SAN DIEGO– Baroreflex activation therapy showed promise as an important new device therapy for patients with New York Heart Association Class III heart failure, according to researchers.

In a preliminary randomized trial, the investigational therapy demonstrated safety comparable to that of established device therapies for heart failure. And it significantly improved functional status, exercise capacity, and quality of life while reducing levels of the biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP) and days-in-hospital for worsening heart failure, Dr. William T. Abraham said at the annual meeting of the American College of Cardiology.

“The trial showed important results,” he said. “If these observations are confirmed in larger studies, baroreflex activation therapy may offer a new addition for the treatment of advanced heart failure patients with a reduced left ventricular ejection fraction.”

Novel therapies for patients with NYHA class III heart failure with a reduced ejection fraction (HFrEF) are sorely needed, he added, as 25%-35% of patients with HFrEF remain in NYHA class III despite current drug and device therapies. These patients are moderately symptomatic, meaning they are sick enough that their quality of life is sharply diminished, but not sufficiently ill to qualify for advanced heart therapies, such as cardiac transplantation or a left ventricular assist device.

Dr. Abraham presented the findings of a multinational, prospective, randomized, 6-month, controlled trial involving 140 NYHA class III HFrEF patients in the United States, Canada, Germany, and France. They were randomized to optimal guideline-directed medical therapy alone or in conjunction with baroreflex activation therapy (BAT), a form of neuromodulatory therapy involving electrical stimulation of the carotid baroreflex baroreceptor delivered by an implanted device similar to a pacemaker.

Progressive heart failure is characterized by increased sympathetic and reduced parasympathetic nerve activity. BAT addresses both abnormalities.

“This form of neuromodulation differs from other forms of neuromodulation in that it does not target a peripheral efferent nerve, but rather it targets the carotid baroreceptor. It targets afferent signals to the brain, which then produce an integrated autonomic nervous system response resulting in inhibition of sympathetic activity and enhancement of parasympathetic activity. So this is a physiologic form of autonomic rebalancing that is mediated via the CNS,” explained Dr. Abraham, professor of medicine and director of the division of cardiovascular medicine at Ohio State University, Columbus.

The primary safety endpoint was freedom from system- and procedure-related major adverse neurologic and cardiovascular events at 6 months. The rate was 97.2%. There were no deaths, and complications – all of which occurred within the first 7 days – were few and short lived, with rates similar to those seen with implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (CRT). The BAT device, known as the CVRx Barostim neo, did not interact with the ICDs and CRT devices present in a large number of participants. No hypotension occurred in this normotensive HFrEF population.

To place the efficacy outcomes in perspective, Dr. Abraham continued, it’s worth noting that the average 19.5-point between-group difference favoring BAT in scores on the Minnesota Living with Heart Failure Quality of Life Questionnaire (MLHFQ) at 6 months compared to a baseline of 45 points dwarfs the benefits obtainable with standard therapies.

“Please remember that our best drug therapies for HFrEF – ACE inhibitors and beta blockers– improve the MLHFQ score by 4 or 5 points, and cardiac resynchronization therapy improves that score by an average of 9 or 10 points,” he said. From a baseline of 300 meters, the 6-minute hall walk distance improved by 58 meters more in the BAT group than in controls. By comparison, CRT improves the distance walked in 6 minutes by about 30 meters.

“The magnitude of benefit of BAT exceeds that seen with standard therapies, it was seen on top of those standard therapies, and it certainly falls into a range that would be considered clinically meaningful,” the cardiologist asserted.

Left ventricular ejection fraction improved in the BAT group by an average of 2.4% from a baseline of 24% while decreasing by 0.1% in controls. The between-group difference in NT-proBNP at 6 months was 342 pg/mL in favor of the BAT group, starting from a baseline level of roughly 1,300 pg/mL.

The BAT group averaged 6.95 hospital days per year for worsening heart failure during the 6 months prior to enrollment and 0.67 days per year in the 6 months following device activation, for an adjusted 82% relative risk reduction. In contrast, hospital days for heart failure remained steady in controls. The possibility of a new treatment that reduces heart failure hospitalizations is of particular interest in light of the enormous financial burden such hospitalizations currently place upon the Medicare system.

Simultaneously with Dr. Abraham’s presentation at ACC 15, the study manuscript was published online (JACC: Heart Failure 2015 [ doi: 10.1016/j.jchf.2015.02.006 ]).

Dr. Abraham is a consultant to CVRx (which funded the study), as well as Novartis, St. Jude Medical, CardioMEMS, and Abbott Vascular.