Ho Carolyn Y, McMurray John J V, Cirino Allison L, Colan Steven D, Day Sharlene M, Desai Akshay S, Lipshultz Steven E, MacRae Calum A, Shi Ling, Solomon Scott D, Orav E John, Braunwald Eugene
Brigham and Women's Hospital, Boston, MA, USA.
University of Glasgow, Glasgow, United Kingdom.
Am Heart J. 2017 May;187:145-155. doi: 10.1016/j.ahj.2017.02.008. Epub 2017 Feb 16.
Hypertrophic cardiomyopathy (HCM) is often caused by sarcomere gene mutations, resulting in left ventricular hypertrophy (LVH), myocardial fibrosis, and increased risk of sudden cardiac death and heart failure. Studies in mouse models of sarcomeric HCM demonstrated that early treatment with an angiotensin receptor blocker (ARB) reduced development of LVH and fibrosis. In contrast, prior human studies using ARBs for HCM have targeted heterogeneous adult cohorts with well-established disease. The VANISH trial is testing the safety and feasibility of disease-modifying therapy with an ARB in genotyped HCM patients with early disease.
A randomized, placebo-controlled, double-blind clinical trial is being conducted in sarcomere mutation carriers, 8 to 45 years old, with HCM and no/minimal symptoms, or those with early phenotypic manifestations but no LVH. Participants are randomly assigned to receive valsartan 80 to 320 mg daily (depending on age and weight) or placebo. The primary endpoint is a composite of 9 z-scores in domains representing myocardial injury/hemodynamic stress, cardiac morphology, and function. Total z-scores reflecting change from baseline to final visits will be compared between treatment groups. Secondary endpoints will assess the impact of treatment on mutation carriers without LVH, and analyze the influence of age, sex, and genotype.
The VANISH trial is testing a new strategy of disease modification for treating sarcomere mutation carriers with early HCM, and those at risk for its development. In addition, further insight into disease mechanisms, response to therapy, and phenotypic evolution will be gained.
肥厚型心肌病（HCM）通常由肌节基因突变引起，导致左心室肥厚（LVH）、心肌纤维化，以及心脏性猝死和心力衰竭风险增加。对肌节性HCM小鼠模型的研究表明，早期使用血管紧张素受体阻滞剂（ARB）治疗可减少LVH和纤维化的发展。相比之下，此前针对HCM使用ARB的人体研究针对的是病情已确诊的异质成年人群。VANISH试验正在测试在患有早期疾病的基因分型HCM患者中使用ARB进行疾病修饰治疗的安全性和可行性。
正在对年龄在8至45岁、患有HCM且无症状或症状轻微，或有早期表型表现但无LVH的肌节突变携带者进行一项随机、安慰剂对照、双盲临床试验。参与者被随机分配接受每日80至320毫克缬沙坦（根据年龄和体重）或安慰剂治疗。主要终点是代表心肌损伤/血流动力学应激、心脏形态和功能的9个z评分的综合指标。将比较治疗组之间反映从基线到最后一次访视变化的总z评分。次要终点将评估治疗对无LVH的突变携带者的影响，并分析年龄、性别和基因型的影响。
VANISH试验正在测试一种治疗早期HCM肌节突变携带者及其发病风险人群的疾病修饰新策略。此外，还将进一步深入了解疾病机制、对治疗的反应和表型演变。
