{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:27:25Z","timestamp":1792175245152,"version":"4.4.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"content-version":"vor","delay-in-days":2018,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2020,7,10]],"date-time":"2020-07-10T00:00:00Z","timestamp":1594339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Both left ventricular (LV) and left atrial (LA) dysfunction and remodelling contribute to adverse outcomes in heart failure with reduced ejection fraction (HFrEF). Danicamtiv is a novel, cardiac myosin activator that enhances cardiomyocyte contraction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We studied the effects of danicamtiv on LV and LA function in non-clinical studies (ex vivo: skinned muscle fibres and myofibrils; in vivo: dogs with heart failure) and in a randomized, double-blind, single- and multiple-dose phase 2a trial in patients with stable HFrEF (placebo, n =\u200910; danicamtiv, n =\u200930; 50\u2013100\u2009mg twice daily for 7\u2009days). Danicamtiv increased ATPase activity and calcium sensitivity in LV and LA myofibrils\/muscle fibres. In dogs with heart failure, danicamtiv improved LV stroke volume (+10.6 mL, P &amp;lt;\u20090.05) and LA emptying fraction (+10.7%, P &amp;lt;\u20090.05). In patients with HFrEF (mean age 60\u2009years, 25% women, ischaemic heart disease 48%, mean LV ejection fraction 32%), treatment-emergent adverse events, mostly mild, were reported in 17 patients (57%) receiving danicamtiv and 4 patients (40%) receiving placebo. Danicamtiv (at plasma concentrations \u22652000\u2009ng\/mL) increased stroke volume (up to +7.8 mL, P &amp;lt;\u20090.01), improved global longitudinal (up to \u22121.0%, P &amp;lt;\u20090.05) and circumferential strain (up to \u22123.3%, P &amp;lt;\u20090.01), decreased LA minimal volume index (up to \u22122.4 mL\/m2, P &amp;lt;\u20090.01) and increased LA function index (up to 6.1, P &amp;lt;\u20090.01), when compared with placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Danicamtiv was well tolerated and improved LV systolic function in patients with HFrEF. A marked improvement in LA volume and function was also observed in patients with HFrEF, consistent with pre-clinical findings of direct activation of LA contractility.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.1933","type":"journal-article","created":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T11:00:51Z","timestamp":1592564451000},"page":"1649-1658","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":97,"title":["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"],"prefix":"10.1093","volume":"22","author":[{"given":"Adriaan A.","family":"Voors","sequence":"first","affiliation":[{"name":"University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Tamby","sequence":"additional","affiliation":[{"name":"MyoKardia , Brisbane, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"Cleland","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics and Clinical Trials Unit, University of Glasgow , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Koren","sequence":"additional","affiliation":[{"name":"Jacksonville Center for Clinical Research , Jacksonville, FL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie B.","family":"Forgosh","sequence":"additional","affiliation":[{"name":"HealthEast Heart Care , Saint Paul, MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinesh","family":"Gupta","sequence":"additional","affiliation":[{"name":"Tennova Healthcare-Harton , Tullahoma, TN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars H.","family":"Lund","sequence":"additional","affiliation":[{"name":"Department of Medicine, Karolinska Institutet , Stockholm ,","place":["Sweden"]},{"name":"Karolinska University Hospital, Heart and Vascular Theme , Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Camacho","sequence":"additional","affiliation":[{"name":"Oregon Health & Science University , Portland, OR ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Karra","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center , Durham, NC 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