Danicamtiv, a cardiac myosin activator, improves left ventricular (LV) and left atrial (LA) function in patients with heart failure with reduced ejection fraction (HFrEF). This finding was presented as part of the Heart Failure Association Discoveries webinars. Danicamtiv is a novel small molecule that selectively enhances cardiac actomyosin activity. In ex vivo animal studies, danicamtiv was associated with a dose-dependent increase in sarcomere activity in LV and LA myofibrils and an increase in calcium sensitivity in LV and LA skinned muscle fibres. In a dog model of heart failure, danicamtiv increased LV stroke volume and LA emptying fraction. Finally, in a phase IIa study, patients with HFrEF were randomly assigned to danicamtiv (50–100 mg twice daily for 7 days; n = 30) or placebo (n = 10). Danicamtiv improved LV and LA volumes and function, without impairing relaxation. Adverse events, mostly mild, occurred in 57% and 40% of the patients in the danicamtiv and placebo groups, respectively.
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Voors, A. A. et al. Effects of danicamtiv, a novel cardiac myosin activator, in heart failure with reduced ejection fraction: experimental data and clinical results from a phase 2a trial. Eur. J. Heart Fail. https://doi.org/10.1002/ejhf.1933 (2020)
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Lim, G.B. Myosin activator improves cardiac function. Nat Rev Cardiol 17, 540 (2020). https://doi.org/10.1038/s41569-020-0418-4
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DOI: https://doi.org/10.1038/s41569-020-0418-4