A Novel Automated Algorithm Effectively Titrates Stimulation in an Implantable Vagus Nerve Stimulation Device

Abstract

Background: Autonomic Regulation Therapy (ART) using chronic Vagus Nerve Stimulation (VNS) is in development for patients with heart failure who remain symptomatic despite standard care. In the ANTHEM-HF Pilot Study, a therapeutic VNS intensity was successfully achieved in patients with HFrEF using manually programmed VNS up-titration. An algorithm has been developed for automatically intensifying VNS in small increments to a programmable target intensity, and capable of adjustments during the up-titration process using a hand-held programmer or magnet. Methods: Six healthy canines were implanted with a pulse generator and lead for right cervical VNS. Device programming at implant activated the titration algorithm with (1) A 1-week start delay; (2) Initial stimulation intensity of 0.125 mA, 130 μsec pulse width, and 5 Hz frequency; (3) Target stimulation intensity of 2.5 mA, 250 μsec pulse width, and 5 Hz frequency; and (4) Trajectory to achieve the target intensity in approximately 10 weeks. Magnet placement over the pulse generator at scheduled intervals tested algorithm design intention to decrement VNS intensity, prolong the time to reach the target intensity, and/or temporarily inhibit VNS. Results: All animals underwent successful VNS system implantation and completed all scheduled activities. There was one transient implant-related adverse event (Horner’s Syndrome). The “TitrationAssist” algorithm performed as designed. The targeted VNS intensity was achieved as scheduled and automated titration was well-tolerated in all animals. There were no stimulation-related adverse events. ECG monitoring demonstrated no clinically significant cardiac findings. Detailed gross necropsy and macroscopic examinations revealed vagus nerves and all major organs to be normal in all animals. Conclusion: An implantable VNS device with Titration Assist algorithm for automatically increasing VNS to a target intensity, and capable of adjustment in response to specific magnet applications, was successfully tested in a preclinical study of healthy canines. Titration Assist performed as designed appears to be safe and could dramatically reduce the burden of titration in a clinical setting. BriEf rEPort