Key takeaways:

• Off-label baroreflex activation therapy use was common among well-treated patients with HF.
• Functional capacity and LVEF improved, regardless of on- or off-label use.
• Survival exceeded a model’s predictions.

PHOENIX — Baroreflex activation therapy is commonly used off-label in a registry of real-world patients with heart failure who were well treated with guideline-directed medical therapy, a speaker reported.

Baroreflex activation therapy (Barostim, CVRx) was associated with stable hemodynamics, improved NYHA functional class and left ventricular ejection fraction and promising survival rates out to 3 years in both the overall cohort and in a subgroup who had baseline characteristics consistent with the current FDA indication, according to data from the REBALANCE study presented at the Heart Failure Society of America Annual Scientific Meeting.

Data were derived from Yaranov D, et al. Plenary session 1. Presented at: Heart Failure Society of America Annual Scientific Meeting; Oct. 9-12, 2026; Phoenix.

“Baroreflex activation therapy on a Barostim electrically stimulates carotid baroreceptors with intent to rebalance the autonomic nervous system, decrease sympathetic and increase parasympathetic nervous system and improve heart failure symptoms with a safe extravascular implant with a 97% major adverse neurological or cardiovascular event-free rate,” Dmitry Yaranov, MD, program director of advanced heart failure, heart transplant and mechanical circulatory support at Baptist Memorial Health Care in Memphis, Tennessee, said during a presentation. “Current U.S. indications are for patients with heart failure with reduced ejection fraction 35% or less on guideline-directed medical therapy with persistent symptoms of NYHA class III or class II with previous evidence of class III symptoms and [N-terminal pro-B-type natriuretic peptide] less than 1,600 pg/mL.”

REBALANCE was a large multicenter postmarket registry designed to provide real-world data on the safety and effectiveness of baroreflex activation therapy in patients from 45 U.S. centers, according to the presentation.

The registry included 435 patients (mean age, 68 years; 30% women; 64% white). Among the cohort, 55% had baseline characteristics consistent with the current FDA indication for baroreflex activation therapy (the “on-label” group) and the remaining 45% were either prescribed baroreflex activation therapy outside the FDA indication or had missing baseline NT-proBNP, NYHA or LVEF data (the “off-label” group), according to the study methods.

Patients were enrolled after baroreflex activation therapy implant and prospectively followed up every 6 months for a total of 12 months. Baseline use of HF medications was high and baseline characteristics between the on-label group and the overall cohort were similar.

BP and LVEF data

Mean office systolic BP decreased slightly by 12 months follow-up but with no significant change from baseline (P = .221), while small but significant reductions in mean office diastolic BP were observed (1.5 mm Hg; P = .034).

The researchers reported hemodynamic differences when patients were stratified by baseline systolic BP. Having baseline systolic BP of less than 120 mm Hg was associated with a mean increase of 5.3 mm Hg at 12 months (P < .001), whereas having baseline systolic BP of 120 mm Hg or higher was associated with a mean reduction of 11.9 mm Hg (P < .001), according to the presentation.

“An interesting finding was discovering an organized bidirectional response by baseline systolic blood pressure, in those patients with baseline systolic blood pressure more than 120 mm Hg had a modest decrease in the blood pressure,” Yaranov said during the presentation. “Whereas those patients with blood pressure at baseline of lower than 120 mm Hg have seen a significant increase in blood pressure.”

Researchers reported 53% of patients in the overall and on-label cohort, respectively, experienced at least a 5 percentage point increase in LVEF at 12 months, and improvements were shown regardless of age, sex, BMI, cardiomyopathy etiology, diabetes status or baseline systolic BP in the overall and on-label cohort.

LVEF improvement and the proportion of patients achieving at least one NYHA functional class improvement were also similar between subgroups, according to the study.

In the overall cohort, the researchers reported the rate of survival after baroreflex activation therapy was 92.6% at 1 year and 78.2% at 3 years, exceeding rates predicted by the MAGGIC HF risk score. In the on-label cohort, the rate of survival was 97% at 1 year and 86.5% at 3 years, also exceeding survival rates predicted by the MAGGIC HF risk model.

Among the cohort, 1.4% had baroreflex activation therapy-related serious adverse events, and all were resolved with supportive care, procedural intervention or antibiotic treatment, and one case involving a fractured lead was resolved with implant replacement, according to the presentation.

Evidence to support use of therapy

“REBALANCE represents the largest real-world data set of baroreflex activation therapy in the broad heart failure patient population,” Yaranov said during the presentation. “This is an observational design which supports association, not causality.

“These results generally add to the evidence available to us out there to support objective use of baroreflex therapy in those with persistent symptoms who remain symptomatic despite guideline-directed medical therapy,” Yaranov said.