detection of changes in repolarization parameters, even in this small cohort of healthy individuals, suggests an underappreciated role for air pollutants in urban arrhythmogenesis. [Copyright &y& Elsevier]

Transseptal Dispersion and TdP. Objective: This study was designed to quantitate transseptal dispersion of repolarization (DR) and delineate its role in arrhythmogenesis using the calcium agonist BayK 8644 to mimic the gain of function of calcium channel current responsible for Timothy syndrome. Background: Amplification of transmural dispersion of repolarization (TDR) has been shown to contribute to development of Torsade de Pointes (TdP) arrhythmias under long-QT conditions. Methods: An arterially perfused septal wedge preparation was developed via cannulation of the septal artery. Action potentials (APs) were recorded using floating microelectrodes together with a transseptal electrocardiogram (ECG). These data were compared to those recorded from arterially perfused canine left ventricular (LV) wedge preparations. Results: Under control conditions, the shortest AP duration measured at 90% repolarization (APD90) was observed in right ventricular (RV) endocardium (181.8 ± 15 ms), APD90 peaked close to midseptum (278.0 ± 32 ms), and abbreviated again as LV endocardium was approached (207.3 ± 9 ms). Transseptal DR averaged 106 ± 24 ms and Tpeak–Tend 84 ± 7 ms (n = 6). TDR and Tpeak–Tend recorded from LV wedge were 36 ± 9 ms and 34 ± 19 ms, respectively (n = 30). BayK 8644 increased transseptal DR to 123.2 ± 35 ms (n = 5) and induced early and delayed afterdepolarizations (3/5), rate-dependent ST-T-wave alternans (5/5), and TdP arrhythmias (3/5). Conclusions: Our data indicate that dispersion of repolarization across the interventricular septum is twice that of the LV free wall, predisposing to development of TdP under long-QT conditions. Our findings suggest that the coronary-perfused ventricular septal preparation may be a sensitive model in which to assess the potential arrhythmogenic effects of drugs and pathophysiological conditions. (J Cardiovasc Electrophysiol, Vol. 21, pp. 441–447, April 2010) [ABSTRACT FROM AUTHOR]

Background and purpose:The slow delayed rectifier K+ current (IKs) contributes to ventricular repolarization when the action potential (AP) is prolonged. IKs block during drug-induced AP prolongation may promote Torsades de Pointes (TdP), but whether this is due to additional AP prolongation is uncertain.Experimental approach:In bradycardic perfused rabbit ventricles, the incidence of spontaneous TdP, monophasic AP duration at 90% repolarization (MAPD90) and ECG interval between the peak and the end of T wave (Tpeak−end) (index of dispersion of repolarization) were measured after the administration of veratridine (125 nM, slows Na+ channel inactivation), dofetilide (7.5 or 10 nM, a rapid delayed rectifier blocker) and HMR 1556 (HMR, 100 nM, an IKs blocker), alone or in combinations (n=6 each).Key results:HMR did not prolong MAPD90, whereas veratridine or 7.5 nM dofetilide prolonged MAPD90 (P<0.01) without inducing TdP. Veratridine+7.5 nM dofetilide additively prolonged MAPD90 (P<0.05), induced 4±6 TdP per heart and prolonged Tpeak−end by 12±10 ms. Subsequent addition of HMR did not further prolonged MAPD90, but increased the number of TdP to 22±18 per heart and increased Tpeak−end by 39±21 ms (P<0.05). Increasing dofetilide concentration from 7.5 to 10 nM (added to veratridine) produced a longer MAPD90, but fewer TdP (5±5 per heart) and less Tpeak−end prolongation (17±8 ms) compared to the veratridine+7.5 nM dofetilide+HMR group (P<0.05).Conclusions and implications:Adding IKs block markedly increases TdP incidence in hearts predisposed to TdP development by increasing the dispersion of repolarization, but without additional AP prolongation.British Journal of Pharmacology (2008) 155, 1185–1194; doi:10.1038/bjp.2008.354; published online 6 October 2008 [ABSTRACT FROM AUTHOR]

Background: Proarrhythmic effects of cardiac resynchronization therapy (CRT) as a result of increased transmural dispersion of repolarization (TDR) induced by left ventricular (LV) epicardial pacing in a subset of vulnerable patients have been reported. The possibility of identifying these patients by ECG repolarization indices has been suggested.Objectives: The purpose of this study was to test whether repolarization indices on the ECG can be used to measure dispersion of repolarization during pacing.Methods: CRT devices of 28 heart failure patients were switched among biventricular, LV, and right ventricular (RV) pacing. ECG indices proposed to measure dispersion of repolarization were calculated. The effects of CRT on repolarization were simulated in ECGSIM, a mathematical model of electrocardiogram genesis. TDR was calculated as the difference in repolarization time between the epicardial and endocardial nodes of the heart model.Results: Patients: The interval from the apex to the end of the T wave was shorter during biventricular pacing (102 +/- 18 ms) and LV pacing (106 +/- 21 ms) than during RV pacing (117 +/- 22 ms, P < or =.005). T-wave amplitude and area were low during biventricular pacing (287 +/- 125 microV and 56 +/- 22 microV.s, respectively, P = .0006 vs RV pacing). T-wave complexity was high during biventricular pacing (0.42 +/- 0.26, P = .004 vs RV pacing). Simulations: Repolarization patterns were highly similar to the preceding depolarization patterns. The repolarization patterns of different pacing modes explained the observed magnitudes of the ECG repolarization indices. Average and local TDR were not different between pacing modes.Conclusion: In patients treated with CRT, ECG repolarization indices are related to pacing-induced activation sequences rather than transmural dispersion. TDR during biventricular and LV pacing is not larger than TDR during conventional RV endocardial pacing. [ABSTRACT FROM AUTHOR]

