Transmural Dispersion Research Articles

Is there a relationship between epicardial fat tissue thickness and Tp-Te/QT ratio in healthy individuals?

IntroductionEpicardial fat is a tissue that releases many proinflammatory and atherogenic mediators, with endocrine and paracrine effects on the heart. In this study, the implication of the EFT thickness (EFTt) on transmural dispersion of repolarisation (TDR) was analysed utilizing the T-wave peak to end interval (Tp-Te), the Tp-Te dispersion (Tp-Te (d)), and the Tp-Te/QT ratio.Material and methodsOne thousand seven hundred and thirteen subjects were enrolled in the research. The subjects were chosen to be healthy individuals, without any cardiovascular/systemic disorders or risk factors for atherosclerosis. Transthoracic echocardiography (TTE) was applied to all subjects, and EFTt was measured in both diastole and systole. The ECG measurements were taken from standard 12-lead surface ECG.ResultsCorrelation analysis revealed that the EFTt is highly associated with the Tp-Te interval, Tp-Te/QT ratio, Tp-Te (d), increasing age, body mass index (BMI), body surface area (BSA), left ventricular (LV) mass, LV mass index, plasma glucose during fasting, triglycerides, and low-density lipoprotein cholesterol.ConclusionsThe study results showed that increased EFTt was associated with increased TDR values of Tp-Te, Tp-Te (d), and Tp-Te/QT ratio, even in the absence of other factors that could increase TDR and EFTt. Therefore, it can be stated that increased EFTt may cause an increase the risk for ventricular arrhythmia.

Pro-arrhythmic Effects of Hydrogen Sulfide in Healthy and Ischemic Cardiac Tissues: Insight From a Simulation Study

Hydrogen sulfide (H2S), an ambient air pollutant, has been reported to increase cardiac events in patients with cardiovascular diseases, but the underlying mechanisms remain not elucidated. This study investigated the pro-arrhythmic effects of H2S in healthy and ischemic conditions. Experimental data of H2S effects on ionic channels (including the L-type Ca2+ channel and ATP-sensitive K+ channel) were incorporated into a virtual heart model to evaluate their integral action on cardiac arrhythmogenesis. It was shown that H2S depressed cellular excitability, abbreviated action potential duration, and augmented tissue’s transmural dispersion of repolarization, resulting in an increase in tissue susceptibility to initiation and maintenance of reentry. The observed effects of H2S on cardiac excitation are more remarkable in the ischemic condition than in the healthy condition. This study provides mechanistic insights into the pro-arrhythmic effects of air pollution (H2S), especially in the case with extant ischemic conditions.

Predictive value of Tpeak-Tend interval for ventricular arrhythmia and mortality in heart failure patients with an implantable cardioverter-defibrillator: A cohort study.

Background:Tpeak-Tend interval (TpTe), a measurement of transmural dispersion of repolarization (TDR), has been shown to predict ventricular tachyarrhythmia in cardiac resynchronization therapy with defibrillator (CRT-D) patients. However, the ability of TpTe to predict ventricular tachyarrhythmia and mortality for heart failure patients with a cardioverter-defibrillator (ICD) is not clear. The purpose of this study was to assess the predictive ability of TpTe in heart failure patients with ICD.Methods and results:We enrolled 318 heart failure patients treated after ICD. Patients were divided into 3 groups according to their post-implantation TpTe values and were evaluated every 6 months. The primary endpoint was appropriate ICD therapy. The secondary endpoint was all-cause mortality. During long-term follow-up, the TpTe > 110 ms group (n = 111) experienced more VT/VF episodes (45%) and all-cause mortality (25.2%) than the TpTe 90–110 ms group (n = 109) (26.4%, 14.5%) and TpTe < 90 ms group (n = 98) (11.3%, 11.3%) (overall P < .05, respectively). In Cox regression, longer post-implantation TpTe was associated with an increased number of VT/VF episodes [HR: 1.017; 95% CI: 1.008-1.026; P < .001], all-cause mortality [HR: 1.015; 95% CI: 1.004-1.027; P = .010] and the combined endpoint [HR: 1.018; 95%CI: 1.010-1.026; P < .001].Conclusions:Post-implantation TpTe was an independent predictor of both ventricular arrhythmias and all-cause mortality in heart failure patients with an implanted ICD.

