SAN DIEGO, CA — In a small trial of patients with heart failure and reduced ejection fraction (HF-REF), those who were implanted with the Barostim neo (CVRx) device, which stimulates baroreceptors in the carotid artery and carotid sinus, had greater functional improvements at 6 months compared with their peers who received optimal medical therapy only[1].
Presenting these findings in a featured clinical-research session here at the American College of Cardiology (ACC) 2015 Scientific Sessions, Dr William T Abraham (Ohio State University, Columbus) said, "If the results of our study are confirmed in a larger pivotal trial, baroreflex-activation therapy may become standard therapy for heart-failure patients." The study was simultaneously published in JACC: Heart Failure.
"The present study indicates that [baroreflex-activation therapy] is safe and significantly improves NYHA class, quality of life, exercise capacity, N-terminal pro-brain natriuretic peptide [NT-proBNP] levels, and possibly the burden of heart-failure hospitalizations in NYHA class 3 heart-failure patients with a reduced left ventricular ejection fraction," Abraham summarized.
These "robust data of a new therapy . . . in patients who are already taking multiple medical therapies . . . are very exciting," comoderator Dr Mary Norine Walsh (St Vincent Hospital Heart Center, Indianapolis, IN) and incoming ACC vice president, told heartwire from Medscape. "Importantly, these were patient-centered . . . improvements in functional capacity," she noted, and the device did not interfere with implantable cardioverter-defibrillators (ICDs) or cardiac resynchronization therapy (CRT) devices, which heart-failure patients commonly have.
Does Baroreflex-Activation Therapy Restore Autonomic Balance in HF?
Dr William T Abraham
Baroreceptors, which are sensitive to blood pressure, modulate the balance between the sympathetic and parasympathetic nervous systems; but in heart failure, there is increased sympathetic activity and decreased parasympathetic activity, which leads to vasoconstriction, sodium and water retention in the kidney, and heart remodeling. Abraham told heartwire .
The device, which is usually implanted by a vascular surgeon, consists of a pulse generator (slightly smaller than a pacemaker) that is implanted under the clavicle and a carotid sinus lead, the researchers write. The pulse dosage is uptitrated over a series of patient visits, to reach the full therapeutic dose by about 3 months.
A single-center trial in 11 patients with HF REF showed promising results[2].
The current trial enrolled 146 patients with NYHA class 3 HF and an ejection fraction ≤35%, who were receiving guideline-directed medical therapy, at 45 centers in the US, Canada, Germany, Italy, and France.
Patients were randomly assigned to receive ongoing medical therapy alone (control group, n=70) or medical therapy with baroreflex-activation therapy (treatment group, n=76), for 6 months.
The patients had a mean age of 64, and 14% were women. On average, they walked 300 m in the 6-minute-walk test.
They were already receiving multiple pharmacologic and device therapies. On average, they were taking 4.6 medications—about 80% were receiving an ACE inhibitor or an angiotensin-receptor blocker (ARB), and 86% were receiving a beta-blocker. About a third had a CRT device, and almost nine in 10 had an ICD. They had a mean blood pressure of 118/72 mm Hg. However, on average, patients in the treated group had been hospitalized seven times in the past 6 months, but patients in the control had been hospitalized only 2.4 times.
The primary efficacy end points were changes in NYHA class, quality of life (Minnesota Living with Heart Failure questionnaire score), and 6-minute-walk distance at 6 months.
The primary safety end point was major adverse neurological and cardiovascular events (MANCE) within 6 months, which included cardiovascular-related death, stroke, cardiac arrest, acute MI, acute decompensated heart failure, hypertensive crisis, severe complications of heart-failure treatment, systemic and pulmonary thromboembolism, infection requiring removing part of the system, and cranial nerve damage.
The overall MANCE-free rate was 97.2%. At 6 months, there were two hematomas related to the procedure. More patients in the treatment group than in the control group had an improved NYHA class (55% vs 24%, P=0.002).
Patients tolerated the device well, since the device programming was titrated so that patients did not experience any tingling or hypotension, the researchers report. "I will say, from having experience in a different trial, that there is some degree of sensation that the patient feels in the neck, but that is usually well tolerated and tends to get better over time," Walsh said.
Similarly, on average, patients in the treated group had a 19.5-point better quality-of-life score (P<0.001). "To put this into perspective, our best drug therapies for HF-REF, ACE inhibitors and beta-blockers, improve the Minnesota quality-of-life score by, on average, 4 or 5 points, and cardiac-resynchronization therapy improves the quality-of-life score by 9 or 10 points," Abraham said. Thus, the 19.5-point improvement with this device on top of those standard therapies is clinically meaningful.
On average, patients who received the device were also able to walk 58 m farther in the 6-minute-walk test. "Baroreflex-activation therapy rebalances the autonomic nervous system, [which] effectively unloads the heart, so that patients feel better and can exercise longer (or walk farther on the 6-minute-walk test)," Abraham explained.
On average, NT-pro-BNP was reduced by 69 pg/mL in the treatment group and increased by 129.5 pg/mL in the control group, for a significant between-group difference (-69 pg/mL; P=0.02). There was a trend toward fewer hospitalizations after treatment (P=0.08).
Notably, the therapy did not cause hypotension in these heart-failure patients with normal blood pressure, which is important, because the device is also being studied as a treatment for refractory hypertension.
Study limitations include its small size and lack of a sham procedure. However, "the results of our study are unlikely due to a placebo effect, given the magnitude of benefits and the concordance of results—that is, subjective and objective end points all moved in the same direction favoring active treatment with baroreflex-activation therapy," he said.
Walsh also pointed out that there were few women enrolled, which might make the findings less generalizable, but Abraham said he would expect women to respond in a similar way to men, as the physiology is the same.
The system is approved in Europe for the treatment of hypertension and heart failure under special conditions, and the company is planning to conduct a pivotal larger trial in heart-failure patients.
This study was funded by CVRx. Abraham has received consulting fees and speaking honoraria from CVRx and is a member of the CVRx Heart Failure Executive Steering Committee. Disclosures for the coauthors are listed in the article.
Heartwire from Medscape © 2015
Cite this: Baroreflex-Activation Device Shows Promise in Heart Failure - Medscape - Mar 19, 2015.
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