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Catheter ablation for ventricular tachycardia (VT) in patients with systolic heart failure remains a critical yet challenging area of non-pharmacological therapy. Despite positive outcomes in atrial fibrillation, evidence for the efficacy of VT ablation in reducing cardiac mortality is inconclusive due to the absence of standardized ablation strategies. The primary challenges include difficulties in identifying suitable ablation targets and their deep locations within myocardial tissue. Current techniques, such as voltage mapping, provide valuable insights; however, they are limited by the presence of numerous bystander areas and the occurrence of incomplete transmural scarring. Recent advancements in functional substrate mapping have focused on identifying critical isthmuses without requiring hemodynamic stabilization during VT, thereby shifting the emphasis to the analysis of potentials during baseline rhythm. While methods like isochronal late activation mapping have improved target identification, they primarily address conduction abnormalities without adequately considering repolarization heterogeneity. This review highlights emerging technologies that utilize unipolar potentials to assess repolarization heterogeneities and identify VT isthmuses. Furthermore, novel ablation sources such as pulsed-field ablation, bipolar ablation, and ultra-low temperature cryoablation are being explored to create deeper and more durable lesions, addressing the limitations of traditional radiofrequency ablation. These advancements aim to reduce VT recurrence and improve overall treatment efficacy. Ultimately, understanding these innovative strategies is expected to optimize procedural outcomes and significantly enhance the management of patients with scar-related VT. [ABSTRACT FROM AUTHOR]

Background: The T wave of the electrocardiogram (ECG) reflects ventricular repolarization. Repolarization heterogeneity is associated with reentrant arrhythmias. Several T‐wave markers (including QT interval) have been associated with ventricular arrhythmias, but studies linking such markers to underlying local repolarization time (RT) inhomogeneities are lacking. We aimed to investigate the relation of several T‐wave markers to controlled drug‐induced regional RT gradients in intact pig hearts. Methods: Repolarization time gradients were created by regional infusion of dofetilide and pinacidil in four atrially paced porcine Langendorff‐perfused hearts placed inside a torso tank. From the 12‐lead ECG on the torso tank, the mean, maximum, and dispersion (max–min) of QTtime, JTtime, Tpeak–end, Twidth, TQratio, dV/dtmax, Tarea, Tamp, and T‐upslope duration were determined, as well as upslope end difference between leads V1 and V6. Results: Temporal T‐wave parameters Tpeak–end, Twidth, and TQratio show a significant and high correlation with RT gradient, best reflected by mean value. Tarea (mean, max and dispersion) and dV/dtmax dispersion show only a moderate significant correlation. T‐upslope duration shows a significant correlation in particular for mean values. Mean, maximum, or dispersion of QTtime and V1–V6 upslope end difference were not significantly correlated with RT gradient. Conclusion: Composite 12‐lead ECG T‐wave parameters Tpeak–end, Twidth, TQratio, upslope duration, and Tarea show a good correlation with underlying RT heterogeneity, whereas standard clinical metrics such as QTtime do not reflect local RT heterogeneity. The composite T‐wave metrics may thus provide better insights in arrhythmia susceptibility than traditional QTtime metrics. [ABSTRACT FROM AUTHOR]

Abstract Background The T wave of the electrocardiogram (ECG) reflects ventricular repolarization. Repolarization heterogeneity is associated with reentrant arrhythmias. Several T‐wave markers (including QT interval) have been associated with ventricular arrhythmias, but studies linking such markers to underlying local repolarization time (RT) inhomogeneities are lacking. We aimed to investigate the relation of several T‐wave markers to controlled drug‐induced regional RT gradients in intact pig hearts. Methods Repolarization time gradients were created by regional infusion of dofetilide and pinacidil in four atrially paced porcine Langendorff‐perfused hearts placed inside a torso tank. From the 12‐lead ECG on the torso tank, the mean, maximum, and dispersion (max–min) of QTtime, JTtime, Tpeak–end, Twidth, TQratio, dV/dtmax, Tarea, Tamp, and T‐upslope duration were determined, as well as upslope end difference between leads V1 and V6. Results Temporal T‐wave parameters Tpeak–end, Twidth, and TQratio show a significant and high correlation with RT gradient, best reflected by mean value. Tarea (mean, max and dispersion) and dV/dtmax dispersion show only a moderate significant correlation. T‐upslope duration shows a significant correlation in particular for mean values. Mean, maximum, or dispersion of QTtime and V1–V6 upslope end difference were not significantly correlated with RT gradient. Conclusion Composite 12‐lead ECG T‐wave parameters Tpeak–end, Twidth, TQratio, upslope duration, and Tarea show a good correlation with underlying RT heterogeneity, whereas standard clinical metrics such as QTtime do not reflect local RT heterogeneity. The composite T‐wave metrics may thus provide better insights in arrhythmia susceptibility than traditional QTtime metrics.

Background: Coronavirus disease‐2019 (COVID‐19) has been associated with an increased risk of acute cardiac events. However, the effect of COVID‐19 on repolarization heterogeneity is not yet established. In this study, we evaluated electrocardiogram (ECG) markers of repolarization heterogeneity in patients hospitalized with COVID‐19. In addition, we performed a systematic review and meta‐analysis of the published studies. Methods: QT dispersion (QTd), the interval between T wave peak to T wave end (TpTe), TpTe/QT (with and without correction), QRS width, and the index of cardio‐electrophysiological balance (iCEB) were calculated in 101 hospitalized COVID‐19 patients and it was compared with 101 non‐COVID‐19 matched controls. A systematic review was performed in four databases and meta‐analysis was conducted using Stata software. Results: Tp‐Te, TpTe/QT, QRS width, and iCEB were significantly increased in COVID‐19 patients compared with controls (TpTe = 82.89 vs. 75.33 ms (ms), p‐value =.005; TpTe/QT = 0.217 vs. 0.203 ms, p‐value =.026). After a meta‐analysis of 679 COVID‐19 cases and 526 controls from 9 studies, TpTe interval, TpTe/QT, and TpTe/QTc ratios were significantly increased in COVID‐19 patients. Meta‐regression analysis moderated by age, gender, diabetes mellitus, hypertension, and smoking reduced the heterogeneity. QTd showed no significant correlation with COVID‐19. Conclusion: COVID‐19 adversely influences the ECG markers of transmural heterogeneity of repolarization. Studies evaluating the predictive value of these ECG markers are warranted to determine their clinical utility. [ABSTRACT FROM AUTHOR]

