Dispersion of repolarization in cardiac resynchronization therapy

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.     

QT dispersion, T-wave projection, and heterogeneity of repolarization in patients with coronary artery disease

The clinically useful prognostic value of precordial QT dispersion in patients with heart disease is generally attributed to its measurement of regional heterogeneity of ventricular repolarization. However, when repolarization is abnormal, differences in measured QT intervals might result simply from variation in projection of the T-wave loop. To provide insight into the mechanism of QT dispersion, we used an analog device to transform conventional 12-lead electrocardiograms (ECGs) of 78 patients to derived 12-lead ECGs based on the heart vector. Because the electrical activity of the heart is represented by a single dipole, all QT dispersion in the transformed ECGs results from variation in projection of the T-wave loop and cannot be due to local heterogeneity of repolarization. Measured as the difference between the longest and shortest precordial QT intervals, QT dispersion in the derived ECGs, with no local heterogeneity of repolarization, was 53 +/- 49 ms (mean +/- SD). QT dispersion in these derived ECGs was similar in magnitude to that measured from the original standard 12-lead ECGs in these patients (49 +/- 23 ms, p = NS). Therefore, the precordial QT dispersion measured from standard ECGs of patients with coronary artery disease can be explained by interlead variation in precordial projection of the T-wave loop. Although regional heterogeneity might still contribute to precordial repolarization findings and to prognosis, this is not required to explain the QT dispersion observed in patients with coronary artery disease. Therefore, QT interval dispersion is not equivalent to heterogeneity of repolarization.     

Prevention of ventricular extrasystole by mexiletine in patients with normal QT intervals is associated with a reduction of transmural dispersion of repolarization

BACKGROUNDS: Antiarrhythmic potential of mexiletine in patients with congenital and acquired long-QT syndrome (LQTS) has been attributed to a reduction of transmural dispersion of repolarization (TDR). A similar mechanism could be involved in the antiarrhythmic activity of the drug in patients with normal QT intervals, but the issue remains to be investigated. METHODS AND RESULTS: We analyzed 24-h Holter ECG recordings from 17 patients in sinus rhythm showing premature ventricular complexes (PVCs) with normal QT intervals (age, 62+/-10 years, mean+/-S.D.). Treatment of the patients with oral mexiletine (300 mg/day for 21-40 days) resulted in a significant reduction of PVCs (from 13899+/-18887 to 6949+/-12822 beats/24 h, p<0.01). Rate-dependent behavior of ventricular repolarization was analyzed by plotting QT intervals (QT(peak), QT(end)), and the interval from T-wave peak to T-wave end (TPE) against preceding respective RR intervals of sinus beats. Both the QT(peak) and QT(end) tended to be shortened by mexiletine at RR intervals from 600 ms to 1000 ms, although the changes did not reach statistical significances. TPE, which reflects TDR, was shortened significantly at relatively long RR intervals (by 14+/-9% at RR of 900 ms, p<0.05). There was a linear relationship between the percentage shortening of TPE and the percentage reduction of PVCs (r=0.86, p<0.04). TPE> or =70 ms was significantly associated with PVC suppression >75% with an odds ratio of 0.60 (95% confidence interval 0.36-0.98, per 1 ms increment). CONCLUSION: Inhibitory effect of mexiletine against PVCs in patients with normal QT intervals is mediated at least in part by a reduction of TDR. Mexiletine may be effective in patients exhibiting longer baseline TPE.     

