Fibrosis and Atrial Fibrillation: Computerized and Optical Mapping; A View into the Human Atria at Submillimeter Resolution.

Recent studies strongly suggest that the majority of atrial fibrillation (AF) patients with diagnosed or subclinical cardiac diseases have established or even pre-existing fibrotic structural remodeling, which may lead to conduction abnormalities and reentrant activity that sustain AF. As conventional treatments fail to treat AF in far too many cases, an urgent need exists to identify specific structural arrhythmogenic fibrosis patterns, which may maintain AF, in order to identify effective ablation targets for AF treatment. However, the existing challenge is to define what exact structural remodeling within the complex 3D human atrial wall is arrhythmogenic, as well as linking arrhythmogenic fibrosis to an underlying mechanism of AF maintenance in the clinical setting. This review is focused on the role of 3D fibrosis architecture in the mechanisms of AF maintenance revealed by submillimeter, high-resolution ex-vivo imaging modalities directly of human atria, as well as from in-silico 3D computational techniques that can be able to overcome in-vivo clinical limitations. The systematic integration of functional and structural imaging ex-vivo may inform the necessary integration of electrode and structural mapping in-vivo. A holistic view of AF driver mechanisms may begin to identify the defining characteristics or "fingerprints" of reentrant AF drivers, such as 3D fibrotic architecture, in order to design optimal patient-specific ablation strategies.

[1]  Gopi Dandamudi,et al.  Clinical Benefit of Ablating Localized Sources for Human Atrial Fibrillation: The Indiana University FIRM Registry. , 2017, Journal of the American College of Cardiology.

[2]  D. Sánchez-Quintana,et al.  Standardized Review of Atrial Anatomy for Cardiac Electrophysiologists , 2013, Journal of Cardiovascular Translational Research.

[3]  J Jalife,et al.  Stable microreentrant sources as a mechanism of atrial fibrillation in the isolated sheep heart. , 2000, Circulation.

[4]  Jichao Zhao,et al.  Optimization of Catheter Ablation of Atrial Fibrillation: Insights Gained from Clinically-Derived Computer Models , 2015, International journal of molecular sciences.

[5]  Stefan L. Zimmerman,et al.  Initial experience with magnetic resonance imaging of atrial scar and co-registration with electroanatomic voltage mapping during atrial fibrillation: success and limitations. , 2012, Heart rhythm.

[6]  E. A. Ermakova,et al.  Rotating spiral waves in a modified Fitz-Hugh-Nagumo model , 1984 .

[7]  Jan Berg,et al.  Box Isolation of Fibrotic Areas (BIFA): A Patient‐Tailored Substrate Modification Approach for Ablation of Atrial Fibrillation , 2016, Journal of cardiovascular electrophysiology.

[8]  Jichao Zhao,et al.  Atrial fibrillation driven by micro-anatomic intramural re-entry revealed by simultaneous sub-epicardial and sub-endocardial optical mapping in explanted human hearts. , 2015, European heart journal.

[9]  O. Berenfeld,et al.  Mechanistic Approaches to Detect, Target, and Ablate the Drivers of Atrial Fibrillation. , 2016, Circulation. Arrhythmia and electrophysiology.

[10]  P. Ursell,et al.  Electrophysiologic and anatomic basis for fractionated electrograms recorded from healed myocardial infarcts. , 1985, Circulation.

[11]  Jichao Zhao,et al.  Three‐dimensional Integrated Functional, Structural, and Computational Mapping to Define the Structural “Fingerprints” of Heart‐Specific Atrial Fibrillation Drivers in Human Heart Ex Vivo , 2017, Journal of the American Heart Association.

[12]  Nassir F Marrouche,et al.  Magnetic resonance imaging of atrial fibrosis: redefining atrial fibrillation to a syndrome , 2017, European heart journal.

[13]  Nassir Marrouche,et al.  Diverse Fibrosis Architecture and Premature Stimulation Facilitate Initiation of Reentrant Activity Following Chronic Atrial Fibrillation , 2015, Journal of cardiovascular electrophysiology.

[14]  Zhilin Qu,et al.  Cardiac fibrosis and arrhythmogenesis: the road to repair is paved with perils. , 2014, Journal of molecular and cellular cardiology.

[15]  Natasja M.S. de Groot,et al.  Inhomogeneity and complexity in defining fractionated electrograms , 2017 .

[16]  Y. Rudy,et al.  Methodology Considerations in Phase Mapping of Human Cardiac Arrhythmias , 2016, Circulation. Arrhythmia and electrophysiology.

[17]  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.

