Novel device may work only for less advanced heart failure, though
SAN FRANCISCO -- A novel implanted neuromodulation device substantially improved quality of life and functional capacity in heart failure with reduced ejection fraction (HFrEF) in the BeAT-AF study.
Baroreflex stimulation with the Barostim Neo device also improved the key prognostic biomarker N-terminal pro–B-type natriuretic peptide (NT-proBNP) in the subset of patients with a baseline level of 1,600 pg/mL or less, reflecting less advanced heart failure.
"To our knowledge, this is the first successful pivotal trial of a device-based neuromodulation therapy in HFrEF patients," Michael Zile, MD, of the Medical University of South Carolina in Charleston, said when presenting the results at a late-breaking clinical trial session here at the Heart Rhythm Society meeting.
The device stimulates the baroreceptor with a 2 mm electrode that sits on the right carotid artery sinus and a lead extending to the generator.
"We think this fills the unmet need for those patients who are class III who cannot or should not receive a CRT [cardiac resynchronization therapy], which we think is about 50% of the heart failure reduced ejection fraction population," Zile concluded at a press conference.
"I think they've made a sufficient case that there's clinical utility to be acceptable to [the] FDA," commented Andrew Krahn, MD, of the University of British Columbia in Vancouver and a moderator at the session.
"But as long as you're talking about something that is invasive, that has a single set of data to support its use, adoption will be modest until there are larger scale, more definitive trials; also because of the absence of a true blinded control group," he told MedPage Today.
The study as originally designed included 271 patients with New York Heart Association (NYHA) class III HF with ejection fraction of 35% or lower, a 6-minute hall walk distance of 150 to 400 m, elevated NT-proBNP or prior heart failure hospitalization, and on stable optimal medical therapy, but ineligible for CRT.
They were randomized to be implanted with the device or continue receiving optimal medical therapy alone and followed for 6 months to the initial unblinding for the primary endpoints. Morbidity and mortality would then be followed longer term.
Three of the four efficacy endpoints came out positive for change over baseline: Minnesota Living With Heart Failure Questionnaire quality-of-life scores, 6-minute walk distance, and safety (94% free from major adverse neurological cardiovascular events, compared with a performance criteria of 85%).
However, the objective efficacy endpoint -- NT-proBNP -- failed to show an improvement.
With the blessing of the FDA, which worked closely with the investigators through its Breakthrough Devices Program, the researchers reanalyzed the data using the one difference between BeAT-AF and the positive phase II study -- a restriction on NT-proBNP to no more than 1,600 pg/mL.
After defining that as the "intended use population," there were 162 initial-cohort patients and a second cohort of 102 additional patients randomized with 6-month follow-up.
In the combined analysis, baroreflex stimulation reduced NT-proBNP by 21% over baseline levels compared with a 3.3% increase in the control group (P=0.004). Such a reduction predicts a "marked decrease in morbidity and mortality," Zile noted, and "fits with the pathophysiological mechanism by which we think this works and reinforces and objectifies the 6-minute hall walk and the quality of life."
Quality-of-life scores improved by 14.1 points more than seen among controls (P<0.001). "Most studies consider a positive, successful result a 5-point reduction," Zile noted.
Exercise tolerance on a 6-minute walk test improved by 56.5 meters more than seen with optimal medical therapy alone (P<0.001).
This trial may have succeeded where prior neuromodulation device therapies have come out neutral in heart failure "in part due to differences in mechanism of action," Zile speculated at a press conference. "When you stimulate the carotid baroreceptor, it generates an afferent signal to the brain."
"The brain integrates that signal and creates both a decrease in sympathetic activation and an increase in parasympathetic activation, which is important because these patients are characterized by an increase in sympathetic and decrease in parasympathetic and here we've switched them."
He noted that the device maker is now developing a percutaneous approach that could do away with the surgery required for placement.
Session study discussant Sanjeev Saksena, MD, of Rutgers University Robert Wood Johnson Medical School in New Brunswick, New Jersey, agreed that the concordant results allude to clinical outcome benefits in the future.
"We're looking at a new option for CRT-ineligible, NYHA class IIIa patients, but there is another option and that is the combined use of angiotensin receptor blockade and neprilysin inhibitors," he noted. Those drugs were used in 25% of the study population.
He cautioned that there was no echo data on remodeling and that the supraclavicular placement of the lead could raise questions of long-term durability.
"We have to wait and see the actual data" on long-term outcomes, he said. "It's going to be dependent on what is the true autonomic contribution to heart failure and in the stages of heart failure does it permit correction of the autonomic dysfunction ... will it halt the development of disease at this point, will it delay it or not affect it?"
The trial was sponsored by CVRx.
Zile disclosed relationships with CVRx.
Saksena disclosed no relevant relationships with industry.
Heart Rhythm Society
Source Reference: Zile MR, et al "Baroreflex Activation Therapy In Patients With Heart Failure With A Reduced Ejection Fraction" HRS 2019; Abstract LBCT01-04.
Read the original article on Medpage Today: Baroreflex Device Eases HF Symptoms