A Comparison of T-Wave Alternans and QT Dispersion as Noninvasive Predictors of Ventricular Arrhythmias

Background: The purpose of this study was to compare the utility of T-wave alternans and dispersion markers for predicting vulnerability to ventricular arrhythmias. Microvolt level T-wave alternans, QT dispersion (QT_d), JT dispersion, and other dispersion indices have been postulated as noninvasive markers of vulnerability to ventricular arrhythmias. However, T-wave alternans has not been directly compared to dispersion markers in the same patient population. Methods: Twenty-four patients underwent electrophysiological study to investigate recent syncope, ventricular tachycardia, or ventricular fibrillation. Digitized orthogonal ECGs were obtained to investigate the presence of T-wave alternans using spectral analysis, and standard 12-lead ECGs were obtained for QT and JT dispersion analysis. Results: T-wave alternans measurements showed greater sensitivity than QT or JT dispersion, but similar results as the variation coefficient of the JT interval. There was no statistically significant difference in specificity, predictive values, or clinical accuracy between T-wave alternans and any of the dispersion markers (P = N.S.). The combination of increased QT or JT dispersion and T-wave alternans was the most specific predictor. Conclusions: Heterogeneity of repolarization amplitude and duration may both be important noninvasive ECG markers of ventricular vulnerability. In this small group of high-risk patients, T-wave alternans has similar clinical accuracy as the ECG interlead repolarization dispersion markers. The predictive ability of these markers may improve with standardization of methodology or a combination of these approaches. A.N.E. 1999;4(3):274–280     

QT dispersion: an electrocardiographic derivative of QT prolongation

BACKGROUND: QT dispersion has been considered a surrogate for heterogeneity of repolarization, leading to ventricular arrhythmias. METHODS: High-resolution 12-lead electrocardiograms were obtained in 15 patients with a history of ventricular tachycardia or ventricular fibrillation, 15 patients with congestive heart failure, 17 patients with a history of previous Q-wave myocardial infarction without heart failure, and 23 healthy control subjects. RESULTS: QTc dispersion was prolonged in all 3 patient groups compared with controls (71+/-22, 68 +/-31, 61+/-27 vs 44+/-17 msec, P =. 003), but no difference was seen between heart disease groups. QTc dispersion was strongly correlated with the QTc max (r = 0.73, P<.0001) but did not correlate with the QTc min (r = 0.04, P =.76). QTc dispersion also strongly correlated with the JTc max (r = 0.54, P<.0001) but did not correlate with JTc min (r = -0.007, P =.95). QTc dispersion correlated inversely with T-wave amplitude (r = -0.35, P =.003). When all 876 electrocardiographic signals were considered, a significant negative correlation was present between QTc duration and T-wave amplitude (r = -0.133, P =.0002). Logistic regression analysis failed to demonstrate any independent risk factors that predicted ventricular arrhythmias, including all measures of dispersion. CONCLUSIONS: The measurement of QT dispersion is strongly influenced by the maximum QT interval, as well as by changes in T-wave amplitude. QT "dispersion" may represent a summary of these changes that reflect the underlying myocardial process but does not represent an accurate quantitative measure of heterogeneity of refractoriness.     

Repolarization dynamics in patients with long QT syndrome

INTRODUCTION: Dynamics of ventricular repolarization may contribute to cardiac arrhythmias in subjects with the long QT syndrome (LQTS). The aim of the present study was to assess the dynamics of repolarization duration and the dynamics of repolarization complexity in LQTS patients and their unaffected family members. METHODS AND RESULTS: Twelve-lead 24-hour ambulatory ECG recordings were obtained from LQTS patients (n = 38) and unaffected family members (n = 20). The 24-hour dynamics of the QT interval, T wave complexity (TWC) index measured by principal component analysis, and the RR interval were analyzed using standard deviation (SD) and square root of the mean squared differences of successive values of the parameters (RMSSD). QT variability, mean TWC, and TWC variability were increased in the LQTS patients compared with unaffected family members (QT-SD: 38 +/- 20 msec vs 19 +/- 7 msec, P = 0.0001; QT-RMSSD: 36 +/- 20 msec vs 14 +/- 8 msec, P = 0.0001; TWC: 27.7% +/- 11.1% vs 20.4% +/- 6.7%, P = 0.003; TWC-SD: 6.7% +/- 2.8% vs 4.6% +/- 1.8%, P = 0.003; TWC-RMSSD: 5.3% +/- 2.8% vs 3.7% +/- 1.2%, P = 0.004, respectively). At the same time, the measures of heart rate variability were similar between the affected and unaffected LQTS subjects (SD of normal-to-normal RR intervals [SDNN]: 94 +/- 25 msec vs 89 +/- 37 ms, P = 0.56; RMSSD: 49 +/- 26 msec vs 49 +/- 34 ms, P = 0.97, respectively). CONCLUSION: Despite similar heart rate variability, QT variability and the variability of TWC are significantly increased in LQTS patients compared with unaffected family members, suggesting that disturbances in temporal dynamics of repolarization and repolarization complexity in LQTS patients possibly increase vulnerability to arrhythmias.     

