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

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.

Automaticversusmanual oxygen administration in the emergency department

Oxygen is commonly administered in hospitals, with poor adherence to treatment recommendations.We conducted a multicentre randomised controlled study in patients admitted to the emergency department requiring O2≥3 L·min−1. Patients were randomised to automated closed-loop or manual O2titration during 3 h. Patients were stratified according to arterial carbon dioxide tension (PaCO2) (hypoxaemicPaCO2≤45 mmHg; or hypercapnicPaCO2>45–≤55 mmHg) and study centre. Arterial oxygen saturation measured by pulse oximetry (SpO2) goals were 92–96% for hypoxaemic, or 88–92% for hypercapnic patients. Primary outcome was % time withinSpO2target. Secondary endpoints were hypoxaemia and hyperoxia prevalence, O2weaning, O2duration and hospital length of stay.187 patients were randomised (93 automated, 94 manual) and baseline characteristics were similar between the groups. Time within theSpO2target was higher under automated titration (81±21%versus51±30%, p<0.001). Time with hypoxaemia (3±9%versus5±12%, p=0.04) and hyperoxia under O2(4±9%versus22±30%, p<0.001) were lower with automated titration. O2could be weaned at the end of the study in 14.1%versus4.3% patients in the automated and manual titration group, respectively (p<0.001). O2duration during the hospital stay was significantly reduced (5.6±5.4versus7.1±6.3 days, p=0.002).Automated O2titration in the emergency department improved oxygenation parameters and adherence to guidelines, with potential clinical benefits.