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The objective of this simulation was to study the physiological meaning of the novel index for arrhythmic risk stratification – Tpe/QT ratio (the interval from the peak to the end of the T-wave (Tpe) on electrocardiogram divided by QT interval). Methods and Results: The role of two factors determining Tpe/QT ratio – action potential duration (APD) and dispersion of repolarization (DOR) – was studied in silico at two levels: ventricular wall segment and the whole heart ventricles. The simulations performed in the framework of both the segment and the entire ventricles’ models showed that Tpe/QT magnitude reflects the dynamic relationship between the longest and the shortest APD rather than the magnitude of DOR, as interval Tpe does. Tpe/QT ratio remained unchanged even at large DOR, provided that the longer the ventricular APD, the greater the gap between the longest and the shortest of them. The imbalance between the longest and the shortest APD values led to the increased or decreased Tpe/QT. Conclusion: Simulations showed that Tpe/QT is not just a corrected Tpe interval, but it reflects the balance between the longest and the shortest APD in the heart ventricles.

A noninvasive tool for cardiovascular risk stratification has not yet been established in the clinical routine analysis. Previous studies suggest a prolonged Tpeak-Tend interval (the interval from the peak to the end of the T-wave) to be predictive of death. This meta-analysis was designed to systematically evaluate the association of the Tpeak-Tend interval with mortality outcomes. Medline (via PubMed), Embase and the Cochrane Library were searched from 1 January 2008 to 21 July 2020 for articles reporting the ascertainment of the Tpeak-Tend interval and observation of all-cause-mortality. The search yielded 1920 citations, of which 133 full-texts were retrieved and 29 observational studies involving 23,114 patients met the final criteria. All-cause deaths had longer Tpeak-Tend intervals compared to survivors by a standardized mean difference of 0.41 (95% CI 0.23–0.58) and patients with a long Tpeak-Tend interval had a higher risk of all-cause death compared to patients with a short Tpeak-Tend interval by an overall odds ratio of 2.33 (95% CI 1.57–3.45). Heart rate correction, electrocardiographic (ECG) measurement methods and the selection of ECG leads were major sources of heterogeneity. Subgroup analyses revealed that heart rate correction did not affect the association of the Tpeak-Tend interval with mortality outcomes, whereas this finding was not evident in all measurement methods. The Tpeak-Tend interval was found to be significantly associated with all-cause mortality. Further studies are warranted to confirm the prognostic value of the Tpeak-Tend interval. [ABSTRACT FROM AUTHOR]

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.

Moderate hypothermia has been used to improve outcomes in comatose out‐of‐hospital cardiac arrest survivors during the past two decades, although the effects remain controversial. We have recently shown in an experimental study that myocardial electrophysiological and mechanical relationships were altered during moderate hypothermia. Electromechanical window positivity increased, and electrical dispersion of repolarization decreased, both of which are changes associated with decreased arrhythmogenicity in clinical conditions. Mechanical dispersion, a parameter also linked to arrhythmic risk, remained unaltered. Whether corresponding electrophysiological and mechanical changes occur in humans during moderate hypothermia, has not been previously explored. Twenty patients with normal left ventricular function were included. Measurements were obtained at 36 and 32°C prior to ascending aortic repair while on partial cardiopulmonary bypass and at 36°C after repair. Registrations were performed in the presence of both spontaneous and comparable paced heart rate during standardized loading conditions. The following electrical and mechanical parameters were explored: (1) Electromechanical window, measured as time difference between mechanical and electrical systole, (2) dispersion of repolarization from ECG T‐wave, and (3) mechanical dispersion, measured as segmental variation in time to peak echocardiographic strain. At moderate hypothermia, mechanical systolic prolongation (425 ± 43–588 ± 67 ms, p < 0.001) exceeded electrical systolic prolongation (397 ± 49–497 ± 79 ms, p < 0.001), whereby, electromechanical window positivity increased (29 ± 30–86 ± 50 ms, p < 0.001). Dispersion of repolarization and mechanical dispersion remained unchanged. Corresponding electrophysiological and mechanical relationships were present at comparable paced heart rates. After rewarming, the increased electromechanical window was reversed in the presence of both spontaneous and paced heart rates. Moderate hypothermia increased electromechanical window positivity, while dispersion of repolarization and mechanical dispersion remained unchanged. This impact of hypothermia may be clinically relevant for selected groups of patients after cardiac arrest. [ABSTRACT FROM AUTHOR]

