Heterogeneity Of Ventricular Repolarization Research Articles

Quantification of ventricular repolarization heterogeneity during moxifloxacin or sotalol administration using -index

Drug-induced alterations of ventricular heterogeneity must be limited to avoid induction of lethal ventricular arrhythmias. In here, a new parameter called -index, able to measure the standard deviation of myocites' repolarization times, was evaluated after moxifloxacin and sotalol administration. The two drugs are known to provide different alteration of the QT interval length ranging from subtle (moxifloxacin) to evident (sotalol). In fact, while the former is employed as active-comparator in thorough QT studies, the latter might induce torsades de pointes. 24 h Holter ECGs of 39 (sotalol) and 68 (moxifloxacin) healthy subjects were retrospectively analyzed. The recordings were performed after infusion of the drugs and after the placebo (moxifloxacin) or at baseline (sotalol). The corrected QT interval (QTc) was included as well in the study, for a direct comparison. In both populations, -index and QTc increased along with the drugs' serum concentration and were statistically different from values in the placebo arm or at baseline (p < 0.05).With sotalol, the maximum value of -index occurred, on average, after 5.64 h from the infusion, whereas for QTc after about 4.27 h. The two metrics displayed evident changes (-index: 27.79 ms ± 4.89 ms versus 60.13 ms ± 18.52 ms; QT corrected: 387.07 ms ± 19.84 ms versus 437.76 ± 32.05 ms; p < 0.05). Regarding moxifloxacin, maximum values were reached, on average, 5.01 h after administration for -index (30.70 ms ± 8.32 ms versus 40.48 ms ± 7.61 ms; p < 0.05), and 4.37 h for QTc (404.29 ms ± 29.05 ms versus 426.77 ± 36.67 ms; p < 0.05). They were statistically different from baseline values. With both drugs, the maximal percent variation after administration was higher for -index than QTc (moxifloxacin: 34.56% ± 24.60% versus 5.56% ± 2.98% ; sotalol: 114.77% ± 33.15% versus 12.13% ± 2.85% ; p < 0.05).The study suggests that the standard deviation of the ventricular repolarization times, as quantified by the -index, might be an effective measure of spatial heterogeneity.

Heterogeneity of ventricular repolarization in newborns with intrauterine growth restriction

BackgroundIntrauterine growth restriction (IUGR) is associated with structural and functional cardiac alterations but the electrophysiological consequences of these disturbances remain unknown. AimsTo explore the distribution of ventricular repolarization and its relation to myocardial mechanics in newborns with IUGR. Study design, subjects and outcome measurementsConventional and tissue Doppler echocardiographic data, and electrocardiographic parameters used to describe the distribution of ventricular repolarization (dispersion of QT [QTd] and JT [JTd]), were obtained on the second (D2) and fifth (D5) postnatal day and compared between 25 IUGR newborns and 25 matched-for-gestational age controls. ResultsIUGR was associated with relative interventricular septum hypertrophy, increased left ventricular (LV) E/E′ ratio and higher LV myocardial performance index (MPI). On both study days, the IUGR infants presented higher QTd and JTd compared to controls (QTd-D2: 66±20ms vs. 36±12ms, P<0.001; JTd-D2: 54±13ms vs. 34±9ms, P<0.001; QTd-D5: 61±14ms vs. 27±12ms, P<0.001; JTd-D5: 54±13ms vs. 27±9ms, P<0.001). The association between QTd and LV E/E′ (D2: regression coefficient beta 0.747, R2 0.585; D5: beta 0.843, R2 0.646) and QTd and MPI (D2: beta 0.680, R2 0.576; D5: beta 0.698, R2 0.650) was also significant (P<0.001 for all analyses). ConclusionsOur findings suggest that IUGR is associated with electrophysiological remodeling of the neonatal heart, a process which is closely related to the underlying alterations in ventricular mechanics and might predispose to adverse electrophysiological events.

Survey of the effect of streptokinase on ventricular repolarization by examining the QT dispersion in patients with acute myocardial infraction in Seyed-Al-Shohada hospital, Urmia.

