Multifactorial Benefits of Chronic Vagus Nerve Stimulation on Autonomic Function and Cardiac Electrical Stability in Heart Failure Patients With Reduced Ejection Fraction

Abstract

Heart failure with reduced left ventricular ejection fraction is a progressive disease that claims > 352,000 lives annually in the United States alone. Despite the development of an extensive array of pharmacologic and device therapies, prognosis remains poor. Disruption in autonomic balance in the form of heightened sympathetic nerve activity and reduced vagal tone have been established as major causes of heart failure progression. Interest in chronic neuromodulation mediated by vagus nerve stimulation (VNS) has intensified in recent years. This review focuses on four main goals: (1) To review the preclinical evidence that supports the concept of a cardioprotective effect of VNS on autonomic function and cardiac electrical stability along with the underlying putative mechanisms. (2) To present the initial clinical experience with chronic VNS in patients with heart failure and highlight the controversial aspects of the findings. (3) To discuss the latest findings of the multifactorial effects of VNS on autonomic tone, baroreceptor sensitivity, and cardiac electrical stability and the state-of-the-art methods employed to monitor these relationships. (4) To discuss the implications of the current findings and the gaps in knowledge that require attention in future investigations.

A novel ex-vivo isolated rabbit heart preparation to explore the cardiac effects of cervical and cardiac vagus nerve stimulation

“…Overall, the viability of this ex-vivo model to study the acute cardiac effects of VNS was demonstrated.There is growing evidence showing that various pathological conditions are associated with and affected by autonomic imbalances that manifest as dominance of the sympathetic over the parasympathetic activity 1-4 . Therefore, vagus nerve stimulation (VNS) has been considered to be a promising therapeutic approach to treat diverse pathological conditions, such as epilepsy 5-8 , depression 9 , and cardiac diseases 10-14 by restoring the vagal tone to a physiological level.In cardiac medicine, VNS has proven to promote cardioprotective and anti-fibrillatory effects, thus providing a promising therapeutic approach for non-pharmacological treatment of various cardiac pathological conditions, such as ventricular arrhythmias 15 , atrial fibrillation 13 and heart failure 16,17 . However, the fact that VNS is mostly applied to the cervical level due to surgical ease of access and the possibility to target various organ-related fibers, it is often accompanied by difficultly controllable systemic off-target effects [18][19][20] .Although numerous studies have explored diverse effects of VNS on HR and hemodynamic function, invivo 11,[21][22][23][24] and in-situ 10,[25][26][27] , including anti-antiarrhythmic 15 and cardioprotective effects 28 , or alleviation of hypertension 29 , the outcomes are diverse, and the impact of VNS on the cardiac activity is still not fully understood.…”

“…In cardiac medicine, VNS has proven to promote cardioprotective and anti-fibrillatory effects, thus providing a promising therapeutic approach for non-pharmacological treatment of various cardiac pathological conditions, such as ventricular arrhythmias 15 , atrial fibrillation 13 and heart failure 16,17 . However, the fact that VNS is mostly applied to the cervical level due to surgical ease of access and the possibility to target various organ-related fibers, it is often accompanied by difficultly controllable systemic off-target effects [18][19][20] .…”

Chronic vagus nerve stimulation in patients with heart failure: challenge or failed translation?

“…Multiple mechanisms responsible for the protective effects of VNS on failing hearts have been observed ( 28 ). It has been accepted that VNS directly leads to improved parasympathetic tone and reflexes.…”

A survey on puncture models and path planning algorithms of bevel-tipped flexible needles

“…In recent years, advances in medical technology and brain science have turned previously unthinkable surgeries into reality, and more and more diseases that were once untreatable have found solutions in functional neurosurgery [ 12 ]. For example, deep brain stimulation (DBS) [ 13 , 14 ] can achieve good results in treating movement disorders; chronic neuromodulation with vagus nerve stimulation (VNS) [ 15 ] can be used to treat patients with heart failure; and spinal cord stimulation (SCS) [ 3 ] for paraplegic patients can significantly improve the quality of life of patients. These new technologies and methods have broadened the scope of functional neurosurgery and opened the door to healing for a wide range of patients.…”