Abstract Moderate hypothermia has been used to improve outcomes in comatose out‐of‐hospital cardiac arrest survivors during the past two decades, although the effects remain controversial. We have recently shown in an experimental study that myocardial electrophysiological and mechanical relationships were altered during moderate hypothermia. Electromechanical window positivity increased, and electrical dispersion of repolarization decreased, both of which are changes associated with decreased arrhythmogenicity in clinical conditions. Mechanical dispersion, a parameter also linked to arrhythmic risk, remained unaltered. Whether corresponding electrophysiological and mechanical changes occur in humans during moderate hypothermia, has not been previously explored. Twenty patients with normal left ventricular function were included. Measurements were obtained at 36 and 32°C prior to ascending aortic repair while on partial cardiopulmonary bypass and at 36°C after repair. Registrations were performed in the presence of both spontaneous and comparable paced heart rate during standardized loading conditions. The following electrical and mechanical parameters were explored: (1) Electromechanical window, measured as time difference between mechanical and electrical systole, (2) dispersion of repolarization from ECG T‐wave, and (3) mechanical dispersion, measured as segmental variation in time to peak echocardiographic strain. At moderate hypothermia, mechanical systolic prolongation (425 ± 43–588 ± 67 ms, p

The role of a border zone in arrhythmogenesis is not fully understood. In this study we evaluated independent contributions of action potential duration (APD) and dispersion of repolarization (DOR) across the normal/ischemic border to the development of ventricular tachycardia and/or fibrillation (VT/VF). Ischemia-reperfusion episodes were induced in anesthetized rats by transient coronary occlusion. Unipolar electrograms were recorded from ischemic and perfused areas using a 64-lead array to obtain activation times (ATs), repolarization times (RTs), activationrepolarization intervals (ARIs, a surrogate for APD) and dispersion of repolarization (DOR, as a difference between the earliest and latest RTs). Pinacidil (0.3 mg/kg) and glibenclamide (2 mg/kg) were applied to reduce DOR and to clamp APD at a lower and upper levels, respectively. In the control animals, APD shortened in the ischemic zone, DOR increased to 9 ± 3 ms, and VT/VF developed at reperfusion (6 out of 10). Pre-occlusion application of glibenclamide prolonged APD in the ischemic and perfused zones, decreased DOR to 5 ± 2 ms and did not affect VT/VF development (4 out of 11). Post-occlusion infusion of pinacidil shortened APD in the perfused zone, decreased DOR to 6 ± 3 ms and VT/VF incidence (2 out of 11). Extrasystolic burden at reperfusion was associated with VT/VF incidence in logistic regression analysis (β = 1.182, 95%CI 1.008 - 1.386, p = 0.04) and was lesser (p < 0.01) in the pinacidil group as compared to the control and glibenclamide groups. In conclusion, the results of this study suggest that the APDs in the perfused zone were a superior arrhythmogenic factor in respect to DOR in the present ischemia-reperfusion model. [ABSTRACT FROM AUTHOR]

Aims: Differences of action potential duration (APD) in regions of myocardial scar and their borderzones are poorly defined in the intact human heart. Heterogeneities in APD may play an important role in the generation of ventricular tachycardia (VT) by creating regions of functional block. We aimed to investigate the transmural and planar differences of APD in patients admitted for VT ablation.Methods and Results: Six patients (median age 53 years, five male); (median ejection fraction 35%), were studied. Endocardial (Endo) and epicardial (Epi) 3D electroanatomic mapping was performed. A bipolar voltage of <0.5 mV was defined as dense scar, 0.5-1.5 mV as scar borderzone, and >1.5 mV as normal. Decapolar catheters were positioned transmurally across the scar borderzone to assess differences of APD and repolarization time (RT) during restitution pacing from Endo and Epi. Epi APD was 173 ms in normal tissue vs. 187 ms at scar borderzone and 210 ms in dense scar (P < 0.001). Endocardial APD was 210 ms in normal tissue vs. 222 ms in the scar borderzone and 238 ms in dense scar (P < 0.01). This resulted in significant transmural RT dispersion (ΔRT 22 ms across dense transmural scar vs. 5 ms in normal transmural tissue, P < 0.001), dependent on the scar characteristics in the Endo and Epi, and the pacing site.Conclusion: Areas of myocardial scar have prolonged APD compared with normal tissue. Heterogeneity of regional transmural and planar APD result in localized dispersion of repolarization, which may play an important role in initiating VT. [ABSTRACT FROM AUTHOR]

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.

