{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:29:05Z","timestamp":1787963345268,"version":"build-2784847793"},"reference-count":25,"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":[[2020,6]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by unexplained left ventricular (LV) hypertrophy associated with dynamic LV outflow tract obstruction. Current medical therapies are nonspecific and have limited efficacy in relieving symptoms. Mavacamten is a first-in-class targeted inhibitor of cardiac myosin, which has been shown to reduce LV outflow tract obstruction, improve exercise capacity, and relieve symptoms of oHCM in the PIONEER-HCM phase 2 study.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>EXPLORER-HCM is a multicenter, phase 3, randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of mavacamten in treating symptomatic oHCM. Eligible adults with oHCM and New York Heart Association Functional Class II or III are randomized 1:1 to receive once-daily, oral mavacamten, or matching placebo for 30 weeks. The primary composite functional end point is clinical response at week 30 compared to baseline defined as either (1) an increase in peak oxygen consumption \u22651.5 mL\/kg\/min and reduction of at least one New York Heart Association class; or (2) an improvement of \u22653.0 mL\/kg\/min in peak oxygen consumption with no worsening of New York Heart Association class. Secondary end points include change in postexercise LV outflow tract gradient, New York Heart Association class, peak oxygen consumption, and patient-reported outcomes assessed by the Kansas City Cardiomyopathy Questionnaire and a novel HCM-specific instrument. Exploratory end points aim to characterize the effect of mavacamten on multiple aspects of oHCM pathophysiology.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>EXPLORER-HCM is a phase 3 trial in oHCM testing a first-in-class, targeted strategy of myosin inhibition to improve symptom burden and exercise capacity through reducing LV outflow tract obstruction. Results of this trial will provide evidence to support the first disease-specific treatment for HCM.<\/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: NCT03470545.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.120.006853","type":"journal-article","created":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T09:01:40Z","timestamp":1591347700000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":84,"title":["Study Design and Rationale of EXPLORER-HCM"],"prefix":"10.1161","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7334-7924","authenticated-orcid":false,"given":"Carolyn Y.","family":"Ho","sequence":"first","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Boston, MA (C.Y.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iacopo","family":"Olivotto","sequence":"additional","affiliation":[{"name":"Careggi University Hospital, Florence, Italy (I.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Jacoby","sequence":"additional","affiliation":[{"name":"Yale University, New Haven, CT (D.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Lester","sequence":"additional","affiliation":[{"name":"Mayo Clinic, Phoenix, AZ (S.J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Roe","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Durham, NC (M.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Wang","sequence":"additional","affiliation":[{"name":"Duke University School of Medicine, Durham, NC (A.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia Burstein","family":"Waldman","sequence":"additional","affiliation":[{"name":"HCMBeat.com, Los Angeles, CA (C.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Zhang","sequence":"additional","affiliation":[{"name":"MyoKardia, Inc, Brisbane, CA (D.Z., A.J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy J.","family":"Sehnert","sequence":"additional","affiliation":[{"name":"MyoKardia, Inc, Brisbane, CA (D.Z., A.J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen B.","family":"Heitner","sequence":"additional","affiliation":[{"name":"Knight Cardiovascular Institute, Oregon Health and Sciences University, Portland (S.B.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1710575"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13496"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0b013e318223e2bd"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu284"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.033200"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2015.06.011"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2017.12.031"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2018.4847"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.117.004124"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.136.suppl_1.15415"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2018.02.025"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2017.02.008"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2015-308343"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12551-017-0274-6"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad3456"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.776815"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1809540115"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.7326\/M18-3016"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hft139"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11136-012-0182-y"},{"key":"e_1_3_5_22_2","first-page":"A14251","article-title":"Peak oxygen consumption is an independent predictor of survival and outcomes in obstructive and non-obstructive hypertrophic cardiomyopathy (HCM) patients: results from the international sarcomeric human cardiomyopathies registry (SHaRe).","volume":"138","author":"Tompkins JDV","year":"2018","unstructured":"Tompkins, JDV, Day, SM, Jacoby, DL, Colan, SD, Olivotto, I, Ashley, EA, Sehnert, AJ, Ho, CY. Peak oxygen consumption is an independent predictor of survival and outcomes in obstructive and non-obstructive hypertrophic cardiomyopathy (HCM) patients: results from the international sarcomeric human cardiomyopathies registry (SHaRe). Circulation. 2018;138:A14251.","journal-title":"Circulation"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.111.965186"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.114.002248"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2015.02.006"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1053\/euhj.2002.3285"}],"container-title":["Circulation: Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCHEARTFAILURE.120.006853","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T01:12:15Z","timestamp":1715562735000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCHEARTFAILURE.120.006853"}},"subtitle":["Evaluation of Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy"],"short-title":[],"issued":{"date-parts":[[2020,6]]},"references-count":25,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["10.1161\/CIRCHEARTFAILURE.120.006853"],"URL":"https:\/\/doi.org\/10.1161\/circheartfailure.120.006853","relation":{},"ISSN":["1941-3289","1941-3297"],"issn-type":[{"value":"1941-3289","type":"print"},{"value":"1941-3297","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6]]},"assertion":[{"value":"2020-06-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e006853"}}