Hypertrophic Cardiomyopathy: Genetics, Pathogenesis, Clinical Manifestations, Diagnosis, and Therapy.
Hypertrophic Cardiomyopathy: Genetics, Pathogenesis, Clinical Manifestations, Diagnosis, and Therapy.
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DOI：
10.1161/circresaha.117.311059
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发表时间：
2017-09-15
影响因子：
20.1
通讯作者：
Braunwald E
中科院分区：
文献类型：
--
作者：
Marian AJ;Braunwald E
肥厚性心肌病（HCM）是一种遗传性疾病，其特征是左心室肥大，无法解释继发性原因，左心室未扩张，射血分数保留或增加。它通常是不对称的，最严重的肥厚累及基底室间隔。约三分之一的患者静止时出现左心室流出道梗阻，另外三分之一的患者可引起左心室流出道梗阻。HCM的组织学特征包括心肌细胞肥大和紊乱，以及间质纤维化。肥厚也常伴有左室舒张功能不全。在大多数患者中，HCM具有相对良性的病程。然而，HCM也是心源性猝死的一个重要原因，尤其是在青少年和年轻人中。非持续性室性心动过速、晕厥、心源性猝死家族史和严重心脏肥厚是心源性猝死的主要危险因素。这种并发症通常可以通过在适当的高危患者中植入心律转复除颤器来避免。心房颤动也是一种常见的并发症，耐受性不佳。编码肌瘤相关蛋白的十多个基因的突变会导致HCM。MYH7和MYBPC3分别编码β-肌球蛋白重链和肌球蛋白结合蛋白C，是最常见的两个基因，约占HCM家族的50%。在大约40%的HCM患者中，致病基因仍有待确定。负责贮藏病的基因突变也会导致类似HCM的表型（种族或表型）。基因检测的常规应用和家庭成员的临床前鉴定是一个重要的进步。遗传学的发现增强了对HCM分子发病机制的理解，并刺激了寻找新的治疗药物的努力。
Hypertrophic cardiomyopathy (HCM) is a genetic disorder that is characterized by left ventricular hypertrophy unexplained by secondary causes, and a non-dilated left ventricle with preserved or increased ejection fraction. It is commonly asymmetric with the most severe hypertrophy involving the basal interventricular septum. Left ventricular outflow tract obstruction is present at rest in about one third of the patients, and can be provoked in another third. The histologic features of HCM include myocyte hypertrophy and disarray, as well as interstitial fibrosis. The hypertrophy is also frequently associated with left ventricular diastolic dysfunction. In the majority of patients, HCM has a relatively benign course. However, HCM is also an important cause of sudden cardiac death, particularly in adolescents and young adults. Nonsustained ventricular tachycardia, syncope, a family history of sudden cardiac death, and severe cardiac hypertrophy are major risk factors for sudden cardiac death. This complication can usually be averted by implantation of a cardioverter-defibrillator in appropriate high-risk patients. Atrial fibrillation is also a common complication and is not well tolerated. Mutations in over a dozen genes encoding sarcomere-associated proteins cause HCM. MYH7 and MYBPC3, encoding β-myosin heavy chain and myosin binding protein C, respectively, are the two most common genes involved, together accounting for about 50% of the HCM families. In approximately 40% of HCM patients the causal genes remain to be identified. Mutations in genes responsible for storage diseases also cause a phenotype resembling HCM (genocopy or phenocopy). The routine applications of genetic testing and preclinical identification of family members represents an important advance. The genetic discoveries have enhanced understanding of the molecular pathogenesis of HCM and have stimulated efforts designed to identify new therapeutic agents.