Cardiovascular events are the most common cause of morbidity and mortality throughout the world and myocardial infarction is the most common cause of these accidents. Myocardial infarction impairs the mechanical and electrical activity of the heart that these disorders predispose the patient to cardiac arrhythmias including ventricular tachycardia. QT dispersion is an important parameter to evaluate the heterogeneity of ventricular repolarization that minimal and the maximum interval is QTc in 12-lead EKG. In this study, 200 patients with the diagnosis of acute myocardial infraction with ST-segment elevation were hospitalized and treated with streptokinase. Patient records were extracted from the medical records department. EKG was studied before receiving streptokinase, an hour after receiving streptokinase and 4 days later for calculating and comparing QTd. It was concluded that QTd mean in EKG one hour after receiving streptokinase is decreased compared to pre-operation but this decline is not statistically significant. QTd mean in EKG day 4 after MI is slightly increased compared to the baseline, which is not statistically significant.

Does glycemic control reverse dispersion of ventricular repolarization in type 2 diabetes?

BackgroundAbnormal ventricular repolarization is a predictor of cardiovascular mortality. In this study, we tested the hypothesis that glycemic control reverses abnormal ventricular repolarization in patients with type 2 diabetes.MethodsWe analyzed longitudinal changes in repolarization indices of electrocardiograms in retrospectively enrolled 44 patients with type 2 diabetes and 44 age-matched healthy subjects.ResultsIn the diabetic group, BMI was greater, levels of HbA1c (10.0 ± 1.6 vs. 5.6 ± 0.3%) and triglyceride were higher and level of HDL cholesterol was lower than those in the control group. Although mean QTc intervals were similar (413.6 ± 18.5 vs. 408.3 ± 22.7 ms), QT dispersion (41.8 ± 15.4 vs. 28.7 ± 7.7 ms) and Tpeak-Tend in lead V5 (83.6 ± 13.6 vs. 71.3 ± 10.3 ms) were significantly longer in the diabetic group than in the control group, indicating increased heterogeneity of ventricular repolarization in type 2 diabetes. During follow-up of 36 patients in the diabetic group for 787 ± 301 days, HbA1c level decreased to 7.3 ± 1.6%, while BMI did not significantly change. In contrast to HbA1c, QT dispersion (45.8 ± 15.0 ms) and Tpeak-Tend in lead V5 (83.6 ± 10.6 ms) were not significantly reduced during the follow-up period. There was no correlation between the change in HbA1c and the change in QT dispersion or Tpeak-Tend.ConclusionsIncreased heterogeneity of ventricular repolarization in type 2 diabetic patients was not reduced during the relatively short follow-up period despite significantly improved glycemic control.

Impact of Myocardial Reperfusion Status on QT Dispersion After Successful Recanalization of the Infarct‐Related Artery in Acute Myocardial Infarction

To determine whether adequate myocardial perfusion status after transluminal recanalization is associated with prompt improvement of QT dispersion (QTd). Transluminal recanalization of the infarct-related coronary artery in acute myocardial infarction aims to promptly restore myocardial perfusion, to maximize electrical and mechanical recovery. QTd represents the heterogeneity of ventricular repolarization, which may affect electrical stability. Forty patients who underwent primary percutaneous coronary intervention for their first anterior acute ST-elevation myocardial infarction were prospectively enrolled. Myocardial reperfusion status was assessed by myocardial blush grade (MBG) on the final angiogram after successful recanalization (Thrombolysis In Myocardial Infarction Grade 3 flow). Preprocedural QTd was similar in patients with final MBG 0-1, 2, and 3 (76 ± 24, 67 ± 13, and 69 ± 13 milliseconds, respectively; P = 0.661). After recanalization, QTd decreased in patients with MBG 3 (39 ± 16 milliseconds, P < 0.001) but not in patients with MBG 0-1 (74 ± 20 milliseconds) or MBG 2 (82 ± 16 milliseconds). Multivariate analysis showed that postprocedural MBG was an independent predictor of QTd after recanalization (standardized regression coefficient = -0.628, P < 0.001). Adequate tissue perfusion may be crucial for electrical stability of the myocardium after reperfusion.

