{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:41:07Z","timestamp":1792708867803,"version":"4.5.0"},"reference-count":27,"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>Aficamten significantly improved both functional capacity and patient-reported health status in patients with symptomatic nonobstructive hypertrophic cardiomyopathy in the phase 3 randomized, placebo-controlled ACACIA-HCM trial (Assessment Comparing Aficamten to Placebo on Cardiac Endpoints in Adults with Non-Obstructive HCM; NCT06081894). Serial echocardiographic examinations may provide insights into the mechanisms underlying the therapeutic effect of aficamten in this prespecified exploratory analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Symptomatic patients with nonobstructive hypertrophic cardiomyopathy were randomized 1:1 to receive aficamten (range, 5\u201320 mg, titration based on left ventricular [LV] ejection fraction) or placebo for up to 72 weeks (end of treatment). The effect of aficamten on echocardiographic measures at 36 weeks (time of primary end point) and end of treatment was assessed with linear regression models adjusted for baseline values, intracavity obstruction, and baseline atrial fibrillation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Among 517 participants (mean\u00b1SD: age, 55\u00b116 years; 54% female, 75% White, 13% Asian), mean baseline LV ejection fraction was 68\u00b14% with abnormal measures of diastolic function. Compared with placebo, aficamten decreased LV ejection fraction (\u22124.6% [\u22125.5, \u22123.6];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001) at 36 weeks and increased LV volumes. Aficamten improved measures of diastolic function, including lateral e\u2019 and septal e\u2019 velocities, at 36 weeks (0.9 cm\/s [0.6, 1.2] and 0.7 cm\/s [0.4, 0.9], respectively;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001 for both) and at end of treatment (0.9 cm\/s [0.5, 1.2] and 0.9 cm\/s [0.6, 1.1], respectively;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001 for both) and septal E\/e\u2019 by end of treatment (\u22121.4 [\u22122.1, \u22120.6];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001, respectively). Peak tricuspid regurgitation velocity improved at 36 weeks (\u221210.4 cm\/s [\u221219.9, \u22121.0];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.030) with a sustained effect through end of treatment. Left atrial volume index did not significantly improve at 36 weeks (\u22121.3 [95% CI, \u22122.6, 0.04];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.06) but showed a trend towards improvement with longer treatment exposure (\u22121.7 [\u22123.2, \u22120.3];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.022). Aficamten demonstrated incremental improvements in measures of LV structure and function compared to placebo as doses were increased, with improvement in diastolic indices evident by week 2 of titration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>In patients with nonobstructive hypertrophic cardiomyopathy, aficamten improved echocardiographic measures of diastolic function. These findings suggest that the benefits of aficamten extend beyond the effects of LV outflow tract gradient reduction observed in prior studies.<\/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.126.082343","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T14:15:31Z","timestamp":1788012931000},"page":"1563-1576","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Effect of Aficamten on Cardiac Structure and Function in Patients With Symptomatic Nonobstructive Hypertrophic Cardiomyopathy"],"prefix":"10.1161","volume":"154","clinical-trial-number":[{"clinical-trial-number":"nct06081894","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8157-8899","authenticated-orcid":true,"given":"Sheila M.","family":"Hegde","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Epidemiology, University of Texas Southwestern Medical Center, Dallas (S.M.H.)."},{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Boston, MA (S.M.H., X.W., B.L.C., C.Y.H., N.K.L., M.R., S.D.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5374-7832","authenticated-orcid":true,"given":"Xiaowen","family":"Wang","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Boston, MA (S.M.H., X.W., B.L.C., C.Y.H., N.K.L., M.R., S.D.S.)."}],"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":"General Hospital of H.U. 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