Simulation of Ectopic Pacemakers in the Heart: Multiple Ectopic Beats Generated by Reentry inside Fibrotic Regions

The inclusion of nonconducting media, mimicking cardiac fibrosis, in two models of cardiac tissue produces the formation of ectopic beats. The fraction of nonconducting media in comparison with the fraction of healthy myocytes and the topological distribution of cells determines the probability of ectopic beat generation. First, a detailed subcellular microscopic model that accounts for the microstructure of the cardiac tissue is constructed and employed for the numerical simulation of action potential propagation. Next, an equivalent discrete model is implemented, which permits a faster integration of the equations. This discrete model is a simplified version of the microscopic model that maintains the distribution of connections between cells. Both models produce similar results when describing action potential propagation in homogeneous tissue; however, they slightly differ in the generation of ectopic beats in heterogeneous tissue. Nevertheless, both models present the generation of reentry inside fibrotic tissues. This kind of reentry restricted to microfibrosis regions can result in the formation of ectopic pacemakers, that is, regions that will generate a series of ectopic stimulus at a fast pacing rate. In turn, such activity has been related to trigger fibrillation in the atria and in the ventricles in clinical and animal studies.

[1]  Long Chen FINITE VOLUME METHODS , 2011 .

[2]  B. Strauss,et al.  Experimental studies of atrial fibrillation: a comparison of two pacing models. , 2008, American journal of physiology. Heart and circulatory physiology.

[3]  Alvin Shrier,et al.  Spiral wave generation in heterogeneous excitable media. , 2002, Physical review letters.

[4]  Y. Rudy,et al.  Basic mechanisms of cardiac impulse propagation and associated arrhythmias. , 2004, Physiological reviews.

[5]  Charles Pierre,et al.  A 2D/3D Finite Volume Method used to solve the bidomain equations of electrocardiology , 2009 .

[6]  Karma Spiral breakup in model equations of action potential propagation in cardiac tissue. , 1993, Physical review letters.

[7]  P. Platonov,et al.  Structural abnormalities in atrial walls are associated with presence and persistency of atrial fibrillation but not with age. , 2011, Journal of the American College of Cardiology.

[8]  M. Franz Stretch pulses and cardiac arrhythmias in rat hearts: is it a good model? , 2009, Experimental Physiology.

[9]  Joakim Sundnes,et al.  Computing the electrical activity in the heart , 2006 .

[10]  Rodrigo Weber dos Santos,et al.  Electroanatomical Characterization of Atrial Microfibrosis in a Histologically Detailed Computer Model , 2013, IEEE Transactions on Biomedical Engineering.

[11]  Koji Kumagai,et al.  Combined Dominant Frequency and Complex Fractionated Atrial Electrogram Ablation After Circumferential Pulmonary Vein Isolation of Atrial Fibrillation , 2013, Journal of cardiovascular electrophysiology.

[12]  Robert Ploutz-Snyder,et al.  Mechanisms of Wave Fractionation at Boundaries of High-Frequency Excitation in the Posterior Left Atrium of the Isolated Sheep Heart During Atrial Fibrillation , 2006, Circulation.

[13]  Jian Yu,et al.  A decade of complex fractionated electrograms catheter-based ablation for atrial fibrillation: Literature analysis, meta-analysis and systematic review , 2014 .

[14]  M. Eiswirth,et al.  Turbulence due to spiral breakup in a continuous excitable medium. , 1993, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[15]  S. Rush,et al.  A Practical Algorithm for Solving Dynamic Membrane Equations , 1978, IEEE Transactions on Biomedical Engineering.

[16]  J. Olgin,et al.  Microfibrosis and complex fractionated atrial electrograms. , 2009, Heart rhythm.

[17]  J. Strikwerda Finite Difference Schemes and Partial Differential Equations , 1989 .

[18]  C. Henriquez,et al.  A finite volume model of cardiac propagation , 1997, Annals of Biomedical Engineering.

[19]  J. Weiss,et al.  Spontaneous atrial fibrillation initiated by triggered activity near the pulmonary veins in aged rats subjected to glycolytic inhibition. , 2007, American journal of physiology. Heart and circulatory physiology.

[20]  Caroline Mendonca Costa,et al.  Limitations of the homogenized cardiac Monodomain model for the case of low gap junctional coupling , 2010, 2010 Annual International Conference of the IEEE Engineering in Medicine and Biology.

[21]  Markus Bär,et al.  Effects of reduced discrete coupling on filament tension in excitable media. , 2011, Chaos.