Beta-blocker decreases the increase in QT dispersion and transmural dispersion of repolarization induced by bepridil.

Bepridil is effective for intractable cardiac arrhythmia, but in rare cases will induce torsades de pointes (TdP) associated with QT interval prolongation. Beta-blockers will effectively prevent TdP in some clinical settings, so the effect of beta-blocker on the change in QT interval, QT dispersion and transmural dispersion of repolarization (TDR) induced by bepridil was investigated in 10 patients (7 male, 3 female; 62+/-6 years old) with intractable paroxysmal atrial fibrillation. The QTc interval, QTc dispersion and TDR were measured before and after 1 month of administration of bepridil, and then a beta-blocker was added and the QTc interval, QTc dispersion and TDR re-measured 1 month later. Bepridil significantly prolonged the QTc interval (0.42+/-0.05 to 0.50+/-0.08; p<0.01), and increased both the QT dispersion (0.07+/-0.05 to 0.14+/-0.08; p<0.01) and TDR (0.10+/-0.04 to 0.16+/-0.05; p<0.01). The addition of a beta-blocker decreased the QTc interval (0.50+/-0.08 to 0.47+/-0.04; p=0.09) and significantly decreased both the QTc dispersion (0.14 +/-0.08 to 0.06+/-0.02; p<0.01) and TDR (0.16+/-0.05 to 0.11+/-0.04; p<0.001). Compared with the control, the combination therapy significantly prolonged the QTc interval, but did not increase either QTc dispersion or TDR, and so was effective in all patients with intractable AF. The findings suggest that beta-blocker reduces the increase in QT dispersion and TDR induced by bepridil, and combined therapy with bepridil and beta-blocker might thus be useful for intractable atrial fibrillation.     

Electrophysiological basis of QT dispersion measurements

Dispersion of ventricular repolarization is a now widely used term describing nonhomogeneous recovery of excitability or heterogeneity of ventricular repolarization. It is usually expressed as the difference or the range of various repolarization measurements obtained from a heart. Experimentally, an increased dispersion of ventricular repolarization was found to be tightly associated with increased propensity for ventricular arrhythmias, and, therefore, is considered an important arrhythmogenic mechanism. Noninvasively, this arrhythmogenic substrate was approached using multilead body surface potential mapping, but also QT interval dispersion (QTd) and similar electrocardiogram (ECG) variables from the 12-lead surface ECG. Standard QTd from the ECG correlates significantly with dispersion of repolarization measured from the myocardium. A causal relationship is, however, still unclear, and there are 2 main hypotheses to explain the electrophysiological basis of QTd. The local hypothesis explaining QTd with spatial differences in action potential duration mirrored in the various QT intervals competes with the global hypothesis explaining the variation in surface ECG measurements with different projections of a common T-wave vector. Notwithstanding the final explanation for QTd, and particularly for technical reasons, new markers like advanced T-wave loop variables may best reflect the abnormal repolarization substrate on the surface ECG.     