[18]  I. Shiraishi,et al.  Quantitative Histological Analysis of the Human Sinoatrial Node During Growth and Aging , 1992, Circulation.

[19]  Stefan L. Zimmerman,et al.  Lack of regional association between atrial late gadolinium enhancement on cardiac magnetic resonance and atrial fibrillation rotors. , 2016, Heart rhythm.

[20]  N. Trayanova,et al.  Exploring susceptibility to atrial and ventricular arrhythmias resulting from remodeling of the passive electrical properties in the heart: a simulation approach , 2014, Front. Physiol..

[21]  H. Kottkamp Fibrotic Atrial Cardiomyopathy: A Specific Disease/Syndrome Supplying Substrates for Atrial Fibrillation, Atrial Tachycardia, Sinus Node Disease, AV Node Disease, and Thromboembolic Complications , 2012, Journal of cardiovascular electrophysiology.

[22]  Jens Eckstein,et al.  Role of endo-epicardial dissociation of electrical activity and transmural conduction in the development of persistent atrial fibrillation. , 2014, Progress in biophysics and molecular biology.

[23]  D. Rueckert,et al.  Automated analysis of atrial late gadolinium enhancement imaging that correlates with endocardial voltage and clinical outcomes: A 2-center study , 2013, Heart rhythm.

[24]  J. Hummel,et al.  Maintenance of Atrial Fibrillation: Are Reentrant Drivers With Spatial Stability the Key? , 2016, Circulation: Arrhythmia and Electrophysiology.

[25]  Prashanthan Sanders,et al.  Electrical Remodeling of the Atria in Congestive Heart Failure: Electrophysiological and Electroanatomic Mapping in Humans , 2003, Circulation.

[26]  Leslie M Loew,et al.  Anatomic Localization and Autonomic Modulation of Atrioventricular Junctional Rhythm in Failing Human Hearts , 2011, Circulation. Arrhythmia and electrophysiology.

[27]  Jichao Zhao,et al.  Novel application of 3D contrast-enhanced CMR to define fibrotic structure of the human sinoatrial node in vivo , 2017, European heart journal cardiovascular Imaging.

[28]  Henggui Zhang,et al.  An Image-Based Model of Atrial Muscular Architecture: Effects of Structural Anisotropy on Electrical Activation , 2012, Circulation. Arrhythmia and electrophysiology.

[29]  Natalia A Trayanova,et al.  Towards personalized computational modelling of the fibrotic substrate for atrial arrhythmia. , 2016, 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.

[30]  S. Nattel,et al.  The value of basic research insights into atrial fibrillation mechanisms as a guide to therapeutic innovation: a critical analysis. , 2016, Cardiovascular research.

[31]  L. Mont,et al.  Letter by Bisbal et al regarding article, "Repeat left atrial catheter ablation: cardiac magnetic resonance prediction of endocardial voltage and gaps in ablation lesion sets". , 2015, Circulation. Arrhythmia and electrophysiology.

[32]  O. Berenfeld,et al.  Letter by Jalife et al Regarding Article, "Quantitative Analysis of Localized Sources Identified by Focal Impulse and Rotor Modulation Mapping in Atrial Fibrillation". , 2015, Circulation. Arrhythmia and electrophysiology.

[33]  A. Winfree Electrical instability in cardiac muscle: phase singularities and rotors. , 1989, Journal of theoretical biology.

[34]  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.

[35]  N. Trayanova,et al.  Patient-derived models link re-entrant driver localization in atrial fibrillation to fibrosis spatial pattern. , 2016, Cardiovascular research.

[36]  Jichao Zhao,et al.  Integration of High-Resolution Optical Mapping and 3-Dimensional Micro-Computed Tomographic Imaging to Resolve the Structural Basis of Atrial Conduction in the Human Heart. , 2015, Circulation. Arrhythmia and electrophysiology.

[37]  Wouter-Jan Rappel,et al.  Repolarization and Activation Restitution near Human Pulmonary Veins and Atrial Fibrillation Initiation a Mechanism for the Initiation of Atrial Fibrillation by Premature Beats , 2022 .

[38]  J. Kautzner,et al.  Associations between cardiac fibrosis and permanent atrial fibrillation in advanced heart failure. , 2013, Physiological research.

[39]  G. Seemann,et al.  Slow Conduction in the Border Zones of Patchy Fibrosis Stabilizes the Drivers for Atrial Fibrillation: Insights from Multi-Scale Human Atrial Modeling , 2016, Front. Physiol..

