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肥厚型心肌病患者中心肌球蛋白抑制剂的革命。

The Revolution of Cardiac Myosin Inhibitors in Patients With Hypertrophic Cardiomyopathy.

机构信息

The Hypertrophic Cardiomyopathy Center, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, USA.

The Hypertrophic Cardiomyopathy Center, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, USA.

出版信息

Can J Cardiol. 2024 May;40(5):800-819. doi: 10.1016/j.cjca.2024.01.022. Epub 2024 Jan 26.

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy worldwide and causes significant morbidity and mortality. For decades, medical treatment options have been limited and untargeted, with frequent need for invasive interventions not readily accessible to many HCM patients. More recently, our understanding of the genetic basis and pathophysiologic mechanism of HCM has grown significantly, leading to the discovery of a new class of medications, cardiac myosin inhibitors (CMIs), that shift myosin into the super-relaxed state to counteract the hypercontractility in HCM. Subsequent clinical trials have proven the mechanism and efficacy of CMIs in humans with obstructive HCM, and additional trials are under way in patients with nonobstructive HCM. With favourable results in the completed clinical trials and ongoing research on the horizon, CMIs represent a bright new era in the targeted management of HCM. This review is focused on the discovery of CMIs, provides a summary of the results of clinical trials to date, provides clinicians with a roadmap for implementing CMIs into practice, and identifies gaps in our current understanding as well as areas of ongoing investigation.

摘要

肥厚型心肌病(HCM)是全球最常见的遗传性心肌病,可导致严重的发病率和死亡率。几十年来,医学治疗选择一直受到限制且无针对性,许多 HCM 患者无法轻易获得频繁需要的侵入性干预措施。最近,我们对 HCM 的遗传基础和病理生理机制的理解有了显著的提高,这导致了一类新型药物——肌球蛋白抑制剂(CMIs)的发现,它将肌球蛋白转化为超松弛状态,以抵消 HCM 的过度收缩。随后的临床试验已经证明了 CMI 在梗阻性 HCM 患者中的作用机制和疗效,并且正在进行非梗阻性 HCM 患者的额外试验。在已完成的临床试验中取得了良好的结果,并且正在进行的研究也有了新的进展,CMIs 代表了 HCM 靶向治疗的一个光明新时代。这篇综述重点介绍了 CMI 的发现,总结了迄今为止临床试验的结果,为临床医生提供了将 CMI 应用于实践的路线图,并确定了我们目前理解中的差距以及正在进行的研究领域。

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