Department of Cardiovascular Medicine (P.C.C., W.A.J., S.C.H., Q.W., K.W., S.E.N., M.Y.D.), Cleveland Clinic, OH.
Cleveland Clinic Coordinating Center for Clinical Research Heart Vascular and Thoracic Institute (P.C.C., W.A.J., S.C.H., Q.W., K.W., S.E.N., M.Y.D.), Cleveland Clinic, OH.
Circ Cardiovasc Imaging. 2022 Dec;15(12):e014986. doi: 10.1161/CIRCIMAGING.122.014986. Epub 2022 Nov 6.
In the randomized phase 3 VALOR-HCM study (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy) of patients with obstructive hypertrophic cardiomyopathy, mavacamten reduced the need for septal reduction therapy. Because mavacamten improves ventricular compliance, this sub-study examined the effects of treatment with this cardiac myosin inhibitor on diastolic function.
Symptomatic obstructive hypertrophic cardiomyopathy patients on maximally tolerated medical therapy referred for septal reduction therapy were randomized 1:1 to mavacamten or placebo. At baseline and week 16, a resting and stress echocardiogram was performed with interpretation by a core laboratory. In this exploratory substudy, the principal end point was the change in parameters used to define the grade of diastolic function in patients treated with mavacamten and placebo. A related objective was to assess the proportion of patients with an improvement in diastolic function grade. A secondary aim was to assess for correlation between diastolic function parameters and the secondary end points from VALOR-HCM: New York Heart Association class, quality of life, and cardiac biomarkers.
Diastolic dysfunction grade was evaluable in 98 patients at baseline and week 16. Among patients treated with mavacamten, 29.4% (15 of 51) demonstrated improvement in diastolic function grade compared with 12.8% (6 of 47) patients with placebo (=0.05). Average E/e' ratio decreased significantly in patients treated with mavacamten (-3.4±5.3) compared with placebo (0.57±3.5; <0.001). Indexed left atrial volumes (mL/m) also decreased significantly in patients who received mavacamten (-5.2±7.8) compared with placebo (-0.51±8.1; =0.005). After adjustment for change in left ventricular outflow tract gradient and mitral regurgitation, mavacamten was significantly associated with a decrease in average E/e' ratio and indexed left atrial volumes. Change in average E/e' ratio was significantly correlated with the secondary end points from VALOR-HCM.
In this exploratory substudy, after 16 weeks of therapy, mavacamten improved diastolic function, and this change correlated with improvement in clinical and biomarker end points.
URL: https://www.
gov; Unique identifier: NCT04349072.
在梗阻性肥厚型心肌病的 3 期随机 VALOR-HCM 研究（一项评价米伐卡坦治疗有适应证行间隔心肌切除术的梗阻性肥厚型心肌病成人患者的研究）中，米伐卡坦降低了行间隔心肌切除术的需求。由于米伐卡坦改善心室顺应性，本亚组研究旨在探讨这种心肌肌球蛋白抑制剂对舒张功能的影响。
接受最大耐受药物治疗的有症状梗阻性肥厚型心肌病患者，经转诊后行间隔心肌切除术，按 1:1 随机分为米伐卡坦组或安慰剂组。在基线和 16 周时，由核心实验室进行静息和应激超声心动图检查并进行解读。在这项探索性亚组研究中，主要终点是治疗米伐卡坦和安慰剂的患者舒张功能分级参数的变化。相关目标是评估舒张功能分级改善的患者比例。次要目的是评估舒张功能参数与 VALOR-HCM 的次要终点之间的相关性：纽约心脏协会（NYHA）心功能分级、生活质量和心脏生物标志物。
在基线和 16 周时，98 例患者可评估舒张功能分级。与安慰剂组（6/47，12.8%）相比，米伐卡坦组（15/51，29.4%）有 29.4%的患者舒张功能分级改善（=0.05）。与安慰剂组相比，米伐卡坦组的平均 E/e' 比值显著降低（-3.4±5.3 对 0.57±3.5；<0.001）。米伐卡坦组的左心房容积指数（mL/m）也显著降低（-5.2±7.8 对-0.51±8.1；=0.005）。在校正左心室流出道梯度和二尖瓣反流的变化后，米伐卡坦与平均 E/e' 比值和左心房容积指数的降低显著相关。平均 E/e' 比值的变化与 VALOR-HCM 的次要终点显著相关。
在这项探索性亚组研究中，经过 16 周的治疗，米伐卡坦改善了舒张功能，这种改善与临床和生物标志物终点的改善相关。
网址：https://www.
gov；独特标识符：NCT04349072。
