Virtual electrodes around anatomical structures and their roles in defibrillation

Connolly, Adam; Vigmond, Edward J.; Bishop, Martin J.

doi:10.1371/journal.pone.0173324

Cited by 12 publications

(10 citation statements)

References 34 publications

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“…Vessels have been shown to be an important source of VEs for low-energy defibrillation protocols 6 (as well as standard energy protocols 12 ) However, bidomain simulations and theory suggest that activation occurs preferentially from endocardial invaginations before vessels 2 at lower field strengths 16 . The lack of vessels in our model has allowed us to dissect the specific effects of the trabeculation structure on monophasic shocks, in the absence of vessels.…”

Section: Discussionmentioning

confidence: 98%

“…Trabeculae grooves or invaginations have been shown to provide sources of locally elevated membrane responses, 2,15,16 due to confinement of electric field-lines, 16 locally raising field strength as current takes the path of least resistance outside the myocardium (driven by differences in conductivity between tissue and blood in the cavity). The stronger VEs occurring in such grooves, relative to smooth surfaces, cause them to preferentially act as secondary sources of activation following shock-end, which again have been shown to be of relevance in low-energy defibrillation protocols 2 .…”

Section: Introductionmentioning

confidence: 99%

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Highly trabeculated structure of the human endocardium underlies asymmetrical response to low-energy monophasic shocks

Connolly

Robson

Schneider

et al. 2017

Chaos: An Interdisciplinary Journal of Nonlinear Science

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Novel low-energy defibrillation therapies are thought to be driven by virtual-electrodes (VEs), due to the interaction of applied monophasic electric shocks with fine-scale anatomical structures within the heart. Significant inter-species differences in the cardiac (micro)-anatomy exist, however, particularly with respect to the degree of endocardial trabeculations, which may underlie important differences in response to low-energy defibrillation protocols. Understanding the interaction of monophasic electric fields with the specific human micro-anatomy is therefore imperative in facilitating the translation and optimisation of these promising experimental therapies to the clinic. In this study, we sought to investigate how electric fields from implanted devices interact with the highly trabeculated human endocardial surface to better understand shock success in order to help optimise future clinical protocols. A bi-ventricular human computational model was constructed from high resolution (350 μm) ex-vivo MR data, including anatomically accurate endocardial structures. Monophasic shocks were applied between a basal right ventricular catheter and an exterior ground. Shocks of varying strengths were applied with both anodal [positive right ventricle (RV) electrode] and cathodal (negative RV electrode) polarities at different states of tissue refractoriness and during induced arrhythmias. Anodal shocks induced isolated positive VEs at the distal side of “detached” trabeculations, which rapidly spread into hyperpolarised tissue on the surrounding endocardial surfaces following the shock. Anodal shocks thus depolarised more tissue 10 ms after the shock than cathodal shocks where the propagation of activation from VEs induced on the proximal side of “detached” trabeculations was prevented due to refractory endocardium. Anodal shocks increased arrhythmia complexity more than cathodal shocks during failed anti-arrhythmia shocks. In conclusion, multiple detached trabeculations in the human ventricle interact with anodal stimuli to induce multiple secondary sources from VEs, facilitating more rapid shock-induced ventricular excitation compared to cathodal shocks. Such a mechanism may help explain inter-species differences in response to shocks and help to develop novel defibrillation strategies.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Highly trabeculated structure of the human endocardium underlies asymmetrical response to low-energy monophasic shocks

Connolly

Robson

Schneider

et al. 2017

Chaos: An Interdisciplinary Journal of Nonlinear Science

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“…Here, the authors also demonstrated that V m would be raised higher close to boundaries of negative curvature because of a reduction in diffusive loading compared to boundaries of positive curvature. However, it is important to note that the findings in ( 16 ) were also critically dependent upon the uniformly applied electric field, as discussed in ( 17 ).…”

Section: Discussionmentioning

confidence: 92%

“…In this study, we conduct a combined experimental and computational investigation into the differences in stimulus capture and ERP applied to geometrically distinct spatial locations on the endocardial surface—specifically, endocardial grooves and ridges. Such stimulus locations were chosen because the presence of positive/negative surface curvature in these regions provides differing environments ( 16 , 17 ) for the boundary confinement of the stimulus current. The endocardium is also accessible via experimental electrodes placed on the tissue surface itself and represents an important location for placement of catheters in the electrophysiology catheter laboratory and in experimental animal studies.…”

Section: Introductionmentioning

confidence: 99%

Ventricular Endocardial Tissue Geometry Affects Stimulus Threshold and Effective Refractory Period