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

Key points: T‐wave alternans (TWA) and T‐wave lability (TWL) are precursors of ventricular arrhythmias in long QT syndrome; however, the mechanistic link remains to be clarified. Computer simulations show that action potential duration (APD) prolongation and slowed heart rates promote APD alternans and chaos, manifesting as TWA and TWL, respectively. Regional APD alternans and chaos can exacerbate pre‐existing or induce de novo APD dispersion, which combines with enhanced ICa,L to result in premature ventricular complexes (PVCs) originating from the APD gradient region. These PVCs can directly degenerate into re‐entrant arrhythmias without the need for an additional tissue substrate or further exacerbate the APD dispersion to cause spontaneous initiation of ventricular arrhythmias. Experiments conducted in transgenic long QT rabbits show that PVC alternans occurs at slow heart rates, preceding spontaneous intuition of ventricular arrhythmias. Abstract: T‐wave alternans (TWA) and irregular beat‐to‐beat T‐wave variability or T‐wave lability (TWL), the ECG manifestations of action potential duration (APD) alternans and variability, are precursors of ventricular arrhythmias in long QT syndromes. TWA and TWL in patients tend to occur at normal heart rates and are usually potentiated by bradycardia. Whether or how TWA and TWL at normal or slow heart rates are causally linked to arrhythmogenesis remains unknown. In the present study, we used computer simulations and experiments of a transgenic rabbit model of long QT syndrome to investigate the underlying mechanisms. Computer simulations showed that APD prolongation and slowed heart rates caused early afterdepolarization‐mediated APD alternans and chaos, manifesting as TWA and TWL, respectively. Regional APD alternans and chaos exacerbated pre‐existing APD dispersion and, in addition, APD chaos could also induce APD dispersion de novo via chaos desynchronization. Increased APD dispersion, combined with substantially enhanced ICa,L, resulted in a tissue‐scale dynamical instability that gave rise to the spontaneous occurrence of unidirectionally propagating premature ventricular complexes (PVCs) originating from the APD gradient region. These PVCs could directly degenerate into re‐entrant arrhythmias without the need for an additional tissue substrate or could block the following sinus beat to result in a longer RR interval, which further exacerbated the APD dispersion giving rise to the spontaneous occurrence of ventricular arrhythmias. Slow heart rate‐induced PVC alternans was observed in experiments of transgenic LQT2 rabbits under isoproterenol, which was associated with increased APD dispersion and spontaneous occurrence of ventricular arrhythmias, in agreement with the theoretical predictions. [ABSTRACT FROM AUTHOR]

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 Patients with chronic heart failure are at high risk of sudden cardiac death (SCD). Increased dispersion of repolarization restitution has been associated with SCD, and we hypothesize that this should be reflected in the morphology of the T‐wave and its variations with heart rate. The aim of this study is to propose an electrocardiogram (ECG)‐based index characterizing T‐wave morphology restitution (TMR), and to assess its association with SCD risk in a population of chronic heart failure patients. Methods and Results Holter ECGs from 651 ambulatory patients with chronic heart failure from the MUSIC (MUerte Súbita en Insuficiencia Cardiaca) study were available for the analysis. TMR was quantified by measuring the morphological variation of the T‐wave per RR increment using time‐warping metrics, and its predictive power was compared to that of clinical variables such as the left ventricular ejection fraction and other ECG‐derived indices, such as T‐wave alternans and heart rate variability. TMR was significantly higher in SCD victims than in the rest of patients (median 0.046 versus 0.039, P