Background Early life trauma has been associated with increased cardiovascular risk, but the arrhythmic implications are unclear. We hypothesized that in patients with coronary artery disease, early life trauma predicts increased arrhythmic risk during mental stress, measured by elevated microvolt T‐wave alternans (TWA), a measure of repolarization heterogeneity and sudden cardiac death risk. Methods and Results In a cohort with stable coronary artery disease (NCT04123197), we examined early life trauma with the Early Trauma Inventory Self Report‐Short Form. Participants underwent a laboratory‐based mental stress speech task with Holter monitoring, as well as a structured psychiatric interview. We measured TWA during rest, mental stress, and recovery with ambulatory electrocardiographic monitoring. We adjusted for sociodemographic factors, cardiac history, psychiatric comorbidity, and hemodynamic stress reactivity with multivariable linear regression models. We examined 320 participants with noise‐ and arrhythmia‐free ECGs. The mean (SD) age was 63.8 (8.7) years, 27% were women, and 27% reported significant childhood trauma (Early Trauma Inventory Self Report‐Short Form ≥10). High childhood trauma was associated with a multivariable‐adjusted 17% increase in TWA (P=0.04) during stress, and each unit increase in the Early Trauma Inventory Self Report‐Short Form total score was associated with a 1.7% higher stress TWA (P=0.02). The largest effect sizes were found with the emotional trauma subtype. Conclusions In a cohort with stable coronary artery disease, early life trauma, and in particular emotional trauma, is associated with increased TWA, a marker of increased arrhythmic risk, during mental stress. This association suggests that early trauma exposures may affect long‐term sudden cardiac death risk during emotional triggers, although more studies are warranted.

Background: The detection and localization of electrophysiological substrates currently involve invasive cardiac mapping. Electrocardiographic imaging (ECGI) using the equivalent dipole layer (EDL) method allows the noninvasive estimation of endocardial and epicardial activation and repolarization times (AT and RT), but the RT validation is limited to in silico studies. We aimed to assess the temporal and spatial accuracy of the EDL method in reconstructing the RTs from the surface ECG under physiological circumstances and situations with artificially induced increased repolarization heterogeneity. Methods: In four Langendorff-perfused pig hearts, we simultaneously recorded unipolar electrograms from plunge needles and pseudo-ECGs from a volume-conducting container equipped with 61 electrodes. The RTs were computed from the ECGs during atrial and ventricular pacing and compared with those measured from the local unipolar electrograms. Regional RT prolongation (cooling) or shortening (pinacidil) was achieved by selective perfusion of the left anterior descending artery (LAD) region. Results: The differences between the computed and measured RTs were 19.0 ± 17.8 and 18.6 ± 13.7 ms for atrial and ventricular paced beats, respectively. The region of artificially delayed or shortened repolarization was correctly identified, with minimum/maximum RT roughly in the center of the region in three hearts. In one heart, the reconstructed region was shifted by ~2.5 cm. The total absolute difference between the measured and calculated RTs for all analyzed patterns in selectively perfused hearts (n = 5) was 39.6 ± 27.1 ms. Conclusion: The noninvasive ECG repolarization imaging using the EDL method of atrial and ventricular paced beats allows adequate quantitative reconstruction of regions of altered repolarization. [ABSTRACT FROM AUTHOR]

Background: The detection and localization of electrophysiological substrates currently involve invasive cardiac mapping. Electrocardiographic imaging (ECGI) using the equivalent dipole layer (EDL) method allows the noninvasive estimation of endocardial and epicardial activation and repolarization times (AT and RT), but the RT validation is limited to in silico studies. We aimed to assess the temporal and spatial accuracy of the EDL method in reconstructing the RTs from the surface ECG under physiological circumstances and situations with artificially induced increased repolarization heterogeneity.Methods: In four Langendorff-perfused pig hearts, we simultaneously recorded unipolar electrograms from plunge needles and pseudo-ECGs from a volume-conducting container equipped with 61 electrodes. The RTs were computed from the ECGs during atrial and ventricular pacing and compared with those measured from the local unipolar electrograms. Regional RT prolongation (cooling) or shortening (pinacidil) was achieved by selective perfusion of the left anterior descending artery (LAD) region.Results: The differences between the computed and measured RTs were 19.0 ± 17.8 and 18.6 ± 13.7 ms for atrial and ventricular paced beats, respectively. The region of artificially delayed or shortened repolarization was correctly identified, with minimum/maximum RT roughly in the center of the region in three hearts. In one heart, the reconstructed region was shifted by ~2.5 cm. The total absolute difference between the measured and calculated RTs for all analyzed patterns in selectively perfused hearts (n = 5) was 39.6 ± 27.1 ms.Conclusion: The noninvasive ECG repolarization imaging using the EDL method of atrial and ventricular paced beats allows adequate quantitative reconstruction of regions of altered repolarization.

Aims: Disease-induced repolarization heterogeneity in infarcted myocardium contributes to VT arrhythmogenesis but how apicobasal and transmural (AB-TM) repolarization gradients additionally affect post-infarct VT dynamics is unknown. The goal of this study is to assess how AB-TM repolarization gradients impact post-infarct VT dynamics using patient-specific heart models.Method: 3D late gadolinium-enhanced cardiac magnetic resonance images were acquired from seven post-infarct patients. Models representing the patient-specific scar and infarct border zone distributions were reconstructed without (baseline) and with repolarization gradients along both the AB-TM axes. AB only and TM only models were created to assess the effects of each ventricular gradient on VT dynamics. VTs were induced in all models via rapid pacing.Results: Ten baseline VTs were induced. VT inducibility in AB-TM models was not significantly different from baseline (p>0.05). Reentry pathways in AB-TM models were different than baseline pathways due to alterations in the location of conduction block (p0.05) or AB-TM models (p>0.05). Reentry pathways and VT exit sites in AB only and TM only models were different than in baseline (p

Aims: Disease-induced repolarization heterogeneity in infarcted myocardium contributes to VT arrhythmogenesis but how apicobasal and transmural (AB-TM) repolarization gradients additionally affect post-infarct VT dynamics is unknown. The goal of this study is to assess how AB-TM repolarization gradients impact post-infarct VT dynamics using patient-specific heart models. Method: 3D late gadolinium-enhanced cardiac magnetic resonance images were acquired from seven post-infarct patients. Models representing the patient-specific scar and infarct border zone distributions were reconstructed without (baseline) and with repolarization gradients along both the AB-TM axes. AB only and TM only models were created to assess the effects of each ventricular gradient on VT dynamics. VTs were induced in all models via rapid pacing. Results: Ten baseline VTs were induced. VT inducibility in AB-TM models was not significantly different from baseline (p >0.05). Reentry pathways in AB-TM models were different than baseline pathways due to alterations in the location of conduction block (p <0.05). VT exit sites in AB-TM models were different than baseline VT exit sites (p<0.05). VT inducibility of AB only and TM only models were not significantly different than that of baseline (p >0.05) or AB-TM models (p >0.05). Reentry pathways and VT exit sites in AB only and TM only models were different than in baseline (p <0.05). Lastly, repolarization gradients uncovered multiple VT morphologies with different reentrant pathways and exit sites within the same structural, conducting channels. Conclusion: VT inducibility was not impacted by the addition of AB-TM repolarization gradients, but the VT reentrant pathway and exit sites were greatly affected due to modulation of conduction block. Thus, during ablation procedures, physiological and pharmacological factors that impact the ventricular repolarization gradient might need to be considered when targeting the VTs. [ABSTRACT FROM AUTHOR]