Cellular Basis for Complex T Waves and Arrhythmic Activity Following Combined IKr and IKs Block

INTRODUCTION: A growing number of cardiomyopathies have been shown to result in a reduction in both I(Kr) and I(Ks) yet little is known about the electrophysiologic and ECG characteristics of combined I(Kr) and I(Ks) block. METHODS AND RESULTS: To address this gap in our knowledge, transmembrane action potentials (APs) from epicardial, M, and endocardial cells were recorded simultaneously, together with a transmural ECG from arterially perfused canine left ventricular wedge preparations exposed to combined I(Kr) (d-sotalol; 100 micromol/L) and I(Ks) (chromanol 293B; 30 to 60 micromol/L) block. Under baseline conditions, the T wave was typically upright; epicardium repolarized first, coinciding with the peak of the T wave, and the M cells repolarized last, coinciding with the end of the T wave (T(end)). Complex (inverted, biphasic, and triphasic) T waves developed following combined I(Kr) and I(Ks) block. M and epicardial APs prolonged dramatically, so that the endocardial AP was now the earliest to repolarize, coinciding with the first nadir of the complex T wave. In the case of biphasic/triphasic or inverted T waves, Tend coincided with repolarization of either M or epicardial cells, whichever was the last to repolarize. QT intervals prolonged from 286+/-13 msec up to 744+/-148 msec and transmural dispersion of repolarization (TDR) increased from 33+/-10 msec up to 244+/-71 msec. Early afterdepolarizations (EADs) developed in M and epicardial cells, evoking extrasystoles that precipitated polymorphic ventricular tachycardia. Acceleration-induced EADs and T wave alternans also were observed. CONCLUSION: Combined I(Kr) and I(Ks) block gives rise to inverted, biphasic, and triphasic T wave morphologies, a dramatic increase in TDR, and a high incidence of EADs. The diversity of T wave morphologies derives from a preferential AP prolongation of different transmural layers leading to variation in the predominance of voltage gradients on either side of the M cell region. Our study provides direct evidence linking EADs that arise in ventricular epicardial and M cells to the triggered beats that precipitate polymorphic ventricular tachycardia. Our results also suggest possible guidelines for the estimation of TDR from complex T waves appearing in the precordial leads of the surface ECG.     

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

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

Transmural heterogeneity of ventricular repolarization under baseline and long QT conditions in the canine heart in vivo: torsades de pointes develops with halothane but not pentobarbital anesthesia

INTRODUCTION: In vitro studies have provided evidence for the existence of M cells. The present study examines the contribution of the M cell to transmural dispersion of repolarization (TDR) and to the development of torsades de pointes (TdP) in the canine heart in vivo in animals anesthetized with either pentobarbital or halothane. METHODS AND RESULTS: Monophasic action potentials (MAPs) were recorded from 4 to 7 transmural sites, before and after d-sotalol. Cells displaying the longest MAP duration (MAPD) generally were localized to the deep subendocardium to mid-myocardium (M region) in the anterior wall of the left ventricle. d-Sotalol preferentially prolonged the MAPD of the M region, increasing TDR significantly more (P < 0.05) in animals anesthetized with halothane (31+/-5 to 88+/-17 msec) than in those receiving pentobarbital (24+/-9 to 53+/-7 msec; basic cycle length 1,500 msec). In halothane-anesthetized dogs, a remarkable transient increase in M cell MAPD followed interpolation of one or more extrasystole(s), leading to a transient increase in TDR and TdP. TdP was never observed with pentobarbital anesthesia. CONCLUSION: Our results demonstrate that transmural heterogeneity of repolarization is amplified under acquired long QT conditions and that the increase in TDR underlies the development of TdP in halothane- but not pentobarbital-anesthetized dogs. The data support an important contribution of M cells to TDR and to the development of TdP in the canine heart in vivo. Our data also highlight the importance of acceleration-induced prolongation of MAPD (a phenomena observed principally in M cells) in the development of TdP.     

Precordial QT interval dispersion as a marker of torsade de pointes. Disparate effects of class Ia antiarrhythmic drugs and amiodarone.

