Location of Parasympathetic Innervation Regions From Electrograms to Guide Atrial Fibrillation Ablation Therapy: An in silico Modeling Study.

Chiara Celotto,Esther Pueyo,Pablo Laguna,Konstantinos A Mountris,Carlos Sánchez

doi:10.3389/fphys.2021.674197

Abstract

The autonomic nervous system (ANS) plays an essential role in the generation and maintenance of cardiac arrhythmias. The cardiac ANS can be divided into its extrinsic and intrinsic components, with the latter being organized in an epicardial neural network of interconnecting axons and clusters of autonomic ganglia called ganglionated plexi (GPs). GP ablation has been associated with a decreased risk of atrial fibrillation (AF) recurrence, but the accurate location of GPs is required for ablation to be effective. Although GP stimulation triggers both sympathetic and parasympathetic ANS branches, a predominance of parasympathetic activity has been shown. This study aims was to develop a method to locate atrial parasympathetic innervation sites based on measurements from a grid of electrograms (EGMs). Electrophysiological models representative of non-AF, paroxysmal AF (PxAF), and persistent AF (PsAF) tissues were developed. Parasympathetic effects were modeled by increasing the concentration of the neurotransmitter acetylcholine (ACh) in randomly distributed circles across the tissue. Different circle sizes of ACh and fibrosis geometries were considered, accounting for both uniform diffuse and non-uniform diffuse fibrosis. Computational simulations were performed, from which unipolar EGMs were computed in a 16 × 1 6 electrode mesh. Different distances of the electrodes to the tissue (0.5, 1, and 2 mm) and noise levels with signal-to-noise ratio (SNR) values of 0, 5, 10, 15, and 20 dB were tested. The amplitude of the atrial EGM repolarization wave was found to be representative of the presence or absence of ACh release sites, with larger positive amplitudes indicating that the electrode was placed over an ACh region. Statistical analysis was performed to identify the optimal thresholds for the identification of ACh sites. In all non-AF, PxAF, and PsAF tissues, the repolarization amplitude rendered successful identification. The algorithm performed better in the absence of fibrosis or when fibrosis was uniformly diffuse, with a mean accuracy of 0.94 in contrast with a mean accuracy of 0.89 for non-uniform diffuse fibrotic cases. The algorithm was robust against noise and worked for the tested ranges of electrode-to-tissue distance. In conclusion, the results from this study support the feasibility to locate atrial parasympathetic innervation sites from the amplitude of repolarization wave.

Highlights

The autonomic nervous system (ANS) controls all aspects of cardiac activity, including regulation of heart rate, atrio ventricular conduction, refractoriness, and contractility (Gatti et al, 1995; Dickerson et al, 1998; Gray et al, 2004; Hou et al, 2007)
In non-atrial fibrillation (AF) tissues, and for all the tested ACh geometries, the optimal value of the threshold Rth to distinguish between ACh and non-ACh regions, and computed as later described, was found to lie in a range between 23 and 41% of RA,max, the maximum RAi,j value in the grid is given by the following: RA,max = mi,aj x{RAi,j} = Rim,jm
In all cases, the algorithm was successful in identifying most of the simulated ACh release sites, both when there was no fibrosis in the tissue and when fibrosis was present in uniform diffuse or non-uniform diffuse forms at various degrees

Summary

Introduction

The autonomic nervous system (ANS) controls all aspects of cardiac activity, including regulation of heart rate, atrio ventricular conduction, refractoriness, and contractility (Gatti et al, 1995; Dickerson et al, 1998; Gray et al, 2004; Hou et al, 2007). The extrinsic components of the CANS comprise brain or spinal conglomerations of neuron bodies, connected to the heart through their axons, while the intrinsic cardiac nervous system consists of a neural network formed by nerve axons, interconnecting neurons and clusters of autonomic ganglia called ganglionated plexi (GP) (Pauza et al, 2000; Stavrakis and Po, 2017). The shape and structure of the neural network in the myocardium are not fully known, but some studies have documented that between 500 and 1,500 ganglia of different sizes are present in the atrial and ventricular myocardium (Pauza et al, 2000). Studies have shown that GPs are important mediators in the interaction of the intrinsic CANS with the extrinsic CANS (Hadaya and Ardell, 2020)

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