Predicting mortality using heterogeneity of ventricular repolarization: A meta-analysis

P values are adjusted for age, sex, BMI, total physical activity, hypertension and diabetes. Predicting mortality using heterogeneity of ventricular repolarization: A meta-analysis Salah S. Al-Zaiti, PhD(c), James A. Fallavollita, MD, Yow-Wu B. Wu, PhD, Machiko R. Tomita, PhD, Mary G. Carey, PhD School of Nursing, NY, USA Department of Medicine, NY, USA Department of Public Health and Rehabilitation Sciences, NY, USA Center for Research in Cardiovascular Medicine, NY, USA University at Buffalo and the VA of WNY Healthcare System, NY, USA

Quantification of ventricular repolarization heterogeneity during sotalol administration using the V-index

Drug-induced alterations of repolarization heterogeneity are checked to prevent the risk of lethal arrhythmias. Before drugs approval, FDA mandates a “thorough QT study.” In the last 14 years, the test avoided the withdrawal from the market of related drugs. However, it is questioned if the low specificity of the test might have hindered molecules from being commercialized. Research of alternative indices, linked with the physiology, is therefore supported by regulatory agencies. A new measure of ventricular repolarization heterogeneity (V-index) was recently proposed; it is based on a stochastic model that links the electrical potential of the myocytes with the surface ECG and it provides an estimate of the heterogeneity of the repolarization times. After being tested on synthetic signals, the metric is now undergoing a validation procedure. In this work, we performed a retrospective study to assess the metric as a function of the sotalol concentration. Since sotalol leads to an increased dispersion of the repolarization times, due to the block of the beta-adrenergic receptors, it provides a good test bench for the V-index. Briefly, 12-lead digital ECG recordings of 38 healthy subjects were collected in three consecutive days. At the first day no drugs were administrated. A 160-mg dose of sotalol was injected at the second day and 320-mg dose at the third one. The serum concentration of the drug was assessed at predefined intervals during the second and the third days. The QT interval and the V-index were computed at the same instants to support a proper comparison. The goals were as follows: evaluation of i) sensitivity of the metric to the effects of the drug and ii) time evolution of the metric as a function of serum concentration. All measures were collected during rest conditions and only on stable beats. A beat was defined stable whether its RR value was within of an interval of 20 ms around the local mean. The metric showed a different mean value in presence of sotalol (baseline: 26.17 ± 9.23 ms vs single-drug dose: 36.00 ± 14.51 ms; p b 0.001 paired t-test). The cross-correlation among QT and V-index showed a high level of similarity (N0.9, p b 0.001). The results confirmed a study performed on the same data set using only the QT interval (Extramiana et al. 2010, Ann Noninvasive Electrocardiol). Further studies are still necessary, but the research showed that quantification of repolarization heterogeneity through the V-index is effective. Moreover, being directly linked to a physiological model, the Vindex could offer additional insights in risk stratification.

Increased Propensity to Arrhythmia in Patients with Myocardial Bridging

PP-306 Increased risk of lethal ventricular arrhythmia is generally caused by increased heterogeneity of ventricular repolarization probably due to ischemia or myocardial disarray. Recently novel parameters derived from T wave and QT interval and representative of increased electrical heterogeneity

Effects of hypokalemia on transmural dispersion of ventricular repolarization in left ventricular myocardium

