Genetic Risk of Arrhythmic Phenotypes in Patients With Dilated Cardiomyopathy
Genetic Risk of Arrhythmic Phenotypes in Patients With Dilated Cardiomyopathy
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DOI：
10.1016/j.jacc.2019.06.072
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发表时间：
2019-09-17
影响因子：
24
通讯作者：
Mestroni, Luisa
中科院分区：
文献类型：
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作者：
Gigli, Marta;Merlo, Marco;Mestroni, Luisa
背景扩张型心肌病(DCM)患者的基因表型相关性，尤其是基因变异对临床预后的影响尚不清楚。目的本研究的目的是探讨扩张型心肌病患者中基因变异携带者状态对预后的影响。方法对487例扩张型心肌病患者进行下一代测序分析，并将疾病基因分为功能基因组。结果在178例患者(37%)中发现183个致病/可能致病变异：titin 54个(11%)，Lamin A/C 19个(4%)，结构细胞骨架-Z盘状基因24个(5%)，桥体基因16个(3.5%)；其中肉瘤基因46个(9.5%)，离子通道基因8个(1.6%)，其他基因11个(2.5%)。变异携带者和非携带者的全因死亡率差异无统计学意义(p=0.99)。携带者有SCD/VT/VF(p=0.062)和DHF/HTx/VAD(p=0.061)加重的趋势。桥粒和LMNA基因变异体携带者SCD/VT/VF的发生率最高，与左心室射血分数无关。结论桥粒基因和LMNA基因变异识别出DCM患者中SCD和危及生命的室性心律失常的风险最高的亚群，与左心室射血分数无关。(C)2019年，由美国心脏病学会基金会主办。
BACKGROUND Genotype-phenotype correlations in dilated cardiomyopathy (DCM) and, in particular, the effects of gene variants on clinical outcomes remain poorly understood.OBJECTIVES The purpose of this study was to investigate the prognostic role of genetic variant carrier status in a large cohort of DCM patients.METHODS A total of 487 DCM patients were analyzed by next-generation sequencing and categorized the disease genes into functional gene groups. The following composite outcome measures were assessed: 1) all-cause mortality; 2) heart failure-related death, heart transplantation, or destination left ventricular assist device implantation (DHF/HTx/VAD); and 3) sudden cardiac death/sustained ventricular tachycardia/ventricular fibrillation (SCD/VT/VF).RESULTS A total of 183 pathogenic/likely pathogenic variants were found in 178 patients (37%): 54 (11%) Titin; 19 (4%) Lamin A/C (LMNA); 24 (5%) structural cytoskeleton-Z disk genes; 16 (3.5%) desmosomal genes; 46 (9.5%) sarcomeric genes; 8 (1.6%) ion channel genes; and 11 (2.5%) other genes. All-cause mortality was no different between variant carriers and noncarriers (p = 0.99). A trend toward worse SCD/VT/VF (p = 0.062) and DHF/HTx/VAD (p = 0.061) was found in carriers. Carriers of desmosomal and LMNA variants experienced the highest rate of SCD/VT/VF, which was independent of the left ventricular ejection fraction.CONCLUSIONS Desmosomal and LMNA gene variants identify the subset of DCM patients who are at greatest risk for SCD and life-threatening ventricular arrhythmias, regardless of the left ventricular ejection fraction. (C) 2019 by the American College of Cardiology Foundation.