Balancing the autonomic scale: the promise of transcutaneous vagus nerve stimulation in combating cardiovascular diseases

Figures

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  Figure 1. Anatomical target and central pathways of taVNS (transcutaneous auricular vagus nerve stimulation). The auricular branch of the vagus nerve (ABVN) innervates the external auditory canal and concha region, where it is accessible for non-invasive stimulation. Afferent fibers project to the nucleus tractus solitarius (NTS), which relays signals to the locus coeruleus (LC) and amygdala. Solid arrows indicate established anatomical connections. The inset shows typical electrode placement on the cymba concha (active) and tragus/earlobe (sham/control sites). This framework underpins the use of taVNS to modulate autonomic outflow and cardiovascular function.

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  Figure 2. Schematic overview of the proposed mechanisms by which tVNS exerts. Central pathways (NTS→RVLM inhibition, DMNV activation) reduce sympathetic outflow and enhance parasympathetic tone. Peripheral effects include reduced heart rate, increased HRV, improved baroreflex sensitivity, and activation of the cholinergic anti-inflammatory pathway (ACh→α7nAChR→NF-κB inhibition→reduced TNF-α, IL-6). Solid arrows indicate mechanisms supported by direct human evidence; dashed arrows indicate pathways derived predominantly from animal models and remain speculative in CVD.

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  Figure 3. Comparative analysis of tVNS and traditional neuromodulation techniques. The four panels compare invasiveness (tVNS: non-invasive; iVNS/RDN: invasive), stimulation target (ABVN versus cervical vagus versus renal nerves), clinical indications (tVNS: investigational for CVD; iVNS: approved for epilepsy/depression; RDN: approved for resistant hypertension), and safety profile (tVNS: favorable, mild transient effects; iVNS/RDN: procedure-related risks). The comparison highlights tVNS’s unique advantages—non-invasiveness and favorable safety—while acknowledging the need to establish cardiovascular efficacy.

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  Figure 4. Overview of clinical applications of tVNS in different CVD. For each condition, the figure shows proposed mechanisms, key clinical studies, and reported effects. An evidence-level bar indicates the strength of evidence: moderate for surrogate endpoints in heart failure (based on meta-analyses), low to very low for hard clinical outcomes across all conditions, and no demonstrated mortality or hospitalization benefit. Solid lines indicate mechanisms with direct human evidence in cardiovascular populations; dashed lines indicate pathways requiring further clinical confirmation. tVNS remains investigational and is not recommended by any major cardiovascular guideline for routine clinical use.