Desai, Milind Y. and Okushi, Yuichiro and Jadam, Shada and Olivotto, Iacopo and Owens, Anjali and Nissen, Steven E. and Popovic, Zoran B. and Garcia-Pavia, Pablo and Lopes, Renato D. and Elliott, Perry M. and Fernandes, Fabio and Geske, Jeffrey B. and Maier, Lars S. and Wolski, Kathy and Wang, Qiuqing and Jaber, Wael and Gong, Zhiqun and Florea, Victoria and Fronheiser, Matthew and Leva, Arlene and Aronson, Ron and Abraham, Theodore (2025) Echocardiographic Changes With Mavacamten in Nonobstructive Hypertrophic Cardiomyopathy Exploratory Insights From the ODYSSEY-HCM Trial. JACC-JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 86 (24): PMID 83013. pp. 2434-2449. ISSN 0735-1097, 1558-3597
Full text not available from this repository. (Request a copy)Abstract
BACKGROUND Symptomatic nonobstructive hypertrophic cardiomyopathy (nHCM) lacks approved therapies. The ODYSSEY-HCM trial (A Study of Mavacamten in Non-Obstructive Hypertrophic Cardiomyopathy; NCT05582395), the largest to date in HCM patients, evaluating the efficacy of mavacamten in symptomatic adults with nHCM, did not demonstrate improvements in its primary endpoints (functional capacity and patient-reported health status). OBJECTIVES This exploratory analysis of the phase 3, randomized, placebo-controlled trial evaluated echocardiographic changes in nHCM patients from baseline to week 48. METHODS Symptomatic nHCM patients were randomized to placebo or mavacamten (5 mg/d, titrated between 1 and 15 mg based on left ventricular ejection fraction [LVEF]). Echocardiographic assessments of LV systolic/diastolic function and left atrial (LA) function were performed at baseline and week 48. RESULTS Among 580 randomized patients (mean age 56 +/- 15 years, 45.9% women), baseline measures included LVEF (65.8 +/- 4%), maximal LV wall thickness (20.8 +/- 4 mm), LV mass index (122.3 +/- 31 g/m(2)), average E/e' (13.3 +/- 6), and LV-global longitudinal strain (-13.2 +/- 4%). LA parameters included volume index (43.5 +/- 16 mL/m(2)), reservoir strain (19.1 +/- 9%), and conduit strain (-11.6 +/- 6%). At week 48, there was significant placebo-corrected treatment difference with patients on mavacamten demonstrating significant reduction in maximal LV wall thickness (-2.1 mm [95% CI: -2.5 to -1.7 mm]), LV mass index (-3.8 g/m(2) [95% CI: -7.1 to -0.5 g/m(2)]), and E/e' (-1.3 [95% CI: -2.0 to -0.7]), with a -5.3% [95% CI: -5.9% to -4.1%]; P < 0.01) reduction in LVEF. A reduction in LVEF <50% occurred in 62 patients (21.5%) in the mavacamten arm vs 5 (1.7%) in the placebo arm and recovered following drug interruption. Patients in the mavacamten group maintaining LVEF >= 50% throughout the study (n = 212) demonstrated an improvement in LV-global longitudinal strain at week 48 (-0.4% [95% CI: -0.8% to -0.05%]; P < 0.05). LA functional parameters including contractile (-1.1% [95% CI: -1.8% to -0.4%]) and conduit (-1.4% [95% CI: -0.6% to -2.3%]) strain also improved significantly at week 48 (P < 0.05), whereas LA volume was significantly reduced in patients without atrial fibrillation (-2.6 mL/m(2) [95% CI: -4.7 to -1.11 mL/m(2)]; P = 0.009). CONCLUSIONS Symptomatic nHCM patients treated with mavacamten demonstrated directional improvements in markers of LV diastolic and LA function, modest regression in LV hypertrophy-related parameters, but 1 in 5 demonstrated an LVEF <50%, which reversed following therapy interruption. (JACC. 2025;86:2434-2449) (c) 2025 by the American College of Cardiology Foundation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | EXPLORER-HCM; DOUBLE-BLIND; LEFT ATRIAL; E/E; echocardiography; mavacamten; nonobstructive HCM; randomized placebo-controlled trial |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Apr 2026 12:31 |
| Last Modified: | 20 Apr 2026 12:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67607 |
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