Scroll Waves Research Articles

Stabilization of collapsing scroll waves in systems with random heterogeneities.

In three-dimensional reaction-diffusion systems, excitation waves may form and rotate around a one-dimensional phase singularity called the filament. If the filament forms a closed curve, it will shrink over time and eventually collapse. However, filaments may pin to non-reactive objects present in the medium, reducing their rate of collapse or even allowing them to persist indefinitely. We use numerical simulations to study how different arrangements of non-reactive spheres affect the dynamics of circular filaments. As the filament contracts, it gets closer to and eventually touches and pins to objects in its path. This causes two possible behaviors. The filament can detach from the spheres in its path, slowing down the rate of contraction, or it can remain pinned to a collection of spheres. In general, more or larger spheres increase the chance that the filament remains pinned, but there are exceptions. It is possible for a small number of small spheres to support the filament and possible for the filament to pass through a large number of large spheres. Our work yields insights into the pinning of scroll waves in excitable tissue such as cardiac muscle, where scar tissue acts in a way similar to the non-reactive domains.

Pinning of scroll waves to flat and highly branched unexcitable heterogeneities.

System heterogeneities such as organelles, cells, and anatomical features strongly affect nonlinear wave patterns in biological systems. These effects are more readily studied in otherwise homogeneous chemical reactions that allow the introduction of tailored structures. Following this approach, we investigate the dynamics of three-dimensional excitation vortices pinned to inert sheets with circular holes arranged on a hexagonal lattice. Experiments with the Belousov-Zhabotinsky reaction and numerical simulations of an excitable reaction-diffusion model reveal vortex pinning that circumvents the rapid collapse of free vortex rings. The pinned scroll waves are affected by the topological mismatch between their looplike rotation backbone and the branched pinning structure. Depending on the initial condition, a multitude of stable vortex states exist, all of which obey topological constraints, suggesting spinlike states for the involved obstacle holes.

Novel non-invasive algorithm to identify the origins of re-entry and ectopic foci in the atria from 64-lead ECGs: A computational study.

Atrial tachy-arrhytmias, such as atrial fibrillation (AF), are characterised by irregular electrical activity in the atria, generally associated with erratic excitation underlain by re-entrant scroll waves, fibrillatory conduction of multiple wavelets or rapid focal activity. Epidemiological studies have shown an increase in AF prevalence in the developed world associated with an ageing society, highlighting the need for effective treatment options. Catheter ablation therapy, commonly used in the treatment of AF, requires spatial information on atrial electrical excitation. The standard 12-lead electrocardiogram (ECG) provides a method for non-invasive identification of the presence of arrhythmia, due to irregularity in the ECG signal associated with atrial activation compared to sinus rhythm, but has limitations in providing specific spatial information. There is therefore a pressing need to develop novel methods to identify and locate the origin of arrhythmic excitation. Invasive methods provide direct information on atrial activity, but may induce clinical complications. Non-invasive methods avoid such complications, but their development presents a greater challenge due to the non-direct nature of monitoring. Algorithms based on the ECG signals in multiple leads (e.g. a 64-lead vest) may provide a viable approach. In this study, we used a biophysically detailed model of the human atria and torso to investigate the correlation between the morphology of the ECG signals from a 64-lead vest and the location of the origin of rapid atrial excitation arising from rapid focal activity and/or re-entrant scroll waves. A focus-location algorithm was then constructed from this correlation. The algorithm had success rates of 93% and 76% for correctly identifying the origin of focal and re-entrant excitation with a spatial resolution of 40 mm, respectively. The general approach allows its application to any multi-lead ECG system. This represents a significant extension to our previously developed algorithms to predict the AF origins in association with focal activities.

Effect of anisotropy on ventricular vulnerability to unidirectional block and reentry by single premature stimulation during normal sinus rhythm in rat heart.

