Autonomic Neuromodulation Acutely Ameliorates Left Ventricular Strain in Humans

Abstract

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.

Keywords: Diastolic dysfunction; Heart rate variability; Left ventricular strain imaging; Neuromodulation; Transcutaneous vagus nerve stimulation.

Figures

Figure 1.

Schematic representation of the study design and timeline of events (A, B). Active low-level transcutaneous vagus nerve stimulation (LLTS) was accomplished by attaching an electrode clip at the tragus of the right ear (C).

Figure 2.

Comparison of the effect of LLTS on global longitudinal strain (GLS) during active vs. sham stimulation. A. Active LLTS resulted in a significant improvement in GLS (p=0.001) compared to sham stimulation. B. Representative example of left ventricular strain analysis (apical 4-chamber view) showing the effect of LLTS (lower panel) compared to sham (upper panel) on the same patient. There was a decrease in GLS from −19.3% to −23.1%, which represents a favorable change.

Figure 3.

Effect of active vs sham LLTS on measures of heart rate variability. A. Low frequency (LF). B. High frequency (HF). C. Ratio of LF to HF (LF/HF ratio). All 3 parameters were favorably altered after 1 hour of active LLTS compared to sham stimulation.

Figure 4.

Association of the difference in global longitudinal strain between active and sham stimulation (ΔGLS) with GLS during sham stimulation (tertiles) (A) and the difference in low frequency to high frequency ratio between active and sham stimulation ((ΔLF/HF; tertiles) (B).