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BARCELONA -- Stimulation of either the right or left vagus nerve appeared to improve cardiac function in patients with heart failure, researchers said here.
In the ANTHEM-HF (Autonomic Neural Regulation Therapy to Enhance Myocardial Function in Heart Failure) trial, left ventricular ejection fraction (LVEF) increased from 32.4% to 37.2% with the stimulation device (VNS Therapy System) after 6 months, a statistically significant and clinically meaningful change (P<0.0001), reported , from the University of Minnesota in Minneapolis, and colleagues.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
"We pooled the results of the left and right side vagus nerve stimulation because there were no major differences in outcomes based on which nerve is stimulated," Anand said at a press conference at the European Society of Cardiology meeting. The study results will also be published in the .
In addition to the improvement in left ventricular function, about 70% of the patients in the ANTHEM-HF study improved their NYHA heart failure class by at least one class, Anand reported, and those changes were also statistically significant (P<0.0001).
"No patients' conditions worsened," he told ľֱ.
Anand also reported that the patients significantly bolstered their distance in the 6-Minute Walk Test, improving by 56 m from baseline (P<0.0001) and saw their heart rates slowed by 3.9 beats per minute (P<0.005). Also, patients recorded an 18-point reduction in the Minnesota Living with Heart Failure Questionnaire (P<0.0001).
"We saw both improvements in objective measures of heart failure and in subjective measures," he said.
The results of the ANTHEM-HF trial differed from another trial of vagal stimulation presented at ESC -- NECTAR-HF showed no benefit was observed.
"ANTHEM showed a very significant effect on beneficial remodeling as a result of vagus nerve stimulation,"professor of medicine at the University of Pennsylvania in Philadelphia told ľֱ. "They compared right sided vagus nerve stimulation to left sided stimulation and both were effective. This is in contrast to NECTAR-HF which showed absolutely no signal, but was done primarily on the right side."
"So we are kind of confused," she added. "We will really have to understand, in a better way, what the differences were in the techniques and how they used the stimulation. There is still a possibility that this is going to offer a new avenue of therapy."
The researchers set out to test whether stimulating the right vagus nerve or the left vagus nerve would better improve outcomes, but Anand said that stimulation of either nerve appeared to help patients achieve changes in cardiac function. There were 60 patients -- all with chronic symptomatic heart failure with LVEF ≤40% -- enrolled, and outcomes were studied at 6 months. Patients were on optimal medical therapy including beta-blockers. There was no control group.
The experimental autonomic regulation therapy system delivered chronic intermittent stimulation to the vagus (10 Hz natural frequency, 250-microsecond pulse width). The stimulation intensity titrated over 10 weeks to maximum tolerable current. The average stimulation current was 2.0 mA.
There were three deaths in the study, including one that involved implantation of the device (postsurgical embolic stroke). The other two deaths were adjudicated as due to worsening heart failure and sudden death. Other serious adverse events were equally distributed among patients with either right or left implantation. The most common nonserious adverse events included voice alternation and hoarseness, cough, and oropharyngeal pain.
There were no instances of system malfunction, the authors reported.
"There is attractiveness to using the left side because that is where we put most of our devices," explained Jessup, who is immediate past president of the American Heart Association. "In theory, if you were implanting a device, you could be implanting the vagal nerve stimulator and, I suppose, you could put the generators in one single pocket."
professor of medicine at the University of Bergen, Norway, said the use of the right vagus nerve has been targeted because it was believed that method provided more of a baroreceptor impact than the left side vagus nerve. He said that ANTHEM-HF indicated that the left vagus nerve is at least as effective as the right side and may be easier to access.
Disclosures
The study was sponsored by Cyberonics.
Anand disclosed relevant relationships with Amgen, Critical Diagnostics, Cyberonics, Novartis, and Zensun.
Jessup disclosed no relevant relationships with industry.
Primary Source
European Society of Cardiology
Source Reference: Premchand R, et al "Autonomic regulation therapy for the improvement of left ventricular function and heart failure symptoms: The ANTHEM-HF Study" ESC 2014.