Single high-intensity premature stimuli when applied to the ventricles during ventricular drive of an ectopic site, as in Winfree's "pinwheel experiment," usually induce reentry arrhythmias in the normal heart, while single low-intensity stimuli barely do. Yet ventricular arrhythmia vulnerability during normal sinus rhythm remains largely unexplored. With a view to define the role of anisotropy on ventricular vulnerability to unidirectional conduction block and reentry, we revisited the pinwheel experiment with reduced constraints in the in situ rat heart. New features included single premature stimulation during normal sinus rhythm, stimulation and unipolar potential mapping from the same high-resolution epicardial electrode array, and progressive increase in stimulation strength and prematurity from diastolic threshold until arrhythmia induction. Measurements were performed with 1-ms cathodal stimuli at multiple test sites (n = 26) in seven rats. Stimulus-induced virtual electrode polarization during sinus beat recovery phase influenced premature ventricular responses. Specifically, gradual increase in stimulus strength and prematurity progressively induced make, break, and graded-response stimulation mechanisms. Hence unidirectional conduction block occurred as follows: 1) along fiber direction, on right and left ventricular free walls (n = 23), initiating figure-eight reentry (n = 17) and tachycardia (n = 12), and 2) across fiber direction, on lower interventricular septum (n = 3), initiating spiral wave reentry (n = 2) and tachycardia (n = 1). Critical time window (55.1 ± 4.7 ms, 68.2 ± 6.0 ms) and stimulus strength lower limit (4.9 ± 0.6 mA) defined vulnerability to reentry. A novel finding of this study was that ventricular tachycardia evolves and is maintained by episodes of scroll-like wave and focal activation couplets. We also found that single low-intensity premature stimuli can induce repetitive ventricular response (n = 13) characterized by focal activations.NEW & NOTEWORTHY We performed ventricular cathodal point stimulation during sinus rhythm by progressively increasing stimulus strength and prematurity. Virtual electrode polarization and recovery gradient progressively induced make, break, and graded-response stimulation mechanisms. Unidirectional conduction block occurred along or across fiber direction, initiating figure-eight or spiral wave reentry, respectively, and tachycardia sustained by scroll wave and focal activations.

Instability of spiral and scroll waves in the presence of a gradient in the fibroblast density: the effects of fibroblast–myocyte coupling

Fibroblast–myocyte coupling can modulate electrical-wave dynamics in cardiac tissue. In diseased hearts, the distribution of fibroblasts is heterogeneous, so there can be gradients in the fibroblast density (henceforth we call this GFD) especially from highly injured regions, like infarcted or ischemic zones, to less-wounded regions of the tissue. Fibrotic hearts are known to be prone to arrhythmias, so it is important to understand the effects of GFD in the formation and sustenance of arrhythmic re-entrant waves, like spiral or scroll waves. Therefore, we investigate the effects of GFD on the stability of spiral and scroll waves of electrical activation in a state-of-the-art mathematical model for cardiac tissue in which we also include fibroblasts. By introducing GFD in controlled ways, we show that spiral and scroll waves can be unstable in the presence of GFDs because of regions with varying spiral- or scroll-wave frequency ω, induced by the GFD. We examine the effects of the resting membrane potential of the fibroblast and the number of fibroblasts attached to the myocytes on the stability of these waves. Finally, we show that the presence of GFDs can lead to the formation of spiral waves at high-frequency pacing.

Scroll-wave dynamics in the presence of ionic and conduction inhomogeneities in an anatomically realistic mathematical model for the pig heart

Nonlinear waves of the reaction-diffusion (RD) type occur in many biophysical systems, including the heart, where they initiate cardiac contraction. Such waves can form vortices called scroll waves, which result in the onset of life-threatening cardiac arrhythmias. The dynamics of scroll waves is affected by the presence of inhomogeneities, which, in a very general way, can be of \textit{(i)} ionic type, i.e., they affect the reaction part, or \textit{(ii)} conduction type, i.e., they affect the diffusion part of an RD equation. We demostrate, for the first time, by using a state-of-the-art, anatomically realistic model of the pig heart, how differences in the geometrical and biophysical nature of such inhomogeneities can influence scroll-wave dynamics in different ways. Our study reveals that conduction-type inhomogeneities become increasingly important at small length scales, i.e., in the case of multiple, randomly distributed, obstacles in space at the cellular scale ($0.2-0.4{\rm mm}$). Such configurations can lead to scroll-wave break up. In contrast, ionic inhomogeneities, affect scroll-wave dynamics significantly at large length scales, when these inhomogeneities are localized in space at the tissue level ($5-10$ mm). In such configurations, these inhomogeneities can (a) attract scroll waves, by pinning them to the heterogeneity, or (b) lead to scroll-wave breakup.

Erratum to: “Scroll Wave dynamics in a model of the heterogeneous heart”

Erratum to: “Scroll Wave dynamics in a model of the heterogeneous heart”

Mechanisms of arrhythmogenesis related to calcium-driven alternans in a model of human atrial fibrillation.

The occurrence of atrial fibrillation (AF) is associated with progressive changes in the calcium handling system of atrial myocytes. Calcium cycling instability has been implicated as an underlying mechanism of electrical alternans observed in patients who experience AF. However, the extent to which calcium-induced alternation of electrical activity in the atria contributes to arrhythmogenesis is unknown. In this study, we investigated the effects of calcium-driven alternans (CDA) on arrhythmia susceptibility in a biophysically detailed, 3D computer model of the human atria representing electrical and structural remodeling secondary to chronic AF. We found that elevated propensity to CDA rendered the atria vulnerable to ectopy-induced arrhythmia. It also increased the complexity and persistence of arrhythmias induced by fast pacing, with unstable scroll waves meandering and frequently breaking up to produce multiple wavelets. Our results suggest that calcium-induced electrical instability may increase arrhythmia vulnerability and promote increasing disorganization of arrhythmias in the chronic AF-remodeled atria, thus playing an important role in the progression of the disease.