ObjectiveTo observe effects of hypokalemia on transmural heterogeneity of ventricular repolarization in left ventricular myocardium of rabbit, and explore the role of hypokalemia in malignant ventricular arrhythmia (MVA). MethodsA total of 20 rabbits were randomly divided into control group and hypokalemic group. Isolated hearts in the control group were simply perfused with modified Tyrode's solution, and were perfused with hypokalemic Tyrode's solution in hypokalemic group. Ventricular fibrillation threshold (VFT), 90% monophasic action potential repolarization duration (APD90) of subepicardial, midmyocardial and subendocardial myocardium, transmural dispersion of repolarization (TDR) and C×43 protein expression in three layers of myocardium were measured in both groups. ResultsVFT in the control group and the hypokalemic group were (13.40±2.95) V, and (7.00±1.49) V, respectively. There was a significant difference between two groups (P<0.01). APD90 of three myocardial layers in the hypokalemic group were significantly prolonged than those in the control group (P<0.01). ΔAPD90 in the hypokalemic group and the control group were (38.10±10.29) ms and (23.70±5.68) ms, and TDR were (52.90±14.55) ms and (36.10±12.44) ms, respectively. ΔAPD90 and TDR in the hypokalemic group were significantly higher than those in the control group (P<0.05), and the increase in APD90 of midmyocardium was more significant in the hypokalemic group. Cx43 protein expression of all three myocardial layers were decreased significantly in the hypokalemic group (P<0.01), and ΔCx43 was significantly increased (P<0.05). Reduction of Cx43 protein expression was more significant in the midmyocardium. ConclusionsHypokalemic can increase transmural heterogeneity of C×43 expression and repolarization in left ventricular myocardium of rabbit, and decrease VFT and can induce MVA more easily.

Circulation: Clinical Summaries

<i>Circulation:</i> Clinical Summaries

Abstract 19613: Ventricular Repolarization in Transient Apical And Midventricular Ballooning

The aim of the present study was to assess potential differences in cardiac repolarization dynamics in patients with transient left ventricular apical ballooning syndrome (AB) and the midventricular variant (MB). Even though repolarization abnormalities and QT interval prolongation in the surface electrocardiogram (ECG) have been consistently reported, repolarization dynamics have not yet been investigated in the AB and MB variants. We hypothesized that differences in regional sympathetic denervation may induce differential effects on cardiac repolarization. METHODS: In a prospective single-center study, 49 consecutive patients with transient left ventricular dysfunction syndrome underwent 3-channel-Holter-ECG-recording on the third day after admission. A total of 27 recordings of patients with AB and 10 recordings of patients with MB were valid for beat-to-beat-QT-interval-analyses. RESULTS: There were no significant differences in baseline clinical characteristics between AB and MB patients. Patients with MB showed significantly lower values for mean RR interval (835 ± 104 vs. 908 ± 118 ms; P&lt;.05). Both, Bazett- and Fridericia-corrected QT-intervals were significantly longer in MB patients (QTcB 441.9 ± 38 vs. 483.4 ± 40ms; P&lt;.05; QTcF 435.0 ± 36 vs.469.4 ± 36.5 ms; P&lt;.05). Parameters of QT-interval variability (QTSD) and QT-interval dynamicity (QT/RR-slope) also exhibited significant differences between groups (diagram). CONCLUSION: There are significant differences in cardiac repolarization between AB and MB syndromes. Patients with MB show more prolonged QT-intervals and a higher degree of heterogeneity of ventricular repolarization. Thus, regional midventricular sympathetic denervation may be associated with even higher arrhythmic risk in transient left ventricular dysfunction syndrome.

The Effect of Diabetes Mellitus on the Ventricular Epicardial Activation and Repolarization in Mice

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.

QT wave dispersion in patients with panic disorder

QT dispersion (QTd), defined as the maximal inter-lead difference in QT intervals on 12 leads of the surface electrocardiogram (ECG), reflects the regional heterogeneity of ventricular repolarization and has been suggested as an important marker for risk of arrhythmia in addition to the QT interval. Some investigators proposed that it might be a predisposing factor for arrhythmic events and sudden death. Thus, we aimed to investigate whether QTd differs in patients with panic disorder from that in healthy controls. In 40 panic disorder patients and 40 healthy controls, Q(max), Q(min), and QTd values were measured. In addition, the Hamilton depression rating scale and the panic agoraphobia scale were scored for both patients and healthy volunteers. Q(max) and Q(min) values in the panic disorder patients were significantly higher than those in healthy controls. The mean corrected QTd was significantly greater in the patients than in the controls. One-way analysis of covariance (ANCOVA; using left atrial size, age and heart rate as covariates) also corrected the significant difference. In addition, ANCOVA revealed a significant main effect for the diagnosis, indicating a significantly higher QTd for patients compared with controls. QTd might be associated with panic disorder. Future studies in larger samples evaluating the effects of treatment are required.

