Abstract：
BACKGROUND: 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.
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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).
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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).
摘要：
背景：高血压（HTN）在肥厚型心肌病（HCM）患者中很常见，但其对左心室流出道（LVOT）梗阻的治疗效果尚不明确。尽管收缩压（SBP）升高可能会影响动态LVOT梯度，它对心肌肌球蛋白抑制的反应是未知的。
目的：在EXPLORER-HCM试验的事后探索性分析中（评估Mavacamten[MYK-461]在成人症状性阻塞性肥厚性心肌病中的临床研究），作者检查了阻塞性HCM和HTN患者的特征以及HTN之间的关联，SBP,以及对Mavacampen治疗LVOT梗阻的反应。
方法：在使用mavacampen或安慰剂的30周治疗期间，根据基线HTN病史和平均SBP对患者进行分层。该研究评估了治疗差异，并通过治疗相互作用评估了HTN和SBP组。协方差分析用于对连续端点的变化进行建模，并将广义线性模型用于二元端点。
结果：HTN在251例患者中有119例（47.4％），包括60名接受mavacamten和59名接受安慰剂。HTN患者与无HTN患者年龄较大（63.4vs54.0岁；P<0.001），SBP较高（134±15.1mmHgvs123±13.8mmHg；P<0.001），更多的合并症，和较低的峰值耗氧量（19±3vs20±4mL/kg/min；P=0.021）。患有HTN的患者具有相似的NYHA功能等级（NYHA功能等级II，72%对73%)，ValsalvaLVOT梯度（72±34mmHgvs74±30mmHg），堪萨斯城心肌病问卷-临床摘要评分（70.6±18.8vs68.9±23.1），和NTB型利钠肽前体水平（几何平均值632±129pg/mLvs745±130pg/mL）。Mavacamten治疗的患者在所有原发性患者中都有改善，次要,和探索性终点，无论HTN状态或平均SBP。
结论：mavacamten在症状，阻塞性HCM在有和没有HTN的患者中相似，尽管基线特征存在差异。（评估Mavacamten[MYK-461]在有症状的阻塞性肥厚型心肌病[EXPLORER-HCM]成人中的临床研究；NCT03470545）。
目的：在EXPLORER-HCM试验的事后探索性分析中（评估Mavacamten[MYK-461]在成人症状性阻塞性肥厚性心肌病中的临床研究），作者检查了阻塞性HCM和HTN患者的特征以及HTN之间的关联，SBP,以及对Mavacampen治疗LVOT梗阻的反应。
方法：在使用mavacampen或安慰剂的30周治疗期间，根据基线HTN病史和平均SBP对患者进行分层。该研究评估了治疗差异，并通过治疗相互作用评估了HTN和SBP组。协方差分析用于对连续端点的变化进行建模，并将广义线性模型用于二元端点。
结果：HTN在251例患者中有119例（47.4％），包括60名接受mavacamten和59名接受安慰剂。HTN患者与无HTN患者年龄较大（63.4vs54.0岁；P<0.001），SBP较高（134±15.1mmHgvs123±13.8mmHg；P<0.001），更多的合并症，和较低的峰值耗氧量（19±3vs20±4mL/kg/min；P=0.021）。患有HTN的患者具有相似的NYHA功能等级（NYHA功能等级II，72%对73%)，ValsalvaLVOT梯度（72±34mmHgvs74±30mmHg），堪萨斯城心肌病问卷-临床摘要评分（70.6±18.8vs68.9±23.1），和NTB型利钠肽前体水平（几何平均值632±129pg/mLvs745±130pg/mL）。Mavacamten治疗的患者在所有原发性患者中都有改善，次要,和探索性终点，无论HTN状态或平均SBP。
结论：mavacamten在症状，阻塞性HCM在有和没有HTN的患者中相似，尽管基线特征存在差异。（评估Mavacamten[MYK-461]在有症状的阻塞性肥厚型心肌病[EXPLORER-HCM]成人中的临床研究；NCT03470545）。