A Mathematical Spline-Based Model of Cardiac Left Ventricle Anatomy and Morphology

Computer simulation of normal and diseased human heart activity requires a 3D anatomical model of the myocardium, including myofibers. For clinical applications, such a model has to be constructed based on routine methods of cardiac visualization, such as sonography. Symmetrical models are shown to be too rigid, so an analytical non-symmetrical model with enough flexibility is necessary. Based on previously-made anatomical models of the left ventricle, we propose a new, much more flexible spline-based analytical model. The model is fully described and verified against DT-MRI data. We show a way to construct it on the basis of sonography data. To use this model in further physiological simulations, we propose a numerical method to utilize finite differences in solving the reaction-diffusion problem together with an example of scroll wave dynamics simulation.

Linked and knotted chimera filaments in oscillatory systems.

While the existence of stable knotted and linked vortex lines has been established in many experimental and theoretical systems, their existence in oscillatory systems and systems with nonlocal coupling has remained elusive. Here, we present strong numerical evidence that stable knots and links such as trefoils and Hopf links do exist in simple, complex, and chaotic oscillatory systems if the coupling between the oscillators is neither too short ranged nor too long ranged. In this case, effective repulsive forces between vortex lines in knotted and linked structures stabilize curvature-driven shrinkage observed for single vortex rings. In contrast to real fluids and excitable media, the vortex lines correspond to scroll wave chimeras [synchronized scroll waves with spatially extended (tubelike) unsynchronized filaments], a prime example of spontaneous synchrony breaking in systems of identical oscillators. In the case of complex oscillatory systems, this leads to a topological superstructure combining knotted filaments and synchronization defect sheets.

Scroll wave dynamics in a model of the heterogeneous heart

Scroll waves are found in physical, chemical and biological systems and underlie many significant processes including life-threatening cardiac arrhythmias. The theory of scroll waves predicts scroll wave dynamics should be substantially affected by heterogeneity of cardiac tissue together with other factors including shape and anisotropy. In this study, we used our recently developed analytical model of the human ventricle to identify effects of shape, anisotropy, and regional heterogeneity of myocardium on scroll wave dynamics. We found that the main effects of apical-base heterogeneity were an increased scroll wave drift velocity and a shift towards the region of maximum action potential duration. We also found that transmural heterogeneity does not substantially affect scroll wave dynamics and only in extreme cases changes the attractor position.

A novel technique to initiate and investigate scroll waves in thin layers of the photosensitive Belousov-Zhabotinsky reaction.

While free scroll rings are non-stationary objects that either grow or contract with time, spatial confinement can have a large impact on their evolution reaching from significant lifetime extension (J.F. Totz, H. Engel, O. Steinbock, New J. Phys. 17, 093043 (2015)) up to formation of stable stationary and breathing pacemakers (A. Azhand, J.F. Totz, H. Engel, EPL 108, 10004 (2014)). Here, we explore the parameter range in which the interaction between an axis-symmetric scroll ring and a confining planar no-flux boundary can be studied experimentally in transparent gel layers supporting chemical wave propagation in the photosensitive variant of the Belousov-Zhabotinsky medium. Based on full three-dimensional simulations of the underlying modified complete Oregonator model for experimentally realistic parameters, we determine the conditions for successful initiation of scroll rings in a phase diagram spanned by the layer thickness and the applied light intensity. Furthermore, we discuss whether the illumination-induced excitability gradient due to Lambert-Beer's law as well as a possible inclination of the filament plane with respect to the no-flux boundary can destabilize the scroll ring.

Dynamics of Scroll Wave in a Three-Dimensional System with Changing Gradient.

The dynamics of a scroll wave in an excitable medium with gradient excitability is studied in detail. Three parameter regimes can be distinguished by the degree of gradient. For a small gradient, the system reaches a simple rotating synchronization. In this regime, the rigid rotating velocity of spiral waves is maximal in the layers with the highest filament twist. As the excitability gradient increases, the scroll wave evolutes into a meandering synchronous state. This transition is accompanied by a variation in twisting rate. Filament twisting may prevent the breakup of spiral waves in the bottom layers with a low excitability with which a spiral breaks in a 2D medium. When the gradient is large enough, the twisted filament breaks up, which results in a semi-turbulent state where the lower part is turbulent while the upper part contains a scroll wave with a low twisting filament.

Removal of pinned scroll waves in cardiac tissues by electric fields in a generic model of three-dimensional excitable media.