Doxorubicin-induced Changes of Ventricular Repolarization Heterogeneity: Results of a Chronic Rat Study

Anthracycline chemotherapy produces cardiac repolarization abnormalities and arrhythmias because of cardiac toxicity of drugs. Ventricular arrhythmogenesis is attributable to increase in repolarization heterogeneity that is characterized by spatial dispersion of repolarization. The purpose of this work was to study the delayed effects of doxorubicin, the most frequently used anthracycline, on repolarization heterogeneity of the ventricular epicardium. Doxorubicin was administered to rats in a cumulative dose of 15 mg/kg (six equal intraperitoneal injections over a period of 2 weeks). Six weeks after the last injection, electrophysiological mapping of the ventricular epicardium was performed by sequential superimposition of a 64-electrode array on the left ventricular base, left ventricular apex, right ventricular base, and right ventricular apex. Activation-recovery intervals (ARIs) were measured. In doxorubicin-treated rats, ARIs were inhomogeneously prolonged, the overall ARI dispersion and local ARI dispersions were increased, and the interregional differences in ARI dispersion were decreased. These data demonstrate that doxorubicin-induced inhomogeneous prolongation of repolarization of the ventricular epicardium results in increasing heterogeneity of ventricular repolarization because of increasing intraregional heterogeneity while interregional differences are lost. Repolarization of the right ventricle is more sensitive to doxorubicin than that of the left one.

Enhanced Transmural Dispersion of Repolarization in Patients with J Wave Syndromes

Recently, great attention has been paid to the risk stratification of asymptomatic patients with an electrocardiographic early repolarization (ER) pattern. We investigated several repolarization parameters including the Tpeak-Tend interval and Tpeak-Tend/QT ratio in healthy individuals and patients with J wave syndrome who were aborted from sudden cardiac death. Ninety-two subjects were enrolled: 12 patients with ventricular fibrillation associated with J waves, 40 healthy subjects with an uneventful ER pattern and 40 healthy control subjects (C) without any evident J waves. Using ambulatory electrocardiogram recordings, the average QT interval, corrected QT interval (QTc), Tpeak-Tend (Tp-e) interval, which is the interval from the peak to the end of the T wave, and Tp-e/QT ratio were calculated. Using ANOVA and post hoc analysis, there was no significant difference in the average QT and QTc in all 3 groups (QT; 396 ± 27 vs 405 ± 27 vs 403 ± 27 m, QTc; 420 ± 26 vs 421 ± 21 vs 403 ± 19 milliseconds in the C, ER pattern and J groups, respectively). The Tp-e interval and Tp-e/QT ratio were significantly more increased in the J wave group than the ER Pattern group (Tp-e: 86.7 ± 14 milliseconds vs 68 ± 13.2 milliseconds, P < 0.001, Tp-e/QT; 0.209 ± 0.04 vs 0.171 ± 0.03, P < 0.001), but they did not significantly differ between the C and ER pattern groups (Tp-e: 68.6 ± 7.5 vs 68 ± 13.2, P = 0.97, Tp-e/QT 0.174 ± 0.02 vs 0.171 ± 0.03, P = 0.4). As novel markers of heterogeneity of ventricular repolarization, Tpeak-Tend interval and Tp-Te/QT ratio are significantly increased in patients with J wave syndromes compared to age and sex-matched uneventful ER.

