高水平血清可溶性致瘤抑制素2扩张型心肌病患儿的生存状况分析

Survival analysis for children with dilated cardiomyopathy under the condition of high serum level of soluble suppression of tumorigenicity 2

目的探讨高水平血清可溶性致瘤抑制素2(sST2)扩张型心肌病(DCM)患儿的生存状况。方法选取2015年9月至2019年3月于首都医科大学附属北京安贞医院就诊的149例DCM患儿,根据临床表现和影像学、实验室检查结果,最终纳入104例。记录患儿的基线资料,检测血清sST2水平。记录复合终点事件(心脏移植、心力衰竭及死亡)发生率,多因素Cox回归模型分析不同sST2水平DCM患儿复合终点事件发生风险以及性别、是否服用β受体阻滞剂、是否有既往心力衰竭史与血清sST2间的交互作用。结果104例DCM患儿血清sST2中位水平为23.4(19.7,30.9)μg/L,根据sST2水平四分位数,将患儿分为Q1组(≤19.7μg/L,26例)、Q2组(>19.7~23.4μg/L,26例)、Q3组(>23.4~30.9μg/L,26例)、Q4组(>30.9μg/L,26例)。104例DCM患儿中位随访时间为682(536,792)d,Q1组[11.5%(3/26)]、Q2组[15.4%(4/26)]、Q3组[26.9%(7/26)]、Q4组[65.4%(17/26)]复合终点事件发生率比较,差异有统计学意义(P<0.001)。多因素Cox风险回归模型分析显示,在校正年龄、性别、左心室射血分数、左心室舒张末期内径Z分数、B型脑钠肽、是否应用β受体阻滞剂及既往心力衰竭史后,按sST2四分位水平分组,Q4组患儿发生复合终点事件的风险最高(风险比=9.17,95%置信区间:2.31~36.49,P=0.002),而将sST2作为连续变量,血清sST2水平每增加1μg/L,复合终点事件发生风险增加5.00%(风险比=1.05,95%置信区间:1.03~1.07,P<0.001)。限制性立方样条曲线显示,复合终点事件发生风险随血清sST2水平增加而增加,呈现J型关系。将患儿按照性别、是否服用β受体阻滞剂以及有无既往心力衰竭史进行分层分析,结果显示,Q4组复合终点事件发生风险均较高。sST2水平与上述变量均无显著交互作用(均P>0.05)。Kaplan-Meier生存曲线分析显示,Q4组无事件生存率最低(Log-rankχ2=18.544,P<0.001)。结论高水平血清sST2是DCM患儿发生心脏移植、心力衰竭及死亡的危险因素。

Objective To investigate the survival of children with dilated cardiomyopathy(DCM)under the condition of high serum level of soluble suppression of tumorigenicity 2(sST2).Methods From September2015 to March 2019,149 children with DCM admitted to Beijing Anzhen Hospital,Capital Medical University were selected.According to the clinical manifestations and imaging,laboratory examination results,there were 104 children enrolled finally.The baseline data of children were recorded,and serum sST2 level was measured.The incidence of composite endpoint events(cardiac transplantation,heart failure and death)were recorded.Multivariate Cox regression model was used to analyze the risk of composite endpoint events and the interaction between gender,βblockers use,history of heart failure and serum sST2.Results The median serum sST2 level in 104 children with DCM was 23.4(19.7,30.9)μg/L.According to sST2 level quartiles,they were divided into Q1 group(≤19.7μg/L,26 cases),Q2 group(>19.7-23.4μg/L,26 cases),Q3 group(>23.4-30.9μg/L,26 cases)and Q4 group(>30.9μg/L,26 cases).The median follow-up time of 104 children was 682(536,792)d.There was significant difference in incidence of composite endpoint events among Q1 group[11.5%(3/26)],Q2 group[15.4%(4/26)],Q3 group[26.9%(7/26)]and Q4 group[65.4%(17/26)](P<0.001).After adjustment for age,gender,left ventricular ejection fraction,Z fraction of left ventricular end diastolic diameter,brain natriuretic peptide,β-blockers use and previous history of heart failure,the multivariate Cox regression model analysis showed that children in Q4 group had the highest risk of composite endpoint events by grouping with sST2 quartile level[hazard ratio=9.17,95%confidence interval(CI):2.31-36.49,P=0.002].Using sST2 as a continuous variable,the serum sST2 level increased by 1μg/L,and the risk of composite endpoint events increased by 5%(hazard ratio=1.05,95%CI:1.03-1.07,P<0.001).The restricted cubic spline curve showed that the risk of composite endpoint events increased with the increase of serum sST2 level,presenting a J-shaped relationship.Stratified analysis was conducted on gender,β-blockers use and history of heart failure,and showed that the risks of composite endpoint events in Q4 group were higher.There were no significant interactions between sST2 level and above variables(all P>0.05).The Kaplan-Meier survival curve analysis showed that the Q4 group had the lowest event-free survival rate(Log-rankχ2=18.544,P<0.001).Conclusion High serum level of sST2 is a risk factor for cardiac transplantation,heart failure and death in DCM children.