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

ABSTRACT

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.

KEYWORDS:

• Vagus nerve stimulation
• low-level vagus nerve stimulation
• autonomic nervous system
• neuromodulation
• arrhythmia
• ischemia/reperfusion injury
• heart failure
• hypertension

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by a grant from National Key R&D Program of China (No. 2017YFC1307802), and grants from National Natural Science Foundation of China (No. 81530011, 81770364, 81570463, 81871486, 81700444 and 81600395). This paper was also funded by a fund of Key Laboratory of Myocardial Ischemia, Ministry of Education (KF201821).