BACKGROUND. Patients with a history of class Ia drug-induced torsade de pointes have been treated with chronic amiodarone without recurrence of torsade de pointes despite comparable prolongation of the QT interval. We hypothesized that in such patients, class Ia drugs cause nonhomogeneous prolongation of cardiac repolarization times, whereas amiodarone causes homogeneous prolongation of cardiac repolarization times. METHODS AND RESULTS. Thirty-eight consecutive patients who received both class Ia drug therapy and chronic amiodarone therapy were evaluated. Standard 12-lead ECGs at baseline and during each therapy were used to calculate precordial QT interval dispersion (maximum QT in leads V1 through V6 minus minimum QT leads V1 through V6) as a measure of regional variabilities in ventricular repolarization times. Nine of these patients had torsade de pointes during class Ia drug therapy. In these nine patients, class Ia drug therapy and amiodarone significantly prolonged the maximum QT interval to comparable extents. However, class Ia drug therapy but not amiodarone therapy significantly increased precordial QT interval dispersion (101 +/- 37 versus 49 +/- 26 msec; baseline, 44 +/- 12 msec; p = 0.002). In the 29 patients without class Ia drug-induced torsade de pointes, neither class Ia drug therapy nor amiodarone therapy significantly increased QT interval dispersion (50 +/- 6 versus 69 +/- 7 msec; baseline, 54 +/- 5 msec). None of the patients with class Ia drug-induced torsade de pointes had recurrent torsade de pointes during chronic amiodarone therapy. CONCLUSIONS. An increase in regional QT interval dispersion during class Ia antiarrhythmic drug therapy is associated with torsade de pointes. Chronic amiodarone therapy in patients with a history of class Ia drug-induced torsade de pointes produces comparable maximum QT interval prolongation but does not increase QT interval dispersion. This characteristic may explain its apparent safe use in patients with a history of class Ia drug-induced torsade de pointes.     

跨室壁复极离散变化及其对心电图T波影响的在体实验研究

为探讨在体情况下心肌跨室壁复极离散变化及其对心电图T波影响的可能机制。运用单相动作电位 (MAP)记录技术 ,同步记录 2 1只开胸兔的左室心肌心外膜层 (Epi) ,中层 (Mid) ,内膜层 (Endo)的MAP ,分别予以减慢心率、静脉注射索他洛尔 (dl sotalol)、海葵毒素 (ATX Ⅱ )后 ,观察跨室壁复极离散的变化以及心电图T波的相应改变。结果 :①慢频率导致Mid层细胞MAP复极时间 (RT)显著延长 (从 2 0 2± 19ms到 370± 34ms,P <0 .0 5 ) ,跨壁复极离散度 (TDR)增大 (从 11± 4ms到 40± 2 1ms,P <0 .0 5 ) ,QT间期延长 (从 2 0 5± 2 1ms到 371± 30ms,P <0 .0 5 ) ,T波增宽。②dl sotalol导致Mid层细胞MAP的RT显著的延长 (从 2 0 2± 19ms到 395± 34ms,P <0 .0 5 ) ,TDR增大 (从 10± 3ms到 75± 2 5ms ,P <0 .0 5 ) ,QT间期延长 (从 2 0 8± 16ms到 397± 33ms,P <0 .0 5 ) ,三层心肌MAP的 3相复极不同程度的延长 ,使复极电位梯度变化 ,产生增宽、低幅有切迹的T波。③ATX Ⅱ导致Mid层细胞MAP的RT显著的延长 (从370± 34ms到 473± 35ms,P <0 .0 5 ) ,TDR增大 (从 40± 2 1ms到 6 2± 19ms,P <0 .0 5 ) ,QT间期延长 (从 372± 33ms到 479± 33ms,P <0 .0 5 ) ,三层心肌MAP的 2相平台期不同程度延长 ,使复极电位梯     

QT dispersion does not represent electrocardiographic interlead heterogeneity of ventricular repolarization