Background: Regional differences in ventricular activation sequence and action potential duration and morphology result in dispersion in ventricular repolarization (VR). VR dispersion is a key factor in arrhythmogenesis. We studied the adaptation of global VR dispersion in humans during normal and abnormal ventricular activation, and the relation to the QT adaptation (hysteresis).Methods: We measured global VR dispersion as T amplitude, T area, and ventricular gradient (VG), using continuous Frank vectorcardiography, in response to abrupt and sustained atrial (AP) or ventricular pacing (VP) aiming at 120 bpm, in 21 subjects with permanent pacemakers.Results: Following pacing start, VR adaptation showed an initially rapid and complex tri-phasic pattern, most pronounced for T amplitude. There were major differences in the patterns of VR dispersion adaptation following abrupt AP vs VP, confirming that the adaptation pattern is activation dependent. In response to AP, an instantaneous decrease in VR dispersion occurred, followed by an increase and then a slow decrease, all at a lower level than baseline. In contrast, following VP there was an immediate increase to ~4× baseline in T amplitude and T area (but not in VG), with a subsequent biphasic adaptation lasting longer during VP than AP. The initial rapid changes occurred within the time for QT adaptation to reach steady-state.Conclusions: Our results corroborate and expand data from animal and invasive human studies, showing similarities of the adaptation pattern on different scales. The initial rapidly changing VR adaptation phase presumably reflects a window of increased vulnerability to arrhythmias. [ABSTRACT FROM AUTHOR]

QT interval extends from the beginning of QRS complex to the end of T wave. Thus, it includes the duration of ventricular depolarization (QRS) and repolarization (J point to end of T wave). It corresponds to the duration of cellular action potential. “long-” and “short”-QT intervals are considered as risk markers for cardiac arrhythmias and sudden death. In the last decade, there have been significant advances in our understanding about measurement and significance of QT interval. We have made an attempt to review the literature to find the limitations and queries surrounding the present status of measurement of QT interval and its significance as a risk marker for cardiac arrhythmias and sudden death.

Heart failure (HF) with recovered ejection fraction (HFrecEF) is an increasingly recognized yet not well understood phenotype. Little is known about electrical parameters associated with myocardial recovery in acute systolic HF. We identified a subset of 87 patients from a non-ischemic cardiomyopathy cohort with left ventricular ejection fraction (LVEF) < 40% during index HF hospitalization. HFrecEF was defined as follow-up LVEF ≥40% and ≥ 10% improvement from baseline. We analyzed baseline and follow up electrocardiograms (ECG) in this group for several electrical parameters known to reflect repolarization heterogeneity. Among 87 patients, 30 (34%) patients recovered in a median of 122 (IQR: 58-275) days after index hospitalization. Baseline demographics were similar among HFrecEF versus persistent HFrEF except for increased diabetes in the persistent HFrEF cohort. Patients with HFrecEF had baseline decreased QRST angle, decreased QT dispersion, and less negative signed JT area compared to persistent HFrEF. Patients with HFrecEF had greater decrease in QT dispersion and QTc duration, and greater increase in the signed JT and TpTe areas over time. Baseline QRST angle correlated with longitudinal and circumferential strain and myocardial systolic performance (MSP). Signed JT area correlated with increased baseline LVEF, smaller baseline LV dimensions, increased longitudinal and circumferential strain, and MSP. Signed TpTe correlated with increased longitudinal and circumferential strain, and MSP. Several conventional and novel ECG parameters that reflect repolarization heterogeneity may differentiate patients with acute HF who ultimately recover LVEF. These parameters are associated with baseline structural parameters and are dynamic during recovery. • Heart failure with recovered ejection fraction is a newly recognized phenotype. • Increased repolarization heterogeneity on ECG is associated with adverse outcomes. • Repolarization is less heterogeneous on ECG in patients with HFrEF who recover. • Repolarization heterogeneity correlates with baseline structural parameters. • ECG parameters of repolarization are dynamic during the recovery process. [ABSTRACT FROM AUTHOR]

• Early afterdepolarization (EAD) is repolarization abnormalities in ventricular cardiomyocytes. • Depolarizing waves by EADs accentuate repolarization heterogeneity within the ventricle. • Synchronous EAD developments form repolarization potential difference boundaries within the tissue. • Repolarization potential difference boundary shape is a key to triggered activity formation. • Repolarization heterogeneity due to EAD developments could trigger lethal ventricular tachyarrhythmias. Excessive prolongation of QT interval on ECGs in patients with congenital/acquired long QT syndrome and heart failure is a sign suggesting the development of early afterdepolarization (EAD), an abnormal repolarization in the action potential of ventricular cardiomyocytes. The development of EAD has been believed to be a trigger for fatal tachyarrhythmia, which can be a risk for sudden cardiac death. The role of EAD in triggering ventricular tachycardia (VT) remains unclear. The aim of this study was to elucidate the mechanism of EAD-induced triggered activity formation that leads to the VT such as Torsades de Pointes. We investigated the relationship between EAD and tachyarrhythmia initiation by constructing homogeneous myocardial sheet models consisting of the mid-myocardial cell version of a human ventricular myocyte model and performing simulations of excitation propagation. A solitary island-like (clustering) occurrence of EADs in the homogeneous myocardial sheet could induce a focal excitation wave. However, reentrant excitation, an entity of tachyarrhythmia, was not able to be triggered regardless of the EAD cluster size when the focal excitation wave formed a repolarization potential difference boundary consisting of only a convex surface. The discontinuous distribution of multiple EAD clusters in the ventricular tissue formed a specific repolarization heterogeneity due to the repolarization potential difference, the shape of which depended on EAD cluster size and placed intervals. We found that the triggered activity was formed in such a manner that the repolarization potential difference boundary included a concave surface. The formation of triggered activity that led to tachyarrhythmia required not only the occurrence of EAD onset-mediated focal excitation wave but also a repolarization heterogeneity-based specific repolarization potential difference boundary shape formed within the tissue. [ABSTRACT FROM AUTHOR]

The mechanisms underlying atrial fibrillation (AF), the most common sustained cardiac rhythm disturbance, remain elusive. Atrial fibrosis plays an important role in the development of AF and rotor dynamics. Both electrical wavelength (WL) and the degree of atrial fibrosis change as AF progresses. However, their combined effect on rotor core location remains unknown. The aim of this study was to analyze the effects of WL change on rotor core location in both fibrotic and non-fibrotic atria. Three patient specific fibrosis distributions (total fibrosis content: 16.6, 22.8, and 19.2%) obtained from clinical imaging data of persistent AF patients were incorporated in a bilayer atrial computational model. Fibrotic effects were modeled as myocyte-fibroblast coupling + conductivity remodeling; structural remodeling; ionic current changes + conductivity remodeling; and combinations of these methods. To change WL, action potential duration (APD) was varied from 120 to 240ms, representing the range of clinically observed AF cycle length, by modifying the inward rectifier potassium current (IK1) conductance between 80 and 140% of the original value. Phase singularities (PSs) were computed to identify rotor core locations. Our results show that IK1 conductance variation resulted in a decrease of APD and WL across the atria. For large WL in the absence of fibrosis, PSs anchored to regions with high APD gradient at the center of the left atrium (LA) anterior wall and near the junctions of the inferior pulmonary veins (PVs) with the LA. Decreasing the WL induced more PSs, whose distribution became less clustered. With fibrosis, PS locations depended on the fibrosis distribution and the fibrosis implementation method. The proportion of PSs in fibrotic areas and along the borders varied with both WL and fibrosis modeling method: for patient one, this was 4.2–14.9% as IK1 varied for the structural remodeling representation, but 12.3–88.4% using the combination of structural remodeling with myocyte-fibroblast coupling. The degree and distribution of fibrosis and the choice of implementation technique had a larger effect on PS locations than the WL variation. Thus, distinguishing the fibrotic mechanisms present in a patient is important for interpreting clinical fibrosis maps to create personalized models.

