A microstructural model of reentry arising from focal breakthrough at sites of source-load mismatch in a central region of slow conduction

Hubbard, Marjorie Letitia; Henriquez, Craig S.

doi:10.1152/ajpheart.00385.2013

Cited by 19 publications

(28 citation statements)

References 44 publications

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“…They concluded that fibrosis increases the vulnerability to fast pacing. Similar results using multiple stimulus protocols were obtained by different groups [16, 18–22] and confirmed that fibrosis or other micro-structural heterogeneities may facilitate the initiation of reentries and help to sustain reentry or fibrillation. The use of the words facilitate and help appears naturally, since it is well known that S1–S2 or fast-pacing protocols can per se generate reentries.…”

Section: Introductionsupporting

confidence: 86%

“…However, it was only recently shown [23, 24] that we can generate microreentries and ectopic pacemakers in 2D computer simulations of cardiac electrophysiology without the use of a second premature stimulus (S2) [16] or fast pacing [18]. If only a single stimulus is used, the usual interactions between subsequent waves are not present; and therefore, one can relate the genesis of the microrentries inside the fibrosis to the specific heterogeneity of the tissue, i.e.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, the topology of the maze is crucial for the emergence of a reentry inside the fibrotic region [23, 24]. This wave activity may continuously or transiently generate ectopic beats when it crosses the border of the microfibrosis region [18] into the healthy tissue areas. Such zig-zag dynamics was previously observed in experimental studies [25].…”

Section: Introductionmentioning

confidence: 99%

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Reentry and Ectopic Pacemakers Emerge in a Three-Dimensional Model for a Slab of Cardiac Tissue with Diffuse Microfibrosis near the Percolation Threshold

Alonso¹,

Santos²,

Bär³

2016

PLoS ONE

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Arrhythmias in cardiac tissue are generally associated with irregular electrical wave propagation in the heart. Cardiac tissue is formed by a discrete cell network, which is often heterogeneous. Recently, it was shown in simulations of two-dimensional (2D) discrete models of cardiac tissue that a wave crossing a fibrotic, heterogeneous region may produce reentry and transient or persistent ectopic activity provided the fraction of conducting connections is just above the percolation threshold. Here, we investigate the occurrence of these phenomena in three-dimensions by simulations of a discrete model representing a thin slab of cardiac tissue. This is motivated (i) by the necessity to study the relevance and properties of the percolation-related mechanism for the emergence of microreentries in three dimensions and (ii) by the fact that atrial tissue is quite thin in comparison with ventricular tissue. Here, we simplify the model by neglecting details of tissue anatomy, e. g. geometries of atria or ventricles and the anisotropy in the conductivity. Hence, our modeling study is confined to the investigation of the effect of the tissue thickness as well as to the comparison of the dynamics of electrical excitation in a 2D layer with the one in a 3D slab. Our results indicate a strong and non-trivial effect of the thickness even for thin tissue slabs on the probability of microreentries and ectopic beat generation. The strong correlation of the occurrence of microreentry with the percolation threshold reported earlier in 2D layers persists in 3D slabs. Finally, a qualitative agreement of 3D simulated electrograms in the fibrotic region with the experimentally observed complex fractional atrial electrograms (CFAE) as well as strong difference between simulated electrograms in 2D and 3D were found for the cases where reentry and ectopic activity were triggered by the micro-fibrotic region.

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Section: Introductionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Reentry and Ectopic Pacemakers Emerge in a Three-Dimensional Model for a Slab of Cardiac Tissue with Diffuse Microfibrosis near the Percolation Threshold

Alonso¹,

Santos²,

Bär³

2016

PLoS ONE

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“…While this approach reproduces the macroscopic conduction behavior, it does not capture the microscopic effects of fibrosis that could be implicated in arrhythmogenesis [6]. The more recent approach by Costa et al [7] of decoupling FEM elements to reproduce the effects of fibrosis is analogous to the approach of Spach et al in the discrete model, and has shown promise in reproducing microscale conduction.…”

