肥厚型心肌病(HCM)是当代常见的,可治疗,可以与正常寿命相容的遗传性疾病。虽然目前的医疗疗法无处不在,他们受到缺乏确凿证据的限制,往往是不够的,耐受性差,并且不改变自然病程。因此,长期以来一直需要有效的,以证据为基础,和针对HCM的靶向疾病修饰疗法。在这次审查中,我们将HCM重新定义为可治疗的疾病,评估当前的治疗干预策略,并讨论了新型肌球蛋白抑制剂。大多数HCM患者的左心室流出道梯度升高,这预示了更严重的症状和不良后果。有症状的HCM的常规药物治疗可以帮助改善症状,但通常不足且耐受性差。中隔复位治疗(手术性肌切除术和酒精中隔消融)可以安全有效地减轻阻塞性HCM患者的难治性症状并改善预后。然而,它们需要的专业知识不是普遍可用的,也不是没有风险的。目前,可用的治疗方法不会改变病程或随之而来的进行性心脏重塑,也没有随后的心力衰竭和心律失常。这被认为是HCM患者护理中未满足的需求。新型靶向药物疗法,即心肌肌球蛋白抑制剂,已经出现逆转关键的病理生理变化并改变疾病进程。他们的有利结果导致了食品和药物管理局的早期批准,一流的肌球蛋白调节剂,改变了HCM的药物治疗模式。
Hypertrophic cardiomyopathy (HCM) is a common contemporary, treatable, genetic disorder that can be compatible with normal longevity. While current medical therapies are ubiquitous, they are limited by a lack of solid evidence, are often inadequate, poorly tolerated, and do not alter the natural disease course. As such, there has long been a need for effective, evidence-based, and targeted disease-modifying therapies for HCM. In this
review, we redefine HCM as a treatable condition, evaluate current strategies for therapeutic intervention, and discuss novel myosin inhibitors. The majority of patients with HCM have elevated left ventricular outflow tract gradients, which predicts worse symptoms and adverse outcomes. Conventional pharmacological therapies for symptomatic HCM can help improve symptoms but are often inadequate and poorly tolerated. Septal reduction therapies (surgical myectomy and alcohol septal ablation) can safely and effectively reduce refractory symptoms and improve outcomes in patients with obstructive HCM. However, they require expertise that is not universally available and are not without risks. Currently, available therapies do not alter the disease course or the progressive cardiac remodeling that ensues, nor subsequent heart failure and arrhythmias. This has been regarded as an unmet need in the care of HCM patients. Novel targeted pharmacotherapies, namely cardiac myosin inhibitors, have emerged to reverse key pathophysiological changes and alter disease course. Their favorable outcomes led to the early Food and Drug Administration approval of mavacamten, a first-in-class myosin modulator, changing the paradigm for the pharmacological treatment of HCM.