Noninvasive Assessment of Complexity of Atrial Fibrillation Correlation With Contact Mapping and Impact of Ablation

[EN] Background: It is difficult to noninvasively phenotype atrial fibrillation (AF) in a way that reflects clinical end points such as response to therapy. We set out to map electrical patterns of disorganization and regions of reentrant activity in AF from the body surface using electrocardiographic imaging, calibrated to panoramic intracardiac recordings and referenced to AF termination by ablation. Methods: Bi-atrial intracardiac electrograms of 47 patients with AF at ablation (30 persistent, 29 male, 63 +/- 9 years) were recorded with 64-pole basket catheters and simultaneous 57-lead body surface ECGs. Atrial epicardial electrical activity was reconstructed and organized sites were invasively and noninvasively tracked in 3-dimension using phase singularity. In a subset of 17 patients, sites of AF organization were targeted for ablation. Results: Body surface mapping showed greater AF organization near intracardially detected drivers than elsewhere, both in phase singularity density (2.3 +/- 2.1 versus 1.9 +/- 1.6; P=0.02) and number of drivers (3.2 +/- 2.3 versus 2.7 +/- 1.7; P=0.02). Complexity, defined as the number of stable AF reentrant sites, was concordant between noninvasive and invasive methods (r(2)=0.5; CC=0.71). In the subset receiving targeted ablation, AF complexity showed lower values in those in whom AF terminated than those in whom AF did not terminate (P<0.01). Conclusions: AF complexity tracked noninvasively correlates well with organized and disorganized regions detected by panoramic intracardiac mapping and correlates with the acute outcome by ablation. This approach may assist in bedside monitoring of therapy or in improving the efficacy of ongoing ablation procedures.This article was supported in part by: Instituto de Salud Carlos III FEDER (Fondo Europeo de Desarrollo Regional; IJCI-2014-22178, DTS16/00160; PI14/00857, PI16/01123; PI17/01059; PI17/01106), Generalitat Valenciana Grants (APOSTD/2017 and APOSTD/2018) and projects (GVA/2018/103); National Institutes of Health (Dr Narayan: R01 HL85537; K24 HL103800); EITHealth 19600 AFFINE.Rodrigo Bort, M.; Martínez Climent, BA.; Hernández-Romero, I.; Liberos Mascarell, A.; Baykaner, T.; Rogers, AJ.; Alhusseini, M.... (2020). Noninvasive Assessment of Complexity of Atrial Fibrillation Correlation With Contact Mapping and Impact of Ablation. 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Targeting the Substrate in Ablation of Persistent Atrial Fibrillation: Recent Lessons and Future Directions

While isolation of the pulmonary veins is firmly established as effective treatment for the majority of paroxysmal atrial fibrillation (AF) patients, there is recognition that patients with persistent AF have substrate for perpetuation of arrhythmia existing outside of the pulmonary veins. Various computational approaches have been used to identify targets for effective ablation of persistent AF. This paper aims to discuss the clinical aspects of computational approaches that aim to identify critical sites for treatment. Various analyses of electrogram characteristics have been performed with this aim. Leading techniques for electrogram analysis are Complex Fractionated Atrial Electrograms (CFAE) and Dominant Frequency (DF). These techniques have been the subject of clinical trials of which the results are discussed. Evaluation of the activation patterns of atria in AF has been another avenue of research. Focal Impulse and Rotor Modulation (FIRM) mapping and forms of Body Surface Mapping aim to characterize multiple atrial wavelets, macro-reentry and focal sources which have been proposed as basic mechanisms perpetuating AF. Both invasive and non-invasive activation mapping techniques are reviewed. The presence of atrial fibrosis causes non-uniform anisotropic impulse propagation. Therefore, identification of fibrosis by imaging techniques is an avenue of potential research. The leading contender for imaging-based techniques is Cardiac Magnetic Resonance (CMR). As this technology advances, improvements in resolution and scar identification have positioned CMR as the mode of choice for analysis of atrial structure. AF has been demonstrated to be associated with obesity, inactivity and diseases of modern life. An opportunity exists for detailed computational analysis of the impact of risk factor modification on atrial substrate. This ranges from microstructural investigation through to examination at a population level via registries and public health interventions. Computational analysis of atrial substrate has moved from basic science toward clinical application. Future directions and potential limitations of such analyses are examined in this review

Challenges associated with interpreting mechanisms of AF

Determining optimal treatment strategies for complex arrhythmogenesis in AF is confounded by the lack of consensus regarding the mechanisms causing AF. Studies report different mechanisms for AF, ranging from hierarchical drivers to anarchical multiple activation wavelets. Differences in the assessment of AF mechanisms are likely due to AF being recorded across diverse models using different investigational tools, spatial scales and clinical populations. The authors review different AF mechanisms, including anatomical and functional re-entry, hierarchical drivers and anarchical multiple wavelets. They then describe different cardiac mapping techniques and analysis tools, including activation mapping, phase mapping and fibrosis identification. They explain and review different data challenges, including differences between recording devices in spatial and temporal resolutions, spatial coverage and recording surface, and report clinical outcomes using different data modalities. They suggest future research directions for investigating the mechanisms underlying human AF

Factors Affecting Catheter Contact in the Human Left Atrium, its Impact on the Electrogram and Radiofrequency Ablation.

PhDThe interaction between the mapping/ablation catheter and left atrial (LA) myocardium potentially affects the LA electrical and mechanical properties and impacts on ablation efficacy. Using catheters able to provide real-time contact force (CF) measurement, it has become possible to explore these relationships in vivo. In 60 persistent atrial fibrillation (AF) patients, ablation CF was higher in the right than left wide area circumferential (WACA) lines and where steerable transseptal sheaths were used. Differences were also apparent in the burden of WACA segment reconnection but did not just reflect differences in ablation CFs, suggesting factors other than CF contribute to ablation efficacy. Relationships between ablation force time integral (FTI), impedance drop and electrogram attenuation were assessed in 15 persistent AF patients. FTI significantly correlated with electrogram attenuation and impedance drop from ablation. The relationship was stronger for the former but in both cases plateaued at 500g.s, suggesting no ablation efficacy gains beyond this. Factors further affecting CF and ablation efficacy, the latter judged by impedance drop, were assessed in 30 patients. The variability of the CF waveform and catheter locational stability were both affected by factors including atrial rhythm and catheter delivery mode. Greater CF variability, catheter drift and perpendicular catheter contact were associated with reduced ablation efficacy. The relationship between CF and the electrogram was assessed in 30 patients. The size of the electrogram complexes was affected by CF increases but only where initial CF was <10g. This was also the case for electrogram fractionation measurements. Increasing CF was associated with an increasing incidence of atrial ~ 3 ~ ectopics during sinus rhythm. Spectral parameters (dominant frequency and organisation index) were unaffected by CF. Various factors affect the contact between the catheter and LA myocardium. In turn, catheter contact significantly affects the electrogram during LA mapping and the efficacy of clinical radiofrequency ablation

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