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. METHODS: To clarify this issue, we performed computer simulations of antegrade AP conduction using a simplified wall model. We focused on the bundle size of the AP and myocardial electrical conductivity during antegrade conduction (from the atrium to the ventricle). RESULTS: We found that a thick AP and high ventricular conductivity promoted antegrade conduction, whereas a thin AP is unable to deliver the transmembrane current required for electric conduction. High ventricular conductivity amplifies transmembrane current. These findings suggest the involvement of a source-sink mechanism. Furthermore, we found that high AP conductivity blocked antegrade conduction. As AP conductivity increased, sustained outward transmembrane currents were observed. This finding suggests the involvement of an electrotonic effect. CONCLUSIONS: The findings of our theoretical simulation suggest that AP size, ventricular conductivity, and AP conductivity affect antegrade conduction through different mechanisms. Our findings provide new insights into the morphological and electrophysiological details of the AP.

Development of Helical Myofiber Tracts in the Human Fetal Heart: Analysis of Myocardial Fiber Formation in the Left Ventricle From the Late Human Embryonic Period Using Diffusion Tensor Magnetic Resonance Imaging.

Background Detection of the fiber orientation pattern of the myocardium using diffusion tensor magnetic resonance imaging lags ≈12 weeks of gestational age (WGA) behind fetal myocardial remodeling with invasion by the developing coronary vasculature (8 WGA). We aimed to use diffusion tensor magnetic resonance imaging tractography to characterize the evolution of fiber architecture in the developing human heart from the later embryonic period. Methods and Results Twenty human specimens (8-24 WGA) from the Kyoto Collection of Human Embryos and Fetuses, including specimens from the embryonic period (Carnegie stages 20-23), were used. Diffusion tensor magnetic resonance imaging data were acquired with a 7T magnetic resonance system. Fractional anisotropy and helix angle were calculated using standard definitions. In all samples, the fibers ran helically in an organized pattern in both the left and right ventricles. A smooth transmural change in helix angle values (from positive to negative) was detected in all 16 directions of the ventricles. This feature was observed in almost all small (Carnegie stage 23) and large samples. A higher fractional anisotropy value was detected at the outer side of the anterior wall and septum at Carnegie stage 20 to 22, which spread around the ventricular wall at Carnegie stage 23 and in the early fetal samples (11-12 WGA). The fractional anisotropy value of the left ventricular walls decreased in samples with ≥13 WGA, which remained low (≈0.09) in larger samples. Conclusions From the human late embryonic period (from 8 WGA), the helix angle arrangement of the myocardium is comparable to that of the adult, indicating that the myocardial structure blueprint, organization, and integrity are already formed.

Three-dimensional histologic reconstruction of remnant functional accessory atrioventricular myocardial connections in a case of Wolff-Parkinson-White syndrome.

Myocardial bundles working as accessory pathways in Wolff-Parkinson-White (WPW) syndrome are generally tiny tissues, so elucidating the culprit histology of atrioventricular (AV) myocardial connections requires careful serial sectioning of the AV junction. We performed a postmortem examination of accessory AV myocardial connections in an 84-year-old man who died from pneumonia 20 years after surgical cryoablation for WPW syndrome. Three-dimensional reconstruction images of serial histologic sections revealed accessory AV connections between the atrial and ventricular myocardium in the vicinity of the cryoablation scar. The remnant myocardial bridge was 4 mm wide and made up of multiple discontinuous fibers. This case was informative in that it provided for visualization of the histologic morphology of a remnant bundle of Kent.

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. Conclusion: Real-time rotor imaging, rather than conventional indirect indicators only, might be very useful for detecting non-PAF drivers.

