Tian Zhuang, Li Xiaoyan, Li Liwen, Zhang Qing, Wang Jian'an, Shi Yunqi, Peng Daoquan, Yang Ping, Ma Wei, Wang Fang, Jin Wei, Cheng Xiang, Chen Yu-Mao, Zhong Yue, Barrett Yu Chen, Zheng Jing, Zhang Shuyang
Peking Union Medical College Hospital, No. 1 Shuaifuyuan, Wangfujing Dongcheng District, Beijing, China.
Renmin Hospital of Wuhan University, Hubei General Hospital, Wuhan, China.
Cardiol Ther. 2025 Jun;14(2):267-282. doi: 10.1007/s40119-025-00409-5. Epub 2025 Apr 29.
Mavacamten, a cardiac myosin inhibitor, has demonstrated positive outcomes in left ventricular outflow tract (LVOT) gradient reduction and improvements of symptoms and function in Chinese patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) in EXPLORER-CN. This exploratory analysis aimed to evaluate the effect of mavacamten on echocardiographic measures of cardiac structure and function and its relationship with other clinical biomarkers.
Key echocardiographic parameters acquired over 30 weeks from 81 patients (n = 54 on mavacamten and n = 27 on placebo) were assessed in a central laboratory.
At 30 weeks, greater improvements in measures of diastolic function were observed with mavacamten versus placebo, including lateral E/e' (least-squares mean [LSM] change from baseline [CFB] - 5.1 vs. 0.6; between-group LSM difference - 5.7; 95% confidence interval [CI] - 7.6 to - 3.7), septal E/e' (LSM CFB - 6.0 vs. - 0.3; between-group LSM difference - 5.7; 95% CI - 7.8 to - 3.7), and left atrial volume index (LAVI) (LSM CFB - 11.7 vs. - 3.5 ml/m; between-group LSM difference - 8.2; 95% CI - 12.0 to - 4.4) (nominal p < 0.001 for all). Twelve patients (23.1%) treated with mavacamten had complete resolution of mitral valve systolic anterior motion (SAM) versus two patients (7.4%) receiving placebo. Among mavacamten-treated patients, reductions in resting and Valsalva LVOT gradients, left ventricular (LV) mass index, LAVI, and lateral and septal E/e' were associated with reduced N-terminal pro-B-type natriuretic peptide levels (nominal p < 0.0001 for all). In the mavacamten group, reductions in LVOT gradients and LV end-diastolic interventricular septal thickness were associated with improved patient-reported Kansas City Cardiomyopathy Questionnaire Overall Summary Score (nominal p < 0.05 for all).
Clinically meaningful improvements were evident in Chinese patients treated with mavacamten compared with placebo in several hallmarks of obstructive HCM, including measures of LV diastolic function, SAM, and LVOT gradient. These results add further evidence to support the positive effects of mavacamten in cardiac remodeling.
ClinicalTrials.gov identifier: NCT05174416.
麦卡姆坦是一种心肌肌球蛋白抑制剂，在EXPLORER-CN研究中，已证明其在降低中国有症状梗阻性肥厚型心肌病（HCM）患者的左心室流出道（LVOT）梯度以及改善症状和功能方面有积极效果。这项探索性分析旨在评估麦卡姆坦对心脏结构和功能的超声心动图测量指标的影响及其与其他临床生物标志物的关系。
在一个中心实验室对81例患者（54例服用麦卡姆坦，27例服用安慰剂）在30周内获取的关键超声心动图参数进行了评估。
在30周时，与安慰剂相比，麦卡姆坦在舒张功能指标方面有更大改善，包括侧壁E/e'（从基线[CFB]的最小二乘均值[LSM]变化为-5.1对0.6；组间LSM差异为-5.7；95%置信区间[CI]-7.6至-3.7）、室间隔E/e'（LSM CFB为-6.0对-0.3；组间LSM差异为-5.7；95%CI-7.8至-3.7）和左心房容积指数（LAVI）（LSM CFB为-11.7对-3.5ml/m²；组间LSM差异为-8.2；95%CI-12.0至-4.4）（所有名义p<0.001）。12例（23.1%）接受麦卡姆坦治疗的患者二尖瓣收缩期前向运动（SAM）完全消失，而接受安慰剂治疗的患者有2例（7.4%）。在接受麦卡姆坦治疗的患者中，静息和瓦尔萨尔瓦动作时LVOT梯度、左心室（LV）质量指数、LAVI以及侧壁和室间隔E/e'的降低与N末端B型利钠肽前体水平降低相关（所有名义p<0.0001）。在麦卡姆坦组中，LVOT梯度和LV舒张末期室间隔厚度的降低与患者报告的堪萨斯城心肌病问卷总体总结评分改善相关（所有名义p<0.05）。
与安慰剂相比，接受麦卡姆坦治疗的中国患者在梗阻性HCM的几个特征方面有明显的临床意义上的改善，包括LV舒张功能指标、SAM和LVOT梯度。这些结果进一步证明了麦卡姆坦在心脏重塑方面的积极作用。
ClinicalTrials.gov标识符：NCT05174416。
