Autonomic Neuromodulation Acutely Ameliorates Left Ventricular Strain in Humans

  • Nicole Tran
  • Zain Asad
  • Khaled Elkholey
  • Benjamin J. Scherlag
  • Sunny S. Po
  • Stavros StavrakisEmail author
Original Article


Low-level transcutaneous vagus nerve stimulation at the tragus (LLTS) is anti-adrenergic. We aimed to evaluate the acute effects of LLTS on left ventricular (LV) function and autonomic tone. Patients with diastolic dysfunction and preserved LV ejection fraction were enrolled in a prospective, randomized, double-blind, 2 × 2 cross-over study. Patients received two separate, 1-h sessions, at least 1 day apart, of active LLTS (20 Hz, 1 mA below the discomfort threshold) and sham stimulation. Echocardiography was performed after LLTS or sham stimulation to assess cardiac function. A 5-min ECG was performed to assess heart rate variability (HRV). Twenty-four patients were enrolled. LV global longitudinal strain improved by 1.8 ± 0.9% during active LLTS compared to sham stimulation (p = 0.001). Relative to baseline, HRV frequency domain components (low frequency, high frequency, and their ratio) were favorably altered after LLTS compared to sham stimulation (all p < 0.05). We concluded that LLTS acutely ameliorates cardiac mechanics by modulating the autonomic tone. Trial registration: NCT02983448


Neuromodulation Transcutaneous vagus nerve stimulation Heart rate variability Diastolic dysfunction Left ventricular strain imaging 



Heart failure with preserved ejection fraction


Left ventricle


Heart failure with reduced ejection fraction


Vagus nerve stimulation


Low-level transcutaneous vagus nerve stimulation


Transcutaneous electrical nerve stimulation


Global longitudinal strain


Heart rate variability


High frequency


Low frequency


Sources of Funding

This study was funded by an Oklahoma Shared Clinical and Translational Resources pilot grant (NIGMS IDeA-CTR U54-GM104938) to Stavros Stavrakis.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interests.

Human Subjects/Informed Consent Statement

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.

Animal Studies

No animal studies were carried out by the authors for this article.


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Authors and Affiliations

  1. 1.University of Oklahoma Health Sciences CenterOklahoma CityUSA

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