{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:55:12Z","timestamp":1788951312795,"version":"build-2803163510"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract\u2014<\/jats:title>\n                    <jats:p>Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder, with an overall prevalence of at least 1:500 in the adult population although only a fraction of affected patients come to clinical recognition. It is also the most common cause of sudden cardiac death in young adults and a major cause of morbidity caused by chronic heart failure symptoms. However, more than half a century since the original description of the disease, there is no currently approved therapy for the treatment of patients with HCM, and to date there have been only 5 randomized studies of medical therapies in HCM. As such, unmet medical need in HCM has been highlighted by the National Heart, Lung, and Blood Institute (NHLBI) as a research priority. Encouragingly, the infrastructure needed to conduct rigorous clinical trials in HCM has recently emerged because of the heightened awareness and understanding of the disease, development of clinical centers of excellence, and advances in diagnostic imaging. In this article, we will discuss the complex pathophysiology of HCM, review the current therapeutic landscape, describe new mechanistic insights into the central role of the late sodium current in HCM, and introduce the scientific rationale and execution of the Impact of Late Sodium Current Inhibition on Exercise Capacity in Subjects with Symptomatic Hypertrophic Cardiomyopathy (LIBERTY-HCM) trial, the largest randomized, double-blind, placebo controlled clinical trial, now underway, designed to evaluate the effect of a novel pharmacological approach in patients with symptomatic HCM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration\u2014<\/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=\"http:\/\/www.clinicaltrials.gov\">http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      . Unique identifier: NCT02291237.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circheartfailure.115.002764","type":"journal-article","created":{"date-parts":[[2016,2,25]],"date-time":"2016-02-25T23:33:29Z","timestamp":1456443209000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":57,"title":["Novel Approach Targeting the Complex Pathophysiology of Hypertrophic Cardiomyopathy"],"prefix":"10.1161","volume":"9","author":[{"given":"Iacopo","family":"Olivotto","sequence":"first","affiliation":[{"name":"From the Referral Center for Cardiomyopathies, Careggi University Hospital, Florence, Italy (I.O.); Gilead Sciences, Inc, Foster City, CA (J.L.H., R.F.-F., C.B., L.B.); Department of Preclinical and Clinical Pharmacology and Center of Molecular Medicine, University of Florence, Florence, Italy (R.C.); Veterans Affairs Palo Alto Health Care System and Stanford University, Palo Alto, CA (J.M.); and Hypertrophic Cardiomyopathy Center, Division of Cardiology, Tufts Medical Center, Boston, MA (M.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Hellawell","sequence":"additional","affiliation":[{"name":"From the Referral Center for Cardiomyopathies, Careggi University Hospital, Florence, Italy (I.O.); Gilead Sciences, Inc, Foster City, CA (J.L.H., R.F.-F., C.B., L.B.); Department of Preclinical and Clinical Pharmacology and Center of Molecular Medicine, University of Florence, Florence, Italy (R.C.); Veterans Affairs Palo Alto Health Care System and Stanford University, Palo Alto, CA (J.M.); and Hypertrophic Cardiomyopathy Center, Division of Cardiology, Tufts Medical Center, Boston, MA (M.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramin","family":"Farzaneh-Far","sequence":"additional","affiliation":[{"name":"From the Referral Center for Cardiomyopathies, Careggi University Hospital, Florence, Italy (I.O.); Gilead Sciences, Inc, Foster City, CA (J.L.H., R.F.-F., C.B., L.B.); Department of Preclinical and Clinical Pharmacology and Center of Molecular Medicine, University of Florence, Florence, Italy (R.C.); Veterans Affairs Palo Alto Health Care System and Stanford University, Palo Alto, CA (J.M.); and Hypertrophic Cardiomyopathy Center, Division of Cardiology, Tufts Medical Center, Boston, MA (M.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiana","family":"Blair","sequence":"additional","affiliation":[{"name":"From the Referral Center for Cardiomyopathies, Careggi University Hospital, Florence, Italy (I.O.); Gilead Sciences, Inc, Foster City, CA (J.L.H., R.F.-F., C.B., L.B.); Department of Preclinical and Clinical Pharmacology and Center of Molecular Medicine, University of Florence, Florence, Italy (R.C.); Veterans Affairs Palo Alto Health Care System and Stanford University, Palo Alto, CA (J.M.); and Hypertrophic Cardiomyopathy Center, Division of Cardiology, Tufts Medical Center, Boston, MA (M.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Coppini","sequence":"additional","affiliation":[{"name":"From the Referral Center for Cardiomyopathies, Careggi University Hospital, Florence, Italy (I.O.); Gilead Sciences, Inc, Foster City, CA (J.L.H., R.F.-F., C.B., L.B.); Department of Preclinical and Clinical Pharmacology and Center of Molecular Medicine, University of Florence, Florence, Italy (R.C.); Veterans Affairs Palo Alto Health Care System and Stanford University, Palo Alto, CA (J.M.); and Hypertrophic Cardiomyopathy Center, Division of Cardiology, Tufts Medical Center, Boston, MA (M.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Myers","sequence":"additional","affiliation":[{"name":"From the Referral Center for Cardiomyopathies, Careggi University Hospital, Florence, Italy (I.O.); Gilead Sciences, Inc, Foster City, CA (J.L.H., R.F.-F., C.B., L.B.); Department of Preclinical and Clinical Pharmacology and Center of Molecular Medicine, University of Florence, Florence, Italy (R.C.); Veterans Affairs Palo Alto Health Care System and Stanford University, Palo Alto, CA (J.M.); and Hypertrophic Cardiomyopathy Center, Division of Cardiology, Tufts Medical Center, Boston, MA (M.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz","family":"Belardinelli","sequence":"additional","affiliation":[{"name":"From the Referral Center for Cardiomyopathies, Careggi University Hospital, Florence, Italy (I.O.); Gilead Sciences, Inc, Foster City, CA (J.L.H., R.F.-F., C.B., L.B.); Department of Preclinical and Clinical Pharmacology and Center of Molecular Medicine, University of Florence, Florence, Italy (R.C.); Veterans Affairs Palo Alto Health Care System and Stanford University, Palo Alto, CA (J.M.); and Hypertrophic Cardiomyopathy Center, Division of Cardiology, Tufts Medical Center, Boston, MA (M.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin S.","family":"Maron","sequence":"additional","affiliation":[{"name":"From the Referral Center for Cardiomyopathies, Careggi University Hospital, Florence, Italy (I.O.); Gilead Sciences, Inc, Foster City, CA (J.L.H., R.F.-F., C.B., L.B.); Department of Preclinical and Clinical Pharmacology and Center of Molecular Medicine, University of Florence, Florence, Italy (R.C.); Veterans Affairs Palo Alto Health Care System and Stanford University, Palo Alto, CA (J.M.); and Hypertrophic Cardiomyopathy Center, Division of Cardiology, Tufts Medical Center, Boston, MA (M.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.10.1308"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60397-3"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht439"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.950089"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.644682"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht309.P2969"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0b013e318223e2bd"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0b013e318223e230"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs150"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.02.090"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCINTERVENTIONS.109.916676"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa021332"},{"key":"e_1_3_3_14_2","article-title":"Hypertrophic cardiomyopathy.","author":"Maron, BJ.","year":"2011","unstructured":"Maron, BJ. 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