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 QHS 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. [ABSTRACT FROM AUTHOR]

QT interval dispersion may provide little information about repolarization dispersion. Some clinical measurements demonstrate an association bet ween high QT interval dispersion and high morbidity and mortality, but what is being measured is not clear. This study was designed to help resolve this dilemma. We compared the association between different clinical measures of QT interval dispersion and the £CG lead amplitudes derived from a heart vector model of repolarization with no repolarization dispersion whatsoever. We compared our clinical QT interval dispersion data obtained from 25 subjects without cardiac disease with similar data from published studies, and correlated these QT dispersion results with the distribution of lead amplitudes den vs from the projection of the heart vector onto the body surface during repolarization. Published results were available for mean relative QT intervals and mean differences from the maximum QT interval. The leads were derived from Uijen and Dower lead vector data. Using the Uijen lead vector data, the correlation between measurements of dispersion and derived lead amplitudes ranged from 0.78 to 0.99 for limb leads, and using the Dower values ranged from 0.81 to 0.94 for the precordial leads. These results show a clear association between the measured QT interval dispersion and the variation in ECG lead amplitudes derived from a simple heart vector model of repolarization with no regional information. Therefore, measured QT dispersion is related mostly to a projection effect and is not a true measure of repolarization dispersion. Our existing interpretation of QT dispersion must be reexamined, and other measurements that provide true repolarization dispersion data investigated. [ABSTRACT FROM AUTHOR]

Background: Coronary-perfused ventricular wedge preparations have proven valuable in the elucidation of the mechanisms of arrhythmias. This study was undertaken to develop an arterially perfused model of the interventricular (IV) septum.Methods: A canine septal preparation was developed via cannulation of the septal artery. Action potentials were recorded from ventricular endocardial surfaces and locations within the septum using floating microelectrodes; a transseptal electrocardiogram was simultaneously recorded. In some experiments, the calcium agonist BayK 8644 was used to enhance transseptal heterogeneity of action potential (AP) duration.Results: Distinctive electrocardiographic waveforms and dissimilar AP morphologies and durations were observed across the IV septum. The range of AP durations observed exceeded that found in the left ventricular wedge. BayK 8644 further accentuated these differences and induced torsades de pointes arrhythmias.Conclusions: The arterially perfused septal preparation is a sensitive model for the study of arrhythmias that may arise from the IV septum. [ABSTRACT FROM AUTHOR]

Experimental studies have shown that transmural dispersion of repolarization (DoR), defined as the difference in action potential duration between mid-myocardial M-cells, epicardial, and endocardial cells is reflected in the duration of the terminal portion of the T wave (TpTe) on the surface ECG. Since DoR is an important factor associated with the propensity for reentrant arrhythmias, this study examined if TpTe may serve as a marker of risk of ventricular arrhythmias. Data from 18 patients with coronary artery disease and inducible sustained ventricular tachycardia (VT group) were compared with those of 16 survivors of myocardial infarction with out inducible VT (control group). TpTe was automatically measured in each beat of 24-hour ECG recordings, and programmed ventricular stimulation was performed in the antiarrhythmic drug-free state. TpTe was expressed as the absolute interval in milliseconds, and relative to the duration of QTe (TpTe/QTe X 100%). TpTe duration was 74 ± 14 ms in the VT group versus 63 ± 16 ms in the control group (P < 0.004). The TpTe interval expressed as a percent of the QT interval was 21 ± 4% in the VT group versus 17 ± 3% in the control group (P = 0.02). In patients with coronary artery disease, TpTe was longer in patients with, versus without, inducible VT. The results of this study support the hypothesis that TpTe reflects transmural dispersion of repolarization. [ABSTRACT FROM AUTHOR]

Abstract: The surface potential at any given electrode location is the net result of simultaneously acting and variously directed electrical forces in the myocardium. The degree to which the electrical forces in the heart are thus opposing each other has been defined as cancellation, and this mechanism plays a major role in the formation of the electrocardiogram (ECG). However, previous studies did not take into account the locations of the electrical sources. In this study, we used a computer model of the left ventricle to study the effect of source locations on cancellation during the T and U waves. The model represents an anatomically stylized cross-sectional slice of the left ventricle, containing 1961 hexagonal cells in a single layer. An action potential (AP) is assigned to each cell. The timing of the APs follows a simulated excitation sequence. The potential differences between the APs of adjacent cells produce time-varying electrical sources, each of which contributes to the potential in an arbitrary point P on the body proportionally to its own, location-dependent, transfer function (lead vector). The ECG at P is the sum of all potential contributions. For each time point in the ECG at P, the contribution of each cell is mapped back onto the slice. Adjacent cells with equal contributions form iso-source strings, together forming iso-source maps. The T-U wave as observed in P will be the sum of positive and negative contributions from the iso-source distributions as they change with time. The iso-source maps for an anteriorly located observation point P at 4.2 cm from the epicardial surface show a continuous interplay of positive and negative contributions. During the near-zero ST segment, cancellation varies between 80% and 100%. In the ascending limb of the T wave, positive contributions substantially increase, giving a decrease in cancellation to about 40%. At the end of the T wave (with almost zero amplitude), the positive contributions are only slightly reduced as compared with those at peak T, but greatly increased negative contributions cancel them out. This is contrary to the generally held view that the end of T signifies the end of the repolarization process. The manifest shape of the T and U waves is the result of complex interactions of varying and often largely canceling contributions. The iso-source maps are helpful to understand the genesis of the T and U waves. [Copyright &y& Elsevier]