ORLANDO — Chronic vagus nerve stimulation delivered by an implantable device resulted in significant functional and quality of life improvements in patients with advanced heart failure in a first-in-man study.
The 32-patient trial documented significant reductions in heart rate, New York Heart Association functional class, and Minnesota Living With Heart Failure scores along with increased left ventricular ejection fraction and improved 6-minute walk distance at assessment after 3 months of treatment, Dr. Gaetano M. De Ferrari reported at the annual meeting of the American College of Cardiology.
All of these benefits were maintained at the 6-month mark (see box).
“We believe that a large controlled study is now warranted,” said Dr. De Ferrari, head of cardiac intensive care at San Matteo Polyclinic in Pavia, Italy.
Vagus nerve stimulation (VNS) is approved for drug-refractory epilepsy and drug-refractory depression. Dr. De Ferrari presented the first-ever experience with the therapy in heart failure patients.
The rationale for VNS as a novel therapy for heart failure lies in the observation that reduced vagal activity and increased sympathetic tone are associated with increased mortality following acute MI as well as in heart failure. Moreover, additional vagal withdrawal often precedes episodes of acute decompensated heart failure.
Animal studies conducted by Dr. De Ferrari and coworkers at the University of Pavia 2 decades ago showed that chronic VNS markedly reduced mortality in the setting of post-MI heart failure, the cardiologist reported.
In the new clinical trial, 32 participants with NYHA class II-III heart failure each had an investigational CardioFit stimulator made by BioControl, an Israeli company, implanted in the right upper chest under the clavicle. The device was connected to a cuff electrode wrapped around the right cervical vagus nerve. The system is capable of sensing the R wave and delivering one or more pulse-synchronous stimuli of 0.5-msec duration. The stimulatory pulses were delivered at an average amplitude of 4.1 mAmp. The device was on an average of 21% of the time.
In this study, intended to establish safety, six patients experienced minor treatment-related adverse events such as cough, pain at stimulation site, or voice difficulties, all of which resolved with device tuning or adaptation. In addition, there were two serious device-related adverse events: a case of postoperative pulmonary edema, and a surgical revision after device implantation.
While there was no control group in this early study, Dr. De Ferrari dismissed the notion that the observed benefits might be due to the placebo effect.
“Most often the placebo effect lasts a few months. It's unlikely to continue for a 6-month period,” he said.
He and his coworkers are now trying to pin down which patients with advanced heart failure are most likely to respond to VNS. The five diabetic patients in the study did not benefit. The best responders were patients with a slightly higher baseline heart rate and those who could tolerate more intensive vagal stimulation.
Discussant Marvin A. Konstam called chronic VNS an intriguing and promising new therapeutic approach.
“The opportunity for benefit from increasing vagal tone is multifactorial. In the very simplest of terms, just the reduction in heart rate may be beneficial. I think to this day we don't know for sure how much of the benefit of beta-blockade in heart failure may simply be heart rate reduction, so on that ground alone I think there's potential benefit. Also, there's a potential antiarrhythmic effect from increasing vagal tone,” said Dr. Konstam, professor of medicine at Tufts University, Boston.
Dr. De Ferrari replied that there are several additional plausible mechanisms of benefit for chronic VNS, including anti-apoptotic and anti-inflammatory effects.
He disclosed having received research grants from, and serving as a paid consultant to, BioControl.
VNS benefits were maintained after 6 months. 'We believe that a large controlled study is now warranted.' DR. DE FERRARI
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