INTRODUCTION: QT dispersion (QTd, range of QT intervals in 12 ECG leads) is thought to reflect spatial heterogeneity of ventricular refractoriness. However, QTd may be largely due to projections of the repolarization dipole rather than "nondipolar" signals. METHODS AND RESULTS: Seventy-eight normal subjects (47+/-16 years, 23 women), 68 hypertrophic cardiomyopathy patients (HCM; 38+/-15 years, 21 women), 72 dilated cardiomyopathy patients (DCM; 48+/-15 years, 29 women), and 81 survivors of acute myocardial infarction (AMI; 63+/-12 years, 20 women) had digital 12-lead resting supine ECGs recorded (10 ECGs recorded in each subject and results averaged). In each ECG lead, QT interval was measured under operator review by QT Guard (GE Marquette) to obtain QTd. QTd was expressed as the range, standard deviation, and highest-to-lowest quartile difference of QT interval in all measurable leads. Singular value decomposition transferred ECGs into a minimum dimensional time orthogonal space. The first three components represented the ECG dipole; other components represented nondipolar signals. The power of the T wave nondipolar within the total components was computed to measure spatial repolarization heterogeneity (relative T wave residuum, TWR). QTd was 33.6+/-18.3, 47.0+/-19.3, 34.8+/-21.2, and 57.5+/-25.3 msec in normals, HCM, DCM, and AMI, respectively (normals vs DCM: NS, other P < 0.009). TWR was 0.029%+/-0.031%, 0.067%+/-0.067%, 0.112%+/-0.154%, and 0.186%+/-0.308% in normals, HCM, DCM, and AMI (HCM vs DCM: NS, other P < 0.006). The correlations between QTd and TWR were r = -0.0446, 0.2805, -0.1531, and 0.0771 (P = 0.03 for HCM, other NS) in normals, HCM, DCM, and AMI, respectively. CONCLUSION: Spatial heterogeneity of ventricular repolarization exists and is measurable in 12-lead resting ECGs. It differs between different clinical groups, but the so-called QT dispersion is unrelated to it.     

Reduction in QT dispersion with rheolytic thrombectomy in acute myocardial infarction: evidence of electrial stability with reperfusion therapy.

An increase in QT dispersion (QTd) is associated with myocardial ischemia and may serve as a marker of ischemia and ventricular arrhythmia. We studied the effect of early reperfusion with rheolytic thrombectomy using an angiojet catheter (Possis, Minneapolis, MN) on QTd in 12 patients who presented with acute myocardial infarction. QTd and QT dispersion, rate-corrected for RR interval, were significantly reduced from 57 +/- 16 and 68 +/- 13 msec before reperfusion to 34 +/- 16 and 44 +/- 19 msec after reperfusion respectively (mean +/- SD; P < 0.002 and P < 0.0008, respectively). Successful reperfusion with rheolytic thrombectomy reduces QTd and may confer electrical stability to vulnerable myocardium. Reduction in indexes of repolarization inhomogeneity with reperfusion may serve as a noninvasive marker of coronary patency.     

Study of repolarization heterogeneity and electrocardiographic morphology with a modeling approach

Background

Increase of heart repolarization heterogeneity has been linked to severe or even life-threatening arrhythmia like torsades de pointes and other forms of ventricular tachycardia. Although electrocardiography (ECG) still remains as the most convenient and cost-effective method of monitoring electrical activity of the heart, the link between ECG morphology and repolarization heterogeneity is not clear. Previous attempts of using QT interval dispersion from multiple leads to assess the heterogeneity changes were not successful either.

Method

The aim of this study is to use a cell-to-ECG model to study ECG morphology changes while varying transmural heterogeneity. The heterogeneity is simulated by increasing the difference of M cell Ikr block factors from either endocardial or epicardial cells. The model-simulated ECGs were processed and measured. The ECG parameters studied include QT interval dispersion of standard 12-lead ECG, QT peak dispersion, and T-peak to T-end interval (TpTe). An ECG vector magnitude signal based on 12-lead ECG was formed to estimate the global QT interval (vs lead-by-lead QT interval used for calculating QT dispersion) and also the global TpTe (TpTe_VM).

Results

The results based on the model simulation show that the TpTe_VM is highly correlated with transmural dispersion of repolarization (TDR), with a correlation coefficient of 0.97. The correlation coefficients of QT interval dispersion and QT peak dispersion with TDR are 0.44 and 0.80, respectively.