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. However, the roles of the subcellular redistribution of Na+ channels in the arrhythmogenicity under ischemia remain unclear. METHODS: Computer simulations of excitation conduction were performed in a myofiber model incorporating both subcellular Na+ channel redistribution and the electric field mechanism, taking into account the intercellular cleft potentials. RESULTS: We found in the myofiber model that the subcellular redistribution of the Na+ channels under myocardial ischemia, decreasing in Na+ channel expression of the lateral cell membrane of each myocyte, decreased the tissue excitability, resulting in conduction slowing even without any ischemia-related electrophysiological change. The conventional model (i.e., without the electric field mechanism) did not reproduce the conduction slowing caused by the subcellular Na+ channel redistribution. Furthermore, Na+ channel blockade with the coexistence of a non-ischemic zone with an ischemic border zone expanded the vulnerable period for reentrant tachyarrhythmias compared to the model without the ischemic border zone. Na+ channel blockade tended to cause unidirectional conduction block at sites near the ischemic border zone. Thus, such a unidirectional conduction block induced by a premature stimulus at sites near the ischemic border zone is associated with the initiation of reentrant tachyarrhythmias. CONCLUSIONS: Proarrhythmia of Na+ channel blockade in patients with old myocardial infarction might be partly attributable to the ischemia-related subcellular Na+ channel redistribution.

Feasibility for the enhancement of an online support system for persons with metabolic syndrome, aimed at applications for ischemic heart disease and heart failure.

Previously, we developed of an online support system for persons with metabolic syndrome. In this study, we investigated the possibility of enhancing our system for applications in ischemic heart disease (IHD) and heart failure (HF). The main causes of IHD are obesity, hypertension, arteriosclerosis, hyperglycemia and other metabolic disorders. These conditions are related to lifestyle issues, such as diet and exercise. Dietary management becomes more difficult as the patient's condition worsens. We primarily focused on behavior changes. To raise the user's awareness of food intake, we improved a number of functions of the developed system: an entry of the user's lifestyle information, a calculation of the total calorie intake and a reference of food model pictures in 80 kcal standard quantities. IHD encompasses many of the causes of HF. Management tools appropriate for HF are few. We describe the main functions of our system and promote self-management as a requirement for IHD and HF. We expect that the framework of our system is applicable to the management of patients with chronic HF.

Simulation study of complex action potential conduction in atrioventricular node.

The atrioventricular (AV) node, which is located between the atria and ventricles of the heart, acts as important roles in cardiac excitation conduction between the two chambers. Although there are multiple conduction pathways in the AV node, the structure of the AV node has not been clarified. In this study, we constructed a one-dimensional model of the AV node and simulated excitation conduction between the right atrium and the bundle of His via the AV node. We also investigated several characteristics of the AV node: (1) responses of the AV node to high-rate excitation in the right atrium, (2) the AV nodal reentrant beat induced by premature stimulus, and (3) ventricular rate control during atrial fibrillation with various methods. Our simulation results suggest that multiple conduction pathways act as important roles in controlling the ventricular rate. The one-dimensional model constructed in this study may be useful to analyze complex conduction patterns in the AV node.

A kinematic approach for efficient and robust simulation of the cardiac beating motion.

Computer simulation techniques for cardiac beating motions potentially have many applications and a broad audience. However, most existing methods require enormous computational costs and often show unstable behavior for extreme parameter sets, which interrupts smooth simulation study and make it difficult to apply them to interactive applications. To address this issue, we present an efficient and robust framework for simulating the cardiac beating motion. The global cardiac motion is generated by the accumulation of local myocardial fiber contractions. We compute such local-to-global deformations using a kinematic approach; we divide a heart mesh model into overlapping local regions, contract them independently according to fiber orientation, and compute a global shape that satisfies contracted shapes of all local regions as much as possible. A comparison between our method and a physics-based method showed that our method can generate motion very close to that of a physics-based simulation. Our kinematic method has high controllability; the simulated ventricle-wall-contraction speed can be easily adjusted to that of a real heart by controlling local contraction timing. We demonstrate that our method achieves a highly realistic beating motion of a whole heart in real time on a consumer-level computer. Our method provides an important step to bridge a gap between cardiac simulations and interactive applications.

Cardiovascular modeling of congenital heart disease based on neonatal echocardiographic images.

