Role of Fiber Orientation in Atrial Arrythmogenesis

Electrical wave-front propagation in the atria is determined largely by local fiber orientation. Recent study suggests that atrial fibrillation (AF) progresses with enhanced anisotropy. In this work, a 3D rabbit atrial anatomical model at 20 × 20 × 20 μm3 resolution with realistic fiber orientation was constructed based on the novel contrast-enhanced micro-CT imaging. The Fenton-Karma cellular activation model was adapted to reproduce rabbit atrial action potential period of 80 ms. Diffusivities were estimated for longitudinal and transverse directions of the fiber orientation respectively. Pacing was conducted in the 3D anisotropic atrial model with a reducing S2 interval to facilitate initiation of atrial arrhythmia. Multiple simulations were conducted with varying values of diffusion anisotropy and stimulus locations to evaluate the role of anisotropy in initiating AF. Under physiological anisotropy conditions, a rapid right atrial activation was followed by the left atrial activation. Excitation waves reached the atrio-ventricular border where they terminated. Upon reduction of conduction heterogeneity, re-entry was initiated by the rapid pacing and the activation of both atrial chambers was almost simultaneous. Myofiber orientation is an effective mechanism for regulating atrial activation. Modification of myoarchitecture is proarrhythmic

Characterization and modeling of the human left atrium using optical coherence tomography

With current needs to better understand the interaction between atrial tissue microstructure and atrial fibrillation dynamics, micrometer scale imaging with optical coherence tomography has significant potential to provide further insight on arrhythmia mechanisms and improve treatment guidance. However, optical coherence tomography imaging of cardiac tissue in humans is largely unexplored, and the ability of optical coherence tomography to identify the structural substrate of atrial fibrillation has not yet been investigated. Therefore, the objective of this thesis was to develop an optical coherence tomography imaging atlas of the human heart, study the utility of optical coherence tomography in providing useful features of human left atrial tissues, and develop a framework for optical coherence tomography-informed cardiac modeling that could be used to probe dynamics between electrophysiology and tissue structure. Human left atrial tissues were comprehensively imaged by optical coherence tomography for the first time, providing an imaging atlas that can guide identification of left atrial tissue features from optical coherence tomography imaging. Optical coherence tomography image features corresponding to myofiber and collagen fiber orientation, adipose tissue, endocardial thickness and composition, and venous media were established. Varying collagen fiber distributions in the myocardial sleeves were identified within the pulmonary veins. A scheme for mapping optical coherence tomography data of dissected left atrial tissues to a three-dimensional, anatomical model of the human left atrium was also developed, enabling the mapping of distributions of imaged adipose tissue and fiber orientation to the whole left atrial geometry. These results inform future applications of structural substrate mapping in the human left atrium using optical coherence tomography-integrated catheters, as well as potential directions of ex vivo optical coherence tomography atrial imaging studies. Additionally, we developed a workflow for creating optical mapping models of atrial tissue as informed by optical coherence tomography. Tissue geometry, fiber orientation, ablation lesion geometry, and heterogeneous tissue types were extracted from optical coherence tomography images and incorporated into tissue-specific meshes. Electrophysiological propagation was simulated and combined with photon scattering simulations to evaluate the influence of tissue-specific structure on electrical and optical mapping signals. Through tissue-specific modeling of myofiber orientation, ablation lesions, and heterogeneous tissue types, the influence of myofiber orientation on transmural activation, the relationship between fluorescent signals and lesion geometry, and the blurring of optical mapping signals in the presence of heterogeneous tissue types were investigated. By providing a comprehensive optical coherence tomography image database of the human left atrium and a workflow for developing optical coherence tomography-informed cardiac tissue models, this work establishes the foundation for utilizing optical coherence tomography to improve the structural substrate characterization of atrial fibrillation. Future developments include analysis of optical coherence tomography imaged tissue structure with respect to clinical presentation, development of automated processing to better leverage the large amount of imaging data, enhancements and validation of the modeling scheme, and in vivo evaluation of the left atrial structural substrate through optical coherence tomography-integrated catheter

Will the real ventricular architecture please stand up?

Ventricular twisting, essential for cardiac function, is attributed to the contraction of myocardial helical fibers. The exact relationship between ventricular anatomy and function remains to be determined, but one commonly used explanatory model is the helical ventricular myocardial band (HVMB) model of Torrent-Guasp. This model has been successful in explaining many aspects of ventricular function, (Torrent-Guasp et al. Eur. J. Cardiothorac. Surg., 25, 376, 2004; Buckberg et al. Eur. J. Cardiothorac. Surg., 47, 587, 2015; Buckberg et al. Eur. J. Cardiothorac. Surg. 47, 778, 2015) but the model ignores important aspects of ventricular anatomy and should probably be replaced. The purpose of this review is to compare the HVMB model with a different model (nested layers). A complication when interpreting experimental observations that relate anatomy to function is that, in the myocardium, shortening does not always imply activation and lengthening does not always imply inactivation

