Dilated cardiomyopathy (DCM) is a common cause of sudden cardiac death and heart failure in children, its different etiologies are significantly associated with the prognosis of children with DCM. However, there is a lack of accurate etiologic diagnosis and effective risk stratification programs. Primary DCM has the highest prevalence and relatively poor prognosis, especially in children with genetic factors. Therefore, the analysis of mortality risk factors based on genetic background would be beneficial for the accurate prognosis and risk stratification of children with DCM.

To explore the proportion of genetic etiology, genetic characteristics and factors related to poor prognosis of primary DCM in children.

The clinical data and genetic testing results of 42 children with primary DCM who were hospitalized in Hebei Children's Hospital from July 2018 to December 2022 and completed genetic testing were retrospectively collected, and the included children were regularly followed up in the cardiology outpatient department of Hebei Children's Hospital after discharge. With the time of death or 2022-12-31 as the end point of follow-up, the children were divided into the death group (9 cases) and survival group (33 cases) according to the follow-up outcomes. Survival curves of the children were plotted using the Kaplan-Meier method, and comparisons between groups were performed using the Log-rank test. Multivariate COX proportional risk model was used to analyze the risk factors for death.

The median age of first diagnosis was 12 (7, 96) months, and the median follow-up time was 24 (9, 36) months. The median follow-up time was 8 (0, 11) months in the death group and 30 (12, 39) months in the survival group, the difference was statistically significant (Z=-2.19, P<0.05) . The proportion of male, heart function grade Ⅲ/Ⅳ and gene mutation positive in the death group was higher than that in the survival group, and the left ventricular short axis shortening rate (LVFS) was lower than that in the survival group (P<0.05) . The positive rate of gene mutation was 38.1% (16/42) , of which 25.0% (4/16) were spontaneous mutations and 61.9% (26/42) were negative mutations. All the 9 children in the death group died within 1 year after diagnosis, including 8 patients with positive gene mutation (50.0%, 8/16) and 1 patient with negative gene mutation (3.8%, 1/26) , with statistically significant differences between the two groups (P<0.05) . The heterozygous variation of CSRP3 (c.190C>T) in the dead children with negative gene mutation was classified as unclear clinical significance. The Kaplan-Meier survival curve of the children was plotted, and the Log-rank test results showed that the survival rate of children with negative gene mutation was higher than that of children with positive gene mutation (χ²=18.1, P<0.001) . Multivariate COX proportional risk model analysis showed that gene mutation [HR=23.91, 95%CI= (1.80-317.21) , P=0.016] and cardiac function grade Ⅲ/Ⅳ [HR=11.29, 95%CI (1.13-112.68) , P=0.039] were risk factors for death in children with DCM.

In this study, 38.1% of children with primary DCM were associated with genetic etiology. The first year after diagnosis is the high incidence of death of children with DCM, and the prognosis of children with positive gene mutation is worse. The presence of pathogenic gene mutation and the cardiac function grade of Ⅲ~Ⅳ at the first diagnosis are independent risk factors for death in children.

扩张型心肌病（DCM）是儿童心源性猝死和心力衰竭的常见原因之一，不同病因与DCM患儿的预后显著相关。其中原发性DCM的占比最高且预后相对较差，特别是与遗传因素相关的患儿预后更差。因此基于遗传背景下的死亡危险因素分析将有利于DCM患儿的精准预后评估及危险分层。

探讨儿童原发性DCM的遗传病因占比、遗传学特征及死亡危险因素。

回顾性纳入2018年7月—2022年12月在河北省儿童医院住院治疗并完成基因检测的42例原发性DCM患儿的临床资料，收集患儿的基因检测结果。出院后定期于河北省儿童医院心内科门诊随访。以患儿死亡时间或2022-12-31为随访终点，根据随访结局将患儿分为死亡组（9例）与存活组（33例）。采用Kaplan-Meier法绘制患儿的生存曲线，生存曲线比较采用Log-rank检验。采用多因素COX比例风险模型分析患儿死亡的危险因素。

患儿中位首诊年龄12（7，96）个月，中位随访时间24（9，36）个月。死亡组患儿中位随访时间8（0，11）个月，存活组中位随访时间30（12，39）个月，差异有统计学意义（Z=-2.19，P<0.05）。死亡组患儿男性、心功能分级Ⅲ/Ⅳ级、基因突变阳性占比高于生存组，左心室短轴缩短率（LVFS）低于生存组（P<0.05）。患儿基因突变阳性率为38.1%（16/42），其中自发突变占25.0%（4/16），基因突变阴性为61.9%（26/42）。死亡组9例患儿均在诊断后1年内死亡。基因突变阳性患儿死亡8例（50.0%，8/16），基因突变阴性患儿死亡1例（3.8%，1/26），组间死亡率差异有统计学意义（P<0.05）。基因突变阴性死亡患儿CSRP3（c.190C>T）杂合变异，致病分类为临床意义未明。绘制患儿Kaplan-Meier生存曲线，Log-rank检验结果显示基因突变阴性患儿生存率高于基因突变阳性患儿（χ²=18.1，P<0.001）。多因素COX比例风险模型分析结果显示基因突变[HR=23.91，95%CI=（1.80~317.21），P=0.016]、心功能分级Ⅲ/Ⅳ级[HR=11.29，95%CI（1.13~112.68），P=0.039]为DCM患儿死亡的危险因素。

本研究38.1%的原发性DCM患儿与遗传病因相关，诊断后第1年内是DCM患儿死亡的高发期，基因突变阳性的患儿预后更差。存在致病基因突变、首诊心功能分级Ⅲ/Ⅳ级是患儿死亡的独立危险因素。