Intravenous Infusion of the Novel HNO Donor BMS-986231 Is Associated With Beneficial Inotropic, Lusitropic, and Vasodilatory Properties in 2 Canine Models of Heart Failure.

•1. Mechanism of action: Nitroxyl (HNO) enhances SR calcium uptake and release in cardiomyocytes, and improves myofilament calcium sensitivity without impacting L-type calcium channel or total SR calcium content.•2. Study design: The effects of the nitroxyl donor BMS-986231 on hemodynamics, left ventricular function, and pro-arrhythmic potential were assessed using canine models of HF.•3. Main findings: BMS-986231 was associated with increased cardiac contractility and relaxation, as well as moderate vasodilatory effects; there was also a significant reduction in MVO2.•There were no clinically significant changes in HR, and no de novo arrhythmias were detected; BMS-986231 was also not associated with venotoxicity.•Thus, BMS-986231 has beneficial inotropic, lusitropic, and vasodilatory effects; clinical studies are ongoing.