Diastolic Function in Hypertrophic Cardiomyopathy

肥厚型心肌病(HCM)是一种常染色体显性遗传病，由肌节蛋白编码基因突变引起。心肌细胞肥大、肌原纤维纤维化和肌原纤维紊乱是本病的病理特征，传统上被认为是导致肥厚性心肌病特征之一的舒张期功能障碍。我们推测，舒张期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能力的改变。这项建议将利用AQ基因分型人群来检验这一假设，即舒张期异常是肥厚性心肌病最早的表现，并且在左心室肥厚(LVH)发展之前就存在了。详细的超声心动图研究将在尚未表现出左心室肥厚(即表型阴性)的基因阳性个体身上进行。这些检查将包括利用多普勒组织成像和彩色M型对舒张期功能进行细致的评估。研究对象的舒张期功能指数将与年龄匹配的正常对照组进行比较。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，并最终可能启发新的管理方法。

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.