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Effects of Low-Level Tragus Stimulation on Endothelial Function in Heart Failure With Reduced Ejection Fraction

Published:December 30, 2020DOI:https://doi.org/10.1016/j.cardfail.2020.12.017

      Highlights

      • Improvement in endothelial function is an attractive target in heart failure with reduced ejection fraction and low-level tragus stimulation seems to hold promise.
      • Sustained improvement in endothelial dysfunction with daily low-level tragus stimulation may potentially translate into improved clinical outcomes in patients with heart failure with reduced ejection fraction.
      • Improvement in endothelial function could be driven by several pathways. Future studies of low-level tragus stimulation in heart failure with reduced ejection fraction need to elucidate effects on nitric oxide bioavailability, oxidative stress parameters, vascular adhesion molecules, and inflammation.

      Abstract

      Background

      Autonomic dysregulation in heart failure with reduced ejection fraction plays a major role in endothelial dysfunction. Low-level tragus stimulation (LLTS) is a novel, noninvasive method of autonomic modulation.

      Methods and Results

      We enrolled 50 patients with heart failure with reduced ejection fraction (left ventricular ejection fraction of ≤40%) in a randomized, double-blinded, crossover study. On day 1, patients underwent 60 minutes of LLTS with a transcutaneous stimulator (20 Hz, 200 μs pulse width) or sham (ear lobule) stimulation. Macrovascular function was assessed using flow-mediated dilatation in the brachial artery and cutaneous microcirculation with laser speckle contrast imaging in the hand and nail bed. On day 2, patients were crossed over to the other study arm and underwent sham or LLTS; vascular tests were repeated before and after stimulation. Compared with the sham, LLTS improved flow-mediated dilatation by increasing the percent change in the brachial artery diameter (from 5.0 to 7.5, LLTS on day 1, P = .02; and from 4.9 to 7.1, LLTS on day 2, P = .003), compared with no significant change in the sham group (from 4.6 to 4.7, P = .84 on day 1; and from 5.6 to 5.9 on day 2, P = .65). Cutaneous microcirculation in the hand showed no improvement and perfusion of the nail bed showed a trend toward improvement.

      Conclusions

      Our study demonstrated the beneficial effects of acute neuromodulation on macrovascular function. Larger studies to validate these findings and understand mechanistic links are warranted.

      Key Words

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