Organization of atrial fibrillation using a pure sodium channel blocker: Implications of rotor ablation therapy.

Background: Rotors are the source of atrial fibrillation (AF). However, the ablation of rotors for persistent AF is challenging. The purpose of this study was to identify the dominant rotor by accelerating the organization of AF using a sodium channel blocker and detecting the rotor's preferential area that governs AF.

Effect of pulmonary vein isolation on rotor/multiple wavelet dynamics in persistent atrial fibrillation, association with vagal response and implications for adjunctive ablation.

Persistent atrial fibrillation (PeAF) may develop arrhythmogenic substrates of rotors/multiple wavelets. However, the ways in which pulmonary vein isolation (PVI) affects the dynamics of rotor/multiple wavelets in PeAF patients remain elusive. Real-time phase-mapping (ExTRa mapping, EXT) in the whole left atrium (LA) was performed during PeAF before and after PVI (n = 111).

Excessive folic acid intake combined with undernutrition during gestation alters offspring behavior and brain monoamine profiles.

Dietary folic acid augmentation during gestation reduces neurodevelopmental disorder risk in offspring; however, it is still unclear if excessive maternal folic acid intake can impair brain function in offspring. We examined if excessive folic acid intake throughout gestation altered the behavior of male offspring under poor nutrition during early gestation (E5.5-E11.

The impact of the atrial wall thickness in normal/mild late-gadolinium enhancement areas on atrial fibrillation rotors in persistent atrial fibrillation patients.

Background: Some of atrial fibrillation (AF) drivers are found in normal/mild late-gadolinium enhancement (LGE) areas, as well as moderate ones. The atrial wall thickness (AWT) has been reported to be important as a possible AF substrate. However, the AWT and degree of LGEs as an AF substrate has not been fully validated in humans.

High accessory pathway conductivity blocks antegrade conduction in Wolff-Parkinson-White syndrome: A simulation study.

Background: Wolff-Parkinson-White (WPW) syndrome is characterized by an anomalous accessory pathway (AP) that connects the atrium and ventricles, which can cause abnormal myocardial excitation and cardiac arrhythmias. The morphological and electrophysiological details of the AP remain unclear. The size and conductivity of the AP may affect conduction and WPW syndrome symptoms.

Heart sound recognition technology based on convolutional neural network.

The mortality rate of heart disease continues to rise each year: developing mechanisms to reduce mortality from heart disease is a top concern in today's society. Heart sound auscultation is a crucial skill used to detect and diagnose heart disease. In this study, we propose a heart sound signal classification algorithm based on a convolutional neural network.

Late-gadolinium enhancement properties associated with atrial fibrillation rotors in patients with persistent atrial fibrillation.

Background: A computational model demonstrated that atrial fibrillation (AF) rotors could be distributed in patchy late-gadolinium enhancement (LGE) areas and play an important role in AF drivers. However, this was not validated in humans.

Objective: The purpose of this study was to evaluate the LGE properties of AF rotors in patients with persistent AF.

Spatial phase discontinuity at the center of moving cardiac spiral waves.

Background: Precise analysis of cardiac spiral wave (SW) dynamics is essential for effective arrhythmia treatment. Although the phase singularity (PS) point in the spatial phase map has been used to determine the cardiac SW center for decades, quantitative detection algorithms that assume PS as a point fail to trace complex and rapid PS dynamics. Through a detailed analysis of numerical simulations, we examined our hypothesis that a boundary of spatial phase discontinuity induced by a focal conduction block exists around the moving SW center in the phase map.

Specific decreasing of Na channel expression on the lateral membrane of cardiomyocytes causes fatal arrhythmias in Brugada syndrome.

Reduced cardiac sodium (Na) channel current (I) resulting from the loss-of-function of Na channel is a major cause of lethal arrhythmias in Brugada syndrome (BrS). Inspired by previous experimental studies which showed that in heart diseases I was reduced along with expression changes in Na channel within myocytes, we hypothesized that the local decrease in I caused by the alteration in Na channel expression in myocytes leads to the occurrence of phase-2 reentry, the major triggering mechanism of lethal arrhythmias in BrS. We constructed in silico human ventricular myocardial strand and ring models, and examined whether the Na channel expression changes in each myocyte cause the phase-2 reentry in BrS.

Validation of Intraoperative Catheter Phase Mapping Using a Simultaneous Optical Measurement System in Rabbit Ventricular Myocardium.

Background: Recently, an interoperative catheter electrode mapping system, termed ExTRa Mapping (EXT), was developed for precise diagnosis and effective treatment of non-paroxysmal atrial fibrillations (non-PAF). However, the mapping accuracy of EXT is still unclear.

Methods and results: In this study, the reliability of the EXT in comparison with that of high-resolution optical membrane potential mapping was compared.

Impact of Box Isolation on Rotors and Multiple Wavelets in Persistent Atrial Fibrillation.

Background: Additional benefits of posterior left atrial (LA) box isolation (BOXI) over pulmonary vein isolation (PVI) in persistent atrial fibrillation (perAF) have been reported, but the mechanism is still unclear. We evaluated the effects of BOXI on rotors and multiple wavelets in the whole LA.

Methods and results: Twenty patients with perAF (including 12 cases of longstanding perAF) underwent PVI.

Successful modulation of atrial fibrillation drivers anchoring to fibrotic tissue after box isolation using an online real-time phase mapping system: ExTRa Mapping.

