Echocardiographic strain imaging to assess early and late consequences of sarcomere mutations in hypertrophic cardiomyopathy.
Echocardiographic strain imaging to assess early and late consequences of sarcomere mutations in hypertrophic cardiomyopathy.
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DOI：
10.1161/circgenetics.109.862128
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发表时间：
2009-08
期刊：
影响因子：
--
通讯作者：
Køber L
中科院分区：
文献类型：
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作者：
Ho CY;Carlsen C;Thune JJ;Havndrup O;Bundgaard H;Farrohi F;Rivero J;Cirino AL;Andersen PS;Christiansen M;Maron BJ;Orav EJ;Køber L
基因检测在肥厚型心肌病(HCM)临床诊断前识别肌节突变携带者(G+)，从而能够表征最初的疾病表现。先前的研究表明，松弛功能受损在左心室肥厚(LVH)之前发生。肌节突变对早期和晚期疾病收缩功能的确切影响尚不清楚。对146例5个肌节基因突变的个体进行了应变成像综合超声心动图检查。比较68例临床前期(G+/LVH)−患者、40例显性(G+/LVH+)肥厚性心肌梗死患者和38例突变(−)正常对照亲属的收缩参数。所有受试者的左心室射血分数(EF)均正常。临床前肥厚型心肌病患者的整体和局部收缩峰值应变(ε-sys)和纵向收缩应变率与对照组无显著差异，但二尖瓣环舒张期早期血流速度(Ea)降低了13%。在显性肥厚型心肌病中，与临床前肥厚型心肌病和对照组(所有比较P<；0.013)相比，全球纵向ε系统和SSR分别减少了27%和14%，EA减少了33%。肌节突变对舒缩功能有不同的初始影响。临床前肥厚性心肌病的特点是舒张性受损，但收缩期应变保持不变。相反，尽管EF正常，但舒张期和纵向收缩期异常均存在于临床疾病中。我们认为，舒张期功能障碍是肌节突变的早期结果，而收缩功能障碍是突变和随后的病理重构相结合的结果。识别由这些突变触发的机制通路可能开始重塑基于早期诊断和疾病预防的临床治疗范式。
Genetic testing identifies sarcomere mutation carriers (G+) before clinical diagnosis of hypertrophic cardiomyopathy (HCM), allowing characterization of initial disease manifestations. Prior studies demonstrated that impaired relaxation develops before left ventricular hypertrophy (LVH). The precise impact of sarcomere mutations on systolic function in early and late disease is unclear. Comprehensive echocardiography with strain imaging was performed on 146 genotyped individuals with mutations in 5 sarcomere genes. Contractile parameters were compared in 68 preclinical (G+/LVH−), 40 overt (G+/LVH+) HCM subjects, and 38 mutation (−) normal control relatives. All subjects had normal LV ejection fraction (EF). In preclinical HCM, global and regional peak systolic strain (εsys) and longitudinal systolic strain rate (SSR) were not significantly different from controls, but early diastolic mitral annular velocity (Ea) was reduced by 13%. In overt HCM, there was a significant 27% and 14% decrease in global longitudinal εsys and SSR respectively, compared with both preclinical HCM and controls (p<0.013 for all comparisons), and a 33% reduction in Ea. Sarcomere mutations have disparate initial effects on diastolic and systolic function. Preclinical HCM is characterized by impaired relaxation but preserved systolic strain. In contrast, both diastolic and longitudinal systolic abnormalities are present in overt disease, despite normal EF. We propose that diastolic dysfunction is an early consequence of sarcomere mutations, whereas systolic dysfunction results from mutations combined with subsequent pathologic remodeling. Identifying mechanistic pathways triggered by these mutations may begin to reshape the clinical paradigm for treatment, based on early diagnosis and disease prevention.