Baroreflex activation therapy in patients with heart failure and a reduced ejection fraction: Long-term outcomes

Michael R Zile; JoAnn Lindenfeld; Fred A Weaver; Faiez Zannad; Elizabeth Galle; Tyson Rogers; William T Abraham

doi:10.1002/ejhf.3232

Baroreflex activation therapy in patients with heart failure and a reduced ejection fraction: Long-term outcomes

Eur J Heart Fail. 2024 Apr 12. doi: 10.1002/ejhf.3232. Online ahead of print.

Authors

Michael R Zile¹, JoAnn Lindenfeld², Fred A Weaver³, Faiez Zannad⁴, Elizabeth Galle⁵, Tyson Rogers⁶, William T Abraham⁷

Affiliations

¹ Medical University of South Carolina, Charleston, South Carolina and the Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC, USA.
² Vanderbilt Heart and Vascular Institute, Nashville, TN, USA.
³ Division of Vascular Surgery and Endovascular Therapy, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁴ Université de Lorraine, Inserm Centre d'Investigation, CHU de Nancy, Institute Lorrain du Coeur et des Vaisseaux, Nancy, France.
⁵ CVRx, Inc., Minneapolis, MN, USA.
⁶ NAMSA, Inc., Minneapolis, MN, USA.
⁷ Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH, USA.

PMID: 38606555
DOI: 10.1002/ejhf.3232

Abstract

Aims: Carotid baroreflex activation therapy (BAT) restores baroreflex sensitivity and modulates the imbalance in cardiac autonomic function in patients with heart failure with reduced ejection fraction (HFrEF). We tested the hypothesis that treatment with BAT significantly reduces cardiovascular mortality and heart failure morbidity and provides long-term safety and sustainable symptomatic improvement.

Methods and results: BeAT-HF was a prospective, multicentre, randomized, two-arm, parallel-group, open-label, non-implanted control trial. New York Heart Association (NYHA) class III subjects, ejection fraction ≤35%, previous heart failure hospitalization or N-terminal pro-B-type natriuretic peptide (NT-proBNP) >400 pg/ml, no class I indication for cardiac resynchronization therapy and NT-proBNP <1600 pg/ml were randomized to BAT plus optimal medical management (BAT group) or optimal medical management alone (control). The primary endpoint was cardiovascular mortality and HF morbidity; additional pre-specified endpoints included durability of safety, quality of life (QOL), exercise capacity (6-min hall walk distance [6MHWD]), functional status (NYHA class), hierarchical composite win ratio, freedom from all-cause death, left ventricular assists device (LVAD) implantation, heart transplant. Overall, 323 patients had 332 primary events, median follow-up was 3.6 years/patient. Both primary endpoint (rate ratio 0.94, 95% confidence interval [CI] 0.57-1.57; p = 0.82) and components of the primary endpoints were not significantly different between BAT and control. The system- and procedure-related major adverse neurological and cardiovascular event-free rate remained 97% throughout the trial. Symptom improvement (QOL, 6MHWD, NYHA class, all nominal p < 0.001) in the BAT group was durable in time, sustainable in extent. Win ratio (1.26, 95% CI 1.02-1.58) and freedom from all-cause death, LVAD implantation, heart transplant (hazard ratio 0.66, 95% CI 0.43-1.01) favoured the BAT group but did not reach statistical significance.

Conclusion: The BeAT-HF primary endpoint was neutral; however, BAT provided safe, effective, and sustainable improvements in HFrEF patient's functional status, 6MHWD and QOL.

Keywords: Autonomic nervous system; Baroreflex; Device; Heart failure; Randomized controlled trial.

Grants and funding

CVRx, Inc.