Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, 2108 Tupper Hall, One Shields Ave, Davis, CA, 95616, USA.
Research and Non-Clinical Development, Cytokinetics, Inc., South San Francisco, CA, USA.
Sci Rep. 2023 Jan 2;13(1):32. doi: 10.1038/s41598-022-26630-z.
Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiac disease in humans and cats and lacks efficacious pharmacologic interventions in the preclinical phase of disease. LV outflow tract obstruction (LVOTO) is commonly observed in HCM-affected patients and is a primary driver of heart failure symptoms and reduced quality of life. Novel small-molecule cardiac myosin inhibitors target actin-myosin interactions to alleviate overactive protein interactions. A prospective, randomized, controlled cross-over study was performed to evaluate pharmacodynamic effects of two doses (0.3 and 1 mg/kg) of a next-in-class cardiac myosin inhibitor, aficamten (CK-3773274, CK-274), on cardiac function in cats with the A31P MYBPC3 mutation and oHCM. Dose-dependent reductions in LV systolic function, LVOT pressure gradient, and isovolumetric relaxation times compared to baseline were observed. Promising beneficial effects of reduced systolic function warrant further studies of this next-in-class therapeutic to evaluate the benefit of long-term administration in this patient population.
肥厚型心肌病（HCM）是人类和猫中最常见的遗传性心脏病，在疾病的临床前阶段缺乏有效的药物干预措施。左心室流出道梗阻（LVOTO）在 HCM 受影响的患者中很常见，是心力衰竭症状和生活质量降低的主要驱动因素。新型小分子肌球蛋白抑制剂靶向肌动球蛋白相互作用，以减轻过度活跃的蛋白相互作用。进行了一项前瞻性、随机、对照交叉研究，以评估两种剂量（0.3 和 1mg/kg）新型肌球蛋白抑制剂 aficamten（CK-3773274，CK-274）对 A31P MYBPC3 突变和 oHCM 猫的心脏功能的药效学影响。与基线相比，观察到左心室收缩功能、LVOT 压力梯度和等容舒张时间的剂量依赖性降低。收缩功能降低的可喜有益作用，需要进一步研究这种新型治疗方法，以评估该患者人群长期给药的益处。
