Neuromodulation for HF now in pivotal trial

SAN FRANCISCO — Substantial research on many specific approaches to neuromodulatory therapies for HF is ongoing, with some exciting preliminary results. One such therapy, involving vagus nerve stimulation with the CardioFit system, is now in a pivotal, prospective trial that is rapidly accruing patients.

Spencer H. Kubo, MD, of the University of Minnesota, discussed the background data and ongoing INOVATE-HF trial at TCT 2013.

“There is a tremendous amount of interest in neuromodulation therapies for heart failure,” said Kubo, who is also the chief medical officer for CardioFit manufacturer BioControl Medical. “This is probably the next big thing, clearly one of the hottest areas in treatment for HF.”

The autonomic nervous system is essentially out of equilibrium in HF patients, with excess activation of the sympathetic nervous system, and at the same time, withdrawal of parasympathetic activity. Medications such as beta-blockers are capable of reducing sympathetic nervous system activity, but, to date, no therapies have been able to increase parasympathetic tone and balance the system further.

Animal models have shown that stimulation of the vagus nerve can do just that. In one canine study, Kubo said that beta-blockers alone improved LV ejection fraction by about 5%, while vagus nerve stimulation on top of beta-blockers yielded an approximately 10% improvement (P<.01). In a rat model of MI-induced HF, there was a 73% relative risk reduction in mortality comparing vagus nerve stimulation vs. a sham control.

The CardioFit delivers vagus nerve stimulation through a split cathode; it includes a silicon cuff and two connected neural electrodes to limit current leakage. At the 2012 American Heart Association Scientific Sessions, there was a presentation on 2-year follow-up of the 32 patients who were enrolled in a small pilot study conducted in Europe. In a subset of 19 patients who had complete follow-up, Kubo said, there was a sustained improvement seen in quality of life based on the Minneosta living with HF score (P<.01 at 24 months), as well as in exercise capacity, LV end-systolic volume and LVEF. There was also an improvement in NYHA functional class: at baseline, 12 patients were NYHA II and seven were NYHA III. After 24 months, eight had improved to NYHA I, six to NYHA II, four to NYHA III and one patient to NYHA IV (P<.01).

Based on those animal and preclinical data, researchers began the INOVATE-HF trial for vagus nerve stimulation with the CardioFit device in patients with HF and LV dysfunction.

“This is the only neuromodulation therapy that is in a pivotal stage,” Kubo said.

The study will eventually enroll 650 patients. Researchers have currently enrolled about 280 patients, with enrollment completion expected by early 2015.

Patients enrolled in INOVATE-HF will be randomized to CardioFit plus optimal medical therapy or medical therapy alone (3:2 randomization). The primary endpoint is unplanned hospitalization due to HF or all-cause mortality. All patients included will have stable NYHA class III HF and LVEF of no more than 40%. Patients may have cardiac resynchronization devices implanted if they have been in place for at least 12 months with stable and optimal programming for at least 3 months.

Kubo said the FDA recently approved a full expansion of the trial to include 80 US sites and more than 20 European sites.

For more information:

Kubo SH. Session VI: Electrical therapies and autonomic modulation in heart failure. Presented at: TCT 2013; Oct. 27-Nov. 1, 2013; San Francisco.

Disclosure: Kubo is chief medical officer for BioControl Medical.