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

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

Aims: The antiarrhythmic drug vernakalant exerts antiarrhythmic effects in atrial fibrillation. Recent experimental data suggest interactions with the late sodium current and antiarrhythmic effects in ventricular arrhythmias. We aimed at investigating whether treatment with vernakalant reduces polymorphic ventricular tachycardia (VT) in an experimental model of Long-QT-syndrome (LQTS).Methods and Results: Twenty-nine isolated rabbit hearts were assigned to two groups and treated with erythromycin (300 µM, n = 15) or veratridine (0.5 µM, n = 14) after obtaining baseline data. Thereafter, vernakalant (10 µM) was additionally infused. Infusion of erythromycin or veratridine significantly increased action potential duration (APD90) and QT interval. Erythromycin and veratridine also significantly augmented spatial dispersion of repolarization (erythromycin: +43 ms; veratridine: +55 ms, P < 0.01, respectively) and temporal dispersion of repolarization. After lowering extracellular [K+] in bradycardic hearts, 11 of 15 erythromycin-treated hearts and 4 of 14 veratridine-treated hearts showed early afterdepolarizations and subsequent polymorphic VT. Additional treatment with vernakalant resulted in a significant reduction of spatial dispersion of spatial dispersion in both groups (erythromycin: -32 ms; veratridine: -35 ms, P < 0.05 each) and a stabilization of temporal dispersion. After additional treatment with vernakalant, only 5 of 15 erythromycin-treated hearts (P = 0.07) and 1 of 14 veratridine-treated hearts (P = 0.32) presented polymorphic VT.Conclusion: Vernakalant has antiarrhythmic effects in this experimental model of acquired LQTS. A reduction of spatial dispersion of repolarization and a stabilization of temporal dispersion in hearts showing polymorphic VT represent the major underlying electrophysiological mechanisms. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The spatial variation in restitution properties in relation to varying stimulus site is poorly defined. This study aimed to investigate the effect of varying stimulus site on apicobasal and transmural activation time (AT), action potential duration (APD) and repolarization time (RT) during restitution studies in the intact human heart. Ten patients with structurally normal hearts, undergoing clinical electrophysiology studies, were enrolled. Decapolar catheters were placed apex to base in the endocardial right ventricle (RVendo) and left ventricle (LVendo), and an LV branch of the coronary sinus (LVepi) for transmural recording. S1-S2 restitution protocols were performed pacing RVendo apex, LVendo base, and LVepi base. Overall, 725 restitution curves were analyzed, 74% of slopes had a maximum slope of activation recovery interval (ARI) restitution (Smax) > 1 (P < 0.001); mean Smax = 1.76. APD was shorter in the LVepi compared with LVendo, regardless of pacing site (30-ms difference during RVendo pacing, 25-ms during LVendo, and 48-ms during LVepi; 50th quantile, P < 0.01). Basal LVepi pacing resulted in a significant transmural gradient of RT (77 ms, 50th quantile: P < 0.01), due to loss of negative transmural AT-APD coupling (mean slope 0.63 ± 0.3). No significant transmural gradient in RT was demonstrated during endocardial RV or LV pacing, with preserved negative transmural AT-APD coupling (mean slope -1.36 ± 1.9 and -0.71 ± 0.4, respectively). Steep ARI restitution slopes predominate in the normal ventricle and dynamic ARI; RT gradients exist that are modulated by the site of activation. Epicardial stimulation to initiate ventricular activation promotes significant transmural gradients of repolarization that could be proarrhythmic. [ABSTRACT FROM AUTHOR]

The rate of repolarization (RRepol) and so the duration of the cardiac action potential are determined by the balance of inward and outward currents across the cardiac membrane (net ionic current). Plotting action potential duration (APD) as a function of the RRepol reveals an inverse non-linear relationship, arising from the geometric association between these two factors. From the RRepol-APD relationship, it can be observed that a longer action potential will exhibit a greater propensity to shorten, or prolong, for a given change in the RRepol (i.e. net ionic current), when compared with one that is initially shorter. This observation has recently been used to explain why so many interventions that prolong the action potential exert a greater effect at slow rates (reverse rate-dependence). In this article, we will discuss the broader implications of this simple principle and examine how common experimental observations on the electrical behaviour of the myocardium may be explained in terms of the RRepol-APD relationship. An argument is made, with supporting published evidence, that the non-linear relationship between the RRepol and APD is a fundamental, and largely overlooked, property of the myocardium. The RRepol-APD relationship appears to explain why interventions and disease with seemingly disparate mechanisms of action have similar electrophysiological consequences. Furthermore, the RRepol-APD relationship predicts that prolongation of the action potential, by slowing repolarization, will promote conditions of dynamic electrical instability, exacerbating several electrophysiological phenomena associated with arrhythmogenesis, namely, the rate dependence of dispersion of repolarization, APD restitution, and electrical alternans. [ABSTRACT FROM AUTHOR]