A new electrocardiographic parameter associated with sudden cardiac death in pulmonary sarcoidosis.

IntroductionThe interval from the peak to the end of the electrocardiographic T wave (Tp–Te) may correspond to malignant ventricular arrhythmias. In this study we aimed to assess Tp–Te variability and investigate the transmural dispersion of repolarisation in pulmonary sarcoidosis disease without proofed cardiac involvement.Material and methodsThis was a retrospective case-control study that included patients who had a pathologic and radiologic diagnosis of sarcoidosis. All data of the patients’ demographic features and electrocardiographs were analysed.ResultsWe enrolled 78 patients with sarcoidosis and 54 healthy volunteers as controls in our study. Men comprised 36% of the sarcoidosis group and 27% of controls. The mean age in the sarcoidosis and control group was 45.4 ±8.7 years (range: 23–58 years) and 44.6 ±11.9 years (range: 21–73 years), respectively. There was no significant difference between the groups for age or sex (p = 0.654, p = 0.246, respectively). There was a significant increase in Tp–Te results in all precordial leads in the sarcoidosis group compared with the control group (p < 0.05).ConclusionsPulmonary sarcoidosis is suspected to have cardiac involvement; therefore, we need to develop new approaches. We present strong evidence that Tp–Te intervals were increased in patients with pulmonary sarcoidosis, which suggests that there may be a link between sarcoidosis and ventricular arrhythmias without proofed cardiac involvement.

Effects of Dexmedetomidine on Myocardial Repolarization in Children Undergoing General Anesthesia: A Randomized Controlled Trial.

Dexmedetomidine is a highly selective α2-adrenergic agonist, which is increasingly used in pediatric anesthesia and intensive care. Potential adverse effects that have not been rigorously evaluated in children include its effects on myocardial repolarization, which is important given that the drug is listed as a possible risk factor for torsades de pointes. We investigated the effect of 3 different doses of dexmedetomidine on myocardial repolarization and transmural dispersion in children undergoing elective surgery with total IV anesthesia. Sixty-four American Society of Anesthesiologists I-II children 3-10 years of age were randomized to receive dexmedetomidine 0.25 µg/kg, 0.5 µg/kg, 0.75 µg/kg, or 0 µg/kg (control), as a bolus administered over 60 seconds, after induction of anesthesia. Pre- and postintervention 12-lead electrocardiograms were recorded. The interval between the peak and the end of the electrocardiogram T wave (Tp-e; transmural dispersion) and heart rate-corrected QT intervals (myocardial repolarization) were measured by a pediatric electrophysiologist blinded to group allocation. Data were analyzed using an analysis of covariance regression model. The study was powered to detect a 25-millisecond difference in Tp-e. Forty-eight children completed the study, with data analyzed from 12 participants per group. There were no instances of dysrhythmias. Tp-e values were unaffected by dexmedetomidine administration at any of the studied doses (F = 0.09; P = .96). Mean (99% CI) within-group differences were all <2 milliseconds (-5 to 8). Postintervention, corrected QT interval increased in the control group, but decreased in some dexmedetomidine groups (F = 7.23; P < .001), specifically the dexmedetomidine 0.5 and 0.75 µg/kg doses. Within groups, the mean (99% CI) differences between pre- and postintervention corrected QT interval were 12.4 milliseconds (-5.8 to 30.6) in the control group, -9.0 milliseconds (-24.9 to 6.9) for dexmedetomidine 0.25 µg/kg, -18.6 milliseconds (-33.7 to -3.5) for dexmedetomidine 0.5 µg/kg, and -14.1 milliseconds (-27.4 to -0.8) for dexmedetomidine 0.75 µg/kg. Of the bolus doses of dexmedetomidine studied, none had an effect on Tp-e and the dexmedetomidine 0.5 and 0.75 µg/kg doses shortened corrected QT intervals when measured at 1 minute after dexmedetomidine bolus injection during total IV anesthesia. There is no evidence for an increased risk of torsades de pointes in this context.

Sevoflurane Alleviates Reperfusion Arrhythmia by Ameliorating TDR and MAPD90 in Isolated Rat Hearts after Ischemia-Reperfusion.

