Neuromodulation for Atrial Fibrillation Control

Abstract

Trigger and functional substrate are related to the tone of autonomic nervous system, and the role of the autonomic nerve is more significant in paroxysmal atrial fibrillation (AF) compared to non-paroxysmal AF. We have several options for neuromodulation to help to manage patients with AF. Neuromodulation targets can be divided into efferent and afferent pathways. On the efferent side, block would be an intuitive approach. However, permanent block is hard to achieve due to completeness of the procedure and reinnervation issues. Temporary block such as botulinum toxin injection into ganglionated plexi would be a possible option for post-cardiac surgery AF. Low-level subthreshold stimulation could also prevent AF, but the invasiveness of the procedure is the barrier for the general use. On the afferent side, block is also an option. Various renal denervation approaches are currently under investigation. Auditory vagus nerve stimulation is one of the representative low-level afferent stimulation methods. This technique is noninvasive and easy to apply, so it has the potential to be widely utilized if its efficacy is confirmed.

Keywords: Atrial fibrillation; Autonomic nerves; Denervation; Ganglionated plexus; Stimulation.

Figure 1. Autonomic innervation of the heart.

DMV = dorsal motor nucleus of the vagus; NA = nucleus ambiguus; NST = nucleus of the solitary tract.

Figure 2. Major human cardiac ganglionated plexi: locations and number of ganglia. Numbers indicate number of ganglia per heart based on Armour’s work. Blue and red color indicates atrial and ventricular GPs, respectively. Ganglionated plexus with large number of ganglia is expressed with large font size.

GP = ganglionated plexi; LA = left atrium; RA = right atrium.

Figure 3. Autonomic contribution to arrhythmia mechanisms.

DAD = delayed afterdepolarization; EAD = early afterdepolarization; WL = wavelength.

Figure 4. Targets of neuromodulation.

GP = ganglionated plexi.

Figure 5. Cutaneous innervation of the ear. The distribution of these cutaneous nerves exhibits varying degrees of overlap.