Objective To 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. Methods Twenty 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. Results After Ang Ⅱ perfusion, 90% monophasic action potential repolarization duration among three myocardial layer were significantly prolonged ( P < 0.05 and P < 0.01), and transmural dispersion of repolarization also significantly increased compared with the MIR group ( P < 0.05). Compare with the MIR group, three myocardial Cx43-pro and Cx43-Cq expression in the Ang Ⅱ group were significantly decreased ( P < 0.05 and P < 0.01), but ΔCx43-pro and ΔCx43-Cq were significant increased. Conclusions Renin-angiotensin system increases transmural heterogeneity of Cx43 expression in the rabbit model with MIR by Ang Ⅱ, and enlarge transmural dispersion of repolarization among three myocardial layers of left ventricular which induces malignant ventricular arrhythmia. [ABSTRACT FROM AUTHOR]

Aim The most recent European Society of Cardiology (ESC) update on atrial fibrillation has introduced vernakalant (VER) for pharmacological cardioversion of atrial fibrillation. The aim of the present study was to investigate the safety profile of VER in a sensitive model of proarrhythmia. Methods and results In 36 Langendorff-perfused rabbit hearts, VER (10, 30 µM, n = 12); ranolazine (RAN, 10, 30 µM, n = 12), or sotalol (SOT, 50; 100 µM, n = 12) were infused after obtaining baseline data. Monophasic action potentials and a 12-lead electrocardiogram showed a significant QT prolongation after application of VER as compared with baseline (10 µM: +25 ms, 30 µM: +50 ms, P < 0.05) accompanied by an increase of action potential duration (APD). The increase in APD90 was accompanied by a more marked increase in effective refractory period (ERP) leading to a significant increase in post-repolarization refractoriness (PRR, 10 µM: +30 ms, 30 µM: +36 ms, P < 0.05). Vernakalant did not affect the dispersion of repolarization. Lowered potassium concentration in bradycardic hearts did not provoke early afterdepolarizations (EADs) or polymorphic ventricular tachycardia (pVT). Comparable results were obtained with RAN. Hundred micromolars of SOT led to an increase in QT interval (+49 ms) and APD90 combined with an increased ERP and PRR (+23 ms). In contrast to VER, 100 µM SOT led to a significant increase in dispersion of repolarization and to the occurrence of EAD in 10 of 12 and pVT in 8 of 12 hearts. Conclusion In the present study, application of VER and SOT led to a comparable prolongation of myocardial repolarization. Both drugs increased the PRR. However, VER neither affect the dispersion of repolarization nor induce EAD and therefore did not cause proarrhythmia. [ABSTRACT FROM PUBLISHER]

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<0.05). However, after the termination of induced VF by ICD shock with NIF administration, the QTc‐D did not differ significantly from that in the CONTROL‐1 group (63±20 and 61±14 ms1/2, respectively). Conclusions: NIF suppressed the deterioration of the SDR after ICD shock. This might be one of the mechanisms by which NIF suppresses recurrence of ventricular tachyarrhythmia just after ICD shock in patients with oral amiodarone and β‐blocker therapy. [ABSTRACT FROM AUTHOR]