Objective To investigate the effect of sevoflurane on the monophasic action potentials (MAPs) in isolated rat hearts after ischemia-reperfusion. Methods Twenty-four healthy SD male rats, weighing 280–320 g, were randomly divided into three groups after successful preparation of a Langendorff isolated heart perfusion model with a stabilization period perfusion of 15 min with Krebs–Henseleit (K–H) fluid (n = 8): the control group (group A, continuously perfused with K–H fluid for 105 min), the ischemia-reperfusion group (group B, continuously perfused with K–H fluid for 15 min, and then exposed to 60 min of global ischemia induced by Thomas solution followed by 30 min of reperfusion), and the sevoflurane group (group C, K–H fluid contained 1.0 MAC sevoflurane, and other procedures were same as in group B). Heart rate (HR) and MAPs including time course (MAPD50 or MAPD90) of the epicardium (Epi) and endocardium (Endo) were recorded at the time of balance perfusion for 15 min (T0), continuous perfusion for 15 min (T1), reperfusion for 15 min/continuous perfusion for 105 min (T2), and reperfusion for 30 min/continuous perfusion for 120 min (T3), and the transmural dispersion of repolarization (TDR) was calculated. The incidence of arrhythmia, time for restoration of spontaneous heart beat, and duration of arrhythmia were recorded during the period of reperfusion. Results HR in group B and group C was lower at T2 and T3 than that in group A, while that in group B was significantly lower than that in group A at T2 and T3, and HR in group C was higher than that in group B at T2 and T3 (P < 0.05). There was no difference of TDR in each group at T0 and T1 (P > 0.05), while TDR in group B was increased at T2 and T3 compared with that in group C and group A (P < 0.05). TDR in group C was decreased compared with that in group B at T2 and T3 (P < 0.05), while there was no such difference between group C and group A (P > 0.05). The time for restoration of spontaneous heart beat and duration of arrhythmia in group C were shorter than those in group B (P < 0.05), while cardiac arrhythmia scores in group B were higher than those in group C (P < 0.05). There was no difference of MAPD50 in each group (P > 0.05). The MAPD90 in group B was much longer than that in other groups at T2 and T3 (P < 0.05), while there was no such difference between group C and group A (P > 0.05). The prolonged MAPD90 at T2 and T3 in group B strikingly differed from that at T0 and T1 (P < 0.05). Nevertheless, there was no such difference in other groups at different time points (P > 0.05). Conclusion Sevoflurane alleviates reperfusion arrhythmia induced by myocardial ischemia-reperfusion through the shortening of MPAD90 in isolated rat hearts.

Experimental verification of the value of the Tpeak -Tend interval in ventricular arrhythmia inducibility in an early repolarization syndrome model.

In patients with early repolarization patterns on ECG, many researchers have studied to find predictors of fatal arrhythmia. However, there are no satisfying clinical predictors. We evaluated the value of the Tpeak -Tend interval on pseudo-ECG in canine myocardial wedge preparation models of early repolarization syndrome. Transmural pseudo-ECG and endocardial/epicardial action potentials were recorded from coronary-perfused canine left ventricular wedge preparations (n = 34). The Ito agonist NS5806 (8-10 µM), the calcium channel blocker verapamil (3 µM) and acetylcholine (2-3 µM) were used to mimic the disease model. A ventricular arrhythmia induction test was performed. QTpeak , QTend , Tpeak -Tend , and Tpeak -Tend /QTend were measured at 15 to 20 minutes after the provocative agent infusion. Polymorphic ventricular tachycardias (pVT) developed in 23 of the 34 preparations (67%). The maximal values of Tpeak -Tend and Tpeak -Tend /QTend were recorded just before pVT induction. At baseline, without the provocative agents, Tpeak -Tend and Tpeak -Tend /QTend were not different between pVT-induced and pVT-noninduced preparations. The Tpeak -Tend of the pVT-induced preparations was longer than that of non-induced preparations (58 ± 26.8 msec vs 33 ± 6.8 msec, P < .001). The Tpeak -Tend /QTend of pVT- induced preparations was larger than that of noninduced preparations (0.220 ± 0.1017 vs 0.128 ± 0.0312, P < .001). The transmural and epicardial dispersion of repolarization of pVT-induced preparations were larger than those of pVT-noninduced preparations. The transmural dispersion of repolarization showed a positive correlation with Tpeak -Tend . Tpeak -Tend predicted malignant ventricular arrhythmias in early repolarization syndrome models. Tpeak -Tend reflects the repolarization heterogeneity of ventricular myocardium.

