合并瓣膜性心脏病孕妇妊娠期发生心血管不良事件的危险因素分析及预测模型构建

Risk factors analysis and prediction model construction of major adverse cardiovascular events in pregnant women with valvular heart disease

目的分析合并瓣膜性心脏病(VHD)孕妇妊娠期发生心血管不良事件(MACE)的危险因素并构建预测模型。方法回顾性分析2012年1月1日至2023年6月1日于首都医科大学附属北京安贞医院住院的245例次合并VHD孕产妇的临床资料, 包括一般情况、孕前及妊娠期心脏相关指标、MACE的发生情况。通过单因素分析、二元logistic回归模型等方法分析合并VHD孕妇妊娠期发生MACE的危险因素, 构建预测模型及进行自助重抽样法内部验证。结果 (1)245例次合并VHD孕妇中, MACE的发生率为18.0%(44/245), 最常见的MACE是心力衰竭(61.4%, 27/44);二尖瓣是最常受累的瓣膜(64.9%, 159/245);妊娠前接受的瓣膜手术中最常见的类型是机械瓣置换术(31.4%, 77/245), 妊娠前未行瓣膜手术孕妇最常见的病变类型是二尖瓣反流(17.6%, 43/245)。(2)比较华法林、低分子肝素(LMWH)及LMWH与华法林序贯3种抗凝方式的母儿结局, 华法林抗凝者的胎儿丢失率(36%, 15/42)及畸形率(7%, 3/42)最高, 但MACE率(12%, 5/42)最低, LMWH与华法林序贯抗凝的胎儿丢失率(1/19)、畸形率(1/19)及人工瓣膜血栓率(0)均最低, 3种抗凝方式的胎儿丢失率、人工瓣膜血栓率比较, 差异均有统计学意义(P均<0.05)。(3)发生MACE与未发生MACE孕妇的妊娠年龄、心脏病确诊年龄、产时体重、妊娠前体重指数、经产妇比例、既往不良孕产史以及慢性病史分别比较, 差异均无统计学意义(P均>0.05)。(4)二元logistic回归模型分析发现, 孕前有心脏不适症状、先天性心脏病矫正术后、妊娠风险Ⅴ级、LMWH抗凝、合并心律失常是合并VHD孕妇妊娠中期发生MACE的危险因素(P均<0.05)。通过二元logistic回归模型分析结果构建合并VHD孕妇发生MACE的受试者工作特征曲线, 其曲线下面积为0.837, 标准曲线与校准预测模型曲线贴合, 预测模型具有较好的校准度。结论合并VHD孕妇妊娠期发生MACE的风险高, 孕前有心脏不适症状、先天性心脏病矫正术后、妊娠风险Ⅴ级、LMWH抗凝、合并心律失常5个危险因素可协助识别高危孕妇。

Objective:To analysis the risk factors for major adverse cardiovascular event(MACE)in pregnant women with valvular heart disease(VHD)and to construct a risk prediction model.Methods:The clinical data of 245 pregnant women with VHD who were hospitalized in Beijing Anzhen Hospital from January 1,2012,to June 1,2023 were retrospectively analyzed,including general information,pre-pregnancy and pregnancy-associated cardiac conditions,and MACE.Univariate analysis and logistic regression models were employed to identify risk factors for MACE during pregnancy among pregnant women with VHD.Furthermore,a predictive model was constructed and internal validation was conducted using bootstrap techniques.Results:(1)Among 245 pregnant women with VHD,the incidence of MACE was 18.0%(44/245),and the most common MACE was heart failure(61.4%,27/44).The mitral valve was the most frequently affected valve(64.9%,159/245).Prior to pregnancy,the most common type of valve surgery undertaken was mechanical valve replacement,representing 31.4%(77/245)of surgeries.In contrast,among those pregnant women who did not undergo valve surgery before pregnancy,the most common lesion type was mitral regurgitation(17.6%,43/245).(2)Comparing the maternal and infant outcomes of warfarin,low molecular weight heparin(LMWH)and LMWH sequential with warfarin,the fetal loss rate(36%,15/42)and malformation rate(7%,3/42)were the highest,but the MACE rate(12%,5/42)was the lowest in warfarin group.The fetal loss rate(1/19),malformation rate(1/19)and artificial valve thrombosis rate(0)of LMWH sequential with warfarin were the lowest,and the fetal loss rate and artificial valve thrombosis rate of the three anticoagulation methods were statistically significant(all P<0.05).(3)There were no significant differences in gestational age,age of diagnosis of heart disease,weight at delivery,pre-pregnancy body mass index,proportion of multiparous women and chronic medical history between women with MACE and those without MACE(all P>0.05).(4)Binary logistic regression analysis identified the following as risk factors for MACE during the second trimester of pregnancy among pregnant women with VHD:pre-pregnancy cardiac symptoms,history of corrective surgery for congenital heart disease,pregnancy risk gradeⅤ,anticoagulation with LMWH during pregnancy,and arrhythmia(all P<0.05).Based on the results of multivariate analysis,a receiver operating characteristic curve was constructed,with an area under the curve of 0.837,indicating good discriminative ability.The calibration plot demonstrated a close alignment between the standard curve and the calibration prediction curve,suggesting excellent calibration of the model.Conclusions:Pregnant women with VHD are at a high risk of experiencing MACE during gestation.Five risk factors,including pre-pregnancy cardiac symptoms,history of corrective surgery for congenital heart disease,pregnancy risk gradeⅤ,anticoagulation with LMWH,and arrhythmia,could aid in identifying high-risk pregnant women.