Search

Background The presence of dynamic substrate changes may facilitate functional block and reentry in ventricular tachycardia (VT). Objective We aimed to study dynamic ventricular repolarization changes in critical regions of the VT circuit during sensed single extrastimulus pacing known as the Sense Protocol (SP). Methods Twenty patients (aged 67 ± 9 years, 17 male) underwent VT ablation. A bipolar voltage map was obtained during sinus rhythm (SR) and right ventricular SP pacing at 20 ms above ventricular effective refractory period. Ventricular repolarization maps were constructed. Ventricular repolarization time (RT) was calculated from unipolar electrogram T waves, using the Wyatt method, as the dV/dtmax of the unipolar T wave. Entrainment or pace mapping confirmed critical sites for ablation. Results The median global repolarization range (max-min RT per patient) was 166 ms (interquartile range [IQR] 143–181 ms) during SR mapping vs 208 ms (IQR 182–234) during SP mapping (P = .0003 vs intrinsic rhythm). Regions of late potentials (LP) had a longer RT during SP mapping compared to regions without LP (mean 394 ± 40 ms vs 342 ± 25 ms, P < .001). In paired regions of normal myocardium there was no significant spatial dispersion of repolarization (SDR)/10 mm2 during SP mapping vs SR mapping (SDR 11 ± 6 ms vs 10 ± 6 ms, P = .54). SDR/10 mm2 was greater in critical areas of the VT circuit during SP mapping 63 ± 29 ms vs SR mapping 16 ± 9 ms (P < .001). Conclusion Ventricular repolarization is prolonged in regions of LP and increases dynamically, resulting in dynamic SDR in critical areas of the VT circuit. These dynamic substrate changes may be an important factor that facilitates VT circuits., Graphical abstract

Background Epicardial pacing increases risk of ventricular tachycardia (VT) in patients with ischemic cardiomyopathy (ICM) when pacing in proximity to scar. Endocardial pacing may be less arrhythmogenic as it preserves the physiological sequences of activation and repolarization. Objective The purpose of this study was to determine the relative arrhythmogenic risk of endocardial compared to epicardial pacing, and the role of the transmural gradient of action potential duration (APD) and pacing location relative to scar on arrhythmogenic risk during endocardial pacing. Methods Computational models of ICM patients (n = 24) were used to simulate left ventricular (LV) epicardial and endocardial pacing 0.2–3.5 cm from a scar. Mechanisms were investigated in idealized models of the ventricular wall and scar. Simulations were run with/without a 20-ms transmural APD gradient in the physiological direction and with the gradient inverted. Dispersion of repolarization was computed as a surrogate of VT risk. Results Patient-specific models with a physiological APD gradient predict that endocardial pacing decreases VT risk (34%; P

Objective. Dibornol-HES, a water-soluble drug based on the derivative of 2,6-diisobornyl-4-methylphenol Dibornol conjugated with hydroxyethyl starch, can reduce the occurrence and severity of arrhythmias by preventive intravenous administration, but it is unknown whether the drug could reduce the myocardial arrhythmogenicity once ischemia has developed at the developed ischemia.Materials and methods. In the model of acute ischemia / reperfusion of the rabbit heart, the effect of Dibornol-HEC (80 mg/kg body weight of the animal) on the electrophysiological indices characterizing myocardial arrhythmogenicity (global and border dispersion of repolarization) was studied during the restoration of blood flow. In the model of acute ischemia / reperfusion with 64 unipolar epicardial leads, the activation-recovery intervals were measured and global and border dispersion of repolarization in the native rabbits (control group, n = 9) and in the rabbits treated by Dibornol-HES (on the 25th minute of occlusion, the experimental group, n = 6).Results. The introduction of Dibornol-HES did not lead to a change in the electrocardiographic parameters of rabbits. By the 30th minute of the coronary occlusion on the ECG in the animals of the control and the experimental groups, the intervals RR, QT, QTc were shortened (p < 0.05). In the animals of both groups by the 30th minute of coronary occlusion, the global dispersion of repolarization increased (p < 0.05), the boundary dispersion of repolarization also increased (p < 0.05), due to the decrease in the duration of the activation-recovery intervals in the ischemic zone (p < 0.05). During the 30-minute reperfusion the magnitude of the global dispersion of repolarization did not change in animals of the both groups, and the magnitude of the border dispersion of repolarization in the control rabbits decreased (p < 0.05), while in the rabbits treated by Dibornol-HES the border dispersion of repolarization did not changed.Conclusion. In rabbits of the experimental group, the values of the global and border dispersions of repolarization did not differ from those of the animals in the control group. Therefore, the administration to Dibornol-HES just prior to reperfusion does not lead to the decrease in the dispersion of repolarization increased as a result of acute ischemic myocardial damage.