ECG changes and markers of increased risk of arrhythmia in patients with myocardial bridge

BackgroundThe clinical significance and prognosis of myocardial bridge (MB) is still a matter of debate. ObjectivesTo assess the novel ECG markers of T peak-to-end (Tp-e) interval, transmural dispersion of repolarization (TDR), is assessed by Tp-e/QT ratio, and index of electrophysiogical index(iCEB),is defined by QT/QRS ratio and changes (ST-T changes) in MB patients. Patients and methodsForty one patients who were diagnosed as having MB (MB group) and other 41 patients without MB (non-MB group) at multi-detector CT (MDCT) exam matched by age, sex were enrolled in the study. ResultsiCEB was significantly increased in MB group in comparison to non-MB group particularly in patients with no coronary atherosclerosis (5.3 Vs 4.5, p = 0.04). Tp-e and TDR values were decreased in MB in comparison to non-MB patients particularly in patients with coronary atherosclerosis (69 Vs 80, p = 0.003 and 0.18 Vs 0.2, p = 0.01 respectively). Isolated T inversion in V1 was observed more in MB compared to non-MB patients (58% Vs 5%, p ≤ 0.0001) particularly in patients without coronary atherosclerosis. ConclusionMB patients have shown decreased Tp-e and TDR markers particularly in MB patients with coronary atherosclerosis.

Endocardial biventricular pacing for chronic heart failure patients: Effect on transmural dispersion of repolarization.

Background and AimConventional epicardial cardiac resynchronization therapy (CRT) can cause fatal arrhythmia associated with increased transmural dispersion of repolarization (TDR). It is unknown whether endocardial biventricular pacing in various locations will decrease TDR and hence the occurrence of fatal arrhythmia. This study aimed to find out the most effective location of endocardial biventricular pacing resulting in the shortest homogenous TDR.MethodsA before‐and‐after study on adult chronic heart failure (CHF) patients undergoing endocardial biventricular pacing in several defined locations. The changes in TDR from baseline were compared among various pacing locations.ResultsFourteen subjects were included with age ranged 36‐74 years old, of which 10 were males. Location revealed the highest post biventricular pacing TDR (113.4 (SD 13.8) ms) was the outlet septum of right ventricle in combination with lateral wall of left ventricle (RVOTseptum‐LVlateral) while the lowest one (106.1 (SD 11.6) ms) was of the right ventricular apex and posterolateral left ventricle (RVapex‐LVposterolateral). Two CRT locations resulted in the most homogenous TDR, that is the right ventricular apex ‐ left ventricular lateral wall (RVapex‐LVlateral, mean difference −9.43; 95% CI (−19.72;0.87) ms, P = 0.07) and right ventricular apex ‐ left ventricle posterolateral wall (RVapex‐LVposterolateral, mean difference −6.85; 95% CI (−13.93;0.22) ms, P = 0.056).ConclusionEndocardial biventricular pacing on right ventricular apex and left ventricular lateral/posterolateral walls results in the most homogenous TDR.

Effect of sevoflurane on electrophysiological stability of isolated rat hearts subjected to hypothermic perfusion

Objective To evaluate the effect of sevoflurane on the electrophysiological stability of isolated rat hearts subjected to hypothermic perfusion. Methods Clean-grade healthy adult male Sprague-Dawley rats, weighing 280-360 g, were heparinized and anesthetized with pentobarbital sodium.Their hearts were excised and perfused in a Langendorff apparatus with K-H solution saturated with 95% O2-5% CO2 at 37 ℃.Twenty-four Langendorff-perfused hearts were divided into 4 groups (n=6 each) using a random number table method: control group (C group), sevoflurane group (S group), 32 ℃ hypothermia group (H group) and 32 ℃ hypothermia plus sevoflurane group (HS group). After 15 min of equilibration, the isolated hearts were continuously perfused for 30 min with K-H solution at 37 ℃, with K-H solution containing 2.3% sevoflurane at 37 ℃, with K-H solution at 32 ℃, and with K-H solution containing 2.3% sevoflurane at 32 ℃ in C, S, H and HS groups, respectively.Heart rate and monophasic action potential in three layers of the left ventricular anterior wall were recorded at 15 min of equilibration (T0) and 30 of continuous perfusion (T2), the transmural dispersion of repolarization (TDR) were calculated, and the occurrence of arrhythmia was observed. Results Compared with C and S groups, the heart rate was significantly decreased and TDR was enlarged at T1, and the incidence of arrhythmia was increased in H and HS groups (P<0.05). Compared with H group, TDR was significantly reduced at T1, and the incidence of arrhythmia was decreased in HS group (P<0.05). Conclusion Sevoflurane can improve the electrophysiological instability of isolated rat hearts subjected to hypothermic perfusion, and thus decrease the development of arrhythmia. Key words: Anesthetics, inhalation; Hypothermia; Cardiac electrophysiology

