{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:05:07Z","timestamp":1793329507640,"version":"4.5.0"},"reference-count":37,"publisher":"American Medical Association (AMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2023,3,1]]},"abstract":"\n Importance<\/jats:title>\n \n Mavacamten, a cardiac myosin inhibitor, improved peak oxygen uptake (pVO\n 2<\/jats:sub>\n ) in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) in the EXPLORER-HCM study. However, the full extent of mavacamten\u2019s effects on exercise performance remains unclear.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To investigate the effect of mavacamten on exercise physiology using cardiopulmonary exercise testing (CPET).<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n Exploratory analyses of the data from the EXPLORER-HCM study, a randomized, double-blind, placebo-controlled, phase 3 trial that was conducted in 68 cardiovascular centers in 13 countries. In total, 251 patients with symptomatic obstructive HCM were enrolled.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Patients were randomly assigned in a 1:1 ratio to mavacamten or placebo.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n \n The following prespecified exploratory cardiovascular and performance parameters were assessed with a standardized treadmill or bicycle ergometer test protocol at baseline and week 30: carbon dioxide output (VCO\n 2<\/jats:sub>\n ), minute ventilation (V\n E<\/jats:sub>\n ), peak V\n E<\/jats:sub>\n \/VCO\n 2<\/jats:sub>\n ratio, ventilatory efficiency (V\n E<\/jats:sub>\n \/VCO\n 2<\/jats:sub>\n slope), peak respiratory exchange ratio (RER), peak circulatory power, ventilatory power, ventilatory threshold, peak metabolic equivalents (METs), peak exercise time, partial pressure of end-tidal carbon dioxide (PETCO\n 2<\/jats:sub>\n ), and VO\n 2<\/jats:sub>\n \/workload slope.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Two hundred fifty-one patients were enrolled. The mean (SD) age was 58.5 (11.9) years and 59% of patients were male. There were significant improvements with mavacamten vs placebo in the following peak-exercise CPET parameters: peak V\n E<\/jats:sub>\n \/VCO\n 2<\/jats:sub>\n ratio (least squares [LS] mean difference, \u22122.2; 95% CI, \u22123.05 to \u22121.26;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001), peak METs (LS mean difference, 0.4; 95% CI, 0.17-0.60;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001), peak circulatory power (LS mean difference, 372.9 mL\/kg\/min\u2009\u00d7\u2009mm Hg; 95% CI, 153.12-592.61;\n P<\/jats:italic>\n \u2009=\u2009.001), and peak PETCO\n 2<\/jats:sub>\n (LS mean difference, 2.0 mm Hg; 95% CI, 1.12-2.79;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). Mavacamten also improved peak exercise time compared with placebo (LS mean difference, 0.7 minutes; 95% CI, 0.13-1.24;\n P<\/jats:italic>\n = .02). There was a significant improvement in nonpeak-exercise CPET parameters, such as V\n E<\/jats:sub>\n \/VCO\n 2<\/jats:sub>\n slope (LS mean difference, \u22122.6; 95% CI, \u22123.58 to \u22121.52;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001) and ventilatory power (LS mean difference, 0.6 mm Hg; 95% CI, 0.29-0.90;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001) favoring mavacamten vs placebo.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n Mavacamten improved a range of CPET parameters beyond pVO\n 2<\/jats:sub>\n , indicating consistent and broad benefits on maximal exercise capacity. Although improvements in peak-exercise CPET parameters are clinically meaningful, the favorable effects of mavacamten on submaximal exertional tolerance provide further insights into the beneficial impact of mavacamten in patients with obstructive HCM.\n <\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT03470545<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamacardio.2022.5099","type":"journal-article","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T11:02:30Z","timestamp":1674039750000},"page":"240","source":"Crossref","is-referenced-by-count":64,"title":["Effects of Mavacamten on Measures of Cardiopulmonary Exercise Testing Beyond Peak Oxygen Consumption"],"prefix":"10.1001","volume":"8","author":[{"given":"Matthew T.","family":"Wheeler","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iacopo","family":"Olivotto","sequence":"additional","affiliation":[{"name":"Azienda Ospedaliera Universitaria Careggi, Florence, Italy"},{"name":"University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perry M.","family":"Elliott","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Science, University College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Saberi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjali T.","family":"Owens","sequence":"additional","affiliation":[{"name":"Center for Inherited Cardiovascular Disease, University of Pennsylvania Perelman School of Medicine, 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