Remodeling of ventricular repolarization in a chronic doxorubicin cardiotoxicity rat model

Doxorubicin, one of the most effective anticancer drugs, is characterized by severe cardiotoxic effects, which induce cardiac remodeling and congestive heart failure. The aim of the study was to evaluate remodeling of ventricular repolarization heterogeneity in chronic doxorubicin cardiotoxicity in rats. Doxorubicin cardiotoxicity was produced by six equal intraperitoneal injections of the drug in a cumulative dose of 15 mg/kg in a 2-week period. Electrophysiological mapping of the ventricular epicardium in situ was performed 6 weeks after the last injection of doxorubicin. Activation-recovery intervals (ARIs) were used for the evaluation of the heterogeneity in repolarization durations. The major findings were as follows: (1) ARIs on the ventricular epicardium of both ventricles were significantly prolonged in the doxorubicin group and (2) this inhomogeneous prolongation of ARIs on the ventricular epicardium resulted in (i) the increase in the dispersion of repolarization across the ventricular epicardium and (ii) the inhomogeneous alterations of the regional ARI gradients on the ventricular epicardium. These changes in repolarization could explain the electrocardiographic alterations, that is, the prolongation of the QT interval and flattening of the T wave.

Increased dispersion of ventricular repolarization in emery dreifuss muscular dystrophy patients

SummaryBackgroundSudden cardiac death (SCD) is common in patients with Emery-Dreifuss muscular dystrophy (EDMD) and is attributed to the development of life-threatening arrhythmias that occur in the presence of normal left ventricular systolic function. Heterogeneity of ventricular repolarization is considered to provide an electrophysiological substrate for malignant arrhythmias. QTc dispersion (QTc-D) and JTc dispersion (JTc-D) are electrocardiographic parameters indicative of heterogeneity of ventricular repolarization. The aim of our study was to evaluate the heterogeneity of ventricular repolarization in patients with Emery-Dreifuss muscular dystrophy with preserved systolic and diastolic cardiac functionMaterial/MethodsThe study involved 36 EDMD patients (age 20±12, 26 M) and 36 healthy subjects used as controls, matched for age and sex. Heart rate, QRS duration, maximum and minimum QT and JT interval, QTc-D and JTc-D measurements were performed.ResultsCompared to the healthy control group, the EDMD group presented increased values of QTc-D (82.7±44.2 vs. 53.1±13.7; P=0,003) and JTc-D (73.6±32.3 vs. 60.4±11.1 ms; P=0.001). No correlation between QTc dispersion and ejection fraction (R=0.2, P=0.3) was found.ConclusionsOur study showed a significant increase of QTc-D and JTc-D in Emery-Dreifuss muscular dystrophy patients with preserved systolic and diastolic cardiac function.

Novel indexes of heterogeneity of ventricular repolarization in subjects with early repolarization pattern

The presence of early repolarization (ER) in inferior or inferolateral leads has been associated with malignant arrhythmias and increased mortality. Transmural dispersion of repolarization (TDR) has been proposed to underlie arrhythmogenesis in J-wave syndromes. The present study investigated specific electrocardiographic (ECG) markers including Tpeak-Tend interval and (Tpeak-Tend)/QT ratio that reflect TDR in subjects with ER. The ECGs of 47 healthy individuals (43 males, mean age: 45.7 ± 13.1 years) with an ER pattern in lateral (n = 15) or infero-lateral leads (n = 32) who successfully completed an exercise stress test were analysed at rest, peak workload, and recovery. The ER pattern was defined as slurring or notching of the terminal part of the QRS complex (J-point) ≥ 1 mm, in at least two contiguous leads. Thirty-five age- and sex-matched healthy subjects without ER (28 males, mean age: 48.6 ± 10.2 years) served as comparative controls. Subjects with ER displayed increased Tpeak-Tend interval in lead V(2), Tpeak-Tend dispersion of the precordial leads, and (Tpeak-Tend)/QT ratio in lead V(2) compared with those without ER in all three phases of the exercise test (P < 0.05). In addition, Tpeak-Tend dispersion and the (Tpeak-Tend)/QT ratio in lead V(2) were significantly increased at recovery phase compared with peak exercise only in subjects with ER (P< 0.05). There were no significant differences among the studied ECG parameters regarding the ER location (lateral vs. infero-lateral), the ER type (slurring or notching), or the maximum J-point amplitude (≥ 1.5 vs. <1.5 mm) at baseline ECGs. Individuals with ER display an increased TDR that may be related to an increased arrhythmic risk.