Background: Prolongation of the Tpeak-Tend (TpTe) interval as a measurement of transmural dispersion of repolarization (TDR) is an independent risk factor for chronic heart failure mortality. However, the cardiac resynchronization therapy's (CRT) effect on TDR is controversial. Therefore, this study aimed to evaluate CRTs acute and chronic effects on repolarization dispersion. Furthermore, we aimed to investigate the relationship between TpTe changes and ventricular arrhythmia. Methods: The study group consisted of 101 patients treated with CRT-defibrillator (CRT-D). According to whether TpTe was shortened, patients were grouped at immediate and 1-year follow-up after CRT, respectively. The echocardiogram index and ventricular arrhythmia were observed and compared in these subgroups. Results: For all patients, TpTe slightly increased immediately after CRT-D implantation, and then decreased at the 1-year follow-up (from 107 ± 23 to 110 ± 21 ms within 24 h, to 94 ± 24 ms at 1-year follow-up, F = 19.366, P < 0.001). No significant difference in the left ventricular reverse remodeling and ventricular tachycardia/ventricular fibrillation (VT/VF) episodes between the TpTe immediately shortened and TpTe immediately nonshortened groups. However, patients in the TpTe at 1-year shorten had a higher rate of the left ventricular (LV) reverse remodeling (65% vs. 44%, χ2 = 4.495, P = 0.038) and less VT/VF episodes (log-rank test, χ2 = 10.207, P = 0.001) compared with TpTe 1-year nonshortened group. TpTe immediately after CRT-D independently predicted VT/VF episodes at 1-year follow-up (hazard ratio [HR], 1.030; P = 0.001). Conclusions: Patients with TpTe shortened at 1-year after CRT had a higher rate of LV reverse remodeling and less VT/VF episodes. The acute changes of TpTe after CRT have minimal value on mechanical reverse remodeling and ventricular arrhythmia.

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

ObjectiveTo observe the effects of angiotensin Ⅱ(Ang Ⅱ) perfusion on transmural heterogeneity of Cx43 expression in the rabbit model with acute myocardial ischemia reperfusion (MIR), and investigate the role of rennin-angiotensin system in malignant ventricular arrhythmia induced by MIR.MethodsTwenty rabbits were randomly divided into MIR group (n = 10) and Ang Ⅱ group (n = 10). MIR model was produced with traditional ligation and opening of the anterior descending coronary artery in all animal. The hearts in vitro in the MIR group and the Ang Ⅱ group were perfused with simply improved Tyrode's solution and containing Ang Ⅱ Tyrode's solution respectively. 90% monophasic action potential repolarization duration, transmural dispersion of repolarization, Cx43 protein (Cx43-pro) and mRNA (Cx43-Cq) expression in subepicardial, midmyocardial and subendocardial myocardium were measured in both groups. The greatest differences of Cx43-pro and Cx43-Cq among three myocardial layers were calculated and shown with ΔCx43-pro and ΔCx43-Cq respectively.ResultsAfter Ang Ⅱ perfusion, 90% monophasic action potential repolarization duration among three myocardial layer were significantly prolonged (P

Background Striking temporal associations exist between ventricular arrhythmia and acute mental stress, for example, during natural disasters, or defibrillator shocks associated with stressful events. We hypothesized that electrophysiological changes in response to mental stress may be exaggerated at short coupling intervals and hence relevant to arrhythmia initiation. Objective The aim of this study was to determine the dynamic response in human electrophysiology during mental stress. Methods Patients with normal hearts and supraventricular tachycardia underwent electrophysiological studies avoiding sedation. Conditions of relaxation and stress were induced with standardized psychometric protocols (mental arithmetic and anger recall) during decremental S1S2 right ventricular (RV) pacing. Unipolar electrograms were acquired simultaneously from the RV endocardium, left ventricular (LV) endocardium (LV endo), and epicardium (LV epi), and activation-recovery intervals (ARIs) computed. Results Twelve patients ( 9 women; median age 34 years) were studied. During stress, effective refractory period (ERP) reduced from 228 ± 23 to 221 ± 21 ms (P < .001). ARIs reduced during mental stress (P < .001), with greater reductions in LV endocardium than in the epicardium or RV endocardium (LV endo −8 ms; LV epi −5 ms; RV endo −4 ms; P < .001). Mental stress depressed the entire electrical restitution curve, with minimal effect on slope. A substantial reduction in minimal ARIs on the restitution curve in LV endo occurred, commensurate with the reduction in ERP (LV endo ARI 195 ± 31 ms at rest to 182 ± 32 ms during mental stress; P < .001). Dispersion of repolarization increased sharply at coupling intervals approaching ERP during stress but not at rest. Conclusion Mental stress induces significant electrophysiological changes. The increase in dispersion of repolarization at short coupling intervals may be relevant to observed phenomena of arousal-associated arrhythmia., Graphical abstract

