Autonomic dysregulation and atrial arrhythmias

Abstract

The autonomic nervous system (ANS) and its dysregulation are recognized as important mechanisms underlying atrial arrhythmias, such as atrial fibrillation (AF). In this review, we describe the anatomy of the cardiac nervous system, sympathetic and parasympathetic effects on atrial electrophysiology, and how dysregulation of those may predispose to AF initiation and promote its maintenance. We then discuss how the ANS itself undergoes functional and structural remodeling in the setting of atrial arrhythmias, and what are the current neuromodulation approaches for AF prevention and treatment. These strategies include destruction of cardiac ANS structures or modification of autonomic signaling using nerve stimulation, pharmacological or gene therapy. Autonomic mechanisms of AF have been a focus of basic and translational research for many years, and now with the development of new diagnostic tools and therapeutic methods, ANS-targeted approaches have a potential to become an important part of AF treatment.

Keywords: atrial arrhythmias; autonomic nervous system; electrophysiology.

Figure 1.

Cardiac ANS and neuromodulation approaches. Cardiac ANS is composed of sympathetic (green, predominant effect – increase in Ca²⁺ cycling) and parasympathetic (blue, predominant effect – I_KAch-induced APD shortening) branches. Approaches to neuromodulation can be conceptually divided into three groups – nerve stimulation (spinal cord, auricular branch of the vagus nerve or the nerve itself; depicted in green color), destruction of anatomical structures important for heart innervation (GP ablation, VOM ethanol infusion, renal denervation; depicted in red), blockade of autonomic signaling (GP botulotoxin injection, stellate ganglion block, pharmacological agents, gene therapy; depicted in blue). Abbreviations: Ach – acetylcholine; ANS – autonomic nervous system; APD – action potential duration; cAMP – cyclic adenosine monophosphate; GP – ganglionated plexi; VOM – vein of Marshall.