Background:Genetic analysis is a first-tier test in dilated cardiomyopathy (DCM). Electrical phenotypes are common in genetic DCM, but their exact contribution to the clinical course and outcome is unknown. We determined the prevalence of pathogenic gene variants in a large unselected DCM population and determined the role of electrical phenotypes in association with outcome.Methods:This study included 689 patients with DCM from the Maastricht Cardiomyopathy Registry, undergoing genetic evaluation using a 48 cardiomyopathy-associated gene-panel, echocardiography, endomyocardial biopsies, and Holter monitoring. Upon detection of a pathogenic variant in a patient with DCM, familial segregation was performed. Outcome was defined as cardiovascular death, heart transplantation, heart failure hospitalization, and/or occurrence of life-threatening arrhythmias.Results:A (likely) pathogenic gene variant was found in 19% of patients, varying from 36% in familial to 13% in nonfamilial DCM. Family segregation analysis showed familial disease in 46% of patients with DCM who were initially deemed nonfamilial by history. Overall, 18% of patients with a nongenetic risk factor had a pathogenic gene variant. Almost all pathogenic gene variants occurred in just 12 genes previously shown to have robust disease association with DCM. Genetic DCM was independently associated with electrical phenotypes such as atrial fibrillation, nonsustained ventricular tachycardia, and atrioventricular block and inversely correlated with the presence of a left bundle branch block (P<0.01). After a median follow-up of 4 years, event-free survival was reduced in genetic versus patients with nongenetic DCM (P=0.01). This effect on outcome was mediated by the associated electrical phenotypes of genetic DCM (P<0.001).Conclusions:One in 5 patients with an established nongenetic risk factor or a nonfamilial disease still carries a pathogenic gene variant. Genetic DCM is characterized by a profile of electrical phenotypes (atrial fibrillation, nonsustained ventricular tachycardia, and atrioventricular block), which carries increased risk for adverse outcomes. Based on these findings, we envisage a broader role for genetic testing in DCM.

中文翻译：

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基因检测对扩张型心肌病的影响。

背景：基因分析是扩张型心肌病 (DCM) 的一级检测。电表型在遗传性 DCM 中很常见，但它们对临床过程和结果的确切贡献尚不清楚。我们确定了大量未选择的 DCM 人群中致病基因变异的患病率，并确定了电表型与结果相关的作用。基因面板、超声心动图、心内膜心肌活检和动态心电图监测。在 DCM 患者中检测到致病性变异后，进行了家族隔离。结果定义为心血管死亡、心脏移植、心力衰竭住院、和/或发生危及生命的心律失常。结果：在 19% 的患者中发现了（可能的）致病基因变异，从家族性 36% 到非家族性 DCM 的 13% 不等。家族隔离分析显示 46% 的 DCM 患者有家族病史，这些 DCM 患者最初被认为是非家族性病史。总体而言，18% 的具有非遗传风险因素的患者具有致病基因变异。几乎所有的致病基因变异都发生在 12 个先前显示与 DCM 具有强烈疾病关联的基因中。遗传性 DCM 与心房颤动、非持续性室性心动过速和房室传导阻滞等电表型独立相关，与左束支传导阻滞呈负相关。从家族性 36% 到非家族性 DCM 的 13% 不等。家族隔离分析显示，46% 的 DCM 患者最初被认为是非家族性病史。总体而言，18% 的具有非遗传风险因素的患者具有致病基因变异。几乎所有的致病基因变异都发生在 12 个先前显示与 DCM 具有强烈疾病关联的基因中。遗传性 DCM 与心房颤动、非持续性室性心动过速和房室传导阻滞等电表型独立相关，与左束支传导阻滞呈负相关。从家族性 36% 到非家族性 DCM 的 13% 不等。家族隔离分析显示，46% 的 DCM 患者最初被认为是非家族性病史。总体而言，18% 的具有非遗传风险因素的患者具有致病基因变异。几乎所有的致病基因变异都发生在 12 个先前显示与 DCM 具有强烈疾病关联的基因中。遗传性 DCM 与心房颤动、非持续性室性心动过速和房室传导阻滞等电表型独立相关，与左束支传导阻滞呈负相关。18% 的具有非遗传危险因素的患者具有致病基因变异。几乎所有的致病基因变异都发生在 12 个先前显示与 DCM 具有强烈疾病关联的基因中。遗传性 DCM 与心房颤动、非持续性室性心动过速和房室传导阻滞等电表型独立相关，与左束支传导阻滞呈负相关。18% 的具有非遗传风险因素的患者具有致病基因变异。几乎所有的致病基因变异都发生在 12 个先前显示与 DCM 具有强烈疾病关联的基因中。遗传性 DCM 与心房颤动、非持续性室性心动过速和房室传导阻滞等电表型独立相关，与左束支传导阻滞呈负相关。P <0.01）。中位随访 4 年后，与非遗传性 DCM 患者相比，遗传性 DCM 患者的无事件生存率降低（P = 0.01）。这种对结果的影响是由遗传性 DCM 的相关电表型介导的（P <0.001）。结论：五分之一具有已确定的非遗传危险因素或非家族性疾病的患者仍携带致病基因变异。遗传性 DCM 的特征在于电表型（心房颤动、非持续性室性心动过速和房室传导阻滞）的特征，这会增加不良结果的风险。基于这些发现，我们设想基因检测在 DCM 中发挥更广泛的作用。