Circ Arrhythm Electrophysiol

BackgroundAccurate knowledge of the human atrial fibrous structure is paramount in understanding the mechanisms of atrial electrical function in health and disease. Thus far such knowledge has been acquired from destructive sectioning, and there is a paucity of data regarding atrial fiber architecture variability in the human population.Methods and ResultsIn this study, we have developed a customized 3D diffusion tensor magnetic resonance imaging (DTMRI) sequence on a clinical scanner that makes it possible to image an entire intact human heart specimen ex vivo at sub-millimeter resolution. The data from eight human atrial specimens obtained with this technique present complete maps of the fibrous organization of the human atria. The findings demonstrate that the main features of atrial anatomy are mostly preserved across subjects, although the exact location and orientation of atrial bundles vary. Using the full tractography data, we were able to cluster, visualize, and characterize the distinct major bundles in the human atria. Further, quantitative characterization of the fiber angles across the atrial wall revealed that the transmural fiber angle distribution is heterogeneous throughout different regions of the atria.ConclusionsThe application of sub-millimeter DTMRI provides an unprecedented level of information regarding both human atrial structure as well as its inter-subject variability. The high resolution and fidelity of this data could enhance our understanding of structural contributions to atrial rhythm and pump disorders, and lead to improvements in their targeted treatment.DP1HL123271/DP/NCCDPHP CDC HHS/United StatesR01 HL142893/HL/NHLBI NIH HHS/United StatesDP1 HL123271/HL/NHLBI NIH HHS/United StatesImNIH/Intramural NIH HHS/United StatesR01 HL142496/HL/NHLBI NIH HHS/United StatesR01 HL126802/HL/NHLBI NIH HHS/United States2020-02-22T00:00:00Z27071829PMC70358847696vault:3467

Endocardial activation mapping of human atrial fibrillation

Successful ablation of arrhythmias depends upon interpretation of the mechanism. However, in persistent atrial fibrillation (AF) ablation is currently directed towards the mechanism that initiates paroxysmal AF. We sought to address the hypothesis that atrial activation patterns during persistent AF may help determine the underlying mechanism. Activation mapping of AF wavefronts is labor intensive and often restricted to short time segments in limited atrial locations. RETRO-Mapping was developed to identify uniform wavefronts that occur during AF, and summate all wavefront vectors on to an orbital plot. Uniform wavefronts were mapped using RETRO-Mapping during sinus rhythm, atrial tachycardia, and atrial fibrillation, and validated against detailed manual analysis of the same wavefronts with conventional isochronal mapping. RETRO-Mapping was found to have comparable accuracy to isochronal mapping. RETRO-Mapping was then used to investigate atrial activation patterns during persistent AF. Atrial activation patterns demonstrated evidence of spatiotemporal stability over long time periods. Orbital plots created at different time points in the same location remained unchanged. Together with this important discovery, both fractionation and bipolar voltage were also demonstrated to express stability over time. Spatiotemporal stability during persistent AF enables sequential mapping as an acceptable technique. This property also allowed the development of a method for displaying sequentially mapped locations on a single map – RETRO-Choropleth Map. These findings go against the multiple wavelet hypothesis with random activation. Having gained insights in to these stable activation patterns, extensive analysis was undertaken to identify the presence of focal activation. Focal activations were identified during persistent AF. RETRO-Mapping was used to show that adjacent activation patterns were not related to focal activations. Lastly, the effect of pulmonary vein isolation (PVI) was studied by mapping atrial activation patterns before and after PVI. RETRO-Mapping showed that PVI leads to increased organisation of AF in most patients, supporting a mechanistic role of the pulmonary veins in persistent AF. In conclusion, a new technique has been developed and validated for automated activation mapping of persistent AF. These techniques could be used to guide additional ablation strategies beyond PVI for patients with persistent AF.Open Acces

High-Resolution Whole-Heart Imaging and Modeling for Studying Cardiac Arrhythmia

Cardiac arrhythmia is a life-threatening heart rhythm disorder affecting millions of people worldwide. The underlying structure of the heart plays an important role in cardiac activity and could promote rhythm disorders. Accurate knowledge of whole-heart cardiac geometry and microstructure in normal and disease hearts is essential for a complete understanding of the mechanisms of arrhythmias. This dissertation presents novel structural data at the whole-heart level aimed at advancing knowledge of cardiac structure in normal and infarcted hearts, and at constructing whole-heart computational models. A 3D diffusion tensor MRI (DTMRI) technique was implemented on a clinical scanner to image intact large animal and human hearts with high image quality and spatial resolution ex vivo. This method was first applied to reconstruct the 3D myofiber organization in 8 human atria nondestructively and at submillimeter resolution. The findings showed that the main features of atrial anatomy are mostly preserved across subjects despite variability in the exact location and orientation of the bundles. Further, we were able to cluster, visualize, and characterize the distinct major bundles in the human atria. Quantitative analysis of the fiber angles across the atrial wall revealed that the transmural fiber angle distribution is heterogeneous throughout the atria. We next studied microstructural remodeling in infarcted porcine and human hearts by combining DTMRI with high-resolution Late Gadolinium Enhancement imaging. This enabled us to provide reconstructions of both fiber architecture and scar distribution in infarcted hearts with an unprecedented level of detail, and to systematically quantify the transmural pattern of diffusion eigenvector orientation. Our results demonstrated that the fiber orientation is generally preserved inside the scar but at a higher transmural gradient of inclination angle. Lastly, we employed the obtained data to generate whole-heart computational models of infarcted hearts with detailed scar geometry and subject-specific fiber orientation. We used these models in simulations to investigate the contribution of the infarct microarchitecture to ventricular tachycardia. The simulation results showed that the reentry circuits traverse thin viable tissues with complex geometries located inside of the infarct. The high resolution of the images enabled 3D reconstruction and characterization of such structures