Functional analysis of the L-type calcium channel has shown that the CACNA1C R858H mutation associated with severe QT interval prolongation may lead to ventricular fibrillation (VF). This study investigated multiple potential mechanisms by which the CACNA1C R858H mutation facilitates and perpetuates VF. The Ten Tusscher-Panfilov (TP06) human ventricular cell models incorporating the experimental data on the kinetic properties of L-type calcium channels were integrated into one-dimensional (1D) fiber, 2D sheet, and 3D ventricular models to investigate the pro-arrhythmic effects of CACNA1C mutations by quantifying changes in intracellular calcium handling, action potential profiles, action potential duration restitution (APDR) curves, dispersion of repolarization (DOR), QT interval and spiral wave dynamics. R858H "mutant" L-type calcium current (ICaL) augmented sarcoplasmic reticulum calcium content, leading to the development of afterdepolarizations at the single cell level and focal activities at the tissue level. It also produced inhomogeneous APD prolongation, causing QT prolongation and repolarization dispersion amplification, rendering R858H "mutant" tissue more vulnerable to the induction of reentry compared with other conditions. In conclusion, altered ICaL due to the CACNA1C R858H mutation increases arrhythmia risk due to afterdepolarizations and increased tissue vulnerability to unidirectional conduction block. However, the observed reentry is not due to afterdepolarizations (not present in our model), but rather to a novel blocking mechanism.

Background: Although nifekalant hydrochloride (NIF) has been demonstrated to suppress ventricular tachyarrhythmias, especially electrical storms, the mechanism by which it does so is still unclear. We examined the effects of NIF on the spatial dispersion of repolarization (SDR) after implantable cardioverter-defibrillator (ICD) shock. Methods and Results: In 35 patients with oral amiodarone and β-blocker therapy, and an ICD, we recorded the 87-lead electrocardiogram during sinus rhythm (CONTROL-1 group) under general anesthesia, and just after the termination of induced ventricular fibrillation (VF) by ICD shock, with or without NIF administration. In all recordings, the corrected QT interval (QTc) was measured in each lead. The dispersion of QTc (QTc-D; maximum QTc minus minimum QTc) was also measured. Compared with that in the CONTROL-1 group, the QTc-D exhibited significant deterioration after ICD shock (61±14 and 90±19 ms1/2, respectively; p

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

International audience; Aims: Class III and IV drugs affect cardiac human ether-a-go-go related gene (IKr) and L-type calcium (ICaL) channels, resulting in complex alterations in repolarization with both anti- and pro-arrhythmic consequences. Interpretation of their effects on cellular and electrocardiogram (ECG)-based biomarkers for risk stratification is challenging. As pharmaceutical compounds often exhibit multiple ion channel effects, our goal is to investigate the simultaneous effect of ICaL and IKr block on human ventricular electrophysiology from ionic to ECG level. Methods and results: Simulations are conducted using a human body torso bidomain model, which includes realistic representation of human membrane kinetics, anatomy, and fibre orientation. A simple block pore model is incorporated to simulate drug-induced ICaL and IKr blocks, for drug dose = 0, IC50, 2× IC50, 10× IC50, and 30× IC50. Drug effects on human ventricular activity are quantified for different degrees and combinations of ICaL and IKr blocks from the ionic to the body surface ECG level. Electrocardiogram simulations show that ICaL block results in shortening of the QT interval, ST elevation, and reduced T-wave amplitude, caused by reduction in action potential duration and action potential amplitude during the plateau phase, and in repolarization times. In contrast, IKr block results in QT prolongation and reduced T-wave amplitude. When ICaL and IKr blocks are combined, the degree of ICaL block strongly determines QT interval whereas the effect of IKr block is more pronounced on the T-wave amplitude. Conclusion: Our simulation study provides new insights into the combined effect of ICaL and IKr blocks on human ventricular activity using a multiscale computational human torso model.

Aims: The chronic complete atrioventricular block (CAVB) dog is highly sensitive for drug-induced torsade de pointes (TdP) arrhythmias. Focal mechanisms have been suggested as trigger for TdP onset; however, its exact mechanism remains unclear. In this study, detailed mapping of the ventricles was performed to assess intraventricular heterogeneity of repolarization in relation to the initiation of TdP. Methods and results: In 8 CAVB animals, 56 needles, each containing 4 electrodes, were inserted in the ventricles. During right ventricular apex pacing (cycle length: 1000 – 1500 ms), local unipolar electrograms were recorded before and after administration of dofetilide to determine activation and repolarization times (RTs). Maximal RT differences were calculated in the left ventricle (LV) within adjacent electrodes in different orientations (transmural, vertical, and horizontal) and within a square of four needles (cubic dispersion). Dofetilide induced TdP in five out of eight animals. Right ventricle – LV was similar between inducible and non-inducible dogs at baseline (327 + 30 vs. 345 + 17 ms) and after dofetilide administration (525 + 95 vs. 508 + 15 ms). All measurements of intraventricular dispersion were not different at baseline, but this changed for horizontal (206 + 20 vs. 142 + 34 ms) and cubic dispersion (272 + 29 vs. 176 + 48 ms) after dofetilide: significantly higher values in inducible animals. Single ectopic beats and the first TdP beat arose consistently from a subendocardially located electrode terminal with the shortest RT in the region with largest RT differences. Conclusion: Chronic complete atrioventricular block dogs susceptible for TdP demonstrate higher RT differences. Torsade de pointes arises from a region with maximal heterogeneity of repolarization suggesting that a minimal gradient is required in order to initiate TdP.

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