Non-invasive Neuromodulation of Vagus Activity Improves Endothelial Function in Patients with Heart Failure with Reduced Ejection Fraction: A Randomized Study

Abstract

Introduction Heart Failure with reduced ejection fraction (HFrEF) is a major cause of morbidity and mortality. Endothelial dysfunction is common in HFrEF. We propose a novel non-invasive stimulation of vagus nerve via direct low-level tragus stimulation (LLTS) as a potential to improve endothelial function in HFrEF. Effects of LLTS mimic direct vagal stimulation, which is proven to reduce sympathetic drive and nitric oxide synthesis. We conducted a first in human pilot clinical study to investigate the effects of LLTS on endothelial function. Methods We enrolled 20 patients with HFrEF in a randomized, double-blinded crossover study. The cohort characteristics were: 75%-male, 65%-Caucasians, Ischemic etiology-80%, HTN-65%, Diabetes-20%, ICD- 60%. All patients had LVEF Results Experimental LLTS for 60 minutes resulted in the improved microcirculation/endothelial function when measured using LSCI in nail beds Figure 1C, 1.78±0.17 vs. 2.47±0.27, p Conclusion Our first human pilot study demonstrated the beneficial effects of neuromodulation/LLTS on microcirculation/endothelial function in patients with HFrEF. Larger studies are underway to further validate these findings.