Pagel Paul S, Hang Dustin, Freed Julie K, Crystal George J
Department of Anesthesiology, the Medical College of Wisconsin, Milwaukee, WI.
Department of Anesthesiology, the Medical College of Wisconsin, Milwaukee, WI.
J Cardiothorac Vasc Anesth. 2025 May;39(5):1287-1305. doi: 10.1053/j.jvca.2025.02.009. Epub 2025 Feb 7.
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy. The disease is characterized by asymmetric left ventricular (LV) remodeling with myocyte disarray and interstitial fibrosis, a hypercontractile state, dynamic subaortic obstruction of the LV outflow tract, impaired LV diastolic function, atrial and ventricular arrhythmias, and sudden cardiac death. HCM occurs as a result of pathological alterations in the cardiac myocyte's chemomechanical cycle, in which an enhanced rate of myosin-actin crossbridge formation and destabilization of the energy-conserving "super-relaxed off-actin state" of myosin play essential roles. For decades, management of HCM has been limited almost exclusively to medications (eg, beta-blockers, calcium channel blockers, disopyramide) and interventions (eg, septal reduction therapy, implanted cardioverter-defibrillator devices) that palliate symptoms, but do not address the disease's underlying causative mechanisms. A new class of cardiovascular medications, cardiac myosin inhibitors, has surged to the forefront of HCM treatment in recent years. These drugs, including mavacamten and aficamten, show great promise to profoundly affect the disease's clinical course. In this article, the authors review the molecular mechanisms of action of cardiac myosin inhibitors, discuss in detail the most recent data from mavacamten and aficamten clinical trials, describe future planned studies designed to address unanswered questions about their clinical utility in HCM phenotypes, and comment on their potential application to patients with other forms of heart failure with preserved ejection fraction. The possible anesthetic implications of mavacamten and aficamten are also discussed because it is highly likely that patients who are treated with these medications will begin to present for perioperative care with increasing regularity.
肥厚型心肌病（HCM）是最常见的遗传性心肌病。该疾病的特征是左心室（LV）不对称重塑，伴有心肌细胞排列紊乱和间质纤维化、高收缩状态、LV流出道动态主动脉下梗阻、LV舒张功能受损、房性和室性心律失常以及心源性猝死。HCM是心肌细胞化学机械循环发生病理改变的结果，其中肌球蛋白-肌动蛋白横桥形成速率加快以及肌球蛋白节能的“超松弛离肌动蛋白状态”不稳定起着至关重要的作用。几十年来，HCM的治疗几乎完全局限于缓解症状的药物（如β受体阻滞剂、钙通道阻滞剂、丙吡胺）和干预措施（如间隔减容治疗、植入式心脏复律除颤器装置），但并未解决该疾病的潜在致病机制。近年来，一类新型心血管药物——心肌肌球蛋白抑制剂已跃居HCM治疗的前沿。这些药物，包括mavacamten和aficamten，有望对该疾病的临床病程产生深远影响。在本文中，作者回顾了心肌肌球蛋白抑制剂的分子作用机制，详细讨论了mavacamten和aficamten临床试验的最新数据，描述了未来计划开展的研究，旨在解决关于它们在HCM表型中的临床效用的未决问题，并评论了它们在其他射血分数保留的心力衰竭患者中的潜在应用。还讨论了mavacamten和aficamten可能的麻醉影响，因为接受这些药物治疗的患者很可能会越来越频繁地接受围手术期护理。
