Search

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]

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]

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]

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]

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]

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]