SAN FRANCISCO -- Noninvasive vagus nerve stimulation reduced atrial fibrillation (Afib, AF) burden in paroxysmal cases, a small sham-controlled trial showed.
Low-level stimulation via a clip-on electrode at the tragus of the ear for 1 hour daily cut the percentage of time in Afib over a 2-week continuous monitoring period by a relative 85% after 6 months of treatment compared with a sham stimulation treatment with the device clipped on the earlobe (ratio of medians 0.15, 95% CI 0.03 to 0.65, baseline-adjusted P=0.011).
At 6 months, the median AF burden was 2% in the active group and 11% in the sham group, Stavros Stavrakis, MD, PhD, of the University of Oklahoma Health Sciences Center in Oklahoma City, reported here at the Heart Rhythm Society meeting.
Afib burden pooling monitoring periods at 3 and 6 months of treatment showed a similarly significant 75% relative reduction as did total Afib duration at 6 months (ratio of medians 0.17), "suggesting a dose-related effect," he added.
While a modest absolute difference, it would likely be worthwhile from a symptom control perspective and because of the link to stroke risk, Stavrakis suggested at a press conference.
"Our results support the emerging paradigm of noninvasive neuromodulation to treat AF," he said at the late-breaking clinical trial session.
Vagus nerve stimulation devices are FDA approved to treat certain types of epilepsy (invasively), episodic cluster headache (noninvasively), and treatment-resistant depression (invasively).
The system used in the study was originally designed to treat tinnitus.
"Further studies are required to optimize patient selection and discriminate at baseline between responders and non-responders in order to maximize the efficacy of this novel, noninvasive therapy," Stavrakis said.
The trial included 53 patients randomized to active or sham stimulation delivered from the Parasym device via a transcutaneous clip. The parameters were set at 20 Hz, 200 μs, and 1 mA below the discomfort threshold without inducing bradycardia. Monitoring was done with the Zio XT patch.
Enrollment required two or more episodes of at least 30 seconds of Afib in the 3 months prior, documented by ECG, a Holter monitor, or implanted device. Patients couldn't have low ejection fraction, significant valvular disease, a recent stroke or heart attack, severe heart failure, or recurrent vaso-vagal syncope. CHA2DS2-VASc scores averaged 3, patients had mildly dilated atria, and about half were on antiarrhythmic medication.
Adherence to the daily hour of stimulation with no more than four sessions missed per month was a statistically similar 75% in the active treatment group and 83% in the sham group. "Importantly, this adherence rate is comparable to what is seen in studies involving medical therapy," Stavrakis noted.
Heart rate variability, measured in a subset of patients, was higher with active treatment (ratio of median low-frequency to high-frequency band ratio 2.16, 95% CI 1.29 to 3.63), although no difference was seen at 6 months.
"Longest daily AF duration was no different between the two groups, suggesting tragus stimulation suppressed the initiation but had no effect once the AF episode started," Stavrakis noted.
Inflammatory cytokine TNF-alpha was a relative 23% lower with vagus nerve stimulation (P=0.0093), although other cytokines didn't differ between groups.
One patient in each group progressed to persistent Afib and had cardioversion, but there were no device-related adverse events.
Stavrakis acknowledged that the minimum effective duration needed to stimulate the tragus nerve isn't clear, although patients are more likely to adhere to something that is of shorter duration. However, it's unlikely that the treatment would need to be continuous, because human and animal studies have shown a memory effect from vagal nerve stimulation, he suggested.
The study discussant at the session, Peng-Sheng Chen, MD, of Indiana University School of Medicine in Indianapolis, pointed to a functional MRI study showing brain activation with tragus stimulation.
"Because of extensive multi-site activation and deactivation in the CNS, neural remodeling is likely the cause of the 'carry-over' effects of the tragus stimulation that suppressed AF in the remaining 23 hours of the day," he said.
At the same time, it wasn't clear whether the increased AF burden in the sham group was normal progression of AF or pro-arrhythmia, he noted.
Disclosures
Stavrakis and Chen disclosed no relevant relationships with industry.
The trial was funded by the American Heart Association and Oklahoma Shared Clinical and Translational Resources.
Primary Source
Heart Rhythm Society
Stavrakis S, et al "Transcutaneous Electrical Vagus Nerve Stimulation To Suppress Atrial Fibrillation (TREAT AF): A Randomized Clinical Trial" HRS 2019; Abstract LBCT01-01.