PDF(Pubmed)
Abstract：
Hypertrophic cardiomyopathy (HCM) is a genetic disease characterized by unexplained left ventricular hypertrophy (LVH), diastolic dysfunction, and increased sudden-death risk. Early detection of the phenotypic expression of the disease in genetic carriers without LVH (Gen+/Phen-) is crucial for emerging therapies. This clinical study aims to identify echocardiographic predictors of phenotypic development in Gen+/Phen-. Sixteen Gen+/Phen- (one subject with troponin T, six with myosin heavy chain-7, and nine with myosin-binding protein C3 mutations), represented the study population. At first and last visit we performed comprehensive 2D speckle-tracking strain echocardiography. During a follow-up of 8 ± 5 years, five carriers developed LVH (LVH+). At baseline, these patients were older than those who did not develop LVH (LVH-) (30 ± 8 vs. 15 ± 8 years, p = 0.005). LVH+ had reduced peak global strain rate during the isovolumic relaxation period (SRIVR) (0.28 ± 0.05 vs. 0.40 ± 0.11 1/s, p = 0.048) and lower global longitudinal strain (GLS) (-19.8 ± 0.4 vs. -22.3 ± 1.1%; p < 0.0001) than LVH- at baseline. SRIVR and GLS were not correlated with age (overall, p > 0.08). This is the first HCM study investigating subjects before they manifest clinically significant or relevant disease burden or symptomatology, comparing at baseline HCM Gen+/Phen- subjects who will develop LVH with those who will not. Furthermore, we identified highly sensitive, easily obtainable, age- and load-independent echocardiographic predictors of phenotype development in HCM gene carriers who may undergo early preventive treatment.
摘要：
肥厚型心肌病（HCM）是一种以无法解释的左心室肥厚（LVH）为特征的遗传性疾病，舒张功能障碍,增加了猝死的风险。在没有LVH（Gen/Phen-）的遗传携带者中早期检测疾病的表型表达对于新兴疗法至关重要。这项临床研究旨在确定Gen/Phen-表型发展的超声心动图预测因子。16Gen+/Phen-(一名患有肌钙蛋白T的受试者，6个具有肌球蛋白重链7，9个具有肌球蛋白结合蛋白C3突变），代表研究人群。在第一次和最后一次访问时，我们进行了全面的2D斑点追踪应变超声心动图检查。在8±5年的随访中，五个载体发展LVH（LVH+）。在基线,这些患者年龄大于未发生LVH（LVH-）的患者（30±8vs.15±8年,p=0.005)。在等容松弛期（SRIVR）期间，LVH的峰值整体应变率降低（0.28±0.05vs.0.40±0.111/s，p=0.048）和较低的整体纵向应变（GLS）（-19.8±0.4vs.-22.3±1.1%；p<0.0001）比基线时的LVH。SRIVR和GLS与年龄无关(总体而言，p>0.08）。这是第一项HCM研究，在受试者表现出临床意义或相关的疾病负担或症状之前，对受试者进行调查。比较基线HCMGen+/Phen-将发展LVH的受试者与不会发展LVH的受试者。此外，我们发现高度敏感，容易获得,年龄和负荷无关的超声心动图预测可能接受早期预防性治疗的HCM基因携带者表型发展。
