Effect of Aficamten Compared With Metoprolol on Echocardiographic Measures in Symptomatic Obstructive Hypertrophic Cardiomyopathy: MAPLE-HCM.

IF 22.3 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
Sheila M Hegde, Xiaowen Wang, Pablo Garcia-Pavia, Stoyan Getchevski, Ahmad Masri, Bela Merkely, Michael E Nassif, Maria Luisa Peña-Peña, Roberto Barriales-Villa, Ozlem Bilen, Melissa Burroughs, Brian Claggett, Juan Pablo Costabel, Edileide de Barros Correia, Anne M Dybro, Perry Elliott, Neal K Lakdawala, Amy Mann, Martin S Maron, Ajith Nair, Steen H Poulsen, Patricia Reant, P Christian Schulze, Andrew Wang, Regina Sohn, Indrias Berhane, Stephen B Heitner, Daniel L Jacoby, Stuart Kupfer, Fady I Malik, Amy Wohltman, Michael A Fifer, Scott D Solomon
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引用次数: 0

Abstract

Background: Beta-blockers have formed the mainstay of first-line therapy for symptomatic obstructive hypertrophic cardiomyopathy (HCM) for decades. Aficamten, compared with placebo, lowered left ventricular outflow tract gradients (LVOT-G), improved measures of left ventricular (LV) diastolic function, and showed evidence of favorable remodeling when added to standard of care medical therapy in SEQUOIA-HCM. The comparative effectiveness of monotherapy with aficamten vs metoprolol was investigated in MAPLE-HCM.

Objectives: This study evaluated the effect of monotherapy with aficamten compared with metoprolol on cardiac structure and function in participants enrolled in the MAPLE-HCM study.

Methods: Serial echocardiograms and other clinical measures were collected over 24 weeks in participants receiving escalating doses of aficamten 5 to 20 mg or metoprolol 50 to 200 mg.

Results: The study enrolled 175 participants (mean age 58 ± 13 years, 42% women, 80% White, 14% Asian). Mean left ventricular ejection fraction (LVEF) was 68% ± 4% with resting and Valsalva LVOT-G of 47 ± 29 mm Hg and 74 ± 33 mm Hg, respectively. Compared with metoprolol, aficamten decreased resting LVOT-G (-30 mm Hg [95% CI: -37 to -23 mm Hg]; P < 0.001) and Valsalva LVOT-G (-35 mm Hg [95% CI: -44 to -26 mm Hg]; P < 0.001); reduced left atrial volume index (left atrial volume index -7.0 mL/m2 [95% CI: -9.1 to -4.8 mL/m2]; P < 0.001); and improved E/e' (lateral E/e' -2.8 [95% CI: -4.0 to -1.6]; P < 0.001; septal E/e' -3.1 [95% CI: -4.5 to -1.7]; P < 0.001). Maximal wall thickness decreased (-1.0 mm [95% CI: -1.8 to -0.2 mm]; P = 0.02). LVEF, absolute LV global longitudinal strain, and absolute global circumferential strain decreased (LVEF -4% [95% CI: -5% to -3%]; global longitudinal strain -1.2% [95% CI: -1.8% to -0.5%]; global circumferential strain -2.5% [95% CI: -3.7% to -1.3%]; all P < 0.001) with no significant change in resting cardiac output between groups. Mitral valve systolic anterior motion and mitral regurgitation significantly decreased with aficamten at week 24.

Conclusions: In addition to lowering Valsalva LVOT-G and left atrial volume index, treatment with aficamten compared with metoprolol over 24 weeks led to improvement in measures of LV diastolic function, mitral valve systolic anterior motion, and mitral regurgitation. Aficamten therapy resulted in modest reduction in LVEF compared with metoprolol. These exploratory findings further support the overall superiority of therapy with aficamten over metoprolol demonstrated in MAPLE-HCM with evidence of favorable changes in multiple echocardiographic measures of cardiac structure and function in patients with symptomatic obstructive HCM. (Metoprolol vs Aficamten in Patients with LVOT Obstruction on Exercise Capacity in HCM [MAPLE-HCM]; NCT05767346).

