Background The late sodium current inhibitor ranolazine reverses the main electrophysiological and mechanical abnormalities of human hypertrophic cardiomyopathy (HCM) cardiomyocytes in vitro, suggesting potential clinical benefit. We aimed to assess the effect of ranolazine on functional capacity, symptomatic status, diastolic function, and arrhythmias in HCM.

Methods and Results In this multicenter, double-blind, phase 2 study, 80 adult patients with nonobstructive HCM (age 53±14 years, 34 women) were randomly assigned to placebo (n=40) or ranolazine 1000 mg bid (n=40) for 5 months. The primary end point was change in peak VO₂ compared with baseline using cardiopulmonary exercise test. Echocardiographic lateral and septal E/E′ ratio, prohormone brain natriuretic peptide levels, 24-hour Holter arrhythmic profile, and quality of life were assessed. Ranolazine was safe and well tolerated. Overall, there was no significant difference in VO₂ peak change at 5 months in the ranolazine versus placebo group (delta 0.15±3.96 versus −0.02±4.25 mL/kg per minute; P=0.832). Ranolazine treatment was associated with a reduction in 24-hour burden of premature ventricular complexes compared with placebo (>50% reduction versus baseline in 61% versus 31%, respectively; P=0.042). However, changes in prohormone brain natriuretic peptide levels did not differ in the ranolazine compared with the placebo group (geometric mean median [interquartile range], −3 pg/mL [−107, 142 pg/mL] versus 78 pg/mL [−71, 242 pg/mL]; P=0.251). Furthermore, E/E′ ratio and quality of life scores showed no significant difference.

Conclusions In patients with nonobstructive HCM, ranolazine showed no overall effect on exercise performance, plasma prohormone brain natriuretic peptide levels, diastolic function, or quality of life. The drug showed an excellent safety profile and was associated with reduced premature ventricular complex burden. Late sodium current inhibition does not seem to improve functional capacity in HCM.

Clinical Trial Registration: URL: https://www.clinicaltrialsregister.eu. Unique identifier: 2011-004507-20

背景晚期钠电流抑制剂雷诺嗪在体外逆转了人类肥厚型心肌病（HCM）心肌细胞的主要电生理和机械异常，表明潜在的临床益处。我们旨在评估雷诺嗪对HCM功能能力，症状状态，舒张功能和心律不齐的影响。

方法和结果在这项多中心，双盲，2期研究中，将80例成年非阻塞性HCM患者（年龄53±14岁，34名女性）随机分配至安慰剂（n = 40）或雷诺嗪1000 mg bid（n = 40）。 ）的5个月。主要终点是使用心肺运动测试与基线相比，VO ₂峰值的变化。评估了超声心动图的外侧和中隔E / E'比，激素原脑钠肽水平，24小时动态心电图心律失常情况以及生活质量。雷诺嗪是安全的，耐受性良好。总体而言，雷诺嗪组与安慰剂组在5个月时VO ₂峰值变化无显着差异（δ0.15±3.96 vs -0.02±4.25 mL / kg /分钟；P= 0.832）。与安慰剂相比，雷诺嗪治疗可减少24小时过早的心室复合物负担（相对于基线，分别减少61％和31％，减少50％以上；P = 0.042）。但是，雷诺嗪与安慰剂组相比，激素前脑利钠肽水平的变化没有差异（几何平均中位数[四分位间距]，-3 pg / mL [−107，142 pg / mL]与78 pg / mL [- 71，242 pg / mL]; P = 0.251）。此外，E / E'比和生活质量得分无明显差异。

结论在非阻塞性HCM患者中，雷诺嗪对运动表现，血浆激素原脑利钠肽水平，舒张功能或生活质量没有总体影响。该药物显示出极好的安全性，并与减少过早的心室复杂负担相关。晚期钠电流抑制似乎并未改善HCM的功能。

临床试验注册： URL：https://www.clinicaltrialsregister.eu。唯一标识符：2011-004507-20