Diastolic Function in Hypertrophic Cardiomyopathy

肥厚型心肌病 (HCM) 是一种常染色体显性遗传疾病，由编码肌节蛋白的基因突变引起。肌细胞肥大、肌原纤维纤维化和紊乱是这种疾病的病理标志，传统上被认为会导致舒张功能障碍的发生，而舒张功能障碍是 HCM 的一个特征。我们假设舒张功能异常实际上导致了形态变化的发生，反映了突变肌节收缩性的改变。该提案将利用 aq 基因分型群体来检验舒张异常是 HCM 的最早表现并且在左心室肥厚 (LVH) 发展之前就存在的假设。将对尚未表现出 LVH 的基因型阳性个体（即表型阴性）进行详细的超声心动图研究。这些检查将包括通过多普勒组织成像和彩色 M 模式对舒张功能进行细致的评估。研究对象的舒张功能指数将与年龄匹配的正常对照进行比较。这种基因型-表型相关性有可能提高我们对患者进行风险分层和监测的能力，并可能最终激发诺埃尔的管理方法。

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disorder caused by mutations in genes encoding sarcomere proteins. Myocyte hypertrophy, myofibrillar fibrosis and disarray are the pathologic hallmarks of this disease and are traditionally thought to contribute to the development of diastolic dysfunction, a characteristic feature of HCM We postulate that abnormal diastolic function in fact procedures the onset of morphologic changes, reflecting the altered contractility of mutant sarcomeres. This proposal will utilize aq genotyped population to test the hypothesis that diastolic abnormalities are the earliest manifestation of HCM and are present before the development of left ventricular hypertrophy (LVH). Detailed echocardiographic studies will be performed on genotype- positive individuals who do not yet demonstrates LVH (i.e., phenotype- negative). These examinations will include meticulous assessment of diastolic function with Doppler tissue imaging and color M-mode. Indices of diastolic function from study subjects will be compared with age-matched normal controls. Such genotype-phenotype correlations have the potential to improve our ability to risk stratify and monitor patients, and may ultimately inspire noel approaches to management.