Electrophysiological Rotor Ablation in In-Silico Modeling of Atrial Fibrillation: Comparisons with Dominant Frequency, Shannon Entropy, and Phase Singularity

Background Although rotors have been considered among the drivers of atrial fibrillation (AF), the rotor definition is inconsistent. We evaluated the nature of rotors in 2D and 3D in- silico models of persistent AF (PeAF) by analyzing phase singularity (PS), dominant frequency (DF), Shannon entropy (ShEn), and complex fractionated atrial electrogram cycle length (CFAE-CL) and their ablation. Methods Mother rotor was spatiotemporally defined as stationary reentries with a meandering tip remaining within half the wavelength and lasting longer than 5 s. We generated 2D- and 3D-maps of the PS, DF, ShEn, and CFAE-CL during AF. The spatial correlations and ablation outcomes targeting each parameter were analyzed. Results 1. In the 2D PeAF model, we observed a mother rotor that matched relatively well with DF (>9 Hz, 71.0%, p<0.001), ShEn (upper 2.5%, 33.2%, p<0.001), and CFAE-CL (lower 2.5%, 23.7%, p<0.001). 2. The 3D-PeAF model also showed mother rotors that had spatial correlations with DF (>5.5 Hz, 39.7%, p<0.001), ShEn (upper 8.5%, 15.1%, p <0.001), and CFAE (lower 8.5%, 8.0%, p = 0.002). 3. In both the 2D and 3D models, virtual ablation targeting the upper 5% of the DF terminated AF within 20 s, but not the ablations based on long-lasting PS, high ShEn area, or lower CFAE-CL area. Conclusion Mother rotors were observed in both 2D and 3D human AF models. Rotor locations were well represented by DF, and their virtual ablation altered wave dynamics and terminated AF.

[1]  G. Moe,et al.  On the multiple wavelet hypothesis o f atrial fibrillation. , 1962 .

[2]  W. Baxter,et al.  Spiral waves of excitation underlie reentrant activity in isolated cardiac muscle. , 1993, Circulation research.

[3]  M. Allessie,et al.  High-density mapping of electrically induced atrial fibrillation in humans. , 1994, Circulation.

[4]  R. A. Gray,et al.  Mechanisms of Cardiac Fibrillation , 1995, Science.

[5]  M. Courtemanche,et al.  Ionic mechanisms underlying human atrial action potential properties: insights from a mathematical model. , 1998, The American journal of physiology.

[6]  J Jalife,et al.  Mechanisms of atrial fibrillation: mother rotors or multiple daughter wavelets, or both? , 1998, Journal of cardiovascular electrophysiology.

[7]  Alan Garfinkel,et al.  DYNAMICS OF REENTRY AROUND A CIRCULAR OBSTACLE IN CARDIAC TISSUE , 1998 .

[8]  J Jalife,et al.  Ventricular fibrillation: mechanisms of initiation and maintenance. , 2000, Annual review of physiology.

[9]  M. Mansour,et al.  Mother rotors and fibrillatory conduction: a mechanism of atrial fibrillation. , 2002, Cardiovascular research.

[10]  Hui-Nam Pak,et al.  Catheter Ablation of Ventricular Fibrillation in Rabbit Ventricles Treated With &bgr;-Blockers , 2003 .

[11]  C. Henriquez,et al.  Study of Unipolar Electrogram Morphology in a Computer Model of Atrial Fibrillation , 2003, Journal of cardiovascular electrophysiology.

[12]  H. Pak,et al.  Catheter ablation of ventricular fibrillation in rabbit ventricles treated with beta-blockers. , 2003, Circulation.

[13]  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.

[14]  R. Gray,et al.  An Experimentalist's Approach to Accurate Localization of Phase Singularities during Reentry , 2004, Annals of Biomedical Engineering.

[15]  José Jalife,et al.  Ionic determinants of functional reentry in a 2-D model of human atrial cells during simulated chronic atrial fibrillation. , 2005, Biophysical journal.

[16]  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.

[17]  Hui-Nam Pak,et al.  Role of the Posterior Papillary Muscle and Purkinje Potentials in the Mechanism of Ventricular Fibrillation in Open Chest Dogs and Swine: Effects of Catheter Ablation , 2006, Journal of cardiovascular electrophysiology.

[18]  L. Tung,et al.  Representation of collective electrical behavior of cardiac cell sheets. , 2008, Biophysical journal.

[19]  Omer Berenfeld,et al.  Rotor meandering contributes to irregularity in electrograms during atrial fibrillation. , 2008, Heart rhythm.

[20]  H. Pak,et al.  Both Purkinje cells and left ventricular posteroseptal reentry contribute to the maintenance of ventricular fibrillation in open-chest dogs and swine: effects of catheter ablation and the ventricular cut-and-sew operation. , 2008, Circulation journal : official journal of the Japanese Circulation Society.

[21]  José Jalife,et al.  Cardiac fibrillation: from ion channels to rotors in the human heart. , 2008, Heart rhythm.

