Abstract 12955: A Novel Algorithm for Automated Titration of Autonomic Regulation Therapy for Heart Failure

Abstract

Background: Autonomic Regulation Therapy (ART) using chronic vagus nerve stimulation (VNS) is a promising new therapy 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 and capable of adjustments during up-titration process using a hand-held programmer or magnet. Methods: 6 healthy canines were implanted with an implantable pulse generator (IPG) and electrical lead for right cervical VNS. IPG programming at implant activated the TA 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 IPG 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 TA 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 IPG for VNS having a programmable TA algorithm for automatically intensifying VNS to a target intensity and capable of adjustment in response to magnet applications to the IPG, was successfully tested in a preclinical study of healthy canines. The TA algorithm performed as designed, appears to be safe and could dramatically reduce burden of titration in a clinical setting.