Competing Interests: Funding Support and Author Disclosures Drs Yanagisawa and Shibata are affiliated with a department sponsored by Medtronic Japan. Drs Shimojo and Tsuji are affiliated with a department sponsored by Japan Lifeline Co, Ltd, Biotronik Japan, Inc, Fukuda Denshi Co, Ltd, and Suzuken Co, Ltd. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Cardiac resynchronization therapy (CRT) has been shown to induce left ventricular reverse remodeling, but little is known about its influence on ventricular repolarization.Objective: The purpose of this study was to evaluate changes in ventricular repolarization of native conduction after CRT and its relation to ventricular tachycardia (VT) and ventricular fibrillation (VF) during long-term follow-up.Methods: We prospectively included 64 patients with heart failure treated with CRT. QT interval, TpTe, and TpTe/QT ratio were analyzed from 20-minute high-resolution ECGs that were recorded at baseline and 1, 3, 6, 9, and 12 months after CRT implantation. CRT was temporary inhibited during follow-up to record intrinsic ECG. Patients with a decrease of left ventricular end-systolic volume ≥15% at 12-month follow-up (mid-term follow-up) were considered as responders. Occurrences of VT/VF during follow-up were noted.Results: Significant increase of repolarization heterogeneity in the first months after implantation was observed (P <.05) but then declined during 12 months of follow-up. Patients with VT/VF during long-term follow-up had higher repolarization heterogeneity at mid-term follow-up than patients without VT/VF (TpTe/QT ratio: 0.263 [0.204-0.278] vs 0.225 [0.204-0.239]; P = .045). Echocardiographic response at mid-term follow-up did not significantly influence the rate of VT/VF (log-rank P = .252). In multivariate Cox regression analysis, only high repolarization heterogeneity at mid-term follow-up (TpTe/QT ratio >0.260) was independently associated with high risk of VT/VF (hazard ratio 4.29; 95% confidence interval 1.40-13.15; P = .011).Conclusion: CRT induces time-dependent changes in repolarization parameters in the first year after implantation. High repolarization heterogeneity at mid-term follow-up was associated with higher rate of VT/VF during long-term follow-up. [ABSTRACT FROM AUTHOR]

The mechanisms underlying atrial fibrillation (AF), the most common sustained cardiac rhythm disturbance, remain elusive. Atrial fibrosis plays an important role in the development of AF and rotor dynamics. Both electrical wavelength (WL) and the degree of atrial fibrosis change as AF progresses. However, their combined effect on rotor core location remains unknown. The aim of this study was to analyze the effects of WL change on rotor core location in both fibrotic and non-fibrotic atria. Three patient specific fibrosis distributions (total fibrosis content: 16.6, 22.8, and 19.2%) obtained from clinical imaging data of persistent AF patients were incorporated in a bilayer atrial computational model. Fibrotic effects were modeled as myocyte-fibroblast coupling + conductivity remodeling; structural remodeling; ionic current changes + conductivity remodeling; and combinations of these methods. To change WL, action potential duration (APD) was varied from 120 to 240ms, representing the range of clinically observed AF cycle length, by modifying the inward rectifier potassium current (I K 1) conductance between 80 and 140% of the original value. Phase singularities (PSs) were computed to identify rotor core locations. Our results show that I K 1 conductance variation resulted in a decrease of APD and WL across the atria. For large WL in the absence of fibrosis, PSs anchored to regions with high APD gradient at the center of the left atrium (LA) anterior wall and near the junctions of the inferior pulmonary veins (PVs) with the LA. Decreasing the WL induced more PSs, whose distribution became less clustered. With fibrosis, PS locations depended on the fibrosis distribution and the fibrosis implementation method. The proportion of PSs in fibrotic areas and along the borders varied with both WL and fibrosis modeling method: for patient one, this was 4.2–14.9% as I K 1 varied for the structural remodeling representation, but 12.3–88.4% using the combination of structural remodeling with myocyte-fibroblast coupling. The degree and distribution of fibrosis and the choice of implementation technique had a larger effect on PS locations than the WL variation. Thus, distinguishing the fibrotic mechanisms present in a patient is important for interpreting clinical fibrosis maps to create personalized models. [ABSTRACT FROM AUTHOR]

Background: Spatial heterogeneity in repolarization plays an important role in generating and sustaining cardiac arrhythmias. Reliable determination of repolarization times remains challenging., Objectives: The goal of this study was to improve processing of densely sampled noncontact unipolar electrograms to yield reliable high-resolution activation and repolarization maps., Methods: Endocardial noncontact unipolar electrograms were both simulated and recorded in pig left ventricle. Electrical activity on the endocardial surface was processed in terms of a pseudo-electric field. Activation and repolarization times were calculated by using an amplitude-weighted average on QRS and T waves (ie, the E-field method). This was compared vs the conventional Wyatt method on unipolar electrograms. Timing maps were validated against timing on endocardial action potentials in a simulation study. In vivo, activation and repolarization times determined by using this alternative E-field method were validated against simultaneously recorded endocardial monophasic action potentials (MAPs)., Results: Simulation showed that the E-field method provides viable measurements of local endocardial action potential activation and repolarization times. In vivo, correlation of E-field activation times with MAP activation times (r E  = 0.76; P < 0.001) was similar to those of Wyatt (r Wyatt  = 0.80, P < 0.001; P[h 1 :r E > r Wyatt ] = 0.82); for repolarization times, correlation improved significantly (r E  = 0.96, P < 0.001; r Wyatt  = 0.82, P < 0.001; P[h 1 :r E > r Wyatt ] < 0.00001). This resulted in improved correlations of activation-repolarization intervals to endocardial action potential duration on MAP (r E  = 0.96, P < 0.001; r Wyatt  = 0.86, P < 0.001; P[h 1 :r E > r Wyatt ] < 0.00001). Spatial beat-to-beat variation of repolarization could only be calculated by using the E-field methodology and correlated well with the MAP beat-to-beat variation of repolarization (r E  = 0.76; P = 0.001)., Conclusions: The E-field method substantially enhances information from endocardial noncontact electrogram data, allowing for dense maps of activation and repolarization times and derived parameters., Competing Interests: Funding Support and Author Disclosures The work was supported by grants from KU Leuven BOF, C14/18/079, to Drs Willems and Claus and from Fund for Scientific Research-Flanders (FWO) G097021N to Drs Claus and Sipido. Dr Willems is supported as Senior Clinical Investigator and Dr Amoni as PhD fellow by the Fund for Scientific Research-Flanders (FWO)., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

