麦卡姆坦对中国梗阻性肥厚型心肌病患者心脏磁共振特征的影响。

Effects of Mavacamten on Cardiac Magnetic Resonance Features in Chinese Patients With Obstructive Hypertrophic Cardiomyopathy.

作者信息

Tian Zhuang, Li Liwen, Li Xiaoyan, Zhang Qing, Peng Daoquan, Ma Wei, Yang Ping, Wang Fang, Cheng Xiang, Fu Yiqun, Sun Jing, Wang Jian'an, Zhang Shuyang

机构信息

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China.

出版信息

JACC Asia. 2025 Aug;5(8):1064-1074. doi: 10.1016/j.jacasi.2025.05.015. Epub 2025 Jul 8.

DOI:10.1016/j.jacasi.2025.05.015

PMID:40632050

Abstract

BACKGROUND

Mavacamten, a first-in-class cardiac myosin inhibitor and the only approved cardiac myosin inhibitor worldwide, improved clinical symptoms and health status in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) in phase 3 EXPLORER-HCM (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy; NCT03470545) and EXPLORER-CN (A Study to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults With Symptomatic Obstructive HCM; NCT05174416).

OBJECTIVES

The purpose of this work was to study the effect of mavacamten on cardiac structure and function by cardiac magnetic resonance (CMR) imaging in Chinese participants in EXPLORER-CN.

METHODS

Eligible patients with obstructive HCM underwent CMR imaging at screening and week 30. Change from baseline to week 30 in left ventricular (LV) mass index was analyzed as a prespecified secondary outcome. Prespecified exploratory outcomes included changes in cellular hypertrophy, cardiac structure and function, and myocardial fibrosis by CMR.

RESULTS

Among 81 patients randomized, 58 patients (mean age 51.2 years, 74.1% men) with CMR data available were analyzed (mavacamten, n = 39; placebo, n = 19). After 30 weeks, greater reductions from baseline were observed (mean between-group difference) with mavacamten vs placebo in LV mass index (-30.8 g/m [95% CI: -41.5 to -20.1 g/m]), maximal LV wall thickness (-3.5 mm [95% CI: -4.7 to -2.4 mm]), and maximal left atrial volume index (-18.3 mL/m [95% CI: -26.7 to -9.8 mL/m]); all nominal P < 0.001. Reduction from baseline to week 30 in global mass of late gadolinium enhancement by 6 SDs was also observed with mavacamten vs placebo (mean between-group difference, -2.0 g [95% CI: -11.9 to 8.0 g]; nominal P = 0.007).

CONCLUSIONS

At 30 weeks, improvements were observed in measures of cardiac structure and function, with reductions in indicators of myocardial fibrosis, in the mavacamten vs the placebo group. (A Study to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults With Symptomatic Obstructive HCM; NCT05174416).

摘要

背景

玛伐卡坦是首个获批的心脏肌球蛋白抑制剂，也是全球唯一获批的心脏肌球蛋白抑制剂，在3期EXPLORER - HCM（评估玛伐卡坦[MYK - 461]治疗有症状梗阻性肥厚型心肌病成人患者的临床研究；NCT03470545）和EXPLORER - CN（评估玛伐卡坦治疗有症状梗阻性肥厚型心肌病中国成人患者的疗效和安全性的研究；NCT05174416）中改善了有症状梗阻性肥厚型心肌病（HCM）患者的临床症状和健康状况。

目的

本研究旨在通过心脏磁共振成像（CMR）研究玛伐卡坦对EXPLORER - CN研究中中国参与者心脏结构和功能的影响。

方法

符合条件的梗阻性HCM患者在筛选时和第30周接受CMR成像。将左心室（LV）质量指数从基线到第30周的变化作为预先设定的次要结局进行分析。预先设定的探索性结局包括通过CMR评估的细胞肥大、心脏结构和功能以及心肌纤维化的变化。

结果

在81例随机分组的患者中，对58例（平均年龄51.2岁，74.1%为男性）有CMR数据的患者进行了分析（玛伐卡坦组，n = 39；安慰剂组，n = 19）。30周后，与安慰剂相比，玛伐卡坦组左心室质量指数（-30.8 g/m²[95%CI：-41.5至-20.1 g/m²]）、最大左心室壁厚度（-3.5 mm[95%CI：-4.7至-2.4 mm]）和最大左心房容积指数（-18.3 mL/m²[95%CI：-26.7至-9.8 mL/m²]）从基线的降低幅度更大；所有名义P<0.001。与安慰剂相比，玛伐卡坦组从基线到第30周晚期钆增强的总体质量也降低了6个标准差（组间平均差异，-2.0 g[95%CI：-11.9至8.0 g]；名义P = 0.007）。