Bupivacaine Toxicity Increases Transmural Dispersion of Repolarization, Developing of a Brugada-like Pattern and Ventricular Arrhythmias, Which is Reversed by Lipid Emulsion Administration. Study in an Experimental Porcine Model.

Unintentional administration of bupivacaine may be associated with electrocardiogram changes that promote the development cardiac arrhythmias. Ventricular repolarization markers (corrected QT, QT dispersion, Tpeak-Tend and Tpeak-Tend dispersion) are useful to predict cardiac arrhythmias. We aim to investigate the effects of bupivacaine on the transmural dispersion of repolarization and their reversion following intravenous lipid emulsion (ILE) administration. Fourteen pigs were anaesthetized with thiopental and sevoflurane and underwent tracheal intubation. After instrumentation, a 4mgkg-bolus of bupivacaine was administrated followed by an infusion of 100µgkg-1min-1. QT interval, QTc:QT corrected by heart rate, Tpeak-to-Tend interval and QT and Tpeak-to-Tend dispersion were determined in a sequential fashion: after bupivacaine (at 1min, 5min and 10min) and after ILE (1.5mLkg-1 over 1min followed by an infusion of 0.25mLkg-1min-1). Three additional animals received only ILE (control group). Bupivacaine significantly prolonged QT interval (∆:36%), QT dispersion (∆:68%), Tpeak-to-Tend (∆:163%) and Tpeak-to-Tend dispersion (∆:98%), from baseline to 10min. Dispersion of repolarization was related to lethal arrhythmias [three events, including asystole, sustained ventricular tachycardia (VT)] and repeated non-sustained VT (4/14, 28%). A Brugada-like-ECG pattern was visualized at V1-4 leads in 5/14 pigs (35%). ILE significantly decreased the alterations induced by bupivacaine, with the termination of VT within 10min. No ECG changes were observed in control group. Bupivacaine toxicity is associated with an increase of transmural dispersion of repolarization, the occurrence of a Brugada-like pattern and malignant VA. ILE reverses the changes in dispersion of repolarization, favouring the disappearance of the Brugada-like pattern and VT.

Effects of esmolol on QTc interval changes during tracheal intubation: a systematic review

Introduction and aimsEsmolol is an ultra-short-acting β1 antagonist that has been shown to attenuate the corrected QT (QTc) interval prolongation associated with laryngoscopy and endotracheal intubation (LTI). Prolongation of the...

Comparing of Tp-Te Interval and Tp-Te/Qt Ratio in Patients with Preserved, Mid-Range and Reduced Ejection Fraction Heart Failure.