阿非卡坦与美托洛尔对症状性梗阻性肥厚性心肌病超声心动图指标的影响。
背景:几十年来,β受体阻滞剂已成为症状性阻塞性肥厚性心肌病(HCM)一线治疗的主要药物。与安慰剂相比,Aficamten降低了左心室流出道梯度(LVOT-G),改善了左心室舒张功能,并且在SEQUOIA-HCM中加入标准护理药物治疗后显示出有利的重构证据。在MAPLE-HCM中,研究阿非卡坦与美托洛尔单药治疗的比较疗效。目的:本研究评估阿非卡坦单药治疗与美托洛尔对MAPLE-HCM研究参与者心脏结构和功能的影响。方法:在24周内收集连续超声心动图和其他临床指标,受试者接受递增剂量的阿非卡坦5 ~ 20mg或美托洛尔50 ~ 200mg。结果:该研究纳入175名参与者(平均年龄58±13岁,42%为女性,80%为白人,14%为亚洲人)。平均左室射血分数(LVEF)为68%±4%,静息和Valsalva LVOT-G分别为47±29 mm Hg和74±33 mm Hg。与美托洛尔相比,aficamten降低静息LVOT-G (-30 mm Hg [95% CI: -37 ~ -23 mm Hg], P < 0.001)和Valsalva LVOT-G (-35 mm Hg [95% CI: -44 ~ -26 mm Hg], P < 0.001);左房容积指数降低(左房容积指数-7.0 mL/m2 [95% CI: -9.1 ~ -4.8 mL/m2], P < 0.001);改善E/ E′(侧位E/ E′-2.8 [95% CI: -4.0 ~ -1.6], P < 0.001;室间隔E/ E′-3.1 [95% CI: -4.5 ~ -1.7], P < 0.001)。最大壁厚下降(-1.0 mm [95% CI: -1.8至-0.2 mm]; P = 0.02)。LVEF、LV整体绝对纵向应变和整体绝对周向应变下降(LVEF -4% [95% CI: -5%至-3%];整体纵向应变-1.2% [95% CI: -1.8%至-0.5%];整体周向应变-2.5% [95% CI: -3.7%至-1.3%];P均< 0.001),各组间静息心输出量无显著变化。第24周,二尖瓣收缩前运动和二尖瓣反流明显减少。结论:与美托洛尔相比,阿非曲坦治疗24周后,除了降低Valsalva LVOT-G和左房容积指数外,还能改善左室舒张功能、二尖瓣收缩前运动和二尖瓣反流。与美托洛尔相比,阿非曲坦治疗导致LVEF适度降低。这些探索性发现进一步支持了阿非卡坦治疗在MAPLE-HCM中优于美托洛尔的总体优势,并证明了有症状的阻塞性HCM患者的心脏结构和功能的多项超声心动图测量的有利变化。美托洛尔与阿非卡坦在LVOT梗阻患者对HCM运动能力的影响[MAPLE-HCM]; NCT05767346)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
42.70
自引率
3.30%
发文量
5097
审稿时长
2-4 weeks
期刊介绍: The Journal of the American College of Cardiology (JACC) publishes peer-reviewed articles highlighting all aspects of cardiovascular disease, including original clinical studies, experimental investigations with clear clinical relevance, state-of-the-art papers and viewpoints. Content Profile: -Original Investigations -JACC State-of-the-Art Reviews -JACC Review Topics of the Week -Guidelines & Clinical Documents -JACC Guideline Comparisons -JACC Scientific Expert Panels -Cardiovascular Medicine & Society -Editorial Comments (accompanying every Original Investigation) -Research Letters -Fellows-in-Training/Early Career Professional Pages -Editor’s Pages from the Editor-in-Chief or other invited thought leaders
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