T-wave changes are thought to be associated with the repolarization phase of myocardial action potential. Although it has been known that persistent T-wave change is associated with the heart disease or the prognosis, the sensitivity and the specificity are not necessarily satisfactory for clinical therapeutic strategy. Recent basic studies have shown that, in some kinds of pathological states, transient repolarization changes of myocardial action potential were associated with life-threatening arrhythmia. Also clinical studies are being conducted to elucidate the clinical implication of transient T-wave changes on electrocardiography (ECG) in such an arrhythmia. Transient repolarization or T-wave change is thought to occur because of environmental or neurohumoral factors, circadian variation, stretching of myocardium or other triggers in daily life, resulting in fatal arrhythmia. Such fatal arrhythmias are thought to occur under restricted conditions even in the patients with serious heart disease. It is important to clarify and utilize the transient T-wave change directly associated with the fatal arrhythmia on a clinical basis. In this article, we first assess the mechanisms of transient repolarization or T-wave changes on ECG concerning fatal arrhythmia, and afterwards refer to possible attempts at clinical evaluation and application.

Sudden cardiac death (SCD) is a leading cause for sudden death, which is characterized by rapid progression and no omen before the onset of disease. Therefore, it is of great value clinically to identify the patients with high risk of SCD. With the deepening of research, the relationship between cardiac repolarization abnormality and SCD has been gradually revealed. This paper briefly describes the relationship between the manifestations of cardiac repolarization abnormality and SCD, and the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Objective To observe the effects of late Na current (INa-L) and rapidly activating delayed rectifier K current (IKr) on ventricular heterogeneity and frequency dependency by using high resolution voltage sensitive optical mapping technology. Methods The model of 12 isolated hearts was constructed in rabbits. Voltage sensitive dye Di-4-ANEPPS were perfused into the isolated hearts by Langendorff method. LED source with the wave length of 532 nm was used to record APD80 and APD50 of the left and right ventricles. Experimental groups were divided into 3 groups by perfusion drugs dofetillide (30nmol/L), dofetillide+ATX-Ⅱ(1nmol/L), and dofetillide + ATX-Ⅱ+mexiletine (10μmol/L). The subjects were intervened by the above drugs in order, and they were self-compared before dosing. After each drug administration, the hearts were stimulated respectively with the BCL of 2000ms, 1000ms, 500ms, and 300ms. Then we observed the changes of APD80 and APD50 in the left and right ventricles before and after the interventions. Results ① In the control group, APD80 and APD50 of the right ventricle were longer than those of the left ventricle in response to different stimulation, and the differences increased with the decrease of stimulating frequency. ② When BCL was 1000ms, APD80 and APD50 of the left and right ventricles were prolonged respectively after administration of dofetillide, but the differences in APD80 and APD50 were insignificant between the left and right ventricles (P>0.05). ΔAPD80 of the two ventricles increased significantly with the decrease of stimulating frequency. ③ After administration of ATX-Ⅱ, when BCL was 1000ms, APD80 and APD50 of the left and right ventricles increased significantly compared with those in the control group and dofetillide intervention group (P<0.05). And the increase of APD in the left ventricle was greater than that of the right ventricle. ΔAPD80 of the two ventricles increased significantly with the decrease of stimulating frequency. ④ After administration of mexiletine, when BCL was 1000ms, APD80 and APD50 of the left and right ventricles reduced significantly compared with those of the primary state (P<0.05). APD80 and APD50 of the left and right ventricles reduced significantly compared with those of the control group (P<0.05) and ATX-Ⅱ group (P>0.05). The increase of ΔAPD80 of the two ventricles became milder when the stimulating frequency decreased. Conclusion ① IKr blocked by dofetillide did not affect the heterogeneity between the two ventricles, which showed reverse-frequency dependence. ② In the context of blocking IKr, ATX-Ⅱ increased the heterogeneity between the left and right ventricles and enhanced the reverse-frequency dependence. In contrast, mexiletine, the blocker of INa-L, decreased the heterogeneity between the two ventricles and reverse-frequency dependence. [ABSTRACT FROM AUTHOR]

Background: Detection of atrial repolarization waves free of far-field signal contamination by ventricular activation would allow investigation of atrial electrophysiology and factors that influence susceptibility to atrial tachycardia and atrial fibrillation (AF).Objective: The purpose of this study was to identify means for high-resolution intracardiac recording of atrial repolarization (Ta) waves using standard clinical electrocatheters and to assess fundamental electrophysiologic properties relevant to AF risk.Methods: In alpha-chloralose anesthetized Yorkshire pigs, we studied effects of vagus nerve stimulation (VNS) on PTa and QT intervals and effects of acute atrial ischemia or administration of intrapericardial acetylcholine followed by intravenous epinephrine on susceptibility to AF.Results: Electrocatheters with closely spaced (1-mm) electrode pairs yielded high-resolution tracings of atrial repolarization waves. These recordings permitted detection of differential effects of right or left VNS, which shortened atrial PTa interval by 30% vs. 21% (P <.01) and lengthened QT interval by 1.5% vs. 9%, respectively (P < .05). During atrial ischemia, STa segments were elevated 3.4-fold (P < .01), and the threshold for inducing AF was reduced 3.1-fold (P = .004). Ischemia amplified atrial T-wave alternans (TWAa) and spatiotemporal heterogeneity (TWHa) by 23- and 13-fold, respectively, in inverse correlation to AF threshold (r = 0.74, P <.01; r = 0.61, P = .03). TWAa and TWHa increased by 4.5- and 2-fold shortly before autonomically triggered atrial premature beats and AF.Conclusion: This study used standard electrocatheters to demonstrate that TWAa and TWHa analysis provides means to assess vulnerability to AF without provocative electrical stimuli. These parameters could be evaluated in the clinical electrophysiology laboratory to determine risk for this prevalent arrhythmia and efficacy of contemporary and new agents. [ABSTRACT FROM AUTHOR]

Introduction. Sodium channel blockers are associated with arrhythmic sudden death, although they are considered antiarrhythmic agents. The mechanism of these opposing effects is unknown. Methods. We used a model of induction of ventricular fibrillation (VF) based on selective perfusion of the vascular beds of isolated porcine hearts (n=8). One bed was perfused with sotalol (220 µM), the adjacent bed with pinacidil (80 µM), leading to repolarization heterogeneity (late repolarization in the sotalol-, early in the pinacidil-area). Premature stimulation from the area with the short action potential was performed. Epicardial activation/repolarization mapping was done. Results. In 3 of the 8 hearts VF was inducible prior to infusion of flecainide. In those hearts the Fibrillation Factor (FF), the interval between the last activation of the premature beat (S2) in the late repolarizing (sotalol) domain and the earliest S2 repolarization in the early repolarizing (pinacidil) domain, was significantly shorter than in the hearts without VF (33+/-22 vs 93+/-11 ms, m+/-SEM, p

