{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T18:47:43Z","timestamp":1782067663201,"version":"3.54.5"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Heart failure with reduced ejection fraction (HFrEF) affects millions worldwide and is characterized by chronic cardiac dysfunction, impaired perfusion, altered skeletal muscle energetics, and, thus, exercise intolerance. Efficient therapeutic strategies reducing the burden of the impaired muscle metabolism in HFrEF are currently lacking. Hence, in the present study, we sought to determine whether myosin dynamics and its important role in ATP consumption can constitute a potent biochemical target to optimize skeletal muscle energy usage in HFrEF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We used skeletal muscle tissue from 11 human patients with HFrEF and 10 controls with comparable age, sex, and body mass index. We isolated individual myofibres and incubated them ex vivo with varying concentrations of a myosin inhibitor, mavacamten. We then performed 2\u2032-(or-3\u2032)-O-(N-Methylanthraniloyl) adenosine 5\u2032-triphosphate chase experiments, together with LC\/MS-based proteomics profiling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>We observed a distinct regulation of acetyl-lysine sites and higher myosin energy consumption in resting muscle fibers from patients with HFrEF than in controls. When exposed to mavacamten, we found a dose-dependent reduction in myosin ATP consumption in myofibres of patients with HFrEF, reversing the pathological over-consumption.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Skeletal muscle myosin becomes inefficient in HFrEF. Pharmacological inhibition of myosin ATPase activity offers an inventive strategy to lower muscle energy demand and potentially address metabolic disturbances in HFrEF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circheartfailure.125.013827","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T09:00:23Z","timestamp":1778058023000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Myosin ATPase Inhibition Relieves the Energetic Burden in Skeletal Myofibres of Patients With Heart Failure With Reduced Ejection Fraction"],"prefix":"10.1161","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2578-7393","authenticated-orcid":true,"given":"Massimiliano","family":"Ansaldo","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, University of Copenhagen, Denmark (M.A., C.C., C.T.A.L., R.A.E.S., J.O.)."},{"name":"Department of Molecular Medicine, University of Pavia, Italy (M.A., S.P., R.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2597-1566","authenticated-orcid":true,"given":"Chahida","family":"Chaami","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Copenhagen, Denmark (M.A., C.C., C.T.A.L., R.A.E.S., J.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9494-0858","authenticated-orcid":true,"given":"Simone","family":"Porcelli","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Pavia, Italy (M.A., S.P., R.B.)."},{"name":"IRCCS Mondino Foundation, Pavia, Italy (S.P., R.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4960-7490","authenticated-orcid":true,"given":"Roberto","family":"Bottinelli","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Pavia, Italy (M.A., S.P., R.B.)."},{"name":"IRCCS Mondino Foundation, Pavia, Italy (S.P., R.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7290-1324","authenticated-orcid":true,"given":"Chengxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (C.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4477-422X","authenticated-orcid":true,"given":"Christopher T.A.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Copenhagen, Denmark (M.A., C.C., C.T.A.L., R.A.E.S., J.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1740-2474","authenticated-orcid":true,"given":"T. Scott","family":"Bowen","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, United Kingdom (T.S.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2491-3747","authenticated-orcid":true,"given":"Robert A.E.","family":"Seaborne","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Copenhagen, Denmark (M.A., C.C., C.T.A.L., R.A.E.S., J.O.)."},{"name":"Centre of Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences &amp; Medicine, King\u2019s College London, United Kingdom (R.A.E.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6358-8962","authenticated-orcid":true,"given":"Hans Erik","family":"B\u00f8tker","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Aarhus University Hospital, Denmark (H.E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5810-5241","authenticated-orcid":true,"given":"Kristian","family":"Vissing","sequence":"additional","affiliation":[{"name":"Department of Public Health, Aarhus University, Denmark (K.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6358-2920","authenticated-orcid":true,"given":"Julien","family":"Ochala","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Copenhagen, Denmark (M.A., C.C., C.T.A.L., R.A.E.S., J.O.)."},{"name":"Myocardial Homeostasis and Cardiac Injury Program, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (J.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab368"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvac013"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-012-9353-8"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1536\/ihj.15-108"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)07015-8"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.01.072"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.91.2.559"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00049.2015"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jshs.2023.04.001"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.73.6.1127"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.71.1.57"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.191957"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.109.876433"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.2.853"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12551-014-0151-5"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909468107"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-025-06436-0"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI172599"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.172322"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1113\/JP286870"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adg3894"},{"key":"e_1_3_3_23_2","first-page":"919","article-title":"The 6-minute walk: a new measure of exercise capacity in patients with chronic heart failure.","volume":"132","author":"Guyatt GH","year":"1985","unstructured":"Guyatt GH, Sullivan MJ, Thompson PJ, Fallen EL, Pugsley SO, Taylor DW, Berman LB. 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