Heterogeneity of Ventricular Repolarization in Newborns With Severe Aortic Coarctation

Sudden death is a possible occurrence for newborns younger than 1 year with severe aortic coarctation (CoA) before surgical correction. Basic research and animal experiments have shown electrophysiologic changes during mechanical ventricular pressure overload. The current study aimed to evaluate the effect of severe CoA on the heterogeneity of ventricular repolarization by examining corrected QT and JT interval dispersion (respectively, QTc-D and JTc-D) and electrocardiographic parameters of spatial heterogeneity of ventricular repolarization in newborns with no associated congenital cardiac malformations. The study enrolled 30 isolated severe CoA neonates (age, 45 ± 15 days; 17 males) with normal size and wall thickness of the left ventricle before surgical correction and 30 age- and sex-matched healthy newborns used as control subjects. Heart rate, QRS duration, maximum and minimum QT and JT intervals, and QTc-D and JTc-D measurements were performed. The healthy control group did not significantly differ from the CoA group in terms of heart rate, weight, height, and echocardiographic parameters. Compared with the healthy control group, the CoA group presented significantly increased values of QTc-D (109.7 ± 43.4 vs. 23 ± 15 ms; P = 0.03) and JTc-D (99.1 ± 43.3 vs. 65.8 ± 24.1 ms; P = 0.04). A statistically significant correlation was found between the Doppler peak pressure gradient across the coarctation site and the values of QTc-D (r = 0.48; P = 0.03) and JTc-D (r = 0.42; P = 0.04). Our study showed significantly increased QTc-D and JTc-D in isolated CoA newborns with normal left ventricular geometry.

Repolarization heterogeneity and rate dependency in a canine rapid pacing model of heart failure

BackgroundRepolarization heterogeneity and rate dependency have long been established as factors contributing to arrhythmogenic risk. However, there are conflicting observations regarding the nature and extent of ventricular repolarization heterogeneity that complicate understanding of arrhythmogenic mechanisms. To explore these disparate findings, we studied ventricular repolarization heterogeneity and rate dependency in a canine, rapid pacing model of heart failure. Methods and ResultsWe studied ventricular repolarization heterogeneity and rate dependency in 10 canine hearts (5 normal and 5 after 1 month of rapid pacing at 240 beats per minute) by analyzing 64 body surface electrocardiograms, 64 epicardial, and 190 intramural plunge electrograms. We estimated mean ventricular depolarization and repolarization times from R- and T-wave peaks of the root-mean-square electrocardiogram (body surface) and local depolarization and repolarization times using activation-recovery interval (ARI) methods from recordings obtained during a range of fixed rate pacing. In addition, we estimated local epicardial and transmural gradients of ARIs to assess cardiac locations of greatest spatial repolarization heterogeneity. We compared changes in repolarization at different rates between normal and heart failure hearts. Findings documented prolongation of repolarization, repolarization rate dependency, and increased repolarization gradients in the heart failure hearts compared with control as observed from body surface, epicardial, and transmural measurements. Maximum local epicardial and intramural ARI gradients were comparable both in heart failure and control hearts. Intramural ARI distributions tended to be more irregular in the heart failure hearts compared with the systematic epicardium to endocardium ARI increase observed in control animals. ConclusionsThis study documented prolongation of repolarization, increase in both epicardial and transmural repolarization gradients, and irregularity of transmural distribution in a rapid pacing canine model of heart failure compared with control animals. The findings support previously published results of increased repolarization heterogeneity and repolarization prolongation observed in rapid pacing models of heart failure. New findings are the irregularity of transmural heterogeneity and the ability of noninvasive root-mean-square electrocardiogram R-T intervals to estimate mean ventricular repolarization duration in the setting of rapid pacing models of heart failure. These findings suggest increased arrhythmogenic risk in this model and potentially in patients with heart failure.