Chronic vagus nerve stimulation is associated with multi-year improvement in intrinsic heart rate recovery and left ventricular ejection fraction in ANTHEM-HF

Abstract

Purpose Disturbed autonomic function is implicated in high mortality rates in heart failure patients. High-intensity vagus nerve stimulation therapy was shown to improve intrinsic heart rate recovery and left ventricular ejection fraction over a period of 1 year. Whether these beneficial effects are sustained across multiple years and are related to improved baroreceptor response was unknown. Methods All patients (n = 21) enrolled in the ANTHEM-HF clinical trial (NCT01823887, registered 4/3/2013) with 24 h ambulatory electrocardiograms at all time points and 54 normal subjects (PhysioNet database) were included. Intrinsic heart rate recovery, based on ~ 2000 spontaneous daily activity-induced heart rate acceleration/deceleration events per patient, was analyzed at screening and after 12, 24, and 36 months of chronic vagus nerve stimulation therapy (10 or 5 Hz, 250 μs pulse width, 18% duty cycle, maximum tolerable current amplitude). Results In response to chronic high-intensity vagus nerve stimulation (≥ 2.0 mA), intrinsic heart rate recovery (all time points, p < 0.0001), heart rate turbulence slope, an indicator of baroreceptor reflex gain (all, p ≤ 0.02), and left ventricular ejection fraction (all, p ≤ 0.04) were improved over screening at 12, 24, and 36 months. Intrinsic heart rate recovery and heart rate turbulence slope were inversely correlated at both screening (r = 0.67, p < 0.002) and 36 months (r = 0.78, p < 0.005). Conclusion This non-randomized study provides evidence of an association between improvement in intrinsic heart rate recovery and left ventricular ejection fraction during high-intensity vagus nerve stimulation for a period of ≥ 3 years. Correlated favorable effects on heart rate turbulence slope implicate enhanced baroreceptor function in response to chronic, continuously cyclic vagus nerve stimulation as a physiologic mechanism.

Multifactorial Benefits of Chronic Vagus Nerve Stimulation on Autonomic Function and Cardiac Electrical Stability in Heart Failure Patients With Reduced Ejection Fraction

“…A substantial and lasting increase in heart rate turbulence (HRT) slope, an indicator of baroreceptor sensitivity that is associated with reduced cardiovascular mortality ( Bauer et al, 2008 ), was also noted as early as 6 months and was maintained throughout the 3 years of study ( Figure 5 , Nearing et al, 2021a ). Another index of baroreceptor sensitivity, namely, intrinsic heart rate recovery, was also improved in the 3-year analysis ( Nearing et al, 2021b ).…”

Noninvasive Vagus Nerve Stimulation in the Treatment of Methamphetamine Use Disorder: A Review Article

“…Numerous studies have shown that iVNS is a novel intervention to improve patients with heart failure. Similar to autonomic system dysfunction in MA users, heart failure is characterized by a decrease in vagal tone and an increase in sympathetic outflow (50)(51)(52)(53). Several mechanisms have been described for the clinical benefits of VNS in heart failure, including heart rate reduction, antiarrhythmic effects, and suppression of proinflammatory cytokines (54)(55)(56).…”

Exploratory Investigation of the Effects of Tactile Stimulation Using Air Pressure at the Auricular Vagus Nerve on Heart Rate Variability

“…Autonomic modulation via vagus nerve stimulation (VNS) has gained increasing interest as a potential therapeutic strategy in clinical practice. VNS is a neuromodulatory treatment that has shown clinical efficacy in various disorders, including epilepsy, depression, stroke, traumatic brain injury, Alzheimer's disease, rheumatoid arthritis, diabetes, and cardiovascular disorders [1][2][3]. Prior literature has reported several benefits of VNS, including anti-adrenergic effects at central and peripheral levels, anti-apoptotic effects, an increase in nitric oxide, enhanced neuroplasticity, anti-nociception, and antiinflammatory effects [4].…”