Abstract: Although the scientific literature contains ample descriptions of peculiar patterns of repolarization linked to arrhythmic risk, the objective quantification and classification of these patterns continues to be a challenge that impacts their widespread adoption in clinical practice. To advance the science, computerized algorithms spawned in the academic environment have been essential in order to find, extract and measure these patterns. However, outside the strict control of a core lab, these algorithms are exposed to poor quality signals and need to be effective in the presence of different forms of noise that can either obscure or mimic the T-wave variation (TWV) of interest. To provide a practical solution that can be verified and validated for the market, important tradeoffs need to be made that are based on an intimate understanding of the end-user as well as the key characteristics of either the signal or the noise that can be used by the signal processing engineer to best differentiate them. To illustrate this, two contemporary medical devices used for quantifying T-wave variation are presented, including the modified moving average (MMA) for the detection of T-wave Alternans (TWA) and the quantification of T-wave shape as inputs to the Morphology Combination Score (MCS) for the trending of drug-induced repolarization abnormalities. [Copyright &y& Elsevier]

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

Abstract: Assessing repolarization heterogeneity (RH) from surface ECG recording is an open issue in modern electrocardiography, despite the fact that several indexes measured on the T-wave have been proposed and tested. To understand how RH occurring at myocite level is reflected on T-wave shapes, in this paper we propose a mathematical framework that combines a simple statistical model of cardiac repolarization times with the dominant T-wave formalism. Within this framework we compare different T-wave features such as T-wave amplitude, T-wave amplitude variability or QT intervals and we describe mathematically how they are linked to the spatial and temporal components of repolarization heterogeneity. [Copyright &y& Elsevier]

Temporal heterogeneity of ventricular repolarization is a key quantity for the development of ventricular reentrant arrhythmia. In this paper, we introduce the \cal V-index, a novel ECG-based estimator of the standard deviation of ventricular myocytes’ repolarization times s_\vartheta. Differently from other ECG metrics of repolarization heterogeneity, the \cal V-index was derived from the analysis of a biophysical model of the ECG, where repolarization is described by the dominant T-wave (DTW) paradigm. The model explains the shape of T-waves in each lead as a projection of a main waveform (the DTW) and its derivatives weighted by scalars, the lead factors. A mathematical formula is derived to link the heterogeneity of ventricular repolarization s_\vartheta and the \cal V-index. The formula was verified using synthetic 12-lead ECGs generated with a direct electrophysiological model for increasing values of s_\vartheta (in the range 20–70 ms). A linear relationship between the \cal V-index and s_\vartheta was observed, \cal V \approx 0.675 \ s_\vartheta + 1.8 ms (R^2 = 0.9992). Finally, 68 ECGs from the E-OTH-12-0068-010 database of the Telemetric and Holter ECG Warehouse were analyzed. The \cal V-index coherently increased after sotalol administration, a drug known to have QT-prolonging potential (p\ll 0.001). [ABSTRACT FROM AUTHOR]

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

The noninvasive evaluation of ventricular T-wave alternans (TWA) in patients with lethal ventricular arrhythmias is an important issue. In this study, we propose a novel algorithm to identify T-wave current density alternans (TWCA) using synthesized 187-channel vector-projected body surface mapping (187-ch SAVP-ECG). We recorded 10 min of 187-ch SAVP-ECG using a Mason-Likar lead system in the supine position. A recovery time (RT) dispersion map was obtained by averaging the 187-ch SAVP-ECG. The TWCA value was determined from the relative changes in the averaged current density in the T-wave zone (Tpeak ± 50 ms) for two T-wave types. We registered 20 ECG recordings from normal controls and 11 ECG recordings from nine subjects with long QT syndrome (LQT). We divided LQT syndrome subjects into two groups: group 1 provided 9 ECG recordings without visually apparent TWAs, and group 2 provided 2 ECG recordings with visually apparent TWAs. The QTc interval values in the LQT groups were higher than those in the control (515 ± 60 ms in LQT G-1, 600 ± 27 ms in LQT G-2 vs. 415 ± 19 ms in control, P < 0.001). The RTendc dispersion values among the LQT subjects were higher than those of the control subjects (48 ± 19 ms in LQT G-1, 65 ± 30 ms in LQT G-2 vs. 24 ± 10 ms in control, P < 0.01). The mean TWCA value was significantly higher in the LQT G-2 group with visually apparent TWCAs (0.5 ± 0.2% in control, 2.1 ± 1.2% in LQT G-1, and 32.3 ± 6.9% in LQT G-2). Interestingly, the two-dimensional distribution of TWCA in LQT was inhomogeneous and correlated with the distribution of increased RT dispersion. We conclude that a novel algorithm using 187-ch SAVP-ECG might provide new insights into body surface TWCA. [ABSTRACT FROM AUTHOR]

Background: Brugada syndrome (BrS) is characterized by repolarization abnormality with ST-segment elevation in the right ventricular outflow tract (RVOT). Objective: Although action potential (AP) heterogeneity is associated with induction of ventricular arrhythmias (VA) in BrS, clinical evidence and its experimental correlations are still absent and are the focus of this study. Methods: We evaluated repolarization heterogeneity in 15 patients with BrS using body surface mapping and in 8 pairs of isolated canine RVOT and right ventricular anteroinferior (RVAI) preparations having drug-induced BrS using optical mapping. Results: Patients had large J-ST-segment elevation and long QT interval in the RVOT at baseline. Administration of pilsicainide (1 mg/kg) exaggerated J-ST-segment elevation, caused simultaneous long and short QT intervals in the RVOT, and induced polymorphic ventricular tachycardia (VT) and T wave alternans (TWA). Dispersion of QT within the RVOT after pilsicainide was greater in patients that had syncope or ventricular fibrillation than those that did not. Ventricular arrhythmias originated from the RVOT along with local electrocardiogram changes and TWA. Repolarization heterogeneity was much less in areas outside the RVOT. Inducing BrS increased AP heterogeneity (with and without spike-and-dome) within the RVOT epicardium. Phase 2 reentry and TWA originated from the epicardium in 88% and 50% of RVOT preparations, respectively. In contrast, the RVOT endocardium and RVAI had little AP heterogeneity, with neither reentry nor TWA. Conclusion: The instability and heterogeneity of repolarization within the epicardium of the RVOT seem to be associated with arrhythmogenesis in both patients and in the in vitro tissue models of BrS. [Copyright &y& Elsevier]