BACKGROUND:Heart failure (HF) is classified in three class: HF with preserved EF (HFpEF); normal or LVEF ≥ 50%, HF with reduced EF (HFrEF); LEVF < 40% and newly HF mid-range EF (HFmrEF); LVEF 40-49%. On Electrocardiography (ECG) T wave, Tpeak-Tend (Tp-Te) interval reflects transmural dispersion of repolarisation (TDR) which of these indexes have been proposed as predictors of risk for ventricular arrhythmia (VA) in many cardiac diseases.AIM:Aim of this study to asses these indices of TDR among three HF class.METHODS:Total of 192 patients were included in this study.RESULTS:Many of indices like Tp-Te, Tp-Te/QT wasn’t different between groups (P > 0.05). But mean Q-Tpeak (QTp), S-Tend (S-Te) and S-Tpeak (S-Tp) were found significantly different between groups (P < 0.05). Again S-Te was found different according to having fragmented QRS (fQRS) on ECG (P = 0.031). Comparing to mitral inflow E/A parameters showed significant differences for Tp-Te, Tp-Tec, Tp-Te/QT, Tp-Te/QTc and Tp-Tec/QTc parameters. Finally, we found correlations between S-Te and white blood cell (WBC) (r = - 0.171; P = 0.037) and S-Tp and WBC (r = - 0.170; P = 0.038) and between S-Te and fQRS (r = 0.158; P = 0.031).CONCLUSIONS:We didn’t find differences for many of indices of TDR like Tp-Te interval between groups except QTp, S-Te, S-Tp intervals. Also, S-Te and fQRS showed significant correlation. For prediction of ventricular arrhythmia and cardiovascular death newer indexes on ECG are needed to be established in the future which will make us facilitate to distinguish high risk patients.

Twenty-Four-Hour Measures of Heart Rate-Corrected QT Interval, Peak-to-End of the T-Wave, and Peak-to-End of the T-Wave/Corrected QT Interval Ratio During Antipsychotic Treatment.

Prolonged ventricular repolarization, measured by heart rate-corrected QT interval (QTc) prolongation, might be a biomarker for risk of torsade de pointes (TdP) and sudden cardiac death. However, the predictive value of QTc has been challenged, and a component of QTc, peak-to-end of the T-wave (Tpe), and a high Tpe/QT ratio might be superior biomarkers because they better reflect increased transmural dispersion of ventricular myocyte repolarization, which can lead to TDP. The purpose of this pilot study was to provide the first measurements of heart rate, QTc, Tpe, Tpe/QTc, and their variability over 24 hours in medication-free patients with schizophrenia, during treatment with ziprasidone or other antipsychotic drugs, and healthy controls. Subjects included 12 patients treated with ziprasidone, 30 treated with other antipsychotic drugs, 3 unmedicated patients, and 15 normal controls. Subjects underwent 24-hour analog Holter recording, and the recordings were digitized. A cardiologist blind to treatment selected multiple 10-cycle segments throughout each recording and measured the electrocardiogram metrics. Variability in QTc, Tpe, and Tpe/QTc over the 24 hours was present in all groups; 91.1% of patients and 100% of controls had 1 or more QTc values of 450 milliseconds or greater. Mean QTc length was significantly greater in the ziprasidone-treated than the non-ziprasidone-treated patients (P = 0.02). Mean Tpe was not elevated in the ziprasidone patients, whereas mean Tpe/QTc was lower (P < 0.01). The large variability in QTc, Tpe, and Tpe/QTc observed supports the need for 24-hour electrocardiogram recordings to provide an accurate assessment of risk of TdP. Heart rate-corrected QT interval alone does not capture the risk of TdP.

Upregulation of MMP-9 and CaMKII prompts cardiac electrophysiological changes that predispose denervated transplanted hearts to arrhythmogenesis after prolonged cold ischemic storage

BackgroundAlthough the importance of the potential mechanisms of arrhythmogenesis, including cardiac electrophysiology dysfunction and gap junction electrical uncoupling by Cx43 degradation under pathological conditions, has been widely and thoroughly established, the correlations between these mechanisms and biomarkers of cold ischemic insult have not yet been confirmed. Limited evidence suggests that these biomarkers are significantly associated with cardiac dysrhythmia. Thus, in this study, we analyzed such correlations in denervated transplanted hearts. Methods and resultsRat hearts were divided into two groups according to a random number table. The hearts in the first group were stored in histidine-tryptophan-ketoglutarate (HTK) solution for 6 h to produce cold ischemic insult (insult group, n = 8), while the hearts in the second group were left untreated (control group, n = 8). Ventricular arrhythmias (VAs) were successively observed in 8/8 hearts stored in HTK solution and 0/8 untreated hearts (P < 0.05). The analysis of the electrophysiological parameters by programmed electrical stimulation (PES) and monophasic action potential (MAP) recording demonstrated that compared with the control hearts, the insult hearts had increased transmural dispersion of repolarization (TDR) and effective refractory periods (ERPs) (P < 0.001), decreased conduction velocities (CVs) and excitation wavelengths (CV × ERP, λ) (P < 0.05), and longer times between peak MAP values and 90% repolarization (MAPD90) in the epicardium (P < 0.05). However, no significant difference in endocardial MAPD90 was observed between the two groups of hearts. The investigation of biomarkers and Cx43 proteins by a western blot analysis showed that the matrix metalloproteinase-9 (MMP-9) and Ca2+/calmodulin-dependent protein kinase II (CaMKII) levels were strongly elevated and that the Cx43 protein levels were markedly reduced in the insult hearts. ConclusionMMP-9 overexpression mediates gap junction (GJ) electrical uncoupling induced by Cx43 decreases, while CaMKII upregulation induces transmural dispersion of repolarization (TDR) increase, both of which increase the risk of ventricular arrhythmias (VAs) in denervated transplanted hearts after prolonged cold ischemic storage.