A 41-year-old man with persistent atrial fibrillation (AF) underwent radiofrequency (RF) catheter ablation using an online real-time phase mapping system: ExTRa Mapping. Box isolation could not terminate AF. Subsequently, RF applications on nonpassively activated areas (NPAs), where rotational activations were frequently observed, at the posterior bottom of left atrium outside of box lesion could convert AF to common atrial flutter.

Systematic expression analysis of genes related to generation of action potentials in human iPS cell-derived cardiomyocytes.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a valuable tool to characterize the pharmacology and toxic effects of drugs on heart cells. In particular, hiPSC-CMs can be used to identify drugs that generate arrhythmias. However, it is unclear whether the expression of genes related to generation of CM action potentials differs between hiPSC-CM cell lines and the mature human heart.

A de novo gain-of-function KCND3 mutation in early repolarization syndrome.

Background: Early repolarization syndrome (ERS) is characterized by J-point elevation on electrocardiograms and ventricular fibrillation (VF). Early repolarization arises from augmentation of the transmural electrical gradient in the cardiac action potential; therefore, the transient outward potassium current (I) has been regarded as a key candidate current for elucidating the mechanism of ERS. KCND3 encoding Kv4.

Not all rotors, effective ablation targets for nonparoxysmal atrial fibrillation, are included in areas suggested by conventional indirect indicators of atrial fibrillation drivers: ExTRa Mapping project.

Background: Effects of nonparoxysmal atrial fibrillation (non-PAF) ablation targeting complex fractionated atrial electrogram (CFAE) areas and/or low voltage areas (LVAs) are still controversial.

Methods And Results: A recently developed online real-time phase mapping system (ExTRa Mapping) was used to conduct LVA mapping and simultaneous ExTRa and CFAE mapping in 28 non-PAF patients after pulmonary vein isolation (PVI). Nonpassively activated areas, in the form of meandering rotors and/or multiple wavelets assumed to contain non-PAF drivers, partly overlapped with CFAE/LVAs but not always coincided with them.

Modelling Torsade de Pointes arrhythmias in vitro in 3D human iPS cell-engineered heart tissue.

Torsade de Pointes (TdP) is a lethal arrhythmia that is often drug-induced, thus there is an urgent need for development of models to test or predict the drug sensitivity of human cardiac tissue. Here, we present an in vitro TdP model using 3D cardiac tissue sheets (CTSs) that contain a mixture of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and non-myocytes. We simultaneously monitor the extracellular field potential (EFP) and the contractile movement of the CTSs.

Overexpression of KCNJ2 in induced pluripotent stem cell-derived cardiomyocytes for the assessment of QT-prolonging drugs.

Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes hold great potentials to predict pro-arrhythmic risks in preclinical cardiac safety screening, although the hiPSC cardiomyocytes exhibit rather immature functional and structural characteristics, including spontaneous activity. Our physiological characterization and mathematical simulation showed that low expression of the inward-rectifier potassium (I) channel is a determinant of spontaneous activity. To understand impact of the low I expression on the pharmacological properties, we tested if transduction of hiPSC-derived cardiomyocytes with KCNJ2, which encodes the I channel, alters pharmacological response to cardiac repolarization processes.

Significance of integrated in silico transmural ventricular wedge preparation models of human non-failing and failing hearts for safety evaluation of drug candidates.

Introduction: To evaluate the usefulness of in silico assay in predicting drug-induced QTc prolongation and ventricular proarrhythmia, we describe in this study 2-dimensional transmural ventricular wedge preparation model (2D model) of non-failing (non-FH) and failing hearts (FH) based on O'Hara-Rudy dynamic model of human ventricular myocytes.

Methods: Using the prepared 2D model, we simulated ventricular action potential and recorded electrocardiogram for the non-FH and FH. The FH model was constructed based on differences in mRNA, protein, and/or current levels of ion channels between non-diseased heart and failing heart.

Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy.

Myotonic dystrophy (DM) is caused by the expression of mutant RNAs containing expanded CUG repeats that sequester muscleblind-like (MBNL) proteins, leading to alternative splicing changes. Cardiac alterations, characterized by conduction delays and arrhythmia, are the second most common cause of death in DM. Using RNA sequencing, here we identify novel splicing alterations in DM heart samples, including a switch from adult exon 6B towards fetal exon 6A in the cardiac sodium channel, SCN5A.

High Frequency of Early Repolarization and Brugada-Type Electrocardiograms in Hypercalcemia.

Background: J wave, or early repolarization has recently been associated with an increased risk of lethal arrhythmia and sudden death, both in idiopathic ventricular fibrillation and in the general population. Hypercalcemia is one of the causes of J point and ST segment elevation, but the relationship has not been well studied. The aim of this study was to examine the effects of hypercalcemia on J point elevation.

Genotype-dependent differences in age of manifestation and arrhythmia complications in short QT syndrome.

Background: Short QT syndrome (SQTS) is a rare inheritable arrhythmia, associated with atrial and ventricular fibrillations, caused by mutations in six cardiac ion channel genes with high penetrance. However, genotype-specific clinical differences between SQTS patients remain to be elucidated.

Methods And Results: We screened five unrelated Japanese SQTS families, and identified three mutations in KCNH2 and KCNQ1.

Ischemia-related subcellular redistribution of sodium channels enhances the proarrhythmic effect of class I antiarrhythmic drugs: a simulation study.

Background: Cardiomyocytes located at the ischemic border zone of infarcted ventricle are accompanied by redistribution of gap junctions, which mediate electrical transmission between cardiomyocytes. This ischemic border zone provides an arrhythmogenic substrate. It was also shown that sodium (Na+) channels are redistributed within myocytes located in the ischemic border zone.