Reduction Oxidative Stress in Acute Heart Failure Through Auricular Vagal Neuromodulation Therapy (AVNT)

Abstract

Patients with acute decompensated heart failure (ADHF) and left ventricular ejection fraction (LVEF) below 40% underwent Nurosym Auricular Vagus Nerve Therapy (AVNT). The intervention or placebo stimulation were administered for 8 hours. Results showed that Nurosym significantly reduced oxidative stress by lowering reactive oxygen species (ROS) levels and inflammatory markers such as interleukin-6 (IL-6). These findings suggest that Nurosym neuromodulation can improve heart failure outcomes by reducing oxidative stress and systemic inflammation, potentially preventing the progression of heart failure and other related cardiovascular and oxidative stress-related conditions.

Background and aims

The study aimed to assess the effectiveness of Nurosym neuromodulation in hospitalised patients with acute decompensated heart failure (ADHF) and left ventricular ejection fraction (LVEF) below 40%. Oxidative stress is associated with various diseases and complications, especially heart failure. The vagus nerve exerts regulatory control over synaptic activity related to heart rate, inflammation, and oxidative stress. By modulating these pathways, the vagus nerve neuromodulation may be successful in improving heart failure outcomes and reducing the risk of other oxidative stress-related conditions, such as cardiovascular disease, neurodegenerative disorders, and metabolic disorders.

Methods

The study employed a prospective, double-blind, placebo-controlled, randomised clinical trial design. Patients with ADHF were randomly assigned to either an active group, where Nurosym was applied to the tragus region, or a placebo group, where Nurosym was applied to the earlobe region without vagus nerve innervation. The treatment was administered for 8 hours daily throughout the hospitalisation period. The primary outcomes measured reductions in inflammatory activity and reactive oxygen species (ROS) levels during hospital admission. This was evaluated by analysing serum levels of inflammatory markers and assessing oxidative stress using a human cell-based bioassay. Statistical analysis involved comparing baseline data between the active Nurosym neuromodulation group and the placebo control group.

Results

Neuromodulation with Nurosym resulted in favourable modulation of oxidative stress in human coronary endothelial cells. By reducing reactive oxygen species (ROS) production, Nurosym enhanced antioxidant defences. This decrease in ROS levels mitigated oxidative stress and its detrimental effects on cellular functions, thereby indicating a less oxidative cellular environment. Additionally, the elevated concentrations of inflammatory markers in endothelial cells were significantly reduced.

The results show that Nurosym significantly attenuated oxidative stress in the study population. In particular, vagus nerve stimulation led to a significant decrease in reactive oxygen species (ROS) (Nurosym: 1363 to 978.3; p = 0.004), while placebo stimulation did not cause a significant change (p = 0.10). Additionally, the 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).

Conclusion

An aberrant in redox levels, marked by increased pro-oxidant reactive oxygen species (ROS) production and diminished activity of antioxidant mechanisms, significantly contributes to the pathophysiology of heart failure. Endothelial-level oxidative stress, decreased with the use of Nurosym neuromodulation in acute decompensated heart failure patients, potentially directly associated with the alleviation of systemic inflammation. The established link between inflammation, oxidative stress, and adverse cardiac remodelling highlights the Nurosym neuromodulation not only to attenuate the progression of heart failure, but also to inhibit the development and exacerbation of other cardiovascular diseases such as atherosclerosis and hypertension. Better management of ROS levels has broader health implications, including reducing the risk of cancer, metabolic diseases and other age-related complications.