Increased dispersion of repolarization has been suggested to underlie increased arrhythmogenesis in human heart failure (HF). However, no detailed repolarization mapping data were available to support the presence of increased dispersion of repolarization in failing human heart. In the present study, we aimed to determine the existence of enhanced repolarization dispersion in the right ventricular (RV) endocardium from failing human heart and examine its association with arrhythmia inducibility. RV free wall preparations were dissected from five failing and five nonfailing human hearts, cannulated and coronary perfused. RV endocardium was optically mapped from an ~6.3 × 6.3 cm2 field of view. Action potential duration (APD), dispersion of APD, and conduction velocity (CV) were quantified for basic cycle lengths (BCL) ranging from 2,000 ms to the functional refractory period. We found that RV APD was significantly prolonged within the failing group compared with the nonfailing group (560 ± 44 vs. 448 ± 39 ms, at BCL = 2,000 ms, P < 0.05). Dispersion of APD was increased in three failing hearts (161 ± 5 vs. 86 ± 19 ms, at BCL < 2,000 ms). APD alternans were induced by rapid pacing in these same three failing hearts. CV was significantly reduced in the failing group compared with the nonfailing group (81 ± 11 vs. 98 ± 8 cm/s, at BCL = 2,000 ms). Arrhythmias could be induced in two failing hearts exhibiting an abnormally steep CV restitution and increased dispersion of repolarization due to APD alternans. Dispersion of repolarization is enhanced across the RV endocardium in the failing human heart. This dispersion, together with APD alternans and abnormal CV restitution, could be responsible for the arrhythmia susceptibility in human HF. [ABSTRACT FROM AUTHOR]

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

Background: The terminal part of the QT interval (T peak to T end; Tp-e)-an index for dispersion of cardiac repolarization-is often prolonged in patients experiencing malignant ventricular arrhythmias after acute myocardial infarction (AMI). We wanted to explore whether high Tp-e might predict mortality or fatal arrhythmia post-AMI. Methods: Tp-e was measured prospectively in 1359/1384 (98.2%) consecutive patients with ST elevation (n = 525) or non-ST elevation (n = 859) myocardial infarction (STEMI or NSTEMI) admitted for coronary angiography. Results: Tp-e was significantly correlated with age, heart rate (HR), heart failure, LVEF, creatinine, three-vessel disease, previous AMI and QRS and QT duration. During a mean follow-up of 1.3 years (range 0.4-2.3),109 patients (7.9%) died; 25, 45, and 39 from cardiac arrhythmia, nonarrhythmic cardiac causes and other causes, respectively. Long Tp-e was strongly associated with increased risk of death, and Tp-e remained a significant predictor of death in multivariable Cox analyses (RR 1.5, 95% CI[1.3-1.7]). HR-corrected Tp-e (cTp-e) was the strongest predictor of death (RR 1.6 [1.4-1.9]). Tp-e and cTp-e were particularly strong predictors of fatal cardiac arrhythmia (RR 1.6 [1.2-2.1] and RR 1.8 [1.4-2.4]). Findings were similar in STEMI and NSTEMI. When comparing two methods for measuring Tp-e, one including the tail of the T wave and one not, the former had markedly higher predictive power (P < 0.001). Conclusion: Tp-e, and in particular cTp-e, were strong predictors of mortality during the first year post-AMI, and should be further evaluated as prognostic factors additional to established post-AMI risk factors. [ABSTRACT FROM AUTHOR]

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

Aims Cardiac resynchronization therapy (CRT) is associated with reverse left ventricular (LV) remodelling. However, the effects of CRT-induced mechanical remodelling on electrical remodelling, and the occurrence of ventricular arrhythmias have not been clearly established. We studied the relationship between mechanical remodelling, electrical remodelling, and the occurrence of appropriate implantable cardioverter-defibrillator (ICD) therapy 1 year after CRT. Methods and results We analysed data from 45 patients who underwent ICD-CRT implantation at our centre. Significant LV reverse remodelling was defined by a minimum 10% decrease in the LV end-diastolic diameter (LVEDd) at 1 year of follow-up. Electrocardiographic indices of dispersion of repolarization [QTc, Tpeak-Tend (Tp-e) and their dispersion] were measured immediately and 1 year post-CRT implantation. The occurrence of appropriate ICD therapy was noted for each patient. Patients with (n= 21) and without (n= 24) significant LV reverse remodelling had similar baseline characteristics. At 1 year of follow-up, patients with mechanical reverse LV remodelling exhibited a significant decrease in QTc (505 ± 42 vs. 485 ± 52 ms, P < 0.05) and Tp–e (107 ± 26 vs. 92 ± 22 ms, P < 0.0001). However, patients without mechanical LV reverse remodelling exhibited a significant increase in QT dispersion (29 ± 43 vs. 98 ± 47 ms, P = 0.002) and Tp–e dispersion (22 ± 21 vs. 54 ± 36 ms, P = 0.0001). Finally patients with mechanical LV reverse remodelling experienced a lower rate of ICD therapy (P = 0.0025) after a mean follow-up of 19 months. Conclusion Reverse LV mechanical remodelling is associated with reversal of electrical remodelling and a lower rate of appropriate ICD therapy following CRT. [ABSTRACT FROM PUBLISHER]