Connolly

Kelly

Campos

et al. 2018

Biophysical Journal

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Background: Understanding the biophysical processes by which electrical stimuli applied to cardiac tissue may result in local activation is important in both the experimental and clinical electrophysiology laboratory environments, as well as for gaining a more in-depth knowledge of the mechanisms of focal-trigger-induced arrhythmias. Previous computational models have predicted that local myocardial tissue architecture alone may significantly modulate tissue excitability, affecting both the local stimulus current required to excite the tissue and the local effective refractory period (ERP). In this work, we present experimental validation of this structural modulation of local tissue excitability on the endocardial tissue surface, use computational models to provide mechanistic understanding of this phenomena in relation to localized changes in electrotonic loading, and demonstrate its implications for the capture of afterdepolarizations.Methods and Results: Experiments on rabbit ventricular wedge preparations showed that endocardial ridges (surfaces of negative mean curvature) had a stimulus capture threshold that was 0.21 ± 0.03 V less than endocardial grooves (surfaces of positive mean curvature) for pairwise comparison (24% reduction, corresponding to 56.2 ± 6.4% of the energy). When stimulated at the minimal stimulus strength for capture, ridge locations showed a shorter ERP than grooves (n = 6, mean pairwise difference 7.4 ± 4.2 ms). When each site was stimulated with identical-strength stimuli, the difference in ERP was further increased (mean pairwise difference 15.8 ± 5.3 ms). Computational bidomain models of highly idealized cylindrical endocardial structures qualitatively agreed with these findings, showing that such changes in excitability are driven by structural modulation in electrotonic loading, quantifying this relationship as a function of surface curvature. Simulations further showed that capture of delayed afterdepolarizations was more likely in trabecular ridges than grooves, driven by this difference in loading.Conclusions: We have demonstrated experimentally and explained mechanistically in computer simulations that the ability to capture tissue on the endocardial surface depends upon the local tissue architecture. These findings have important implications for deepening our understanding of excitability differences related to anatomical structure during stimulus application that may have important applications in the translation of novel experimental optogenetics pacing strategies. The uncovered preferential vulnerability to capture of afterdepolarizations of endocardial ridges, compared to grooves, provides important insight for understanding the mechanisms of focal-trigger-induced arrhythmias.

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“…For example, they may include ventricular endocardial structures such as papillary muscles and trabeculae (Bishop et al, 2010 ); atrial endocardial structures such as fossa ovalis (Seemann et al, 2006 ); myocardial blood vessels (Bishop et al, 2010 ); and/or the Purkinje system (Romero et al, 2010 ; Bordas et al, 2011 ). The appropriate level of detail for specific applications is not yet clear; in particular there is ongoing research into the role of microstructure on the initiation, maintenance and termination of fibrillation (Bishop and Plank, 2012 ; Connolly et al, 2017 ). As well as geometry, there is a question on the fidelity of the prescribed fiber and sheet orientations.…”

Section: Credibility Of Cep Models At Different Spatial Scalesmentioning

confidence: 99%

Validation and Trustworthiness of Multiscale Models of Cardiac Electrophysiology

Pathmanathan

Gray

2018

Front. Physiol.

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Computational models of cardiac electrophysiology have a long history in basic science applications and device design and evaluation, but have significant potential for clinical applications in all areas of cardiovascular medicine, including functional imaging and mapping, drug safety evaluation, disease diagnosis, patient selection, and therapy optimisation or personalisation. For all stakeholders to be confident in model-based clinical decisions, cardiac electrophysiological (CEP) models must be demonstrated to be trustworthy and reliable. Credibility, that is, the belief in the predictive capability, of a computational model is primarily established by performing validation, in which model predictions are compared to experimental or clinical data. However, there are numerous challenges to performing validation for highly complex multi-scale physiological models such as CEP models. As a result, credibility of CEP model predictions is usually founded upon a wide range of distinct factors, including various types of validation results, underlying theory, evidence supporting model assumptions, evidence from model calibration, all at a variety of scales from ion channel to cell to organ. Consequently, it is often unclear, or a matter for debate, the extent to which a CEP model can be trusted for a given application. The aim of this article is to clarify potential rationale for the trustworthiness of CEP models by reviewing evidence that has been (or could be) presented to support their credibility. We specifically address the complexity and multi-scale nature of CEP models which makes traditional model evaluation difficult. In addition, we make explicit some of the credibility justification that we believe is implicitly embedded in the CEP modeling literature. Overall, we provide a fresh perspective to CEP model credibility, and build a depiction and categorisation of the wide-ranging body of credibility evidence for CEP models. This paper also represents a step toward the extension of model evaluation methodologies that are currently being developed by the medical device community, to physiological models.

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Virtual electrodes around anatomical structures and their roles in defibrillation

Cited by 12 publications

References 34 publications

Highly trabeculated structure of the human endocardium underlies asymmetrical response to low-energy monophasic shocks

Highly trabeculated structure of the human endocardium underlies asymmetrical response to low-energy monophasic shocks

Ventricular Endocardial Tissue Geometry Affects Stimulus Threshold and Effective Refractory Period

Validation and Trustworthiness of Multiscale Models of Cardiac Electrophysiology

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