多模态影像技术对肌小节蛋白基因突变致家族性肥厚型心肌病的早期诊断与风险预测

项目名称： 多模态影像技术对肌小节蛋白基因突变致家族性肥厚型心肌病的早期诊断与风险预测

项目编号： No.81671693

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 医药、卫生

项目作者： 刘丽文

作者单位： 中国人民解放军第四军医大学

项目金额： 25万元

中文摘要： 家族性肥厚型心肌病(FHCM)是一种常见的遗传性心血管疾病,2014年欧洲心脏学会指南公布FHCM一级亲属的诊断标准为左室室壁厚度≥13mm。文献和我们临床工作发现厚度未及此标准的部分一级亲属超声心动图已出现舒张功能减低与心电图异常,但当前指南除建议每年随访外,对这部分人群具体诊断及是否采取干预尚无明确结论。本项目拟在现有研究基础上，通过结合多模态影像诊断方法(超声心动图、心脏核磁、心电图)和血生化捕捉FHCM肌小节蛋白编码基因突变携带者的心脏结构、血流及收缩和舒张功能、纤维化及心脏电活动的早期改变。通过算法建立基因型与表型间的早期诊断关系，并判断FHCM患者的一级亲属(心脏室壁厚度<13 mm)是否肌小节蛋白突变基因携带者以及是否早期发病。对临床随访资料通过使用Cox比例风险模型建立临床期FHCM与预后不良的风险预测模型，优化随访计划并为进展期高风险者的早期干预提供依据。

中文关键词： 家族性肥厚型心肌病；多模态影像；；肌小节蛋白基因；早期诊断；风险预测

英文摘要： Familial hypertrophic cardiomyopathy (FHCM) is one of the most common inherited cardiovascular diseases. The guideline of European Society of Cardiology published in 2014 indicated the diagnosis standard of the FHCM first-degree relatives is the thickness of left ventricular thickness ≥13mm. However, for some FHCM relatives, both our routine clinical practice and previous research indicated the diastolic dysfunction from echocardiography examination and abnormal electrocardiogram (ECG) prior to reaching the 13mm-thickness of wall. Till now, no confirmed conclusion has been given about the early diagnosis and intervention of FHCM relatives except annual screening. This project aims to characterize mutations in sarcomere protein genes, by acquiring the early variation in cardiac structure, variations in blood flow and globally and regionally systolic and diastolic function, fibrosis and cardiac electrical activity by combining multiple imaging modalities (echocardiography, cardiac magnetic resonance imaging, ECG) and blood chemistry. Multiple algorithms would be applied to establish the relationship between the genotype and imaging phenotype in early diagnosis. Additionally, whether FHCM first-degree relatives with left ventricular thickness <13mm are sarcomere protein gene carriers and whether their early onsets start would be determined and predicted. For clinical follow-ups, prediction model of FHCM with poor prognosis would be established using Cox proportional hazards model. The outcome of this research may optimize the follow-up plan of FHCM relatives and provide the basis for early intervention of the subjects in high risk of progression.

英文关键词： Familial hypertrophic cardiomyopathy;multi-modality imaging;sarcomere protein gene;preclinical diagnosis;risk prediction