Effect of Transcutaneous Vagal Stimulation (TVS) on Endothelial Function and Arterial Stiffness in HFrEF

Heart failure (HF) is the leading cause of hospitalization in the US. Endothelial
dysfunction, characterized by the decreased vasodilatory capacity of the vascular
endothelium, is rampant in atherosclerotic diseases such as coronary artery disease and also
in HF. Endothelial dysfunction also correlates with HF severity, progression, and mortality.
It is postulated that endothelial dysfunction may in part be due to enhanced sympathetic
drive, diminished parasympathetic drive, chronic inflammatory state thereby leading to
reduced nitric oxide synthase activity in the vascular endothelium. Low-level vagus nerve
stimulation (LLVNS) is an invasive way to modulate autonomic tone. Recent experimental and
clinical data suggest that low-level transcutaneous vagal stimulation (TVS) (by stimulating
the auricular branch of the vagus nerve located at the tragus of the external ear) may
produce the same desired neuromodulator effect compared to LLVNS. The objective of this study
is to determine the impact of TVS on endothelial dysfunction and arterial stiffness. The
study population will include patients with chronic HFrEF. After performing baseline
flow-mediated dilation (FMD), laser speckle contrast imaging(LSCI) and pulse wave analysis
(PWA) testing, patients will be randomized to TVS or sham stimulation with a crossover design
at different time points. The patient randomized to TVS arm will undergo stimulation for 1
hour followed by immediate measurement of FMD,LSCI and PWA. There will be a washout period of
at least 24 hours with patient crossing over to the other arms thus serving as their
self-control.