Evaluation of myocardial dispersion of repolarization in patients with heart transplantation

Background/aimThe number of patients with heart transplantation has dramatically increased in the last decade. Considerable studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the transmural dispersion of repolarization and increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. We analyzed the dispersion of myocardial repolarization using electrocardiographic Tp-e interval and Tp-e/QTc ratio in patients with heart transplantation. Materials and methodsThis observational study included 38 patients (12 female and 26 male) with heart transplantation and 38 well-matched controls. From electrocardiograms, Tp-e interval and Tp-e/QTc ratio were calculated and compared between the 2 groups.ResultsNoninvasive arrhythmia indicators including Tp-e interval (84.63 ± 14.17 ms vs 71.82 ± 7.47 ms, P < 0.001), Tp-e/QTc ratio (0.19 ± 0.04 vs 0.16 ± 0.02, P < 0.001) and QTc interval except QT interval were significantly higher in transplanted hearts compared to normal hearts.ConclusionPatients with heart transplantation have increased myocardial dispersion of repolarization.

Antiarrhythmic effect of sevoflurane as an additive to HTK solution on reperfusion arrhythmias induced by hypothermia and ischaemia is associated with the phosphorylation of connexin 43 at serine 368

BackgroundReperfusion ventricular arrhythmia (RA) associated with hypothermic ischaemic storage is increasingly recognized as a substantial contributor to adverse consequences after heart transplantation. Ischemia- or hypothermia-induced gap junction (GJ) remodelling is closely linked to RA. Reducing GJ remodelling contributes to RA attenuation and is important in heart transplantation. However, sevoflurane has an antiarrhythmic effect associated with the connexin 43 (Cx43) protein that has not yet been fully established.MethodsHearts were divided into two groups according to a random number table: all hearts were arrested by an infusion of histidine-tryptophan-ketoglutarate (HTK) solution (4 °C) followed by (1) storage in HTK solution (4 °C) alone for 6 h (n = 8, Control group) or (2) storage in HTK solution supplemented with sevoflurane (2.5%) (4 °C) for 6 h (n = 8, Sevo-HTK group). First, the total Cx43 level and the phosphorylation of Cx43 at Ser368 (Cx43-pS368) were assessed by Western blotting, and the distribution of Cx43 was assessed by immunohistochemistry. Second, programmed electrical stimulation (PES) and monophasic action potential (MAP) recording were used to analyse the MAP duration (MAPD), conduction velocity (CV) and transmural repolarization dispersion (TDR). In addition, haematoxylin and eosin (HE) and terminal deoxynucleotidyl transferase-dUTP nick end labelling (TUNEL) staining were individually used to investigate the degree of myocardial pathological damage and cell apoptosis. Finally, bipolar electrograms were used to record the graft re-beating time and monitor RA during reperfusion for 15 to 30 min.ResultsSevo-HTK solution relatively increased the total Cx43 (P < 0.01) and Cx43-pS368 (P < 0.01) levels and prevented Cx43 redistribution (P < 0.05) and CV slowing (P < 0.001) but did not change TDR (P > 0.05). Additionally, the Cx43-pS368/total Cx43 ratio (P>0.05) was similar in the two groups. However, with Sevo-HTK solution, the graft re-beating times were shortened, myocardial pathological damage was ameliorated, and the number of apoptotic cells was markedly decreased.ConclusionThe reduction in hypothermia and ischaemia-induced reperfusion arrhythmias by the addition of sevoflurane to HTK solution may be related to the phosphorylation of Cx43 at serine 368.

