Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
Departments of Internal Medicine and Biomedical and Health Informatics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA.
JACC Heart Fail. 2024 Mar;12(3):567-579. doi: 10.1016/j.jchf.2023.07.030. Epub 2023 Oct 18.
Hypertension (HTN) is common in patients with hypertrophic cardiomyopathy (HCM), but its effect on the treatment of left ventricular outflow tract (LVOT) obstruction is undefined. Although elevated systolic blood pressure (SBP) may impact dynamic LVOT gradients, its response to cardiac myosin inhibition is unknown.
In a post hoc exploratory analysis of the EXPLORER-HCM trial (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy), the authors examined the characteristics of patients with obstructive HCM and HTN and the associations between HTN, SBP, and the response to mavacamten treatment of LVOT obstruction.
Patients were stratified by baseline history of HTN and mean SBP during 30-week treatment with mavacamten or placebo. The study estimated treatment differences and evaluated HTN and SBP groups by treatment interaction. Analysis of covariance was used to model changes in continuous endpoints, and a generalized linear model was used for binary endpoints.
HTN was present in 119 of 251 patients (47.4%), including 60 receiving mavacamten and 59 receiving placebo. Patients with HTN vs no HTN were older (63.4 vs 54.0 years; P < 0.001), had higher SBP (134 ± 15.1 mm Hg vs 123 ± 13.8 mm Hg; P < 0.001), more comorbidities, and lower peak oxygen consumption (19 ± 3 vs 20 ± 4 mL/kg/min; P = 0.021). Patients with HTN had similar NYHA functional class (NYHA functional class II, 72% vs 73%), Valsalva LVOT gradients (72 ± 34 mm Hg vs 74 ± 30 mm Hg), Kansas City Cardiomyopathy Questionnaire-Clinical Summary Scores (70.6 ± 18.8 vs 68.9 ± 23.1), and NT pro-B-type natriuretic peptide levels (geometric mean 632 ± 129 pg/mL vs 745 ± 130 pg/mL). Mavacamten-treated patients had improvement in all primary, secondary, and exploratory endpoints regardless of HTN status or mean SBP.
The clinical benefits of mavacamten in symptomatic, obstructive HCM were similar in patients with and without HTN, despite differences in baseline characteristics. (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy [EXPLORER-HCM]; NCT03470545).
高血压（HTN）在肥厚型心肌病（HCM）患者中很常见，但它对左心室流出道（LVOT）梗阻治疗的影响尚不清楚。尽管收缩压（SBP）升高可能会影响 LVOT 动态梯度，但尚不清楚其对心肌肌球蛋白抑制的反应。
在 EXPLORER-HCM 试验（一项评估 Mavacamten [MYK-461] 治疗有症状的梗阻性肥厚型心肌病成人患者的临床研究）的事后探索性分析中，作者研究了梗阻性 HCM 和 HTN 患者的特征，以及 HTN、SBP 与 mavacamten 治疗 LVOT 梗阻反应之间的关系。
根据基线时 HTN 病史和 30 周 mavacamten 或安慰剂治疗期间的平均 SBP，将患者分层。研究估计了治疗差异，并通过治疗相互作用评估了 HTN 和 SBP 组。采用协方差分析模型对连续终点进行建模，采用广义线性模型对二项终点进行建模。
251 例患者中有 119 例（47.4%）存在 HTN，其中 60 例接受 mavacamten 治疗，59 例接受安慰剂治疗。与无 HTN 患者相比，HTN 患者年龄更大（63.4 岁 vs 54.0 岁；P < 0.001），SBP 更高（134 ± 15.1 mmHg vs 123 ± 13.8 mmHg；P < 0.001），合并症更多，峰值耗氧量更低（19 ± 3 毫升/公斤/分钟 vs 20 ± 4 毫升/公斤/分钟；P = 0.021）。HTN 患者的 NYHA 心功能分级（NYHA 心功能分级 II，72% vs 73%）、瓦尔萨尔瓦左心室流出道梯度（72 ± 34 毫米汞柱 vs 74 ± 30 毫米汞柱）、堪萨斯城心肌病问卷-临床总结评分（70.6 ± 18.8 分 vs 68.9 ± 23.1 分）和 NT pro-B 型利钠肽水平（几何均数 632 ± 129 pg/mL vs 745 ± 130 pg/mL）相似。接受 mavacamten 治疗的患者无论 HTN 状态或平均 SBP 如何，所有主要、次要和探索性终点均有改善。
尽管基线特征存在差异，但在有症状的梗阻性 HCM 患者中，mavacamten 的临床获益在有和无 HTN 的患者中相似。（一项评估 Mavacamten [MYK-461] 治疗有症状的梗阻性肥厚型心肌病成人患者的临床研究[EXPLORER-HCM]；NCT03470545）。
