<\/p>\n
The EXPLORER-HCM study (NCT03470545)<\/a> was a Phase III study assessing the utility of mavacamten in symptomatic and echocardiographic improvement in HOCM; similarly, the MAVA-LTE study (NCT03723655)<\/a> is an ongoing, dose-blinded 5-year study of mavacamten. The EXPLORER-LTE cohort is a subset of patients who initially completed the EXPLORER-HCM study and were subsequently enrolled in MAVA-LTE. \u00a0Patients were initially treated with a starting dose of 5mg daily mavacamten, with dose adjustments at 4,8, 12, and 24 weeks depending on Valsalva LVOT measurements. All recruited patients were adults who were previously eligible for the EXPLORER-HCM study. Patients were also required to have an EF >50%. Some relevant exclusion criteria included pregnancy or lactation, advanced atrioventricular block, or history of sustained ventricular tachyarrhythmia, resuscitated cardiac arrest, or appropriate ICD discharge since initial trial enrollment. Other temporary discontinuation criteria included mavacamten plasma trough concentration \u22651000 ng\/mL or increase in QTc >15%.<\/p>\n A total of 231 patients comprised the EXPLORER-LTE cohort as of April 2019; this had decreased to 217 as of the cutoff analysis date of August 31st<\/sup>, 2021. The mean age was 60; the average baseline resting LVOT gradient was 48.3 mmHg with a Valsalva-induced gradient of 69.5 mmHg. Mavacamten use resulted in rapid and sustained improvements in resting (\u221232.8 mmHg at week 84) and Valsalva (-46.4 mmHg at week 84) LVOT gradients. Concordantly, improvements in NYHA functional class were observed, with 67.5% of patients improving by at least one class by week 48. As expected, mild decreases in LVEF were observed (-9% at week 84). BNP reductions were observed as early as week 4 and were sustained through week 84 (-488ng\/L). No new safety concerns were identified relative to previous trials; 26 patients (11%) had temporary medication discontinuations, and 10 patients (4.3%) required permanent discontinuations (2 of which were for persistent LVEF<50%, 1 for heart failure, 1 for cardiac arrest, 1 for myocardial infarction and 1 for prolonged QTc).<\/p>\n When discussing the implications of the study at an ACC press conference, Dr. Rader stated: \u201cThere have been limited medication options for HCM and many patients end up having to go through surgical removal of a portion of the thickened heart muscle or undergo alcohol septal ablation to reduce the obstruction. Although these invasive treatment options are effective, they also have risks. Mavacamten is the first medication specifically designed to relieve this obstruction\u2026it helps patients feel better, and they are able to live a more active life\u2026over time\u2026it may also help keep patients from having to undergo an invasive procedure or open-heart surgery to relieve the obstruction.\u201d<\/p>\n <\/p>\n","protected":false},"excerpt":{"rendered":" Key Points: In the EXPLORER-LTE study, patients with severely symptomatic obstructive HCM previously enrolled in the EXPLORER-HCM study underwent ongoing therapy with mavacamten. The outcomes of interest included changes in resting and Valsalva LVOT gradient, functional class, LVEF, and reduction in BNP. The presence of adverse safety events was also monitored. Treatment with mavacamten led […]<\/p>\n","protected":false},"author":35656,"featured_media":5287,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"aside","meta":{"footnotes":""},"categories":[860],"tags":[47,185],"ppma_author":[1063],"class_list":{"0":"post-114953","1":"post","2":"type-post","3":"status-publish","4":"format-aside","5":"has-post-thumbnail","7":"category-acc-2022","8":"tag-featured","9":"tag-news","10":"post_format-post-format-aside","11":"author-wallyomar"},"authors":[{"term_id":1063,"user_id":35656,"is_guest":0,"slug":"wallyomar","display_name":"WallyOmar","avatar_url":"https:\/\/secure.gravatar.com\/avatar\/a6f105232fa7a2d967ba5e1e19104eeb3b45b6d9e588caf37850c2d596fbcae1?s=96&r=g","0":null,"1":"","2":"","3":"","4":"","5":"","6":"","7":"","8":""}],"_links":{"self":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/114953","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/users\/35656"}],"replies":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=114953"}],"version-history":[{"count":1,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/114953\/revisions"}],"predecessor-version":[{"id":114955,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/114953\/revisions\/114955"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/media\/5287"}],"wp:attachment":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=114953"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=114953"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=114953"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=114953"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}![\"\"](\"https:\/\/cardiologynownews.org\/wp-content\/uploads\/2022\/04\/rader-298x500.jpg\")
Patients with obstructive hypertrophic cardiomyopathy (HOCM) are frequently severely symptomatic and are at risk of progression to advanced heart failure and sudden cardiac death. If patients have failed conservative medical therapy with negative inotropic agents, they are referred for septal reduction therapies (SRT), including either surgical septal myectomy or alcohol septal ablation. A novel medical therapy, mavacamten (a direct cardiac myosin inhibitor which enables reduction in excessive contractility) has been developed \u00a0for patients with HOCM. In a breaking presentation at the 2022 American College of Cardiology Conference today, Dr. Florian Rader<\/a> (Cedars-Sinai Medical Center, Los Angeles) and his team presented \u201cUpdated cumulative results of treatment with mavacamten from the EXPLORER-LTE cohort of the MAVA-LTE study in patients with obstructive hypertrophic cardiomyopathy.\u201d<\/p>\n