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

University of Oklahoma (OU)

Status: Completed

Conditions: Endothelial Dysfunction; Heart Failure With Reduced Ejection Fraction

Treatments: Device: TVS; Device: Sham TVS

Study type: Interventional

Funder types: Other

Identifiers

NCT03380156

8469

Details and patient eligibility

About

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.

Enrollment: 50 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients (18 years or older) with Heart failure with reduced ejection fraction (HFrEF), which is a history of symptomatic heart failure with left ventricular ejection fraction (LVEF) of < 40%.

Exclusion criteria

1. patients in overt congestive heart failure / recent acute myocardial infarction (< 3 months) or Unstable angina
2. Active malignancy
3. Perimenopausal women and post-menopausal women on hormone supplements.
4. unilateral or bilateral vagotomy
5. Patients with bilateral upper extremity amputation
6. pregnant patients
7. End-stage renal disease
8. End-stage liver disease
9. history of recurrent vasovagal syncope, Sick sinus syndrome, 2nd- or 3rd-degree atrioventricular (AV) block.
10. patients with clinically documented upper extremity arterial disease
11. patients with BMI>34

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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50 participants in 2 patient groups, including a placebo group

Interventional

Experimental group

Description:

Active TVS will be performed by use of a Tragus stimulator device with electrodes attached to the tragus of the ear. Stimulator will be applied continuously for 1 hour.

Treatment:

Device: TVS

Control

Placebo Comparator group

Description:

Sham TVS will be performed by use of a Tragus stimulator device with electrodes attached to the ear lobule. Stimulator will be applied continuously for 1 hour.

Treatment:

Device: Sham TVS