Section: Modeling Of Fibrotic Myocardiummentioning

confidence: 99%

Continuous Models Fail to Capture Details of Reentry in Fibrotic Myocardium

Gokhale¹,

Medvescek²,

Henriquez³

2016

2016 Computing in Cardiology Conference (CinC)

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IntroductionComputational models of cardiac conduction can play an important role in understanding the mechanisms of and developing treatments for fibrosis-induced cardiac arrhythmias. However, most studies investigating the arrhythmogenic role of cardiac fibrosis have modelled the myocardium as a locally homogenous continuum with increased conduction anisotropy in areas of fibrosis. While these continuum methods recreate simple planar conduction behaviour and allow for increased computational efficiency, it remains unclear how effectively they are able to model complex conduction patterns such as reentry. In 1981, Spach et al. [1] were the first to show that while cardiac conduction is continuous on the macroscopic scale, microscopic conduction is discontinuous and affected by the discrete cellular structure of the tissue. Since that time, many studies have used discrete microstructural cardiac models that incorporate individual cellular geometry [2]- [4]. Despite the discrete nature of cardiac conduction, many other studies have relied on continuum models that represent averaged electrical properties of cardiac tissue because these models decrease computational load and allow for large-scale simulations, including those of whole-heart conduction. While these continuous models, where the electrical properties are assigned to match macroscopic conduction properties and anisotropy, have been shown to reproduce simple conduction behaviours with high fidelity, it remains unclear if such models can account for the effects of fibrosis on the microscale. Discrete versus continuous models Modeling of fibrotic myocardiumThe most histologically accurate representation of fibrosis is as space-occupying features separating cells in discrete tissue models. Because collagenous septa are nonconductive, they can be more easily represented as the decoupling of transverse cellular connections [5].In continuous computational models, fibrosis is traditionally incorporated by decreasing conductivity values to reproduce experimentally observed conduction slowing and conduction anisotropy. While this approach reproduces the macroscopic conduction behavior, it does not capture the microscopic effects of fibrosis that could be implicated in arrhythmogenesis [6]. The more recent approach by Costa et al [7] of decoupling FEM elements to reproduce the effects of fibrosis is analogous to the approach of Spach et al. in the discrete model, and has shown promise in reproducing microscale conduction. However, it remains unclear how any of these approaches perform in the setting of reentry spiral wave behavior.In this manuscript, we elicit and compare spiral wave behavior in discrete models as well as in two types of equivalent continuous models to understand whether continuous computational models are sufficient to capture the details of reentry. 2.

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“…Therefore, reentry occurs inside the fibrotic region. This spiral-like wave will continuously try to generate ectopic beats when it touches the border of the microfibrosis region [12].…”

Section: Introductionmentioning

confidence: 99%

Reactive Interstitial and Reparative Fibrosis as Substrates for Cardiac Ectopic Pacemakers and Reentries

Oliveira

Barros

Gomes

et al. 2016

Bioinformatics and Biomedical Engineering

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Abstract. Dangerous cardiac arrhythmias have been frequently associated with focal sources of fast pulses, i.e. ectopic pacemakers. However, there is a lack of experimental evidences that could explain how ectopic pacemakers could be formed in cardiac tissue. In recent studies, we have proposed a new theory for the genesis of ectopic pacemakers in pathological cardiac tissues: reentry inside microfibrosis, i.e., a small region where excitable myocytes and non-conductive material coexist. In this work, we continue this investigation by comparing different types of fibrosis, reparative and reactive interstitial fibrosis. We use detailed and modern models of cardiac electrophysiology that account for the micro-structure of cardiac tissue. In addition, for the solution of our models we use, for the first time, a new numerical algorithm based on the Uniformization method. Our simulation results suggest that both types of fibrosis can support reentries, and therefore can generate in-silico ectopic pacemakers. However, the probability of reentries differs quantitatively for the different types of fibrosis. In addition, the new Uniformization method yields 20-fold increase in cardiac tissue simulation speed and, therefore, was an essential technique that allowed the execution of over a thousand of simulations.

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A microstructural model of reentry arising from focal breakthrough at sites of source-load mismatch in a central region of slow conduction

Cited by 19 publications

References 44 publications

Reentry and Ectopic Pacemakers Emerge in a Three-Dimensional Model for a Slab of Cardiac Tissue with Diffuse Microfibrosis near the Percolation Threshold

Reentry and Ectopic Pacemakers Emerge in a Three-Dimensional Model for a Slab of Cardiac Tissue with Diffuse Microfibrosis near the Percolation Threshold

Continuous Models Fail to Capture Details of Reentry in Fibrotic Myocardium

Reactive Interstitial and Reparative Fibrosis as Substrates for Cardiac Ectopic Pacemakers and Reentries

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