Spirals or scroll waves pinned to heterogeneities in cardiac tissues may cause lethal arrhythmias. To unpin these life-threatening spiral waves, methods of wave emission from heterogeneities (WEH) induced by low-voltage pulsed DC electric fields (PDCEFs) and circularly polarized electric fields (CPEFs) have been used in two-dimensional (2D) cardiac tissues. Nevertheless, the unpinning of scroll waves in three-dimensional (3D) cardiac systems is much more difficult than that of spiral waves in 2D cardiac systems, and there are few reports on the removal of pinned scroll waves in 3D cardiac tissues by electric fields. In this article, we investigate in detail the removal of pinned scroll waves in a generic model of 3D excitable media using PDCEF, AC electric field (ACEF) and CPEF, respectively. We find that spherical waves can be induced from the heterogeneities by these electric fields in initially quiescent excitable media. However, only CPEF can induce spherical waves with frequencies higher than that of the pinned scroll wave. Such higher-frequency spherical waves induced by CPEF can be used to drive the pinned scroll wave out of the cardiac systems. We hope this remarkable ability of CPEF can provide a better alternative to terminate arrhythmias caused by pinned scroll waves.

Reconstructing three-dimensional reentrant cardiac electrical wave dynamics using data assimilation.

For many years, reentrant scroll waves have been predicted and studied as an underlying mechanism for cardiac arrhythmias using numerical techniques, and high-resolution mapping studies using fluorescence recordings from the surfaces of cardiac tissue preparations have confirmed the presence of visible spiral waves. However, assessing the three-dimensional dynamics of these reentrant waves using experimental techniques has been limited to verifying stable scroll-wave dynamics in relatively thin preparations. We propose a different approach to recovering the three-dimensional dynamics of reentrant waves in the heart. By applying techniques commonly used in weather forecasting, we combine dual-surface observations from a particular experiment with predictions from a numerical model to reconstruct the full three-dimensional time series of the experiment. Here, we use model-generated surrogate observations from a numerical experiment to evaluate the performance of the ensemble Kalman filter in reconstructing such time series for a discordant alternans state in one spatial dimension and for scroll waves in three dimensions. We show that our approach is able to recover time series of both observed and unobserved variables matching the truth. Where nearby observations are available, the error is reduced below the synthetic observation error, with a smaller reduction with increased distance from observations. Our findings demonstrate that state reconstruction for spatiotemporally complex cardiac electrical dynamics is possible and will lead naturally to applications using real experimental data.

Parallel Simulation of Scroll Wave Dynamics in the Human Heart Using the FEniCS Framework

In the heart, scroll waves are three-dimensional self-sustaining spiral waves of electrical excitation. They arise only in pathology and underlie dangerous arrhythmias. Computer simulation of human cardiac arrhythmias is time-consuming and requires parallel computing. In addition, heart simulation is a complicated multilevel task (cell, tissue, organ); parallel multilevel simulation codes are difficult to create and maintain. Here we present an approach to parallel simulation of scroll waves in the left ventricle of the human heart utilizing the FEniCS framework, which allows developing software using near-mathematical notation and provides automatic parallelization. We used the Aliev–Panfilov cell model of heart electrical activity and studied the scalability of FEniCS implementation on parallel computing systems.

3-dimensional atrial scroll wave as a mechanism of persistent atrial fibrillation

3-dimensional atrial scroll wave as a mechanism of persistent atrial fibrillation

The study of scroll wave dynamics in personalized models of the left ventricle of the human heart

AbstractThis paper presents first results on the dynamics of filaments of scroll waves of myocardium excitation obtained for personalized models of the left ventricle of the human heart. The paper describes a mathematical model of the left ventricle of the human heart and its electrical activity, numerical methods for the model calculation within the framework of computer implementation, and also the method of personalization of the model according to data of ultrasound examination. We found that regardless of the starting point of wave the filaments of wave drift along a spiral to the attractor located near the apex of the ventricle. The attractor position was essentially different in models constructed from the data of patients without identified pathology and those for patients with an increased left ventricular cavity.

Drift of scroll waves of electrical excitation in an isotropic model of the cardiac left ventricle

AbstractThe dynamics of scroll waves in a symmetric isotropic model of the human cardiac left ventricle is considered. The position of the attractor and the wave rotation velocity over the attractor were determined depending on the wall thickness, parameters of the cell model, chirality of the wave, and the initial position. Mechanisms of observed phenomena are discussed.

Stabilization of three-dimensional scroll waves and suppression of spatiotemporal chaos by heterogeneities.

Scroll waves in a three-dimensional medium with negative filament tension may break up and display spatiotemporal chaos. The presence of heterogeneities can influence the evolution of the medium, in particular scroll waves may pin to such heterogeneities. We show that as a result the medium may be stabilized by heterogeneities of a suitably chosen geometry. Thin rodlike heterogeneities suppress otherwise developing spatiotemporal chaos and additionally clear out already existing chaotic excitation patterns.