Research Progress in Formation and Application of Tp-Te Interval

Tp-Te interval refers to the duration from the peak to the end time points of T wave in electrocardiogram. Tp-Te interval is an electrocardiogram index reflecting mail-gnant ventricular arrhythmia, while Tp-Te interval mainly reflects ventricular transmural repolarization dispersion. The increase of ventricular transmural repolarization dispersion makes it easy to appear depolarization after repolarization, and forms functional conduction block between different regions, which leads to malignant arrhythmias. In this review we discuss how these markers have demonstrated to be effective to predict malignant arr- hythmias in medical conditions such as long and short QT syndromes, Brugada syndrome and so on. However, the same results have not been found in all conditions. Further studies are needed to reach a global consensus in order to incorporate these VR parameters in risk stratification of these patients.

Abnormal Cardiac Electrical Remodelling in POTS: Mechanistic Insights on Potential Autonomic Dysregulation

Background: Postural Orthostatic Tachycardia Syndrome (POTS) is a syndrome characterised by dysautonomia. It remains unknown if POTS individuals have abnormal cardiac electrical changes. Here we assessed electrocardiographic markers of interatrial and ventricular conduction delay in POTS compared to patients with vasovagal syncope (VVS). Methods: Patients who met diagnostic criteria for POTS by tilt table test and free of other autonomic or structural heart disease were compared to VVS patients. 12 lead ECGs taken pre-treatment were digitised (minimum 8 good-quality signals) and analysed by a cardiologist blinded to treatment. P wave and RT dispersion (PWD, RTD) were calculated (maximum – minimum P wave/RT interval duration). Peak of T to end of T wave (TpTe), a marker of transmural dispersion of ventricular repolarisation, also sensitive to sympathetic stimulation, was measured in lead II. Results: 11 POTS patients were compared to 9 age and sex - matched VVS patients. Mean age was similar. Atrial volumes and left ventricular ejection fraction (LVEF) were normal in all patients. There was no difference in LVEF. POTS was associated with abnormal PWD (48 ± 5, normal <38 ms) and higher RTD (66 ± 7 ms); compared to VVS (31 ± 4; P = 0.02 and 46 ± 6 ms; P = 0.04), despite lower left atrial volume. Baseline TpTe did not differ. Conclusion: Compared to VVS, POTS is associated with both longer PWD (above normal limits) and increased RTD, whilst TpTe did not differ, despite systemic sympathetic predominance. Further clinical studies are warranted to assess the relative role of subclinical cardiac structural remodeling and impaired cardiac autonomic nervous system function.

Evaluation of ventricular arrhythmogenesis in children with acute rheumatic carditis.

Recent studies have shown that the Tp-e interval, which on an electrocardiogram (ECG) is the interval between the peak and the end of the T wave, can be used as an index of transmural dispersion of ventricular repolarisation (TDR). Both Tp-e/QT and Tp-e/QTc ratios have also been used in that capacity. However, these novel repolarisation indices have not previously been studied in children with acute rheumaticcarditis (ARC). A hundred and thirty-nine children who were diagnosed with ARC and 153 age- and gender-matched healthy controls were retrospectively reviewed. Twelve-lead ECGs were used to evaluate P-wave, QT and QTc dispersions, Tp-e interval, and Tp-e/QT and Tp-e/QT ratios. The mean age of the patients was 10.9 ± 2.4 years. The P-wave, QT and QTc dispersions were significantly higher in patients compared to the healthy control subjects. The Tp-e interval, and Tp-e/QT and Tp-e/QTc ratios were also significantly increased in patients compared to the controls. When the patients were compared in terms of either one- or two-valve involvement, we found no difference between the groups regarding P-wave, QTd and QTc dispersions, Tp-e interval, and Tp-e/QT and Tp-e/QT c ratios. There was no correlation between acute-phase reactants, white blood cell count and these repolarisation parameters. This study showed that the new transmural dispersion of ventricular repolarisation parameters, Tp-e interval, Tp-e/QT ratios and QTd were increased in children with ARC. Prolongation of the Tp-e interval and an increased Tp-e/QT ratio might be useful markers for predicting myocardial involvement in children with ARC.