Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.
Department of Cardiology, Erasmus Medical Center, Rotterdam, the Netherlands.
J Am Coll Cardiol. 2018 Feb 20;71(7):711-722. doi: 10.1016/j.jacc.2017.12.019.
The clinical outcomes of noncompaction cardiomyopathy (NCCM) range from asymptomatic to heart failure, arrhythmias, and sudden cardiac death. Genetics play an important role in NCCM.
This study investigated the correlations among genetics, clinical features, and outcomes in adults and children diagnosed with NCCM.
A retrospective multicenter study from 4 cardiogenetic centers in the Netherlands classified 327 unrelated NCCM patients into 3 categories: 1) genetic, with a mutation in 32% (81 adults; 23 children) of patients; 2) probably genetic, familial cardiomyopathy without a mutation in 16% (45 adults; 8 children) of patients; or 3) sporadic, no family history, without mutation in 52% (149 adults; 21 children) of patients. Clinical features and major adverse cardiac events (MACE) during follow-up were compared across the children and adults.
MYH7, MYBPC3, and TTN mutations were the most common mutations (71%) found in genetic NCCM. The risk of having reduced left ventricular (LV) systolic dysfunction was higher for genetic patients compared with the probably genetic and sporadic cases (p = 0.024), with the highest risk in patients with multiple mutations and TTN mutations. Mutations were more frequent in children (p = 0.04) and were associated with MACE (p = 0.025). Adults were more likely to have sporadic NCCM. High risk for cardiac events in children and adults was related to LV systolic dysfunction in mutation carriers, but not in sporadic cases. Patients with MYH7 mutations had low risk for MACE (p = 0.03).
NCCM is a heterogeneous condition, and genetic stratification has a role in clinical care. Distinguishing genetic from nongenetic NCCM complements prediction of outcome and may lead to management and follow-up tailored to genetic status.
非致密性心肌病（NCCM）的临床结果范围从无症状到心力衰竭、心律失常和心脏性猝死。遗传学在 NCCM 中起着重要作用。
本研究调查了在诊断为 NCCM 的成人和儿童中，遗传学、临床特征和结果之间的相关性。
来自荷兰 4 个心脏遗传中心的回顾性多中心研究将 327 名无亲缘关系的 NCCM 患者分为 3 类：1）遗传学，32%（81 名成人；23 名儿童）的患者存在突变；2）可能遗传学，16%（45 名成人；8 名儿童）的患者存在家族性心肌病但无突变；或 3）散发性，52%（149 名成人；21 名儿童）的患者无家族史且无突变。比较了儿童和成人在随访期间的临床特征和主要不良心脏事件（MACE）。
MYH7、MYBPC3 和 TTN 突变是遗传学 NCCM 中最常见的突变（71%）。与可能遗传学和散发性病例相比，遗传学患者发生左心室（LV）收缩功能障碍的风险更高（p=0.024），具有多种突变和 TTN 突变的患者风险最高。儿童中突变更为常见（p=0.04），且与 MACE 相关（p=0.025）。成人更可能患有散发性 NCCM。儿童和成人发生心脏事件的高风险与突变携带者的 LV 收缩功能障碍相关，但与散发性病例无关。携带 MYH7 突变的患者发生 MACE 的风险较低（p=0.03）。
NCCM 是一种异质性疾病，遗传分层在临床护理中具有一定作用。将 NCCM 从非遗传性区分开来补充了对结果的预测，并且可能导致根据遗传状态进行管理和随访。