This paper proposes a 3-D cardiovascular modeling system based on neonatal echocardiographic images. With the system, medical doctors can interactively construct patient-specific cardiovascular models, and share the complex topology and the shape information. For the construction of cardiovascular models with a variety of congenital heart diseases, we propose a set of algorithms and interface that enable editing of the topology and shape of the 3-D models. In order to facilitate interactivity, the centerline and radius of the vessels are used to edit the surface of the heart vessels. This forms a skeleton where the centerlines of blood vessel serve as the nodes and edges, while the radius of the blood vessel is given as an attribute value to each node. Moreover, parent-child relationships are given to each skeleton. They are expressed as the directed acyclic graph, where the skeletons are viewed as graph nodes and the connecting points are graph edges. The cardiovascular models generated from some patient data confirmed that the developed technique is capable of constructing cardiovascular disease models in a tolerable timeframe. It is successful in representing the important structures of the patient-specific heart vessels for better understanding in preoperative planning and electric medical recording of the congenital heart disease.

The role of fibroblasts in complex fractionated electrograms during persistent/permanent atrial fibrillation: implications for electrogram-based catheter ablation.

RATIONALE: Electrogram-based catheter ablation, targeting complex fractionated atrial electrograms (CFAEs), is empirically known to be effective in halting persistent/permanent atrial fibrillation (AF). However, the mechanisms underlying CFAEs and electrogram-based ablation remain unclear. OBJECTIVE: Because atrial fibrosis is associated with persistent/permanent AF, we hypothesized that electrotonic interactions between atrial myocytes and fibroblasts play an important role in CFAE genesis and electrogram-based catheter ablation. METHODS AND RESULTS: We used a human atrial tissue model in heart failure and simulated propagation and spiral wave reentry with and without regionally proliferated fibroblasts. Coupling of fibroblasts to atrial myocytes resulted in shorter action potential duration, slower conduction velocity, and lower excitability. Consequently, heterogeneous fibroblast proliferation in the myocardial sheet resulted in frequent spiral wave breakups, and the bipolar electrograms recorded at the fibroblast proliferation area exhibited CFAEs. The simulations demonstrated that ablation targeting such fibroblast-derived CFAEs terminated AF, resulting from the ablation site transiently pinning the spiral wave and then pushing it out of the fibroblast proliferation area. CFAEs could not be attributed to collagen accumulation alone. CONCLUSIONS: Fibroblast proliferation in atria might be responsible for the genesis of CFAEs during persistent/permanent AF. Our findings could contribute to better understanding of the mechanisms underlying CFAE-targeted AF ablation.

Roles of subcellular Na+ channel distributions in the mechanism of cardiac conduction.

The gap junction and voltage-gated Na(+) channel play an important role in the action potential propagation. The purpose of this study was to elucidate the roles of subcellular Na(+) channel distribution in action potential propagation. To achieve this, we constructed the myocardial strand model, which can calculate the current via intercellular cleft (electric-field mechanism) together with gap-junctional current (gap-junctional mechanism). We conducted simulations of action potential propagation in a myofiber model where cardiomyocytes were electrically coupled with gap junctions alone or with both the gap junctions and the electric field mechanism. Then we found that the action potential propagation was greatly affected by the subcellular distribution of Na(+) channels in the presence of the electric field mechanism. The presence of Na(+) channels in the lateral membrane was important to ensure the stability of propagation under conditions of reduced gap-junctional coupling. In the poorly coupled tissue with sufficient Na(+) channels in the lateral membrane, the slowing of action potential propagation resulted from the periodic and intermittent dysfunction of the electric field mechanism. The changes in the subcellular Na(+) channel distribution might be in part responsible for the homeostatic excitation propagation in the diseased heart.

Transmural dispersion of repolarization determines scroll wave behavior during ventricular tachyarrhythmias.