Aims To determine the repolarization duration gradients in different ventricular regions at atrial and ventricular pacing and to test the hypothesis that acute haemodynamic response to ventricular pacing is related to the lead position with respect to repolarization gradients. Methods and results Repolarization durations estimated as activation-recovery intervals (ARIs) were measured from unipolar electrograms recorded in the subepicardial (Epi), mid-myocardial (Mid), and subendocardial (Endo) layers of the apical and basal parts of the right ventricle (RV) and left ventricle (LV) of 15 healthy dogs under atrial and ventricular pacing. Cardiac haemodynamic variables were measured as well. At atrial pacing, ARIs were shorter in Epi than in the innermost layers (P< 0.05) in the RV apex and LV base, but not in the LV apex and RV base. Activation-recovery intervals increased from apex to base and from base to apex in RV and LV, respectively (P ≤ 0.05). At apical or basal pacing of RV and LV, repolarization gradients decayed. The dispersion of repolarization increased at LV apical pacing and preserved at RV apical pacing. The pump function of a ventricle was altered dramatically at pacing of the area with the shorter ARIs and to a lesser degree at pacing of the area with the longer ARIs (P ≤ 0.051). Conclusion The transmural and apicobasal differences in repolarization durations were heterogeneously distributed at atrial pacing. The acute haemodynamic response of the individual ventricle was better with pacing of the region with the longest repolarization suggesting a promising criterion for the lead position selection on the basis of ARIs measurements. [ABSTRACT FROM PUBLISHER]

The article presents the results of a study on the effect of hypothermia-induced transmural dispersion of repolarization (DOR) on patients with arrhythmogenesis. According to the authors, hypothermia amplifies DOR and can increase the prevalence of arrhythmogenesis. They indicate the direct correlation of DOR with the degree of cooling and rewarming. They mention that DOR could help in clinical diagnosis of a low incidence of arrhythmias in therapeutic hypothermia.

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

Background: The T-wave peak to T-wave end (TpTe) interval reflects spatial and transmural dispersion in repolarization and serves as an arrhythmogenic index. Normal TpTe interval data in children are lacking. We evaluated the effects of age, gender, heart rate, leads (II and V5) on TpTe and T-wave voltage. Methods: Four hundred healthy children (age 4 days to 16.7 years) were enrolled. From a resting 12-lead digital ECG, TpTe, RR, QT, JT intervals, and T amplitude were measured (leads II and V5). Bazett and Fridericia formulas were applied to TpTe for heart rate correction and TpTe/QT and TpTe/JT were calculated. Descriptive and analytical statistics were applied, significance level set at P ≤ 0.05. Results: TpTe in leads II and V5 correlate well. Contrary to adults, no gender differences in TpTe were observed in childhood. TpTe lengthens with increasing age, and is inversely related to heart rate. TpTe 98th percentile is 85 msec in first 5 years, increasing to 92 msec in adolescence. TpTe Fridericia is a good correction formula in childhood; TpTe Bazett overcorrects in the younger age. TpTe/QT and TpTe/JT are longer in younger subjects due to greater QT shortening than the TpTe interval at higher heart rates. Conclusions: In children, TpTe in lead II and V5 correlate well. The TpTe interval lengthens with advancing age as heart rate diminishes. TpTe Fridericia is a good correction formula in children. Younger subjects have higher TpTe/QT and TpTe/JT indices compared to older children. T-wave voltage increases with age, tallest in the 5–10-year-age group particularly in V5. Ann Noninvasive Electrocardiol 2010;15(1):11–16 [ABSTRACT FROM AUTHOR]

