Abstract
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.
Highlights
While isolation of the pulmonary veins (PVI) is firmly established as effective treatment for the majority of paroxysmal atrial fibrillation (AF) patients,(Calkins et al, 2017) there is recognition that patients with persistent AF have substrate for perpetuation of arrhythmia existing outside of the pulmonary veins
Hwang et al looked at phase singularity, Dominant Frequency (DF), Shannon entropy and Complex Fractionated Atrial Electrograms (CFAE) cycle length with subsequent ablation in 2D and 3D simulation models and found that DF-based ablation was superior for AF termination (Hwang et al, 2016) no human AF studies have been able to replicate such data and it remains an area where computational based approaches to electrogram analysis may yet yield insights into effective ablation targets for human AF
First descriptions of rotational activations were from studies that undertook sequential mapping with multi-polar spiral catheter (Atienza et al, 2011; Ghoraani et al, 2013) The Focal Impulse and Rotor Modulation (FIRM) guided technique was the first panoramic mapping study that showed high success rates with ablating AF drivers (Narayan et al, 2012)
Summary
While isolation of the pulmonary veins (PVI) is firmly established as effective treatment for the majority of paroxysmal atrial fibrillation (AF) patients,(Calkins et al, 2017) there is recognition that patients with persistent AF have substrate for perpetuation of arrhythmia existing outside of the pulmonary veins. The DF can be displayed on a 3D map to guide the ablator to sites of high DF thought to be driving the AF (focal source or rotor) The aim of such analysis is to detect sites of high frequency that have been hypothesized to “drive” the fibrillation process (Jalife et al, 2002) These sites have been shown by retrospective analysis to identify effective ablation areas (Sanders et al, 2005) In an elegant animal study by Kalifa et al, areas of fractionation were demonstrated at the periphery of areas of high dominant frequency (Kalifa et al, 2006) The proximity of high DF and CFAE sites has been demonstrated in highdensity mapping of human AF (Stiles et al, 2008) Of note, most studies examining DF guided ablation have used off-line analysis, real-time analysis has been reported albeit without incremental outcome (Atienza et al, 2014) In a systematic review of DF-based approaches, Gadenz et al concluded that DF-based approaches are a useful marker of ablation outcome; direct intervention targeting DF sites appears premature with mixed results and too few studies (Gadenz et al, 2017) A more recent study using a novel frequency analysis algorithm and longer duration of AF electrograms in search for temporally stable AF drivers has shown some promise (Kimata et al, 2018) Ongoing work will help refine our armamentarium toward future targeting of high DF sites to improve outcomes (Sanders et al, 2018). Hwang et al looked at phase singularity, DF, Shannon entropy and CFAE cycle length with subsequent ablation in 2D and 3D simulation models and found that DF-based ablation was superior for AF termination (Hwang et al, 2016) no human AF studies have been able to replicate such data and it remains an area where computational based approaches to electrogram analysis may yet yield insights into effective ablation targets for human AF
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