SUMMARYThe cardiac autonomic nervous system has been known to play an important role in the development and progression of cardiovascular diseases. Autonomic modulation by electrical stimulation of the parasympathetic nervous system, which increases the parasympathetic activity and suppresses the sympathetic activity, is emerging as a therapeutic strategy for the treatment of cardiovascular diseases. Here, we review the recent literature on autonomic modulation by electrical stimulation of the parasympathetic nervous system, including vagus nerve stimulation, transcutaneous auricular vagal stimulation, spinal cord stimulation, and ganglionated plexi stimulation, in the treatment of heart failure, atrial fibrillation, and ventricular arrhythmias.The cardiac autonomic nervous system, consisting of the sympathetic and the parasympathetic components, has been shown to play an important role in many cardiovascular diseases, such as heart failure, hypertension, atrial fibrillation, and ventricular arrhythmias [1][2][3][4]. An increased sympathetic nerve activity and a reduction of vagal cardiac tone are shown to be pathogenic in most of these conditions. In light of the autonomic imbalance involved in the development and progression of cardiovascular diseases, therapeutic interventions are focused on the inhibition of the sympathetic activation such as the use of b-receptor blockers, cardiac sympathetic denervation, and renal sympathetic denervation, and the increase of the parasympathetic activity such as vagus nerve stimulation. During the last decades, dysregulation of the autonomic nervous system in cardiovascular diseases has received considerable attention and interventions aiming at autonomic rebalance are emerging as new therapeutic options for the management of cardiovascular diseases. Autonomic modulation by electrical stimulation of the autonomic nervous system has been used clinically in patients with intractable angina pectoris [5][6][7], epilepsy [8], and depression [9,10]. Here, we review the experimental studies and clinical trials that are focused on autonomic modulation by electrical stimulation of the parasympathetic nervous system (ES-PNS), including vagus nerve stimulation (VNS), transcutaneous auricular vagal stimulation (tragus stimulation, TS), spinal cord stimulation (SCS), and ganglionated plexi stimulation (GPS), in the treatment of heart failure (HF), atrial fibrillation (AF), and ventricular arrhythmias (VAs).
ES-PNS and HFSympathetic activation and parasympathetic withdrawal are the characteristics of autonomic imbalance in HF [2,11,12] [19], the ANTHEM-HF Trial, in which either left or right VNS was performed using an open-loop stimulation system. However, another randomized controlled trial, the NECTAR-HF trial [20], in which 96 symptomatic HF patients were randomized in a 2:1 ratio to receive VNS or control for a 6-month period, showed that VNS failed to significantly improve the primary and secondary endpoint measures of cardiac remodeling and functional capacity, even though quality-...