Hypertrophic cardiomyopathy (HCM) is often caused by pathogenic variants in sarcomeric genes and characterized by left ventricular (LV) hypertrophy, myocardial fibrosis and increased risk of heart failure and arrhythmias. There are no existing therapies to modify disease progression. In this study, we conducted a multi-center, double-blind, placebo-controlled phase 2 clinical trial to assess the safety and efficacy of the angiotensin II receptor blocker valsartan in attenuating disease evolution in early HCM. In total, 178 participants with early-stage sarcomeric HCM were randomized (1:1) to receive valsartan (320 mg daily in adults; 80–160 mg daily in children) or placebo for 2 years (NCT01912534). Standardized changes from baseline to year 2 in LV wall thickness, mass and volumes; left atrial volume; tissue Doppler diastolic and systolic velocities; and serum levels of high-sensitivity troponin T and N-terminal pro-B-type natriuretic protein were integrated into a single composite z-score as the primary outcome. Valsartan (n = 88) improved cardiac structure and function compared to placebo (n = 90), as reflected by an increase in the composite z-score (between-group difference +0.231, 95% confidence interval (+0.098, +0.364); P = 0.001), which met the primary endpoint of the study. Treatment was well-tolerated. These results indicate a key opportunity to attenuate disease progression in early-stage sarcomeric HCM with an accessible and safe medication.

肥厚型心肌病 (HCM) 通常由肌节基因的致病变异引起，其特征是左心室 (LV) 肥大、心肌纤维化以及心力衰竭和心律失常的风险增加。没有现有的疗法来改变疾病进展。在这项研究中，我们进行了一项多中心、双盲、安慰剂对照的 2 期临床试验，以评估血管紧张素 II 受体阻滞剂缬沙坦在减轻早期 HCM 疾病进展方面的安全性和有效性。总共有 178 名患有早期肌节性 HCM 的参与者被随机分配（1:1）接受缬沙坦（成人每天 320 毫克；儿童每天 80-160 毫克）或安慰剂治疗 2 年（NCT01912534）。LV 壁厚、质量和体积从基线到第 2 年的标准化变化；左心房容积；组织多普勒舒张和收缩速度；高敏肌钙蛋白 T 和 N 端前 B 型利尿钠蛋白的血清水平被整合到一个单一的复合物中z分数作为主要结果。 与安慰剂 ( n = 90) 相比，缬沙坦 ( n = 88) 改善了心脏结构和功能 ，这反映在复合z评分的增加（组间差异 +0.231, 95% 置信区间 (+0.098, +0.364) ; P  = 0.001)，符合研究的主要终点。治疗耐受性良好。这些结果表明，通过可获得和安全的药物来减缓早期肌节 HCM 疾病进展的关键机会。