Abstract: This study examined the significance of ECG-derived indexes in quantifying ventricular repolarization dispersion (VRD) given its value as a risk marker for severe myocardial arrhythmia. Multilead ECG recordings from an isolated rabbit heart model, including control and globally increased VRD (IVRD) beats, were studied. The IVRD was induced by supplying d-Sotalol (DS) or premature ventricular stimulation (PVS). ECG indexes came from (a) the absolute ECG summation signal, from which we obtained the amplitude and area of the T-wave, and the T-wave width (), which we consider as IVRD indexes, and (b) the Singular Value Decomposition (SVD) of the ECG, from which the (angle between the first SVD principal axis and the repolarization axis), T-wave residuum (), T-wave morphology dispersion (), unnormalized (), and (the angle between the depolarization and the repolarization vectors) were estimated as IVRD indexes. Results were compared with the classical QT-based VRD indexes (, standard deviation of QT end). The main results are : vs. ms, for control vs. IVRD generated using DS, and vs. ms when PVS was used, ; : gives vs. ms, for DS and vs. ms for PVS, ; respectively. : vs. , in DS. We concluded that globally induced IVRD is well reflected by the parameter, being the most sensitive of the studied ones. The IVRD can also be quantified by using the index. [Copyright &y& Elsevier]

T-wave changes are thought to be associated with the repolarization phase of myocardial action potential. Although it has been known that persistent T-wave change is associated with the heart disease or the prognosis, the sensitivity and the specificity are not necessarily satisfactory for clinical therapeutic strategy. Recent basic studies have shown that, in some kinds of pathological states, transient repolarization changes of myocardial action potential were associated with life-threatening arrhythmia. Also clinical studies are being conducted to elucidate the clinical implication of transient T-wave changes on electrocardiography (ECG) in such an arrhythmia. Transient repolarization or T-wave change is thought to occur because of environmental or neurohumoral factors, circadian variation, stretching of myocardium or other triggers in daily life, resulting in fatal arrhythmia. Such fatal arrhythmias are thought to occur under restricted conditions even in the patients with serious heart disease. It is important to clarify and utilize the transient T-wave change directly associated with the fatal arrhythmia on a clinical basis. In this article, we first assess the mechanisms of transient repolarization or T-wave changes on ECG concerning fatal arrhythmia, and afterwards refer to possible attempts at clinical evaluation and application. [Copyright &y& Elsevier]

Abstract: Electrocardiographic repolarization abnormalities characterized by T-wave morphology parameters such as the principal component analysis ratio and the relative and the absolute T-wave residuum (TWRrel and TWRabs) are predictive of cardiovascular and/or all-cause mortality. However, when using a “10-second median beat” for analysis, the reported mean values for TWRrel vary widely and parameter reproducibility is somewhat suspect. In repeated electrocardiographic recordings conducted 1 month and 1 year apart on 15 and 27 healthy individuals, respectively, we studied the said T-wave morphology parameters in single complexes and in reduced noise signal averages containing 10 and 200 complexes. Considering all subjects, the mean (±SD) TWRrel was highest in a single complex (0.0345% ± 0.0183%), intermediate in the 10-beat signal-averaged complexes (0.0125% ± 0.0051%), and lowest in the 200-beat signal-averaged complexes (0.0078% ± 0.0036%) (P < .0001), with the same trend also observed in the TWRabs but not in the principal component analysis ratio. Reproducibility as quantified by within-subject variance and reliability as quantified by the intraclass (intrasubject) correlation coefficient also improved as the number of T-wave complexes analyzed increased. We conclude that signal averages consisting of more than 10 complexes (or more than 10 seconds worth of complexes) are required to produce reproducible and reliable values for TWRrel and TWRabs. [Copyright &y& Elsevier]

To study the effect of of lidocaine and amiodarone on the transmural heterogeneity of ventricular repolarization in isolated rabbit hearts model of sustained global ischemia and to explore the mechanisms underlying the antiarrhythmic activity of lidocaine and amiodarone, rabbits were randomly divided into 4 groups: control group, ischemia group, lidocaine group and amiodarone group. By the monophasic action potential (MAP) recording technique, MAPs of epicardium, midmyocardium and endocardium were simultaneously recorded across the left ventricular free wall in rabbit hearts perfused by low-flow ischemia (2.5 mL/min) in Langendorff method to study the transmural dispersion of repolarization (TDR) and arrhythmic induced by ischemia. Our results showed that TDR of three myocardial layers in ischemia group were significantly lengthened after ischemia. TDR was increased from 17.5±3.9 ms to 31.2±4.6 ms at the time that concided with the onset of sustained ventricle arrhythmic. Amiodarone could decrease TDR, but lidocaine could increase TDR at initial ischemia, and no significant difference was found at other ischemia time points. 5 cases had ventriclar arrhythmia in ischemia group (62.5%), but no case in lidocaine group ( P<0.01) and only 1 case in amiodarone group had ventrilar arrhythmia ( P<0.01). No significant difference was found between amiodarone group and lidocaine group. It is concluded that TDR of of three myocardial layers increases significantly at ischemia and it is closely associated with development of ventricular arrhythmia, and amiodarone could decrease TDR, but lidocaine could increase TDR at initial ischemia and has no effects at other ischemia time points. [ABSTRACT FROM AUTHOR]

Intrinsic spatial variations in repolarization currents in the heart can produce spatial gradients in action potential duration (APD) that serve as possible sites for conduction block and the initiation of reentrant activity. In well-coupled myocardium, however, electrotonic influences at the stimulus site and wavefront collision sites act to modulate any intrinsic heterogeneity in APD. These effects alter APD gradients over an extent larger than that suggested by the length constant associated with propagation and, thus, are hypothesized to play a greater role in smaller hearts used as experimental models of human disease. This study uses computer simulation to investigate how heart size, tissue properties, and the spatial assignment of cell types affect functional APD dispersion. Simulations were carried out using the routine ventricular myocyte model of Pandit et al. or the Luo-Rudy mammalian model in three-dimensional models of mouse and rabbit ventricular geometries. Results show that the spatial extent of the APD dispersion is related to the dynamic changes in transmembrane resistance during recovery. Also, because of the small dimensions of the mouse heart, electrotonic effects on APD primarily determine the functional dispersion of refractoriness, even in the presence of large intrinsic cellular heterogeneity and reduced coupling. APD dispersion, however, is found to increase significantly when the heart size increases to the size of a rabbit heart, unmasking intrinsic cell types. [ABSTRACT FROM AUTHOR]

