Effects of Low-Level Tragus Stimulation on Endothelial Function in Heart Failure With Reduced Ejection Fraction
Section snippets
Patient Characteristics and Study Protocol
In this pilot randomized prospective study (NCT03380156), we enrolled 50 patients (>18 years of age) with HFrEF (with a left ventricular ejection fraction of ≤40%) on guideline-directed medical therapies. Patients with acute congestive heart failure/recent acute myocardial infarction (<4 weeks) or unstable angina, active malignancy, women on estrogen hormone supplements, unilateral or bilateral vagotomy, bilateral upper extremity amputation, pregnancy, end-stage renal disease, recurrent
Results
Fifty patients were enrolled in this study and 45 patients were able to complete both days of the study (NCT03380156). No adverse effects were reported, except for mild tingling of the external ear in 3 patients. The frequency and pulse width of stimulation was set at 20 Hz and 200 µs. The stimulation strength for individual patients (4–65 mA) was set at 3–5 mA below the level that caused discomfort. Mean age was 58 ± 8 years. Demographic and clinical characteristics are outlined in Table 1.
Discussion
To our knowledge, this is the first-in-human study to demonstrate the beneficial effects of acute noninvasive neuromodulation via LLTS on macrovascular endothelial function in patients with HFrEF. We showed that 1 hour of LLTS improves FMD based on brachial artery reactivity testing. Blood perfusion over the nail beds, but not cutaneous perfusion, as assessed by LSCI, showed a trend toward improvement in microvascular endothelial function with 1 hour of LLTS.
Despite use of evidence-based
Limitations
The chronic effects of neuromodulation on EnD are currently unknown, but are being investigated in a randomized clinical trial at our center. In addition, there is a great deal of interest in determining the impact of LLTS on clinical measures such as symptoms, quality of life, exercise capacity, cognition, and biomarkers such as NT-Pro-BNP in patients with HFrEF. Improvement in EnD may potentially lead to improvement in such outcomes in HFrEF. Our sample size also does not permit a secondary
Conclusions
Our study using LLTS in patients with HFrEF demonstrated an improvement in macrovascular endothelial function and showed a trend toward improvement in the microcirculatory function in the nailbed. This holds great promise in the future trials of noninvasive neuromodulation to improve not only endothelial function but to also investigate effects of LLTS on HFrEF end points such as symptoms, exercise capacity, biomarkers, quality of life, and hospitalizations.
Declaration of Competing Interest
The authors declare no conflicts of interest.
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Supported by the Heart Rhythm Institute, Oklahoma Center for the Advancement of Science and Technology, Presbyterian Health Foundation, Oklahoma Shared Clinical and Translational Resources (OSCTR) program funded by the National Institute of General Medical Sciences (GM104938), & Cellular and Molecular GeroScience CoBRE (P20GM125528). This research was also supported by the Oklahoma Shared Clinical and Translational Resources (U54GM104938) with an Institutional Development Award (IDeA) from NIGMS. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.