Diastolic Function in Hypertrophic Cardiomyopathy

肥厚型心肌病（HCM）是由编码肌节蛋白的基因突变引起的常染色体显性遗传疾病。肌细胞肥大、肌原纤维化和紊乱是这种疾病的病理标志，传统上认为这有助于舒张功能障碍的发展，这是HCM的特征。我们假设舒张功能异常实际上是形态学变化的开始，反映了突变肌节的收缩力改变。该提案将利用aq基因型人群来检验舒张异常是HCM的最早表现并且在左心室肥大（LVH）发展之前存在的假设。详细的超声心动图研究将在尚未证实LVH的基因型阳性个体（即，表型-阴性）。这些检查将包括使用多普勒组织成像和彩色M模式对舒张功能进行细致评估。将研究受试者的舒张功能指数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.