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

Effects of cardiac mechanical heterogeneity on the electrical function of the heart are difficult to assess experimentally, yet they pose a serious (patho-)physiological challenge. Here, we present an in silico study of the effects of mechanical heterogeneity on action potential duration (APD) in mechanically interacting muscle regions and consequent effects on the dispersion of repolarization, a well-established determinant of cardiac arrhythmogenesis. Using a novel mathematical description of ventricular electromechanical activity (virtual muscle), we first assessed how differences in intrinsic contractile properties affect the electrical behavior of cardiac muscle representations. In spite of identical electrophysiological model descriptions in virtual muscle samples, faster muscle models show shorter APD than their slower counterparts. This is a consequence of Ca[sup 2+]-mediated feedback from mechanical to electrical activity in the individual muscle models. This mechano-electric feedback (MEF) is, of course, significantly more complex in native cardiac tissue, as the heterogeneous muscle elements interact both mechanically and electrically. Cardiac mechanical heterogeneity, in its most reduced form, can be represented by a duplex consisting of two mechanically interacting muscle segments. Our in silico model of heterogeneous myocardium therefore consists of two individual virtual muscles that are mechanically interconnected in-series to form a virtual heterogeneous duplex. During isometric contraction of the duplex (i.e. at constant external length), internal mechanical interactions affect Ca[sup 2+] handling and APD of muscle elements, resulting in an increased dispersion of repolarization beyond the intrinsic APD differences. Duplex electromechanical activity is strongly affected by the activation sequence of its elements. Late activation of the faster (subepicardial type) duplex element, postponed by time-lags that correspond to normal transmural activation delays, optimizes duplex contractility and smoothes out intrinsic APD differences, thereby reducing dispersion in repolarization. This smoothing effect is not observed upon delayed activation of the slower (subendocardial type) duplex element. In both settings, changes in repolarization timing follow a nonlinear dependence of APD on activation delay. Furthermore, asynchronous activation of identical elements in a homogeneous duplex causes an impairment of contractile function and increases dispersion of repolarization. This suggests that the normal electrical activation sequence in the heart requires matching mechanical and electrical heterogeneity for optimal cardiac performance. On the subcellular level, our results suggest that mechanical modulation of Ca[sup 2+] handling is a key mechanism of MEF in heterogeneous myocardium, which contributes to the matching of local mechanical and/or electrical activity to global hemodynamic demand. [ABSTRACT FROM AUTHOR]

Aims This study was performed to determine whether or not the kinetics of action potential duration restitution during double premature stimuli (S3) differ from that during single premature stimuli (S2) in the human intact right ventricle. Methods and Results A monophasic action potential (MAP) was simultaneously recorded from the right ventricular apex (RVA) and outflow tract (RVOT) during programmed ventricular pacing in 11 patients with symptomatic bradyarrhythmias (five males, six females, mean age 58 years). In the five most recent patients, the RV pressure and its dp/dt were also obtained during the protocol. A substantial difference in the restitution of the MAP duration (MAPD) between S2and S3was observed at short diastolic intervals (<100 ms), that is, the restitution curve of S2showed an early biphasic pattern (upward hump), while such a phenomenon was not seen during the restitution of S3. All the quantitative parameters of MAPD restitution representing its kinetics were significantly greater in S3than S2. Maximum attainable dispersion of repolarization between the two MAPs was significantly greater during S3than S2(76±17 vs 59±17 ms,P< 0·05) and was mainly caused by the difference in the MAPD difference, thus by the difference in the restitution kinetics of S2and S3. The dp/dt of the RV pressure was significantly greater during S3than S2for all diastolic intervals tested. Conclusion It was concluded that similar to previously reported canine experimental studies, the APD restitution of S3is substantially different from that of S2in the human intact ventricle (endocardium). [ABSTRACT FROM PUBLISHER]

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/dt max 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 mm 2 during SP mapping vs SR mapping (SDR 11 ± 6 ms vs 10 ± 6 ms, P = .54). SDR/10 mm 2 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., (© 2021 Heart Rhythm Society. Published by Elsevier Inc.)