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

An In-Silico Study into the Impact of Electrophysiological Variability at the Cellular Level on the Re-entry Patterns in Atrial Fibrillation

Modelling the atria in-silico has become an important method in understanding atrial behaviour. Atrial models typically include regional electrophysiological variability, but neglect cellular variability. The aim of the study is to determine the impact of cellular electrophysiological variability on ectopic beats. Using a population of models approach to introduce regional and cellular variability into the atrial model, ectopic beats were initiated in two locations. Six ectopic beats were applied at a BCL of 130-160ms. The variable model was compared with an equivalent regional homogenous model. Using consistent tissue CV between models, in both the healthy and AF remodeled cases the average model total activation time was later than the variable model (a delay of 26ms and 14ms respectively). After matching activation times, repolarization was later in the average than the variable models. Latest APD90 in the AF remodeled cases were 268ms for the average and 256ms in the variable model. This resulted in a difference in propagation of the ectopic beat. In conclusion, cellular variability has a significant impact on both the depolarization and repolarization phases in the atria for the healthy and AF cases

Influence of Modeling Errors on the Initial Estimate for Nonlinear Myocardial Activation Times Imaging Calculated With Fastest Route Algorithm

Noninvasive reconstruction of cardiac electrical activity has a great potential to support clinical decision making, planning, and treatment. Recently, significant progress has been made in the estimation of the cardiac activation from body surface potential maps (BSPMs) using boundary element method (BEM) with the equivalent double layer (EDL) as a source model. In this formulation, noninvasive assessment of activation times results in a nonlinear optimization problem with an initial estimate calculated with the fastest route algorithm (FRA). Each FRA-simulated activation sequence is converted into the ECG. The best initialization is determined by the sequence providing the highest correlation between predicted and measured potentials. We quantitatively assess the effects of the forward modeling errors on the FRA-based initialization. We present three simulation setups to investigate the effects of volume conductor model simplifications, neglecting the cardiac anisotropy and geometrical errors on the localization of ectopic beats starting on the ventricular surface. For the analysis, 12-lead ECG and 99 electrodes BSPM system were used. The areas in the heart exposing the largest localization errors were volume conductor model and electrode configuration specific with an average error <10 mm. The results show the robustness of the FRA-based initialization with respect to the considered modeling errors

Quantification and classification of potassium and calcium disorders with the electrocardiogram: What do clinical studies, modeling, and reconstruction tell us?

Diseases caused by alterations of ionic concentrations are frequently observed challenges and play an important role in clinical practice. The clinically established method for the diagnosis of electrolyte concentration imbalance is blood tests. A rapid and non-invasive point-of-care method is yet needed. The electrocardiogram (ECG) could meet this need and becomes an established diagnostic tool allowing home monitoring of the electrolyte concentration also by wearable devices. In this review, we present the current state of potassium and calcium concentration monitoring using the ECG and summarize results from previous work. Selected clinical studies are presented, supporting or questioning the use of the ECG for the monitoring of electrolyte concentration imbalances. Differences in the findings from automatic monitoring studies are discussed, and current studies utilizing machine learning are presented demonstrating the potential of the deep learning approach. Furthermore, we demonstrate the potential of computational modeling approaches to gain insight into the mechanisms of relevant clinical findings and as a tool to obtain synthetic data for methodical improvements in monitoring approaches

IFMBE Proceedings

In order to reveal the effect of reuse solution and the hemodialysis environment on the stability of high flux polyamide hollow fiber membranes, mechanical tests, surface and X-ray diffraction studies were performed on both virgin 17S high flux polyamide hollow fiber and used-processed 17S high flux polyamide hollow fiber membranes. Used fibers were left in 4% formaldehyde solution for 14 hours and then in 5% sodium hypochloride (bleach) solution for 6 hours in order to disinfect the membrane for the reuse idea. Tensile tests performed on both virgin and used-processed fibers reveal that toughness and ductility of the used-processed fibers are lower than the virgin ones. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) studies performed on virgin and used-processed fiber visualized the morphological changes. Rough surface with defects and cracks was seen in used-processed fiber, whereas a smoother surface morphology was seen in virgin fibers. Alterations in pore morphology and the size of the pores became greater in used processed fibers. Cracks, merging of pores and also more defects were visualized in used-processed fibers. Thus, easy crack initiations and easy propagations were expected in used-processed fibers which were also confirmed by tensile test experiments. In addition to these mechanical and surface studies experiments, X-ray diffractometry studies also revealed the changes in the structure of the used-processed fibers. New or growth of the existing phases and orientations were observed in used-processed fibers. This study showed that dialysis environment caused structural changes on membranes which may cause clinical complications