BACKGROUND: Ventricular tachyarrhythmia is the leading cause of sudden cardiac death, and scroll wave re-entry is known to underlie this condition. Class III antiarrhythmic drugs are commonly used worldwide to treat ventricular tachyarrhythmias; however, these drugs have a proarrhythmic adverse effect and can cause Torsade de Pointes or ventricular fibrillation. Transmural dispersion of repolarization (TDR) has been suggested to be a strong indicator of ventricular tachyarrhythmia induction. However, the role of TDR during sustained scroll wave re-entry is poorly understood. The purpose of the present study was to investigate how TDR affects scroll wave behavior and to provide a novel analysis of the mechanisms that sustain tachyarrhythmias, using computer simulations. METHODS AND RESULTS: Computer simulations were carried out to quantify the TDR and QT interval under a variety of I(Ks) and I(Kr) during transmural conduction. Simulated scroll wave re-entries were done under a variety of I(Ks) and I(Kr) in a ventricular wall slab model, and the scroll wave behavior and the filament dynamics (3-dimensional organizing center) were analyzed. A slight increase in TDR, but not in the QT interval, reflected antiarrhythmic properties resulting from the restraint of scroll wave breakup, whereas a marked increase in TDR was proarrhythmic, as a result of scroll wave breakup. CONCLUSIONS: The TDR determines the sustainment of ventricular tachyarrhythmias, through control of the scroll wave filament dynamics.

A procedural method for modeling the purkinje fibers of the heart.

The Purkinje fibers are located in the ventricular walls of the heart, just beneath the endocardium and conduct excitation from the right and left bundle branches to the ventricular myocardium. Recently, anatomists succeeded in photographing the Purkinje fibers of a sheep, which clearly showed the mesh structure of the Purkinje fibers. In this study, we present a technique for modeling the mesh structure of Purkinje fibers semiautomatically using an extended L-system. The L-system is a formal grammar that defines the growth of a fractal structure by generating rules (or rewriting rules) and an initial structure. It was originally formulated to describe the growth of plant cells, and has subsequently been applied for various purposes in computer graphics such as modeling plants, buildings, streets, and ornaments. For our purpose, we extended the growth process of the L-system as follows: 1) each growing branch keeps away from existing branches as much as possible to create a uniform distribution, and 2) when branches collide, we connect the colliding branches to construct a closed mesh structure. We designed a generating rule based on observations of the photograph of Purkinje fibers and manually specified three terminal positions on a three-dimensional (3D) heart model: those of the right bundle branch, the anterior fascicle, and the left posterior fascicle of the left branch. Then, we grew fibers starting from each of the three positions based on the specified generating rule. We achieved to generate 3D models of Purkinje fibers of which physical appearances closely resembled the real photograph. The generation takes a few seconds. Variations of the Purkinje fibers could be constructed easily by modifying the generating rules and parameters.

A sketch-based interface for modeling myocardial fiber orientation that considers the layered structure of the ventricles.

We propose a sketch-based interface for modeling the myocardial fiber orientation required in the electrophysiological simulation of the heart, especially the ventricles. The user can create a volumetric vector field that represents the myocardial fiber orientation in two steps. First, a depth field over the three-dimensional (3D) ventricular model is defined to create layers of myocardium. The user can then peel these layers and draw strokes on them to specify the myocardial fiber orientation in each layer. We represent the 3D ventricular model as a tetrahedral mesh and perform Laplacian smoothing over the mesh vertices to interpolate the vector field defined by the user-drawn strokes. Our method also allows the user to perform deformations on volumetric models of myocardial fiber orientation, which is very important for studying heart disease associated with morphological abnormalities. We created several examples of myocardial fiber orientation and applied them to a simplified simulator to demonstrate the effectiveness of our method.

Identification of local myocardial repolarization time by bipolar electrode potential.

PURPOSE: The aim of this study was to investigate whether bipolar electrode potentials (BEPs) reflect local myocardial repolarization dynamics, using computer simulation. METHODS: Simulated action potential and BEP mapping of myocardial tissue during fibrillation was performed. The BEP was modified to make all the fluctuations have the same polarity. Then, the modified BEP (mBEP) was transformed to "dynamic relative amplitude" (DRA) designed to make all the fluctuations have the similar amplitude. RESULTS: The repolarization end point corresponded to the end of the repolarization-related small fluctuation that clearly appeared in the DRA of mBEP. Using the DRA of mBEP, we could reproduce the repolarization dynamics in the myocardial tissue during fibrillation. CONCLUSIONS: The BEP may facilitate identifying the repolarization time. Furthermore, BEP mapping has the possibility that it would be available for evaluating repolarization behavior in myocardial tissue even during fibrillation. The accuracy of activation-recovery interval was also reconfirmed.