In patients with heart failure with preserved ejection fraction (HFpEF), the use of neuromodulation with low-level transcutaneous vagus nerve stimulation over a 3-month period was associated with a significant improvement in global longitudinal strain (GLS), inflammatory cytokines, and quality of life (QOL). Results of the randomized clinical trial were published in the Journal of the American Heart Association.
For the study, researchers conducted a sham-controlled, double-blind, randomized clinical trial (ClinicalTrials.gov Identifier: NCT03327649) to evaluate the effect of chronic low-level transcutaneous vagus nerve stimulation on cardiac function, exercise capacity, and inflammation in patients with HFpEF. All patients in the study were randomly assigned 1:1 to active or sham low-level transcutaneous vagus nerve stimulation, stratified according to sex. The coprimary study outcomes at 3 months were the ratio of early mitral inflow Doppler velocity to early diastolic mitral annulus velocity and the ratio of early mitral inflow Doppler velocity to the GLS. Secondary study outcomes included other echocardiographic parameters, 6-minute walk distance, QOL, brain natriuretic peptide levels, and serum cytokines.
Between January 2018 and September 2020, a total of 132 patients were screened for eligibility, with 52 ultimately enrolled in the study. Among the 52 individuals, 26 were randomly assigned to the low-level transcutaneous vagus nerve stimulation group and 26 to the sham group. Two patients from each group withdrew from the study, thus leaving a total of 48 participants with complete data included in the final analysis. The mean patient age was 70.4±9.2 years and 70% of the participants were women, the majority of whom had history of diabetes, hypertension, and obesity.
Adherence to the protocol of daily stimulation (ie, ≤4 sessions missed on average per month) was 92% at 3 months in both of the arms. The average stimulation amplitude was 22.9±13.4 mA and 23.0±15.2 mA in the active treatment group and sham treatment group, respectively.
Results of the study showed that although the early mitral inflow Doppler velocity to the early diastolic mitral annulus velocity ratio did not differ between the 2 arms, both GLS and tumor necrosis factor-α (TNF-α) levels at 3 months improved significantly in the low-level transcutaneous vagus nerve stimulation group compared with the sham group (-18.6%±2.5% vs -16.0%±2.4%; P=.002 and 8.9±2.8 pg/mL vs 11.3±2.9 pg/mL; P=.007, respectively).
The reduction in TNF-α levels was statistically significantly associated with improvement in GLS (P=.001). Low-level transcutaneous vagus nerve stimulation treatment improved QOL over 3 months, with the improvement significantly greater than that with sham treatment, with no significant adverse events reported.
“Our results support the emerging paradigm of noninvasive neuromodulation to treat selected patients with HFpEF and provide the basis for further randomized trials,” the researchers noted.
Disclosure: None of the study authors has declared affiliations with biotech, pharmaceutical, and/or device companies.
Stavrakis S, Elkholey K, Morris L, Niewiadomska M, Asad ZUA, Humphrey MB. Neuromodulation of inflammation to treat heart failure with preserved ejection fraction: a pilot randomized clinical trial. J Am Heart Assoc. Published online January 13, 2022. doi:10.1161/JAHA.121.023582