Fiber Organization has Little Effect on Electrical Activation Patterns during Focal Arrhythmias in the Left Atrium

Over the past two decades there has been a steady trend towards the development of realistic models of cardiac conduction with increasing levels of detail. However, making models more realistic complicates their personalization and use in clinical practice due to limited availability of tissue and cellular scale data. One such limitation is obtaining information about myocardial fiber organization in the clinical setting. In this study, we investigated a chimeric model of the left atrium utilizing clinically derived patient-specific atrial geometry and a realistic, yet foreign for a given patient fiber organization. We discovered that even significant variability of fiber organization had a relatively small effect on the spatio-temporal activation pattern during regular pacing. For a given pacing site, the activation maps were very similar across all fiber organizations tested

Submillimeter diffusion tensor imaging and late gadolinium enhancement cardiovascular magnetic resonance of chronic myocardial infarction.

BackgroundKnowledge of the three-dimensional (3D) infarct structure and fiber orientation remodeling is essential for complete understanding of infarct pathophysiology and post-infarction electromechanical functioning of the heart. Accurate imaging of infarct microstructure necessitates imaging techniques that produce high image spatial resolution and high signal-to-noise ratio (SNR). The aim of this study is to provide detailed reconstruction of 3D chronic infarcts in order to characterize the infarct microstructural remodeling in porcine and human hearts.MethodsWe employed a customized diffusion tensor imaging (DTI) technique in conjunction with late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) on a 3T clinical scanner to image, at submillimeter resolution, myofiber orientation and scar structure in eight chronically infarcted porcine hearts ex vivo. Systematic quantification of local microstructure was performed and the chronic infarct remodeling was characterized at different levels of wall thickness and scar transmurality. Further, a human heart with myocardial infarction was imaged using the same DTI sequence.ResultsThe SNR of non-diffusion-weighted images was >100 in the infarcted and control hearts. Mean diffusivity and fractional anisotropy (FA) demonstrated a 43% increase, and a 35% decrease respectively, inside the scar tissue. Despite this, the majority of the scar showed anisotropic structure with FA higher than an isotropic liquid. The analysis revealed that the primary eigenvector orientation at the infarcted wall on average followed the pattern of original fiber orientation (imbrication angle mean: 1.96 ± 11.03° vs. 0.84 ± 1.47°, p = 0.61, and inclination angle range: 111.0 ± 10.7° vs. 112.5 ± 6.8°, p = 0.61, infarcted/control wall), but at a higher transmural gradient of inclination angle that increased with scar transmurality (r = 0.36) and the inverse of wall thickness (r = 0.59). Further, the infarcted wall exhibited a significant increase in both the proportion of left-handed epicardial eigenvectors, and in the angle incoherency. The infarcted human heart demonstrated preservation of primary eigenvector orientation at the thinned region of infarct, consistent with the findings in the porcine hearts.ConclusionsThe application of high-resolution DTI and LGE-CMR revealed the detailed organization of anisotropic infarct structure at a chronic state. This information enhances our understanding of chronic post-infarction remodeling in large animal and human hearts

Cardiac re-entry dynamics & self-termination in DT-MRI based model of Human Foetal Heart

The effect of heart geometry and anisotropy on cardiac re-entry dynamics and self-termination is studied here in anatomically realistic computer simulations of human foetal heart. 20 weeks of gestational age human foetal heart isotropic and anisotropic anatomy models from diffusion tensor MRI data sets are used in the computer simulations. The fibre orientation angles of the heart were obtained from the DT-MRI primary eigenvalues. In a spatially homogeneous electrophysiological mono domain model with the DT-MRI based heart geometries, we initiate simplified Fitz-Hugh-Nagumo kinetics cardiac re-entry at a prescribed location in a 2D slice, and in the full 3D anatomy model. In a slice of the heart, the MRI based fibre anisotropy changes the re-entry dynamics from pinned to anatomical re-entry. In the full 3D MRI based model, the foetal heart fibre anisotropy changes the re-entry dynamics from a persistent re-entry to the re-entry self-termination