Effects of Electrical and Structural Remodeling on Atrial Fibrillation Maintenance: A Simulation Study

Atrial fibrillation, a common cardiac arrhythmia, often progresses unfavourably: in patients with long-term atrial fibrillation, fibrillatory episodes are typically of increased duration and frequency of occurrence relative to healthy controls. This is due to electrical, structural, and contractile remodeling processes. We investigated mechanisms of how electrical and structural remodeling contribute to perpetuation of simulated atrial fibrillation, using a mathematical model of the human atrial action potential incorporated into an anatomically realistic three-dimensional structural model of the human atria. Electrical and structural remodeling both shortened the atrial wavelength - electrical remodeling primarily through a decrease in action potential duration, while structural remodeling primarily slowed conduction. The decrease in wavelength correlates with an increase in the average duration of atrial fibrillation/flutter episodes. The dependence of reentry duration on wavelength was the same for electrical vs. structural remodeling. However, the dynamics during atrial reentry varied between electrical, structural, and combined electrical and structural remodeling in several ways, including: (i) with structural remodeling there were more occurrences of fragmented wavefronts and hence more filaments than during electrical remodeling; (ii) dominant waves anchored around different anatomical obstacles in electrical vs. structural remodeling; (iii) dominant waves were often not anchored in combined electrical and structural remodeling. We conclude that, in simulated atrial fibrillation, the wavelength dependence of reentry duration is similar for electrical and structural remodeling, despite major differences in overall dynamics, including maximal number of filaments, wave fragmentation, restitution properties, and whether dominant waves are anchored to anatomical obstacles or spiralling freely

A three-dimensional human atrial model with fiber orientation. Electrograms and arrhythmic activation patterns relationship

The most common sustained cardiac arrhythmias in humans are atrial tachyarrhythmias, mainly atrial fibrillation. Areas of complex fractionated atrial electrograms and high dominant frequency have been proposed as critical regions for maintaining atrial fibrillation; however, there is a paucity of data on the relationship between the characteristics of electrograms and the propagation pattern underlying them. In this study, a realistic 3D computer model of the human atria has been developed to investigate this relationship. The model includes a realistic geometry with fiber orientation, anisotropic conductivity and electrophysiological heterogeneity. We simulated different tachyarrhythmic episodes applying both transient and continuous ectopic activity. Electrograms and their dominant frequency and organization index values were calculated over the entire atrial surface. Our simulations show electrograms with simple potentials, with little or no cycle length variations, narrow frequency peaks and high organization index values during stable and regular activity as the observed in atrial flutter, atrial tachycardia (except in areas of conduction block) and in areas closer to ectopic activity during focal atrial fibrillation. By contrast, cycle length variations and polymorphic electrograms with single, double and fragmented potentials were observed in areas of irregular and unstable activity during atrial fibrillation episodes. Our results also show: 1) electrograms with potentials without negative deflection related to spiral or curved wavefronts that pass over the recording point and move away, 2) potentials with a much greater proportion of positive deflection than negative in areas of wave collisions, 3) double potentials related with wave fragmentations or blocking lines and 4) fragmented electrograms associated with pivot points. Our model is the first human atrial model with realistic fiber orientation used to investigate the relationship between different atrial arrhythmic propagation patterns and the electrograms observed at more than 43000 points on the atrial surface.This work was partially supported by the Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica, Ministerio de Ciencia e Innovacion of Spain (TEC2008-02090), by the Plan Avanza (Accion Estrategica de Telecomunicaciones y Sociedad de la Informacion), Ministerio de Industria Turismo y Comercio of Spain (TSI-020100-2010-469), by the Programa Prometeo 2012 of the Generalitat Valenciana and by the Programa de Apoyo a la Investigacion y Desarrollo de la Universitat Politecnica de Valencia (PAID-06-11-2002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Tobón Zuluaga, C.; Ruiz Villa, CA.; Heidenreich, E.; Romero Pérez, L.; Hornero, F.; Saiz Rodríguez, FJ. (2013). A three-dimensional human atrial model with fiber orientation. Electrograms and arrhythmic activation patterns relationship. PLoS ONE. 8(2):1-13. https://doi.org/10.1371/journal.pone.0050883S11382Ho SY, Sanchez-Quintana D, Anderson RH (1998) Can anatomy define electric pathways? In: International Workshop on Computer Simulation and Experimental Assessment of Electrical Cardiac Function, Lausanne, Switzerland. 77–86.Tobón C (2009) Evaluación de factores que provocan fibrilación auricular y de su tratamiento mediante técnicas quirúrgicas. Estudio de simulación. Master Thesis Universitat Politècnica de València.Ruiz C (2010) Estudio de la vulnerabilidad a reentradas a través de modelos matemáticos y simulación de la aurícula humana. Doctoral Thesis Universitat Politècnica de València.Tobón C (2010) Modelización y evaluación de factores que favorecen las arritmias auriculares y su tratamiento mediante técnicas quirúrgicas. Estudio de simulación. Doctoral Thesis Universitat Politècnica de València.Henriquez, C. S., & Papazoglou, A. A. (1996). Using computer models to understand the roles of tissue structure and membrane dynamics in arrhythmogenesis. Proceedings of the IEEE, 84(3), 334-354. doi:10.1109/5.486738Grimm, R. A., Chandra, S., Klein, A. L., Stewart, W. J., Black, I. W., Kidwell, G. A., & Thomas, J. D. (1996). Characterization of left atrial appendage Doppler flow in atrial fibrillation and flutter by Fourier analysis. American Heart Journal, 132(2), 286-296. doi:10.1016/s0002-8703(96)90424-xMaleckar, M. M., Greenstein, J. L., Giles, W. R., & Trayanova, N. A. (2009). K+ current changes account for the rate dependence of the action potential in the human atrial myocyte. American Journal of Physiology-Heart and Circulatory Physiology, 297(4), H1398-H1410. doi:10.1152/ajpheart.00411.200

Quantifying Irregular Morphology Electrograms in Atrial Fibrillation Using Fractional Fourier Domains

A fractional Fourier transform-based strategy is proposed for the analysis of morphological irregularities of 933 simulated electrograms recorded from a 3D simulated human atria under atrial fibrillation. Optimum fractional domains are considered to quantify the non-stationary features in the signals after preprocessing and segmentation. Optimum order maps obtained with the proposed strategy are compared with approximate entropy maps generated in previous studies. The results indicate that distinct types of electrical activity can be associated with different fractional domains and that the FrFT can be sensitive to different underlying propagation patterns where the approximate entropy exhibits uniform behavior. © 2020, Springer Nature Switzerland AG