Conclusion

In conclusion, the cell-to-ECG model provides a unique way to study electrophysiology and to link physiologic factors to ECG morphology changes. The simulation results suggest that global TpTe can be a strong indicator of TDR.     

The effect of electroconvulsive therapy on QT dispersion

Electroconvulsive therapy (ECT) is used frequently in psychiatric practice and various electrocardiographic (ECG) changes have been described during ECT. QT dispersion (defined as maximal QT interval minus minimal QT interval) as assessed on the surface electrocardiogram has been demonstrated to reflect regional inhomogeneity of ventricular repolarization. The aim of this study is to examine the effect of electroconvulsive therapy on QT dispersion. We studied 27 patients (age range 24-42 y, mean age 34 y, 11 men) without heart disease who were treated with ECT. Structural heart disease was eliminated with routine clinical examination and laboratory tests, echocardiography, and exercise treadmill test. QT interval and corrected QT (QTc) dispersion was measured on a 12-lead ECG before and just after ECT. QTc dispersion increased from 28.9 +/- 7.4 ms at baseline to 81.4 +/- 12.8 ms after the procedure (P < 0.0001). This result demonstrated that QTc dispersion increased significantly during ECT. This finding may explain that increased inhomogeneity of ventricular repolarization is associated with enhanced vulnerability to arrhythmias during ECT.     

Increased QT interval dispersion after hemodialysis: role of peridialytic electrolyte gradients

Chronic renal failure patients on maintenance hemodialysis (HD) have a number of ECG abnormalities and cardiac arrhythmias. Clinical and experimental data have shown that increased QT dispersion is associated with severe ventricular arrhythmias and sudden cardiac death. Therefore, the aim of this study was to investigate whether the uremic patients receiving long-term HD have increased QTc interval and/or QTc dispersion compared to normal subjects and to evaluate the effect of electrolyte changes between the predialysis and postdialysis phases on these parameters. Forty patients with end-stage renal failure on long-term HD (22 men, 18 women, mean age 44 years) were included in this study. Serum concentrations of K+, Na+, Ca++, Mg++, Cl-, phosphate, urea, creatinine, HCO3-, and arterial blood gases (PO2, PCO2), together with blood pH, were monitored and QTc intervals and QTc dispersion were measured from 12-lead ECG in predialysis and postdialysis phases. The hemodialyzed patients had an increased predialysis QTc maximum interval and QTc dispersion compared to normal subjects (480 +/- 51 vs 310 +/- 38 msec, p < 0.001 and 61 +/- 17 vs 42 +/- 14 msec, p < 0.001, respectively). Both QTc maximum interval and QTc dispersion increased significantly at the end of the HD (480 +/- 51 vs 505 +/- 49 msec p < 0.001 and 61 +/- 17 vs 86 +/- 18 msec, p < 0.001, respectively). The serum K+ (5.3 +/- 0.56 vs 3.36 +/- 0.41 mEq/L, p < 0.001), phosphate (7.19 +/- 1.62 vs 3.81 +/- 1.02 mg/dL, p < 0.001), magnesium (0.87 +/- 18 vs 0.75 +/- 0.14 mg/dL) and urea concentrations (174 +/- 22 vs 74 +/- 14 mg/dL, p < 0.001) significantly decreased, whereas the Ca++ (2.21 +/- 0.18 vs 2.47 +/- 0.24 mg/dL, p < 0.001), HCO3- (15.5 +/- 3.2 vs 20.1 +/- 3.4 mmol/L, p<0.001) concentrations and pH (7.27 +/- 1.1 vs 7.43 +/- 1.2, p < 0.001) significantly increased after HD compared to predialysis values. There was significant correlation between the QT dispersion increase and serum electrolyte changes (K+, Ca++, and pH levels) (p < 0.05). The association between serum electrolyte changes, acid-base status and QT measurements might provide new insights into the evaluation of the ionic bases involved in inhomogeneous ventricular repolarization.     

