Michels Michelle, Soliman Osama I I, Kofflard Marcel J, Hoedemaekers Yvonne M, Dooijes Dennis, Majoor-Krakauer Danielle, ten Cate Folkert J
Department of Cardiology, Thoraxcenter, Erasmus University Medical Center Rotterdam, the Netherlands.
JACC Cardiovasc Imaging. 2009 Jan;2(1):58-64. doi: 10.1016/j.jcmg.2008.08.003.
To test the hypothesis that carriers of Dutch founder mutations in cardiac myosin-binding protein C (MYBPC3), without left ventricular hypertrophy (LVH) or electrocardiographic abnormalities, have diastolic dysfunction on tissue Doppler imaging (TDI), which can be used for the screening of family members in the hypertrophic cardiomyopathy (HCM) population.
TDI is a more sensitive technique for the assessment of left ventricular contraction and relaxation abnormalities than is conventional echocardiography.
Echocardiographic studies including TDI were performed in genotyped hypertrophic cardiomyopathy patients (genotype-positive, G+/LVH+; n = 27), mutation carriers without LVH (G+/LVH-; n = 27), and healthy controls (n = 55). The identified mutations in MYBPC3 in the G+/LVH+ subjects were c.2864_2865delCT (12 subjects), c.2373dupG (n = 8), and p. Arg943X (n = 7). In the G+/LVH- subjects, the following mutations were identified: c.2864_2865delCT (n = 11), c.2373dupG (n = 8), and p. Arg943X (n = 8).
Mean TDI-derived systolic and early and late diastolic mitral annular velocities were significantly lower in the G+/LVH+ subjects compared with the other groups. However, there was no difference between controls and G+/LVH- subjects. Mean TDI-derived late mitral annular diastolic velocities were significantly higher in the G+/LVH- subjects compared with controls and G+/LVH+ subjects. Using a cut-off value of mean +/- 2 SD, an abnormal late mitral annular diastolic velocity was found in 14 (51%) of G+/LVH- patients. There was no difference among the 3 different mutations.
In contrast to earlier reports, mean mitral annular systolic velocity and early mitral annular diastolic velocity velocities were not reduced in G+/LVH- subjects, and TDI velocities were not sufficiently sensitive for determination of the affected status of an individual subject. Our findings, however, support the theory that diastolic dysfunction is a primary component of pre-clinical HCM.
检验以下假设：携带荷兰人心脏肌球蛋白结合蛋白C（MYBPC3）始祖突变且无左心室肥厚（LVH）或心电图异常的个体，在组织多普勒成像（TDI）上存在舒张功能障碍，这可用于肥厚型心肌病（HCM）人群中家庭成员的筛查。
与传统超声心动图相比，TDI是评估左心室收缩和舒张异常更为敏感的技术。
对已进行基因分型的肥厚型心肌病患者（基因型阳性，G+/LVH+；n = 27）、无LVH的突变携带者（G+/LVH-；n = 27）和健康对照者（n = 55）进行包括TDI在内的超声心动图研究。在G+/LVH+受试者中鉴定出的MYBPC3突变有c.2864_2865delCT（12例受试者）、c.2373dupG（n = 8）和p.Arg943X（n = 7）。在G+/LVH-受试者中，鉴定出以下突变：c.2864_2865delCT（n = 11）、c.2373dupG（n = 8）和p.Arg943X（n = 8）。
与其他组相比，G+/LVH+受试者TDI得出的平均收缩期、舒张早期和晚期二尖瓣环速度显著降低。然而，对照组与G+/LVH-受试者之间无差异。与对照组和G+/LVH+受试者相比，G+/LVH-受试者TDI得出的二尖瓣环舒张晚期平均速度显著更高。使用平均±2SD的临界值，在14例（51%）G+/LVH-患者中发现二尖瓣环舒张晚期速度异常。3种不同突变之间无差异。
与早期报告相反，G+/LVH-受试者的二尖瓣环平均收缩速度和舒张早期速度并未降低，且TDI速度对确定个体受试者的患病状态不够敏感。然而，我们的研究结果支持舒张功能障碍是临床前HCM主要组成部分的理论。
