Mavacamten: A First-in-class Oral Modulator of Cardiac Myosin for the Treatment of Symptomatic Hypertrophic Obstructive Cardiomyopathy.

IF 1.9 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS Heart International Pub Date : 2022-01-01 DOI:10.17925/HI.2022.16.2.91
Klevin Roger L Reyes, Gizem Bilgili, Florian Rader
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引用次数: 4

Abstract

Hypertrophic cardiomyopathy is the most common monogenic cardiovascular disease that is caused by sarcomeric protein gene mutations. A hallmark of the most common form of the disease is outflow obstruction secondary to systolic narrowing of the left ventricular outflow tract from septal hypertrophy, mitral valve abnormalities and, most importantly, hyperdynamic contractility. Recent mechanistic studies have identified excessive myosin adenosine triphosphatase activation and actin-myosin cross-bridging as major underlying causes. These studies have led to the development of mavacamten, a first-in-class myosin adenosine triphosphatase inhibitor and the first specific therapy for hypertrophic obstructive cardiomyopathy. Preclinical and subsequent pivotal clinical studies have demonstrated the efficacy and safety of mavacamten. A remarkable improvement among treated patients in peak oxygen consumption, functional capacity, symptom relief and post-exercise left ventricular outflow tract gradient, along with dramatic reductions in heart failure biomarkers, suggests that this new medication will be transformative for the symptom management of hypertrophic obstructive cardiomyopathy. There is also hope and early evidence that mavacamten may delay or obviate the need for invasive septal reduction therapies. In this article, we review the current evidence for the efficacy and safety of mavacamten and highlight important considerations for its clinical use.

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马伐卡坦:治疗症状性肥厚性梗阻性心肌病的一流口服心肌蛋白调节剂。
肥厚性心肌病是由肉瘤蛋白基因突变引起的最常见的单基因心血管疾病。该疾病最常见的特征是左心室流出道收缩狭窄继发于流出道梗阻,这是由室间隔肥大、二尖瓣异常引起的,最重要的是,高动力收缩。最近的机制研究已经确定过度的肌球蛋白腺苷三磷酸酶激活和肌动蛋白-肌球蛋白交叉桥是主要的潜在原因。这些研究导致了马伐卡坦的发展,这是一种一流的肌球蛋白腺苷三磷酸酶抑制剂,也是肥厚性阻塞性心肌病的第一种特异性治疗方法。临床前和随后的关键临床研究已经证明了马伐卡坦的有效性和安全性。治疗后患者在峰值耗氧量、功能容量、症状缓解和运动后左心室流出道梯度方面的显著改善,以及心力衰竭生物标志物的显著降低,表明这种新药将对肥厚性阻塞性心肌病的症状管理产生革命性的影响。也有希望和早期证据表明,马伐卡坦可能延迟或消除侵入性间隔缩小治疗的需要。在这篇文章中,我们回顾了目前关于马伐卡坦的有效性和安全性的证据,并强调了其临床使用的重要注意事项。
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来源期刊
Heart International
Heart International Medicine-Cardiology and Cardiovascular Medicine
CiteScore
0.90
自引率
0.00%
发文量
9
审稿时长
7 weeks
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