In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), the VALOR-HCM (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy) trial showed that mavacamten reduced the eligibility for septal reduction therapy with sustained improvement in left ventricular outflow tract gradients. Mavacamten also resulted in favorable cardiac remodeling, including improvement in biomarkers (eg, N-terminal pro–B-type natriuretic peptide and troponin T). However, the impact of mavacamten on left atrial (LA) function is unknown. The aim of this study was to assess serial changes in LA strain measures in patients enrolled in the VALOR-HCM trial. VALOR-HCM included 112 symptomatic patients with obstructive HCM (mean age 60 years; 51% male). Patients assigned to receive mavacamten at baseline (n = 56) continued therapy for 56 weeks and those assigned to placebo transitioned to mavacamten (n = 52) from week 16 to week 56. Echocardiographic LA strain (reservoir, conduit, and contraction) was measured by using a vendor-neutral postprocessing software. At baseline, the mean LA volume index (LAVI) and LA strain values (conduit, contraction, and reservoir) were 41.3 ± 16.5 mL/m, −11.8% ± 6.5%, −8.7% ± 5.0%, and 20.5% ± 8.7%, respectively (all worse than reported normal). LAVI significantly improved by −5.6 ± 9.7 mL/m from baseline to week 56 ( 0.001). There was a significant ( 0.05) improvement in absolute LA strain values from baseline to week 56 (conduit [−1.7% ± 6%], contraction [−1.2% ± 4.5%], and reservoir [2.8% ± 7.7%]). Patients originally receiving placebo had no differences in LA measurements up to week 16. There was no significant improvement in LA strain values (conduit [−0.9% ± 3.8%], contraction [−0.4% ± 3.4%], and reservoir [1.4% ± 6.1%]; all; NS) from baseline to week 56 in patients with history of atrial fibrillation. In VALOR-HCM, mavacamten resulted in an improvement in LAVI and LA strain at week 56, suggesting sustained favorable LA remodeling and improved function, except in the atrial fibrillation subgroup. Whether the advantageous LA remodeling associated with long-term treatment with mavacamten results in a favorable impact on the observed high burden of atrial tachyarrhythmias in HCM remains to be proven. (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy [VALOR-HCM]; )

中文翻译：

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阻塞性 HCM 中 Mavacamten 相关左心房功能的时间变化：来自 VALOR-HCM 试验的见解


在症状严重的梗阻性肥厚型心肌病 (HCM) 患者中，VALOR-HCM（一项评估 Mavacamten 治疗有资格接受室间隔复位治疗的症状性梗阻性肥厚性心肌病成人患者的研究）试验表明，mavacamten 降低了室间隔复位治疗的资格，并且持续左心室流出道梯度的改善。 Mavacamten 还导致了有利的心脏重塑，包括生物标志物的改善（例如，N 端 B 型利尿钠肽原和肌钙蛋白 T）。然而，mavacamten 对左心房 (LA) 功能的影响尚不清楚。本研究的目的是评估参加 VALOR-HCM 试验的患者 LA 应变测量值的连续变化。 VALOR-HCM 包括 112 名有症状的阻塞性 HCM 患者（平均年龄 60 岁；51% 为男性）。基线时分配接受 mavacamten 的患者 (n = 56) 继续治疗 56 周，分配安慰剂的患者从第 16 周至第 56 周过渡到 mavacamten (n = 52)。测量超声心动图 LA 应变（储层、导管和收缩）通过使用供应商中立的后处理软件。基线时，平均 LA 体积指数 (LAVI) 和 LA 应变值（导管、收缩和储库）分别为 41.3 ± 16.5 mL/m、-11.8% ± 6.5%、-8.7% ± 5.0% 和 20.5% ± 8.7 %（均低于报告的正常值）。到第 56 周，LAVI 较基线显着改善 -5.6 ± 9.7 mL/m (0.001)。从基线到第 56 周，绝对 LA 应变值显着 (0.05) 改善（导管 [−1.7% ± 6%]、收缩 [−1.2% ± 4.5%] 和储库 [2.8% ± 7.7%]）。最初接受安慰剂的患者在第 16 周之前 LA 测量值没有差异。 从基线到第 56 周，LA 应变值（导管 [−0.9% ± 3.8%]、收缩 [−0.4% ± 3.4%] 和储库 [1.4% ± 6.1%]；全部；NS）没有显着改善。有房颤病史的患者。在 VALOR-HCM 中，第 56 周时，mavacamten 改善了 LAVI 和 LA 应变，表明除心房颤动亚组外，持续有利的 LA 重塑和功能改善。与长期使用 mavacamten 治疗相关的有利的左心室重构是否会对 HCM 中观察到的房性快速心律失常的高负担产生有利影响仍有待证明。（一项评估 Mavacamten 对有症状的梗阻性肥厚性心肌病成人患者的研究，这些患者有资格接受间隔复位治疗 [VALOR-HCM]；）