{
  "abstract": "BackgroundCardiac myosin inhibitors (CMIs) directly target sarcomeric hypercontractility and have demonstrated clinical efficacy in obstructive hypertrophic cardiomyopathy (HCM). In symptomatic non-obstructive HCM (nHCM), the phase 3 randomized controlled trials (RCT) differed in whether their primary efficacy endpoints reached statistical significance, although the direction and magnitude of treatment effects were broadly comparable. We therefore conducted a systematic review and meta-analysis to synthesize the randomized evidence on the efficacy and safety of CMIs in symptomatic nHCM.\n\nMethodsWe systematically searched for randomized placebo-controlled trials evaluating CMIs in adults with symptomatic nHCM according to PRISMA guidance and a prospectively registered protocol (PROSPERO CRD420261466576). Primary efficacy outcomes were changes from baseline in peak oxygen uptake (pVO2) and Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), assessed at each trials primary endpoint. Secondary outcomes included improvement by at least 1 New York Heart Association (NYHA) functional class and change in N-terminal pro-B-type natriuretic peptide (NT-proBNP). The safety outcome was LVEF <50%. Random-effects models were used to pool mean differences (MDs), risk ratios (RRs), and ratios of geometric mean changes.\n\nResultsThree RCTs comprising 1,156 participants were included: MAVERICK-HCM, ODYSSEY-HCM, and ACACIA-HCM. Compared with placebo, CMIs were associated with improvements in pVO2 (MD, 0.55 mL/kg/min; 95% CI, 0.22-0.87; I2=0%; P=0.001) and KCCQCSS (MD, 2.71 points; 95% CI, 0.87-4.55; I2=0%; P=0.004). Improvement by at least 1 NYHA functional class was more frequent with CMIs (RR, 1.29; 95% CI, 1.03-1.62; I2=24.3%; P=0.024). Across the two phase 3 trials, CMIs reduced NT-proBNP (ratio of geometric mean changes, 0.42; 95% CI, 0.39-0.46; I2=0%; P<0.001), while LVEF <50% occurred more frequently with CMIs (RR, 12.77; 95% CI, 5.98-27.27; I2=0%; P<0.001).\n\nConclusionsIn this meta-analysis of randomized trials in symptomatic nHCM, CMIs pooled estimates favoured CMIs over placebo for improvements in exercise capacity, health status, and NYHA functional class, together with a marked reduction in NT-proBNP. These potential benefits were accompanied by an increased risk of LVEF reduction below 50%.",
  "abstract_shown": true,
  "affiliations": [
    "Institute for Cardiomyopathies Heidelberg (ICH.), University Hospital Heidelberg, Heidelberg Faculty of Medicine, Heidelberg University"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "J. Koelemen"
    },
    {
      "name": "D. Koeckerling"
    },
    {
      "name": "S. Rosskopf"
    },
    {
      "name": "C. Reich"
    },
    {
      "name": "A. Amr"
    },
    {
      "name": "E. Kayvanpour"
    },
    {
      "name": "N. Frey"
    },
    {
      "name": "F. Sedaghat-Hamedani"
    },
    {
      "affs": [
        0
      ],
      "name": "B. Meder"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2x2srw0mhevgs.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.08.26362195",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.08.26362195v1.full",
  "id": "2x2srw0mhevgs",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.08.26362195v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "cardiovascular medicine"
    ],
    [
      "openalex",
      "2705|Cardiomyopathy and Myosin Studies"
    ]
  ],
  "openalex": "W7212368890",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.08.26362195v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-08",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2x2srw0mhevgs.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:23Z",
      "native_id": "10.64898/2026.09.08.26362195",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.08.26362195v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:cardiovascular medicine",
      "subfield": "cardiovascular"
    }
  ],
  "title": "Cardiac Myosin Inhibitors in Adults with Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy: A Systematic Review and Meta-analysis of Randomized Controlled Trials",
  "title_text": "Cardiac Myosin Inhibitors in Adults with Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy: A Systematic Review and Meta-analysis of Randomized Controlled Trials",
  "type": "preprint",
  "updated_at": "2026-10-30T12:18:23Z",
  "url": "https://research.draconitic.com/paper/2x2srw0mhevgs",
  "venue": "medRxiv",
  "versions": []
}