[22]  F. Hornero,et al.  A Three-Dimensional Human Atrial Model with Fiber Orientation. Electrograms and Arrhythmic Activation Patterns Relationship , 2013, PloS one.

[23]  R. Tracy,et al.  Histologically Measured Cardiomyocyte Hypertrophy Correlates with Body Height as Strongly as with Body Mass Index , 2011, Cardiology research and practice.

[24]  C. Henriquez,et al.  Effect of nonuniform interstitial space properties on impulse propagation: a discrete multidomain model. , 2008, Biophysical journal.

[25]  Sanjiv M Narayan,et al.  Mechanisms for the initiation of human atrial fibrillation. , 2009, Heart rhythm.

[26]  P. Santangeli,et al.  Adjunct ablation strategies for persistent atrial fibrillation-beyond pulmonary vein isolation. , 2015, Journal of thoracic disease.

[27]  A. Garfinkel,et al.  Effects of fibroblast-myocyte coupling on cardiac conduction and vulnerability to reentry: A computational study. , 2009, Heart rhythm.

[28]  D. Rosenbaum,et al.  Information learned from animal models of atrial fibrillation. , 2009, Cardiology clinics.

[29]  K. Nademanee,et al.  A new approach for catheter ablation of atrial fibrillation: mapping of the electrophysiologic substrate. , 2004, Journal of the American College of Cardiology.

[30]  M. Spach,et al.  The stochastic nature of cardiac propagation at a microscopic level. Electrical description of myocardial architecture and its application to conduction. , 1995, Circulation research.

[31]  Jacques M. T. de Bakker,et al.  A 50% Reduction of Excitability but Not of Intercellular Coupling Affects Conduction Velocity Restitution and Activation Delay in the Mouse Heart , 2011, PLoS ONE.

[32]  D. Dobrev,et al.  Cellular and molecular correlates of ectopic activity in patients with atrial fibrillation. , 2012, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[33]  A. Garfinkel,et al.  From Pulsus to Pulseless: The Saga of Cardiac Alternans , 2006, Circulation research.

[34]  Rengasayee Veeraraghavan,et al.  Interstitial volume modulates the conduction velocity-gap junction relationship. , 2012, American journal of physiology. Heart and circulatory physiology.

[35]  Markus Bär,et al.  Reentry near the percolation threshold in a heterogeneous discrete model for cardiac tissue. , 2013, Physical review letters.

[36]  Koonlawee Nademanee,et al.  Catheter ablation of atrial fibrillation guided by complex fractionated atrial electrogram mapping of atrial fibrillation substrate. , 2010, Journal of cardiology.

[37]  W. R. Mills,et al.  Optical mapping of late myocardial infarction in rats. , 2006, American journal of physiology. Heart and circulatory physiology.

[38]  P. Hogeweg,et al.  Spiral breakup in a modified FitzHugh-Nagumo model , 1993 .

[39]  J. Keener,et al.  The Effects of Gap Junctions on Propagation in Myocardium: A Modified Cable Theory a , 1990, Annals of the New York Academy of Sciences.

[40]  G. Bett,et al.  Computer model of action potential of mouse ventricular myocytes. , 2004, American journal of physiology. Heart and circulatory physiology.

[41]  Bruno Taccardi,et al.  Epicardial and intramural excitation during ventricular pacing: effect of myocardial structure. , 2008, American journal of physiology. Heart and circulatory physiology.

[42]  Vincent Jacquemet,et al.  Genesis of complex fractionated atrial electrograms in zones of slow conduction: a computer model of microfibrosis. , 2009, Heart rhythm.

[43]  Rodrigo Weber dos Santos,et al.  Simulations of Complex and Microscopic Models of Cardiac Electrophysiology Powered by Multi-GPU Platforms , 2012, Comput. Math. Methods Medicine.

[44]  H. Ishibashi-Ueda,et al.  Intrinsic left atrial histoanatomy as the basis for reentrant excitation causing atrial fibrillation/flutter in rats. , 2013, Heart rhythm.

[45]  K E Muffly,et al.  Structural Remodeling of Cardiac Myocytes in Patients With Ischemic Cardiomyopathy , 1992, Circulation.

[46]  L. Bhatt,et al.  Experimental animal models to induce cardiac arrhythmias , 2005 .

[47]  Spach,et al.  Effects of cardiac microstructure on propagating electrical waveforms , 2000, Circulation research.