{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T18:39:47Z","timestamp":1792435187663,"version":"4.5.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2026,10,20]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>\n                      Nonobstructive hypertrophic cardiomyopathy (nHCM) is associated with significant morbidity with no approved treatment. Aficamten is a cardiac myosin inhibitor targeting excess contractility and diastolic impairment, the predominant mechanism responsible for adverse outcomes in nHCM. In the ACACIA-HCM trial (Assessment Comparing Aficamten to Placebo on Cardiac Endpoints in Adults With Non-Obstructive HCM; URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifier: NCT06081894), aficamten significantly improved outcomes in patients with nHCM versus placebo. To contextualize the observed treatment effects, we performed a responder analysis integrating multiple clinically relevant measures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Patients with symptomatic nHCM were randomized to daily aficamten (n=258) or placebo (n=259) assessed at week 36, including (1) symptom burden (\u22651 improvement in New York Heart Association class or reported improvement in Patient Global Impression of Change); (2) exercise capacity (\u22650.5 mL\/kg per min in peak oxygen uptake); (3) &gt;10% decrease in left atrial volume index; (4) &gt;10% improvement in septal early diastolic mitral annular velocity (e\u2019); (5) \u226550% reduction in NT-proBNP (N-terminal pro-B-type natriuretic peptide). Overall clinical response was classified by the number of favorable outcomes achieved: nonresponder (none), limited (1 or 2), partial (3 or 4), or complete (all 5).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      At 36 weeks, a greater proportion of patients treated with aficamten versus placebo experienced improvements in symptom burden (71% versus 53%), peak exercise capacity (45% versus 37%), left atrial volume index (31% versus 23%), septal e\u2019 (51% versus 26%), and NT-proBNP (63% versus 5%) (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.05 for all except peak oxygen uptake,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.1). Number needed to treat for aficamten ranged from 1.7 (NT-proBNP reduction) to 14 (peak oxygen uptake improvement) relative to placebo. A partial or complete clinical response (\u22653 outcomes) was achieved in 53% of patients on aficamten versus 14% on placebo (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>In patients with nHCM, aficamten was associated with improvements across a broad range of clinically relevant measures including symptom burden and diastolic function. These results underscore a potential benefit of aficamten in the population of patients with nHCM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>REGISTRATION:<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifier: NCT06081894.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.126.082026","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T09:57:07Z","timestamp":1787911027000},"page":"1547-1559","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Global Efficacy of Aficamten in Nonobstructive Hypertrophic Cardiomyopathy: Results From ACACIA-HCM"],"prefix":"10.1161","volume":"154","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9923-3853","authenticated-orcid":true,"given":"Martin S.","family":"Maron","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6390-6526","authenticated-orcid":true,"given":"Ahmad","family":"Masri","sequence":"additional","affiliation":[{"name":"Hypertrophic Cardiomyopathy Center, Knight Cardiovascular Institute,Oregon Health and Science University, Portland (A.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankit","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Lindner Research Center, The Christ Hospital, Cincinnati, OH (A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4861-0831","authenticated-orcid":true,"given":"Maria Luisa","family":"Pe\u00f1a-Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Cardiology Service, General Hospital of HU Virgen del Rocio, Seville, Spain (M.L.P.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4972-7780","authenticated-orcid":true,"given":"Mark V.","family":"Sherrid","sequence":"additional","affiliation":[{"name":"Leon H. Charney Division of Cardiology, New York University Langone Health (M.V.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5420-2482","authenticated-orcid":true,"given":"Estevao Lanna","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"NUPEC Cardio, Belo Horizonte, Minas Gerais, Brazil (E.L.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3723-7493","authenticated-orcid":true,"given":"Michael","family":"Arad","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Chaim Sheba Medical Center, Ramat-Gan and Tel Aviv University, Israel (M.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4039-8490","authenticated-orcid":true,"given":"Lubna","family":"Choudhury","sequence":"additional","affiliation":[{"name":"Department of Medicine, Northwestern Feinberg School of Medicine, Chicago, IL (L.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1748-4340","authenticated-orcid":true,"given":"Brian L.","family":"Claggett","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (B.L.C., C.Y.H., I.K., S.D.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3208-470X","authenticated-orcid":true,"given":"Caroline J.","family":"Coats","sequence":"additional","affiliation":[{"name":"School of Cardiovascular and Metabolic Health, University of Glasgow, United Kingdom (C.J.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6414-8838","authenticated-orcid":true,"given":"Edileide","family":"de Barros Correia","sequence":"additional","affiliation":[{"name":"Dante Pazzanese Institute of Cardiology, Sao P\u00e3ulo, Brazil (E.d.B.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Pablo","family":"Costabel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3383-3984","authenticated-orcid":true,"given":"Perry M.","family":"Elliott","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Science, Barts Heart Centre and University College London, United Kingdom (P.M.E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9493-0932","authenticated-orcid":true,"given":"Jorge E.","family":"Silva Enciso","sequence":"additional","affiliation":[{"name":"University of California-San Diego, La Jolla (J.E.S.E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbo","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongsan Hospital, Shanghai, China (J.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7334-7924","authenticated-orcid":true,"given":"Carolyn Y.","family":"Ho","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (B.L.C., C.Y.H., I.K., S.D.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0710-1088","authenticated-orcid":true,"given":"Ian","family":"Kulac","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (B.L.C., C.Y.H., I.K., S.D.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8108-8240","authenticated-orcid":true,"given":"Gregory D.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Heart and Vascular Institute, Mass General Brigham, Boston, MA (G.D.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9255-4657","authenticated-orcid":true,"given":"Matthew W.","family":"Martinez","sequence":"additional","affiliation":[{"name":"Morristown Medical Center, NJ (M.W.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5400-5008","authenticated-orcid":true,"given":"Mathew S.","family":"Maurer","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Irving Medical Center, Columbia University, New York, NY (M.S. 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