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

[41]  Rémi Dubois,et al.  Modelling methodology of atrial fibrosis affects rotor dynamics and electrograms. , 2016, 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.

[42]  J. Francis Heidlage,et al.  Influence of the Passive Anisotropic Properties on Directional Differences in Propagation Following Modification of the Sodium Conductance in Human Atrial Muscle: A Model of Reentry Based on Anisotropic Discontinuous Propagation , 1988, Circulation research.

[43]  Kawal S. Rhode,et al.  Repeat Left Atrial Catheter Ablation: Cardiac Magnetic Resonance Prediction of Endocardial Voltage and Gaps in Ablation Lesion Sets , 2015, Circulation. Arrhythmia and electrophysiology.

[44]  Alexander V. Panfilov,et al.  Effects of Heterogeneous Diffuse Fibrosis on Arrhythmia Dynamics and Mechanism , 2016, Scientific Reports.

[45]  R. Aliev,et al.  Three-dimensional twisted vortices in an excitable chemical medium , 1990, Nature.

[46]  S. Landas,et al.  Spatial Distribution of Fibrosis Governs Fibrillation Wave Dynamics in the Posterior Left Atrium During Heart Failure , 2007, Circulation research.

[47]  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.

[48]  Jacques M. T. de Bakker,et al.  Fibrosis and Cardiac Arrhythmias , 2011 .

[49]  D. V. Van Wagoner,et al.  Adenosine-Induced Atrial Fibrillation: Localized Reentrant Drivers in Lateral Right Atria due to Heterogeneous Expression of Adenosine A1 Receptors and GIRK4 Subunits in the Human Heart. , 2016, Circulation.

[50]  Prashanthan Sanders,et al.  Approaches to catheter ablation for persistent atrial fibrillation. , 2015, The New England journal of medicine.

[51]  Hubert Cochet,et al.  Complexity and Distribution of Drivers in Relation to Duration of Persistent Atrial Fibrillation. , 2017, Journal of the American College of Cardiology.

[52]  J. Olgin,et al.  Atrial Fibrillation Therapy Now and in the Future: Drugs, Biologicals, and Ablation , 2014, Circulation research.

[53]  P. Kirchhof,et al.  Pathophysiological mechanisms of atrial fibrillation: a translational appraisal. , 2011, Physiological reviews.

[54]  Rob S MacLeod,et al.  Evaluation of Left Atrial Lesions After Initial and Repeat Atrial Fibrillation Ablation: Lessons Learned From Delayed-Enhancement MRI in Repeat Ablation Procedures , 2010, Circulation. Arrhythmia and electrophysiology.

[55]  Ulrich Schotten,et al.  Electropathological Substrate of Long-Standing Persistent Atrial Fibrillation in Patients With Structural Heart Disease: Longitudinal Dissociation , 2010, Circulation. Arrhythmia and electrophysiology.

[56]  Geoffrey Lee,et al.  Atrial Electrical and Structural Changes Associated with Longstanding Hypertension in Humans: Implications for the Substrate for Atrial Fibrillation , 2011, Journal of cardiovascular electrophysiology.

[57]  I. Watanabe,et al.  Electrophysiological effect of adenosine triphosphate and adenosine on atrial and ventricular action potential duration in humans. , 2000, Japanese circulation journal.

[58]  Markus Roos,et al.  Spatial Relationship of Focal Impulses, Rotors and Low Voltage Zones in Patients With Persistent Atrial Fibrillation , 2016, Journal of cardiovascular electrophysiology.

[59]  Nazem Akoum,et al.  Association of atrial tissue fibrosis identified by delayed enhancement MRI and atrial fibrillation catheter ablation: the DECAAF study. , 2014, JAMA.

[60]  V. Fedorov,et al.  Atrial fibrillation driver mechanisms: Insight from the isolated human heart. , 2017, Trends in cardiovascular medicine.

[61]  Peter Kohl,et al.  Fibroblast–myocyte electrotonic coupling: Does it occur in native cardiac tissue?☆ , 2014, Journal of molecular and cellular cardiology.

[62]  Jichao Zhao,et al.  Three-Dimensional Impulse Propagation in Myocardium: Arrhythmogenic Mechanisms at the Tissue Level , 2013, Circulation research.

[63]  U. Schotten,et al.  Lone atrial fibrillation: does it exist? , 2014, Journal of the American College of Cardiology.

[64]  Li Li,et al.  Chronic atrial fibrillation causes left ventricular dysfunction in dogs but not goats: experience with dogs, goats, and pigs. , 2013, American journal of physiology. Heart and circulatory physiology.

[65]  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.