Introduction: QT dispersion (QTd, range of QT intervals in 12 KCG leads) is thought to reflect spatial heterogeneity of ventricular refractoriness. However, QTd may be largely due to projections of the repolarization dipole rather than ‘nondipolar’ signals. Methods and Results: Seventy-eight normal subjects (47 ± 16 years, 23 women), 68 hypertrophic cardiomyopathy patients (HCM; 38 ± 15 years. 21 women), 72 dilated cardiomyopathy patients (DCM; 48 ± 15 years, 29 women), and 81 survivors of acute myocardial infarction (AMI; 63 ± 12 years, 20 women) had digital 12-lead resting supine ECGs recorded (10 ECGs recorded in each subject and results averaged). In each ECG lead, QT interval was measured under operator review by QT Guard (GE Marquette) to obtain QTd. QTd was expressed as the range, standard deviation, and highest-to-lowest quartile difference of QT interval in all measurable leads. Singular value decomposition transferred ECGs into a minimum dimensional time orthogonal space. The first three components represented the ECG dipole; other components represented nondipolar signals. The power of the T wave nondipolar within the total components was computed to measure spatial repolarization heterogeneity (relative T wave residuum, TWR). QTd was 33.6 ± 18.3, 47.0 ± 19.3, 34.8 ± 21.2. and 57.5 ± 25.3 msec in normals, HCM, DCM, and AMI, respectively (normals vs DCM: NS, other P < 0.009). TWR was 0.029% ± 0.031%, 0.067% ± 0.067%, 0.112% ± 0.154%, and 0.186% ± 0.308% in normals, HCM, DCM, and AMI (HCM vs DCM: NS, other P < 0.006), The correlations between QTd and TWR were r = -0.0446, 0.2805, -0.1531, and 0.0771 (P = 0.03 for HCM, other NS) in normals, HCM, DCM, and AMI, respectively. Conclusion: Spatial heterogeneity of ventricular repolarization exists and is measurable in 12-lead resting ECGs. It differs between different clinical groups, but the so-called QT dispersion is unrelated to it. [ABSTRACT FROM AUTHOR]

Background Early life trauma has been associated with increased cardiovascular risk, but the arrhythmic implications are unclear. We hypothesized that in patients with coronary artery disease, early life trauma predicts increased arrhythmic risk during mental stress, measured by elevated microvolt T-wave alternans (TWA), a measure of repolarization heterogeneity and sudden cardiac death risk. Methods and Results In a cohort with stable coronary artery disease (NCT04123197), we examined early life trauma with the Early Trauma Inventory Self Report-Short Form. Participants underwent a laboratory-based mental stress speech task with Holter monitoring, as well as a structured psychiatric interview. We measured TWA during rest, mental stress, and recovery with ambulatory electrocardiographic monitoring. We adjusted for sociodemographic factors, cardiac history, psychiatric comorbidity, and hemodynamic stress reactivity with multivariable linear regression models. We examined 320 participants with noise- and arrhythmia-free ECGs. The mean (SD) age was 63.8 (8.7) years, 27% were women, and 27% reported significant childhood trauma (Early Trauma Inventory Self Report-Short Form ≥10). High childhood trauma was associated with a multivariable-adjusted 17% increase in TWA ( P =0.04) during stress, and each unit increase in the Early Trauma Inventory Self Report-Short Form total score was associated with a 1.7% higher stress TWA ( P =0.02). The largest effect sizes were found with the emotional trauma subtype. Conclusions In a cohort with stable coronary artery disease, early life trauma, and in particular emotional trauma, is associated with increased TWA, a marker of increased arrhythmic risk, during mental stress. This association suggests that early trauma exposures may affect long-term sudden cardiac death risk during emotional triggers, although more studies are warranted.

Background: Many studies have shown that T-peak to T-end (TPTE) interval was associated with sudden cardiac events. Peripartum cardiomyopathy (PPCM) causes reversible left ventricle systolic dysfunction which may deteriorate into sudden cardiac death. This study aimed to evaluate beta-blocker as an antiarrhythmic agent to improve TPTE interval as a prognostic value of sudden cardiac death., Methods: A cohort experimental prospective study was performed. The PPCM was diagnosed from the emergency ward. A total of 54 cases were identified from 2014 to 2016. Thirty-four patients were followed up for further analysis. Electrocardiograms were conducted in all the patients, and TPTE interval was measured. After a follow-up of 6 months of beta-blocker treatment, the echocardiography and TPTE interval were measured again to obtain the repolarization heterogeneity., Results: The mean age of subjects was 32 ± 6.4 years. The mean left ventricular ejection fraction (LVEF) was 32.24±6.3%. The mean TPTE interval was 123.7 ± 28.2 ms. After 6 months of beta-blocker administration, the mean LVEF was 58.26±4.4% and the mean TPTE was 98.7 ± 39.5 ms. The paired t -test showed a significant difference between TPTE interval pre- and post-administration of beta-blocker (P value < 0.001)., Conclusions: There is an improvement of TPTE in PPCM patients after 6 months of beta-blocker administration. Administration of beta-blocker in PPCM patients is expected to prevent sudden cardiac death in PPCM populations., Competing Interests: All authors declare no conflict of interest related to this study., (Copyright 2020, Achmad et al.)

The demonstrated benefits of cardiac resynchronization therapy (CRT) in reducing mortality and hospitalizations for heart failure, improving NYHA functional class and inducing reverse remodeling have led to its increasing use in clinical practice. However, its potential contribution to complex ventricular arrhythmias is controversial.We present the case of a female patient with valvular heart failure and severe systolic dysfunction, in NYHA class III and under optimal medical therapy, without previous documented ventricular arrhythmias. After implantation of a CRT defibrillator, she suffered an arrhythmic storm with multiple episodes of monomorphic ventricular tachycardia (VT), requiring 12 shocks. Subsequently, a pattern of ventricular bigeminy was observed, as well as reproducible VT runs induced by biventricular pacing. Since no other vein of the coronary sinus system was accessible, it was decided to implant an epicardial lead to stimulate the left ventricle, positioned in the left ventricular mid-lateral wall. No arrhythmias were detected in the following six months. This case highlights the possible proarrhythmic effect of biventricular pacing with a left ventricular lead positioned in the coronary sinus venous system., (Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.)

Sodium channel blockers are associated with arrhythmic sudden death, although they are considered antiarrhythmic agents. The mechanism of these opposing effects is unknown. We used a model of induction of ventricular fibrillation (VF) based on selective perfusion of the vascular beds of isolated porcine hearts (n = 8). One bed was perfused with sotalol (220 μM), the adjacent bed with pinacidil (80 μM), leading to repolarization heterogeneity (late repolarization in the sotalol-, early in the pinacidil-area). Premature stimulation from the area with the short action potential was performed. Epicardial activation/repolarization mapping was done. In three of the eight hearts VF was inducible prior to infusion of flecainide. In those hearts the Fibrillation Factor (FF), the interval between the earliest repolarization of the premature beat (S2) in the early repolarizing (pinacidil) domain, and the last S2-activation in the late repolarizing (sotalol) domain, was significantly shorter than in the hearts without VF (33 ± 22 vs 93 ± 11 ms, m ± SEM, p < 0.05). In the three hearts with VF flecainide was infused in the pinacidil domain after defibrillation. This led to shortening of the line of block, local delay of S2 activation and repolarization, an increase in FF and failure to induce VF. In the five hearts without VF, flecainide was subsequently infused in the sotalol domain. This led to a local delay of S2 activation, a shortening of FF (by 47 ± 3 ms) and successful induction of VF in three hearts. In the two remaining hearts FF did not decrease enough (maximally 13 ms) to allow re-entry. Sodium channel blockade applied to myocardium with a short refractory period is antifibrillatory whereas sodium channel blockade of myocardium with a long refractory period is profibrillatory. Our study provides a mechanistic basis for pro- and antiarrhythmic effects of sodium channel blockers in the absence of structural heart disease.