Electrocardiographic morphology changes with different type of repolarization dispersions

Background

T-wave morphology changes have been linked to heterogeneity of ventricular repolarization and increase of arrhythmia vulnerability. Therefore, century-long debates around the genesis of T wave become even more relevant. Here are some interesting questions for the debates: (1) why T waves are usually concordant with QRS complex? (2) Is there a significant and consistent transmural dispersion of repolarization across heart wall? (3) What kind of T-wave morphology changes can be induced by either transmural or apical-basal dispersion of repolarization?

Method

The previously developed GE's cell-to-electrocardiogram (ECG) model (GE Healthcare, Milwaukee, WI) was used to study the relation between cellular behavior and the T-wave morphology. The study focused on 2 types of repolarization dispersions: (1) Transmural (from endocardium to epicardium) and (2) Apical-basal (from apex to base of ventricles). More specifically, the transmural dispersions were created by adjusting the slow and fast delayed potassium rectifier current (Iks, Ikr) and transient outward current (Ito), on endocardial, midmyocardial (M cell) and epicardial cells separately. The apical-basal dispersion was adjusted according to the coordinates along the axis from the base to the apex of the ventricle. The contribution of M cell toward T-wave morphology were studied by adjusting the M cell's repolarization time in the range of shorter to longer than those of endocardial repolarization time.

Results

In the global transmural dispersion cases, QT interval is prolonged from 350 to 450 milliseconds, T-peak to T-end interval (TpTe) is prolonged from 50 to 130 milliseconds, and T-wave notches appeared when the heterogeneity is increased. In the localized transmural dispersion cases, significant T-wave morphology features such as TpTe, T-wave notches appeared in very limited precordial leads. In the global apical-basal dispersion cases, main T-wave change is on the amplitude, and T waves in several precordial leads and lead II turn to positive from negative. And the localized apical-basal dispersion does not generate significant T-wave morphology changes.

Conclusions

The cell-to-ECG model provides a unique way to study electrophysiology and to link physiologic factors to ECG morphology changes. The simulation results suggest that the apical-basal dispersion of repolarization contributes to positive T wave more than the transmural dispersion. The contribution of localized transmural dispersion to surface ECG is very much localized to certain precordial leads.     

Multiparametric electrocardiographic evaluation of left ventricular hypertrophy in idiopathic and hypertensive cardiomyopathy.

BACKGROUND: Electrophysiological abnormalities underlying the increased arrhythmogenicity of left ventricular hypertrophy (LVH) are still under investigation. The aim of this study was to assess non-invasively the electrophysiologic alterations in two different types of LVH, METHODS: Multiparametric non-invasive ECG analysis (R-R interval, QRS and QT intervals, QT dispersion, T-wave complexity, activation-recovery interval [ARI] dispersion, standard deviation of RR intervals [SDNN], filtered QRS duration [fQRS], root-mean-square voltage of the terminal 40 ms of the fQRS [RMS40] and low amplitude signal duration (< 40 microV) in the terminal portion of the fQRS [LAS]) was performed in 57 patients with hypertensive LVH and hypertrophic cardiomyopathy (HCM), and in 105 healthy subjects. RESULTS: The R-R interval and SDNN were similar in hypertrophic patients and controls. QRS and QT intervals were longer in hypertrophic patients without any differences between hypertensive LVH and HCM. QT dispersion, T-wave complexity and fQRS were greater in hypertrophic patients; QT dispersion was the greatest in HCM. ARI dispersion was lesser in hypertrophic patients without any differences between subgroups of LVH. fQRS showed a trend toward higher values in hypertensive patients. LAS at 25 Hz had a trend toward lower values in HCM patients, while LAS at 40 Hz and RMS40 showed no difference between controls and hypertrophic patients. Left ventricular mass index was not correlated with any of the above-mentioned parameters. CONCLUSIONS: The QT interval and dispersion did not identify the type of hypertrophy. Similarly, ARI dispersion which explores local variations of repolarization duration, and T-wave complexity could not distinguish patients with hypertensive LVH from those with HCM indicating that multiparametric ECG data are affected more by the presence of LVH, than by its type.