The Major Role of <i>I</i><sub>K1</sub> in Mechanisms of Rotor Drift in the Atria: A Computational Study

Berenfeld, Omer

doi:10.4137/cmc.s39773

Cited by 11 publications

(16 citation statements)

References 55 publications

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“…The interest in rotor dynamics research has increased since clinical reports claim that rotor ablation improves the rates of success in human CAF treatment (Narayan et al, 2012 ). Using in silico models, mechanistic explanations and therapeutic approaches have been tested (Zhao et al, 2015 ; Berenfeld, 2016 ; Guillem et al, 2016 ; Tobón et al, 2017 ). In this work, we assessed the effect of structural heterogeneities on rotor propagation by varying the complex derivative order γ.…”

Section: Discussionmentioning

confidence: 99%

Atrial Rotor Dynamics Under Complex Fractional Order Diffusion

et al. 2018

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The mechanisms of atrial fibrillation (AF) are a challenging research topic. The rotor hypothesis states that the AF is sustained by a reentrant wave that propagates around an unexcited core. Cardiac tissue heterogeneities, both structural and cellular, play an important role during fibrillatory dynamics, so that the ionic characteristics of the currents, their spatial distribution and their structural heterogeneity determine the meandering of the rotor. Several studies about rotor dynamics implement the standard diffusion equation. However, this mathematical scheme carries some limitations. It assumes the myocardium as a continuous medium, ignoring, therefore, its discrete and heterogeneous aspects. A computational model integrating both, electrical and structural properties could complement experimental and clinical results. A new mathematical model of the action potential propagation, based on complex fractional order derivatives is presented. The complex derivative order appears of considering the myocardium as discrete-scale invariant fractal. The main aim is to study the role of a myocardial, with fractal characteristics, on atrial fibrillatory dynamics. For this purpose, the degree of structural heterogeneity is described through derivatives of complex order γ = α + jβ. A set of variations for γ is tested. The real part α takes values ranging from 1.1 to 2 and the imaginary part β from 0 to 0.28. Under this scheme, the standard diffusion is recovered when α = 2 and β = 0. The effect of γ on the action potential propagation over an atrial strand is investigated. Rotors are generated in a 2D model of atrial tissue under electrical remodeling due to chronic AF. The results show that the degree of structural heterogeneity, given by γ, modulates the electrophysiological properties and the dynamics of rotor-type reentrant mechanisms. The spatial stability of the rotor and the area of its unexcited core are modulated. As the real part decreases and the imaginary part increases, simulating a higher structural heterogeneity, the vulnerable window to reentrant is increased, as the total meandering of the rotor tip. This in silico study suggests that structural heterogeneity, described by means of complex order derivatives, modulates the stability of rotors and that a wide range of rotor dynamics can be generated.

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Section: Discussionmentioning

confidence: 99%

Atrial Rotor Dynamics Under Complex Fractional Order Diffusion

et al. 2018

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“…To simulate fibrillatory activations with non-sustained singularity point reentry, in one simulation (Figure 1H, Supplement Movie 3) we introduced spatial heterogeneity in the inward rectifier channel conductance by increasing the I K1 conductance, which has been shown to be linked to AF-related remodeling [17], in the lower half of the simulated area.…”

Section: Methodsmentioning

confidence: 99%

Iterative navigation of multipole diagnostic catheters to locate repeating‐pattern atrial fibrillation drivers

Ganesan

Salmin

Cherry

et al. 2019

Cardiovasc electrophysiol

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Introduction: Targeting repeating-pattern atrial fibrillation (AF) sources (reentry or focal drivers) can help in patient-specific ablation therapy for AF; however, the development of reliable and accurate tools for locating such sources remains a major challenge. We describe an iterative catheter navigation (ICAN) algorithm to locate AF drivers using a conventional circular Lasso catheter. Methods and Results: At each step, the algorithm analyzes 10 bipolar electrograms recoded at a given catheter location and the history of previous catheter movements to determine if the source is inside the catheter loop. If not, it calculates new coordinates and selects a new position for the catheter. The process continues until a source is located. The algorithm was evaluated in a computer model of atrial tissue with various degrees of fibrosis under a broad range of arrhythmia scenarios. The latter included slow and fast reentry, macroreentry, figure-of-eight reentry, and fibrillatory conduction. Depending on the initial distance of the catheter from the source and scenario, it took about 3–16 steps to localize an AF source. In 94% of cases, the identified location was within 4mm from the source, independently of the initial position of the catheter. The algorithm worked equally well in the presence of patchy fibrosis, low-voltage areas, fragmented electrograms, and dominant-frequency gradients. Conclusions: AF repeating-pattern sources can be localized using circular catheters without the need to map the entire tissue. The proposed algorithm has the potential to become a useful tool for patient-specific ablation of AF sources located outside the pulmonary veins.

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“…The S1 stimulus was applied at the left boundary of the tissue. The S2 stimulus is rectangular (2 x 2 cm) and was applied to a corner of the domain [12]. The approximate volume for a single cardiomyocyte is 2.16 x 10 -5 µl.…”

Section: D Model Of Human Atrial Tissue and Electrical Propagationmentioning

confidence: 99%

Atrial Rotor Modulation by Localized Dofetilide Application: An In Silico Study

Pérez-Buitrago¹,

Ugarte

Tobón

2018

Computing in Cardiology Conference (CinC)

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The rotor ablation has gained favor in recent years to treat chronic atrial fibrillation (CAF). However, it may cause complications in patients and the results remain suboptimal. Besides, antiarrhythmic drugs for the management of AF are not sufficiently effective and can cause significant cardiac and extracardiac side effects. To reduce the risk and increase the effectiveness, a rotor modulation via the localized release of dofetilide is proposed through an in silico study. A computational model of two-dimensional atrial tissue was implemented using human cell model under CAF conditions. Dofetilide was modeled blocking the ionic currents IKr and IKACh using Hill's equation. A CAF episode, sustained by a rotor, was simulated. Different concentrations of dofetilide were applied in specific distributions based on the rotor tip location, detected by phase map analysis. Non-localized application of dofetilide resulted in the benefit of CAF progression. In contrast, localized dofetilide liberation terminated the CAF episode. These results could have therapeutic implications in novel treatments of CAF.

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The Major Role of I_K1 in Mechanisms of Rotor Drift in the Atria: A Computational Study

Cited by 11 publications

References 55 publications

Atrial Rotor Dynamics Under Complex Fractional Order Diffusion

Atrial Rotor Dynamics Under Complex Fractional Order Diffusion

Iterative navigation of multipole diagnostic catheters to locate repeating‐pattern atrial fibrillation drivers

Atrial Rotor Modulation by Localized Dofetilide Application: An In Silico Study

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The Major Role of IK1 in Mechanisms of Rotor Drift in the Atria: A Computational Study

Cited by 11 publications

References 55 publications

Atrial Rotor Dynamics Under Complex Fractional Order Diffusion

Atrial Rotor Dynamics Under Complex Fractional Order Diffusion

Iterative navigation of multipole diagnostic catheters to locate repeating‐pattern atrial fibrillation drivers

Atrial Rotor Modulation by Localized Dofetilide Application: An In Silico Study

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The Major Role of I_K1 in Mechanisms of Rotor Drift in the Atria: A Computational Study