Auricular Vagal Neuromodulation Therapy (AVNT) Acutely Ameliorates Left Ventricular Strain in Humans

Abstract

Auricular Vagal Neuromodulation Therapy (AVNT) was utilised in patients with diastolic dysfunction, focusing on global longitudinal strain (GLS), a key parameter for evaluating heart function. Participants underwent one-hour sessions of either active or placebo Nurosym, followed by echocardiography. Results demonstrated that Nurosym significantly improved GLS by 21% compared to placebo (p = 0.001), with more pronounced benefits in patients with lower baseline GLS (p = 0.004). The improvement in cardiac mechanics was linked to enhanced parasympathetic tone and reduced sympathetic activity. These findings suggest that Nurosym could be a promising non-pharmacological treatment for heart failure with preserved ejection fraction (HFpEF), especially in patients with risk factors like hypertension, diabetes, and obesity.

Background and aims

The study assessed Nurosym’s AVNT on patients diagnosed with diastolic dysfunction via echocardiogram. Global longitudinal strain (GLS) is a critical parameter for evaluating heart function, particularly within the context of heart failure. GLS measures the deformation, or 'strain,' of the heart muscle during contraction, specifically assessing how the myocardial fibres' length changes throughout the cardiac cycle. This measurement is recognized as a more sensitive and earlier indicator of left ventricular dysfunction compared to traditional metrics, capable of detecting subtle myocardial function changes early on. Research has indicated that impaired GLS is linked to a worse prognosis in various cardiac conditions, including heart failure. Importantly, in scenarios such as heart failure following myocardial infarction or in cardiomyopathies, GLS proves invaluable for assessing the heart muscle's recovery or response to regenerative therapies.

Methods

The study employed a prospective, double-blind, placebo-controlled, randomised clinical trial design. Participants underwent two separate 1-hour sessions of either active or placebo Nurosym, administered at least one day and up to one week apart, with the order of sessions randomised. Echocardiography was performed 40 minutes after each stimulation session to assess left ventricular function.  Heart rate variability (HRV) was analysed using 5-minute ECG recordings taken before and after each stimulation session. Global longitudinal strain (GLS) and global circumferential strain were also assessed using a speckle-tracking algorithm. Statistical analysis was conducted using mixed linear models and multiple comparisons were made using Tukey’s method. The study aimed to detect a change in GLS with a power of 90% based on predefined assumptions about baseline GLS values in a similar patient population.

Results

Nurosym for one hour can acutely improve left ventricular longitudinal mechanics in patients with diastolic dysfunction and preserved LV ejection fraction. The observed improvement in global longitudinal strain (GLS) was more pronounced in patients with lower baseline GLS, suggesting that those with more severe longitudinal cardiac dysfunction, such as those with heart failure with preserved ejection fraction (HFpEF), derive greater benefits from this neuromodulation approach.

Findings have shown the improvement in GLS by 21% during Nurosym neuromodulation compared to placebo stimulation (p = 0.001). GLS is expressed as a negative percentage because it measures the percentage of shortening or contraction of the myocardial fibres from their relaxed state. A shift toward more negative values indicates stronger contraction and enhanced cardiac function. Further analysis showed that worse GLS during placebo stimulation was associated with more significant improvement during active Nurosym treatment (p = 0.004). This suggests that patients with more severe baseline left ventricular dysfunction experience greater benefits from Nurosym.

Conclusion

The study highlights that the favourable change in cardiac mechanics is associated with a significant improvement in sympathovagal balance, characterised by enhanced parasympathetic tone and reduced sympathetic activity. This autonomic modulation may contribute to the therapeutic effects of Nurosym, offering a potential non-pharmacological treatment avenue for HFpEF, a condition where current drug therapies have failed to significantly improve clinical outcomes. Furthermore, the results suggest that Nurosym could be particularly beneficial for patients with risk factors such as hypertension, diabetes, and obesity, which are associated with sympathetic hyperactivity and impaired autonomic reflexes leading to cardiac dysfunction.