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Recent insights into the role of the autonomic nervous system in the creation of substrate for atrial fibrillation: implications for therapies targeting the atrial autonomic nervous system.

In this review, we discuss recent developments in our understanding of the role of the autonomic nervous system in creating atrial fibrillation (AF) substrate and on how these findings relate to rapidly evolving therapeutic strategies (eg, ablation, surgery) to disrupt autonomic signaling in AF. AF is the most common sustained arrhythmia disturbance and is associated with significant morbidity and mortality. The morbidity and mortality associated with AF are especially increased in the setting of congestive heart failure (HF), with up to half of all patients with HF having concomitant AF.1

Several mechanisms contribute to the electrophysiological and structural substrate of AF, including fibrosis, stretch, oxidative stress, and altered Ca2+-handling characteristics.2 In addition, neurohumoral factors have been invoked for their possible contribution to the creation of AF substrate. An important neurohumoral factor that has been studied fairly extensively for its involvement in AF is the autonomic nervous system.3 Both the sympathetic and the parasympathetic nervous systems have been shown to play a role in the genesis of AF.4,5

During the past few years, the pulmonary veins (PVs) and the posterior left atrium (PLA) have been shown to play a significant role in the genesis of AF. These regions have been shown to possess unique structural, molecular, and electrophysiologi­cal characteristics, all of which appear to contribute to AF substrate. The autonomic characteristics of this region of the atrium have also been explored.6–8 Since the development of new ablative and surgical techniques during the past few years to treat AF, several investigators have also attempted to target the neural innervation of the atria and PVs at the time of ablation or surgery. These attempts include generalized denervation of the atria, as well as more targeted atrial denervation by using atrial electrograms—specifically, complex …