Reduction of Inflammation in Acute Decompensated Heart Failure and Heart Failure with Preserved Ejection Fraction Through Auricular Vagal Neuromodulation Therapy (AVNT)

Abstract

Studies investigated effects of Nurosym Auricular Vagus Nerve Therapy on inflammation in heart failure patients. Using a double-blind, placebo-controlled, randomised clinical trial design, patients received either active or placebo Nurosym treatments. Results showed significant reductions in pro-inflammatory cytokines, including TNF-α and IL-8 in Study I, and IL-6 in Study II, indicating that Nurosym attenuates systemic inflammation and improves organ function and quality of life without side effects. The findings suggest that Nurosym modulates the inflammatory reflex via the vagus nerve, with potential broader implications for various inflammatory and age-related diseases.

Background and aims

The vagus nerve plays an important role in regulating metabolic homeostasis, and its efferent cholinergic signalling controls immune function and inflammatory responses through the inflammatory reflex. Recent research on Nurosym has demonstrated activation of vagal efferent fibres that release acetylcholine (ACh) in target organs, where it interacts with α7 nicotinic acetylcholine receptors (α7nAChR) expressed on immune cells. Current research on Nurosym examines whether activation of the vagus nerve-mediated inflammatory reflex leads to inhibition of the production of pro-inflammatory cytokines, thereby alleviating systemic inflammation and preventing the progression of chronic diseases. The study aimed to assess the effectiveness of Nurosym neuromodulation in patients with heart failure with preserved ejection fraction (Study I) or in hospitalised patients with acute decompensated heart failure (ADHF) and a left ventricular ejection fraction (LVEF) below 40% (Study II).

Methods

The study employed a prospective, double-blind, placebo-controlled, randomised clinical trial design. Patients were randomly assigned in a 1:1 ratio to receive either active or placebo Nurosym.The treatment was administered for 1 hour daily for 3 months (Study I) or lasted 8 hours daily throughout hospitalisation period (Study II). The outcomes measured reductions in inflammatory activity levels during 3 months home therapy (Study I) or hospital admission (Study II), performing cytokine assays blinded to treatment allocation. Statistical analysis involved comparing baseline data between the active Nurosym neuromodulation group and the placebo control group.

Results

Nurosym favourably altered other cytokines (TNF-α, Il-8 in Study I) (IL-6, CRP in Study II). The reduction in the level of pro-inflammatory cytokines after Nurosym treatment was observed and indicates suppression of the inflammatory cascade, thereby alleviating inflammation and the associated harmful effects on tissues and organs. Permanent reduction of inflammation in the long term facilitated tissue reconstruction and improved organ function. Patients in the active stimulation arm also reported better quality of life. Notably, no device-related side effects were observed.

The significant improvements were observed in tumour necrosis factor-α (23%, p = 0.007) and Interleukin-8 (IL-8) (61%, p = 0.001) in the active stimulation group compared to the placebo group. Moreover, the decrease in tumour necrosis factor-α levels correlated with the improvement in global longitudinal strain (r=-0.73, p = 0.001) (Study I).

The results show that Nurosym significantly attenuated systemic inflammation. In particular, vagus nerve stimulation led to a significant reduction in interleukin-6 (IL-6) levels compared to the control group (Nurosym: -78.48% vs. control: -8.63%; p = 0.012) (Study II).

Conclusion

Inflammation is a primary pathophysiological factor contributing to the progression of heart failure. The use of Nurosym during hospital admission for patients with acute decompensated heart failure was associated with a reduction in systemic inflammatory activity. The study confirmed that Nurosym effectively modulates the inflammatory reflex through the vagus nerve, thereby regulating the immune response. This mechanism is mediated by the parasympathetic vagal system, an integral component in the inflammatory reflex. The inflammatory reflex is triggered during inflammation, pathogen invasion, and tissue damage. Therefore, Nurosym may have broader implications for addressing health risks, including reducing the risk of autoimmune, metabolic, gastrointestinal diseases, and other age-related complications.