The role of low-level vagus nerve stimulation in cardiac therapy

Introduction: Cardiovascular diseases are accompanied by autonomic nervous system (ANS) imbalance which is characterized by decreased vagal tone. Preclinical and clinical studies have revealed that increasing vagal activity via vagus nerve stimulation (VNS) could protect the heart. Based on these studies, VNS has emerged as a potential non-pharmaceutical treatment strategy. Although it's still difficult to find the optimal stimulus parameters, however, in arrhythmia model, it is reported that low-level VNS (LL-VNS) exacts paradoxical effects from the high-level VNS. Thus, the concept of LL-VNS is introduced. Areas covered: Animal and human studies have discussed the safety and efficacy of VNS and LL-VNS, and this review will discuss the research data in cardiovascular diseases, including atrial arrhythmia, ventricular arrhythmia, ischemia/reperfusion injury, heart failure, and hypertension. Expert opinion: In this regard, various clinical studies have been performed to verify the safety and efficacy of VNS. It is shown that VNS is well-tolerated and safe, but the results of its efficacy are conflicting, which may well block the translational process of VNS. The appearance of LL-VNS brings new idea and inspiration, suggesting an important role of subthreshold stimulation. A better understanding of the LL-VNS will contribute to translational research of VNS.