[22]  M. P. Nash,et al.  A computational study of mother rotor VF in the human ventricles , 2008, American journal of physiology. Heart and circulatory physiology.

[23]  Po-Cheng Chang,et al.  Epicardial ablation of rotors suppresses inducibility of acetylcholine-induced atrial fibrillation in left pulmonary vein-left atrium preparations in a beagle heart failure model. , 2011, Journal of the American College of Cardiology.

[24]  A. Verma,et al.  Relationship Between Complex Fractionated Electrograms (CFE) and Dominant Frequency (DF) Sites and Prospective Assessment of Adding DF‐Guided Ablation to Pulmonary Vein Isolation in Persistent Atrial Fibrillation (AF) , 2011, Journal of cardiovascular electrophysiology.

[25]  Wouter-Jan Rappel,et al.  Treatment of atrial fibrillation by the ablation of localized sources: CONFIRM (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation) trial. , 2012, Journal of the American College of Cardiology.

[26]  H. Calkins,et al.  Update on atrial fibrillation catheter ablation technologies and techniques , 2013, Nature Reviews Cardiology.

[27]  Rajiv Mahajan,et al.  Bipolar Electrogram Shannon Entropy at Sites of Rotational Activation: Implications for Ablation of Atrial Fibrillation , 2013, Circulation. Arrhythmia and electrophysiology.

[28]  Peter Spector,et al.  Principles of Cardiac Electric Propagation and Their Implications for Re-entrant Arrhythmias , 2013, Circulation. Arrhythmia and electrophysiology.

[29]  José Jalife,et al.  Rotors and the Dynamics of Cardiac Fibrillation , 2013, Circulation research.

[30]  Hangsik Shin,et al.  The Relationship among Complex Fractionated Electrograms, Wavebreak, Phase Singularity, and Local Dominant Frequency in Fibrillation Wave-Dynamics: a Modeling Comparison Study , 2014, Journal of Korean medical science.

[31]  Laura J. Bonnett,et al.  Efficacy of Catheter Ablation for Persistent Atrial Fibrillation: A Systematic Review and Meta-Analysis of Evidence From Randomized and Nonrandomized Controlled Trials , 2014, Circulation. Arrhythmia and electrophysiology.

[32]  Omer Berenfeld,et al.  Attraction of rotors to the pulmonary veins in paroxysmal atrial fibrillation: a modeling study. , 2014, Biophysical journal.

[33]  O. Berenfeld,et al.  Mechanisms of atrial fibrillation: rotors, ionic determinants, and excitation frequency. , 2014, Cardiology clinics.

[34]  José Jalife,et al.  Comparison of radiofrequency catheter ablation of drivers and circumferential pulmonary vein isolation in atrial fibrillation: a noninferiority randomized multicenter RADAR-AF trial. , 2014, Journal of the American College of Cardiology.

[35]  Prashanthan Sanders,et al.  Origin and Characteristics of High Shannon Entropy at the Pivot of Locally Stable Rotors: Insights from Computational Simulation , 2014, PloS one.

[36]  Soon-Sung Kwon,et al.  Virtual ablation for atrial fibrillation in personalized in-silico three-dimensional left atrial modeling: comparison with clinical catheter ablation. , 2014, Progress in biophysics and molecular biology.

[37]  Ashok J. Shah,et al.  Driver Domains in Persistent Atrial Fibrillation , 2014, Circulation.

[38]  Yves Coudière,et al.  A bilayer model of human atria: mathematical background, construction, and assessment. , 2014, 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.

[39]  Wouter-Jan Rappel,et al.  Mechanisms for the Termination of Atrial Fibrillation by Localized Ablation: Computational and Clinical Studies , 2015, Circulation. Arrhythmia and electrophysiology.

[40]  Pawel Kuklik,et al.  Reconstruction of Instantaneous Phase of Unipolar Atrial Contact Electrogram Using a Concept of Sinusoidal Recomposition and Hilbert Transform , 2015, IEEE Transactions on Biomedical Engineering.

[41]  Joshua J. E. Blauer,et al.  Virtual Electrophysiological Study of Atrial Fibrillation in Fibrotic Remodeling , 2015, PloS one.

[42]  Hui-Nam Pak,et al.  Fibrillation Number Based on Wavelength and Critical Mass in Patients Who Underwent Radiofrequency Catheter Ablation for Atrial Fibrillation , 2015, IEEE Transactions on Biomedical Engineering.

[43]  Kalyanam Shivkumar,et al.  Long-term clinical outcomes of focal impulse and rotor modulation for treatment of atrial fibrillation: A multicenter experience. , 2016, Heart rhythm.

[44]  Gerhard Hindricks,et al.  Successful Repeat Catheter Ablation of Recurrent Longstanding Persistent Atrial Fibrillation With Rotor Elimination as the Procedural Endpoint: A Case Series , 2016, Journal of cardiovascular electrophysiology.