Effects of Auricular Vagal Neuromodulation Therapy (AVNT) on Macrocirculation in Endothelial Cells in Heart Failure with Reduced Ejection Fraction

Pubblicato in: The Journal of Cardiac Failure


The study aimed to evaluate the effectiveness of Nurosym in improving vascular function in patients with heart failure with reduced ejection fraction (HFrEF) through a single-blind, placebo-controlled, randomised clinical trial. Participants received either active tragus stimulation or placebo in a crossover design, with vascular function assessed using flow-mediated dilation (FMD). Results showed that Nurosym significantly improved FMD, indicating enhanced endothelial function and vascular health (p = 0.02 on day 1; p = 0.003 on day 2) compared to placebo (p = 0.84 on day 1; p = 0.65 on day 2). The findings suggest that Nurosym, by stimulating the vagus nerve and enhancing parasympathetic activity, could be an effective non-pharmacological therapy for improving macrovascular function in heart failure and potentially other cardiovascular conditions characterised by endothelial dysfunction. Further research is needed to explore these effects across diverse patient populations.

Background and aims

The aim of the study was to determine the effectiveness of Nurosym compared with a placebo intervention in improving vascular function. The study included patients diagnosed with heart failure with reduced ejection fraction (HFrEF). The parasympathetic nervous system plays a crucial role in cardiovascular health by regulating heart rate and vascular tone. Endothelial function is a vital aspect of macrocirculatory physiology. Research has demonstrated that activation of parasympathetic fibres can increase the release of nitric oxide and other endothelium-dependent relaxant factors, thereby enhancing arterial dilation. This contributes to reduced arterial stiffness, improved blood pressure control, and a decreased risk of atherosclerosis and cardiovascular events. Nurosym's ability to stimulate the vagus nerve, which interacts with the autonomic nervous system, may help positively regulate cardiovascular functions, including vasodilation and blood flow.


The study employed a prospective, single-blind, placebo-controlled, randomised clinical trial design.  Participants were randomly assigned in a 1:1 ratio to receive active tragus stimulation or a placebo equivalent. The study was a crossover design, with participants switching groups on day two to ensure everyone received both treatments. Macrovascular function was assessed using flow-mediated dilation (FMD). Stimulation was adjusted to remain below pain thresholds and lasted for 60 minutes, after which further vascular assessment was performed. Statistical analysis of the data included paired t tests or Wilcoxon signed rank tests based on the distribution of the data, assessing changes in vascular function before and after the intervention. Results are presented in box plots and assessed for statistical significance.


The increase in blood flow and shear stress by Nurosym stimulates the endothelium to release vasodilators such as nitric oxide. An increase in FMD indicates improved endothelial responsiveness and better health, which is crucial for vascular function and overall cardiovascular risk assessment.

Nurosym improved flow-mediated dilation (FMD) by increasing the percentage change in brachial artery diameter by 50%, suggesting a significant positive effect on macrovascular endothelial function (p = 0.02 on day 1; p = 0.003 on day 2) compared to placebo stimulation (p = 0.84 on day 1; p = 0.65 on day 2).


Nurosym, aimed at improving macrovascular function, may serve as an adjunctive or alternative therapy in the treatment of conditions like heart failure, where endothelial dysfunction is a prevalent and challenging issue. Although these results are promising, further research is necessary to fully understand the mechanisms by which Nurosym affects the cardiovascular system, especially across different patient populations and a variety of cardiovascular conditions. Nurosym may also show synergistic benefits in improving macrovascular function not only in patients with heart failure but also in those with hypertension, coronary artery disease, or metabolic syndromes, all characterised by endothelial dysfunction. This could pave new ways for non-pharmacological interventions in the treatment of cardiovascular diseases.

Parole chiave

Vagus Nerve Stimulation; Flow-Mediated Dilation (FMD); Endothelial Function; Cardiovascular Diseases; Macrovascular Health

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