Hypertrophic Cardiomyopathy Center (M.Y.D., Y.O., A.G., Z.B.P.), Heart Vascular and Thoracic Institute, Cleveland Clinic, OH.
Department of Cardiovascular Medicine (M.Y.D., Y.O., A.G., S.E.N., Z.B.P.), Heart Vascular and Thoracic Institute, Cleveland Clinic, OH.
Circ Cardiovasc Imaging. 2024 Sep;17(9):e017185. doi: 10.1161/CIRCIMAGING.124.017185. Epub 2024 Sep 2.
In severely symptomatic patients with obstructive hypertrophic cardiomyopathy, VALOR-HCM (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy) demonstrated that mavacamten reduces the need for septal reduction therapy with sustained improvement in left ventricular (LV) outflow tract gradients and symptoms. Global longitudinal strain (GLS), a measure of regional myocardial function, is a more sensitive marker of systolic function. In VALOR-HCM, we assessed serial changes in LV and right ventricular (RV) strain.
VALOR-HCM included 112 patients with symptomatic obstructive hypertrophic cardiomyopathy (mean, 60 years; 51% male; LV ejection fraction, 68%). Patients assigned to mavacamten at baseline continued the drug for 56 weeks (n=56) and those assigned to placebo (n=52) transitioned to mavacamten from weeks 16 to 56 (40-week exposure). LV-GLS and RV-GLS assessment was performed using a vendor-neutral software. Non-foreshortened apical (4-, 3-, and 2-chamber) views were used to obtain peak LV-GLS. RV focused 4-chamber view was used to calculate RV 4-chamber and free wall strain. A more negative strain value is favorable.
At baseline, the mean LV-GLS, RV 4-chamber, and free wall strain values were -14.7%, -22.2%, and -16.8%, respectively (all worse than reported normal means). In the total study sample, LV-GLS significantly improved from baseline to week 56 (=0.02). Twelve patients had transient reduction in LV ejection fraction (<50%) requiring temporary drug interruption (including 3 permanent discontinuations). The LV-GLS in this subgroup was worse at baseline versus total study population (-11.4%), with no significant worsening from baseline through week 56 (=0.64). Both free wall and 4-chamber RV-GLS remained unchanged from baseline to week 56 (=0.62 and =0.56, respectively).
In VALOR-HCM, treatment with mavacamten improved LV-GLS from baseline through week 56 (with no significant worsening of LV-GLS in patients with a reduction in LV ejection fraction ≤50%), suggesting a favorable long-term impact on regional LV systolic function. Additionally, there was no detrimental impact on RV systolic function.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT04349072.
在有严重症状的梗阻性肥厚型心肌病患者中，VALOR-HCM（一项评估马卡塞坦在有适应证行间隔心肌切除术的有症状梗阻性肥厚型心肌病成人患者中的疗效的研究）显示马卡塞坦可降低行间隔心肌切除术的需求，并持续改善左心室流出道梯度和症状。整体纵向应变（GLS）是一种衡量局部心肌功能的更敏感的指标。在 VALOR-HCM 中，我们评估了 LV 和右心室（RV）应变的连续变化。
VALOR-HCM 纳入了 112 例有症状梗阻性肥厚型心肌病患者（平均年龄 60 岁；51%为男性；左心室射血分数为 68%）。基线时被分配至马卡塞坦的患者继续接受 56 周治疗（n=56），而被分配至安慰剂的患者（n=52）从第 16 周至第 56 周（40 周暴露期）转换为马卡塞坦。使用供应商中立软件进行 LV-GLS 和 RV-GLS 评估。非短缩心尖（4、3 和 2 腔）视图用于获得峰值 LV-GLS。RV 焦点 4 腔视图用于计算 RV 4 腔和游离壁应变。负值越大表示情况越好。
基线时，平均 LV-GLS、RV 4 腔和游离壁应变值分别为-14.7%、-22.2%和-16.8%（均差于报告的正常均值）。在整个研究样本中，LV-GLS 从基线至第 56 周显著改善（=0.02）。12 例患者出现左心室射血分数一过性降低（＜50%），需要暂时中断药物治疗（包括 3 例永久性停药）。该亚组的基线 LV-GLS 差于总体研究人群（-11.4%），且从基线至第 56 周无显著恶化（=0.64）。游离壁和 4 腔 RV-GLS 从基线至第 56 周均无变化（=0.62 和=0.56）。
在 VALOR-HCM 中，马卡塞坦治疗可改善 LV-GLS 从基线至第 56 周（在左心室射血分数降低至≤50%的患者中，LV-GLS 无显著恶化），提示对局部左心室收缩功能有长期的有利影响。此外，对 RV 收缩功能无不良影响。
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