Binder Josepha, Ommen Steve R, Gersh Bernard J, Van Driest Sara L, Tajik A Jamil, Nishimura Rick A, Ackerman Michael J
Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Mayo Clin Proc. 2006 Apr;81(4):459-67. doi: 10.4065/81.4.459.
To examine the relationship among age, septal morphological subtype, and presence of hypertrophic cardiomyopathy (HCM)-associated myofilament mutations.
Comprehensive mutation analysis of the 8 HCM susceptibility genes that encode the myofilaments of the cardiac sarcomere was performed previously in 382 unrelated patients with HCM. Blinded to genotype status, we used echocardiography to characterize the left ventricular morphological features. Multivariate regression was used to assess the relationship among morphological subtypes, clinical data, and genetic variables.
The mean +/- SD age of the patients was 41.6+/-19.0 years, with 126 patients 50 years or older at initial diagnosis. The septal morphological subtype was sigmold in 181 (47%), reverse in 132 (35%), apical variant in 37 (10%), and neutral in 32 (8%). The HCM-associated myofilament mutations were Identified in 143 patients (37%). Multivariate analysis showed that the reverse curvature septal morphological subtype was a strong predictor of genotype-positive status (odds ratio, 21; P<.001). Overall, the yield of HCM genetic testing was 79% in the setting of reverse curvature HCM but only 8% in sigmold septal HCM.
In stark contrast to HCM in young patients, elderly patients with HCM display a predominantly sigmoid septal morphological subtype and uncommonly have perturbations of known HCM susceptibility genes. Independent of age, septal morphological subtype strongly predicts the presence or absence of HCM-associated myofilament mutations and may enable echocardiography-guided genetic testing for HCM.
研究年龄、室间隔形态学亚型与肥厚型心肌病（HCM）相关肌丝突变之间的关系。
先前对382例无亲缘关系的HCM患者进行了编码心肌肌节肌丝的8个HCM易感基因的全面突变分析。在不知基因型状态的情况下，我们使用超声心动图来描述左心室形态特征。采用多变量回归分析来评估形态学亚型、临床数据和基因变量之间的关系。
患者的平均年龄±标准差为41.6±19.0岁，其中126例患者初诊时年龄在50岁及以上。室间隔形态学亚型呈S形的有181例（47%），反向的有132例（35%），心尖变异型有37例（10%），中性的有32例（8%）。143例患者（37%）检测到HCM相关肌丝突变。多变量分析显示，反向弯曲的室间隔形态学亚型是基因型阳性状态的有力预测指标（优势比为21；P<0.001）。总体而言，在反向弯曲型HCM患者中，HCM基因检测的阳性率为79%，而在S形室间隔HCM患者中仅为8%。
与年轻HCM患者形成鲜明对比的是，老年HCM患者主要表现为S形室间隔形态学亚型，且很少有已知HCM易感基因变异。独立于年龄之外，室间隔形态学亚型强烈预测HCM相关肌丝突变的有无，并可能有助于超声心动图引导下的HCM基因检测。
