先天性心脏病相关肺动脉高压复合临床恶化事件的初步研究

Impact of composite clinical worsening events on outcome of patients with pulmonary arterial hypertension associated with congenital heart disease

目的初步探讨复合临床恶化(cCW)事件及其组成部分对先天性心脏病相关肺动脉高压(CHD-PAH)患者预后的影响。方法本研究为回顾性研究。纳入2007年1月至2018年7月于北京安贞医院明确诊断为CHD-PAH的患者。收集其基线资料,包括人口统计学资料、临床症状、纽约心脏病协会(NYHA)心功能分级等。随访纳入患者临床恶化事件和全因死亡的发生情况。临床恶化事件包括晕厥、肺动脉高压(PAH)相关住院治疗、心功能恶化及≥2个PAH相关临床症状(呼吸困难、咯血、水肿、胸痛、心悸、紫绀)出现/进展。依据纳入患者在随访期间发生临床恶化事件的情况,设定3种cCW事件:cCW1(包括PAH相关住院治疗和心功能恶化)、cCW2(在cCW1基础上增加晕厥)和cCW3(在cCW1基础上增加≥2个PAH相关临床症状出现/进展)。采用Kaplan-Meier生存曲线描述纳入患者的中远期生存情况。利用单变量及多变量Cox回归模型评价cCW事件及其组成部分对全因死亡发生风险的影响。结果共纳入CHD-PAH患者525例,首诊时的年龄为20.7(11.2,30.3)岁,其中儿童(<18岁)占比43.8%,女性占比68.8%,NYHA心功能Ⅱ级患者431例(82.1%)。180例患者在确诊时已出现晕厥/PAH相关临床症状。随访时间为4.5(2.6,6.7)年,随访期间共有47例(9.0%)患者死亡。CHD-PAH患者确诊后第1、5、10年生存率分别为98.0%、89.9%和84.4%。多因素Cox回归分析结果显示,随访期间发生心功能恶化(HR=3.901,95%CI 1.863~8.169,P<0.001)、≥2个PAH相关临床症状出现/进展(HR=4.458,95%CI 1.870~10.625,P<0.001)、PAH相关住院治疗(HR=4.058,95%CI 1.851~8.896,P<0.001)及晕厥(HR=11.313,95%CI 4.860~26.332,P<0.001)的患者死亡风险均增加。3种复合事件均与全因死亡的风险增加有关,其中发生cCW2事件者死亡风险增加最为明显(HR=15.476,95%CI 4.346~37.576,P<0.001)。结论CHD-PAH患者的中远期预后较好。心功能恶化、≥2个PAH相关临床症状出现/进展、PAH相关住院治疗和晕厥及上述因素构成的cCW事件对全因死亡发生风险有不良影响。

Objective To explore the impact of composite clinical worsening(cCW)events and its components on the prognosis of patients with pulmonary arterial hypertension associated with congenital heart disease(CHD-PAH).Methods This is a retrospective study.Patients who were diagnosed with CHD-PAH in Beijing Anzhen Hospital between January 2007 and July 2018,were included,and their baseline clinical data including demographic,clinical manifestations and New York Heart Association(NYHA)classification were collected retrospectively.All-cause deaths and clinical worsening events were recorded,which included syncope,PAH related hospitalization,NYHA classification deterioration and≥2 PAH related clinical symptoms(dyspnea,hemoptysis,edema,chest pain,palpitations,cyanosis)appearance/progress.Three kinds of cCW events were defined:cCW1(included PAH related hospitalization,NYHA classification deterioration),cCW2(increased syncope on the basis of cCW1)and cCW3(increased≥2 PAH related clinical symptoms appearance/progress on the basis of cCW2).The Kaplan-Meier survival curve was used to analyze the long-term survival of the included patients.Univariate and multivariate Cox regression models were used to evaluate the impact of cCW events and their components on the risk of all-cause mortality.Results A total of 525 patients with CHD-PAH were included in this study.The median age at diagnosis was 20.7(11.2,30.3)years.There were 43.8%children(<18 years),and 68.8%female patients.There were 431 patients(82.1%)with NYHA classification II.A total of 180 patients had PAH symptoms at diagnosis.The median follow-up time was 4.5(2.6,6.7)years.Forty-seven patients(9.0%)died during the follow-up period.Survival rates at 1,5 and 10 years after diagnosis of PAH were 98.0%,89.9%and 84.4%,respectively.Cox multivariate analysis showed that NYHA classification deterioration(HR=3.901,95%CI 1.863-8.169,P<0.001),≥2 PAH symptoms appearance/progress(HR=4.458,95%CI 1.870-10.625,P<0.001),PAH-related hospitalization(HR=4.058,95%CI 1.851-8.896,P<0.001)and syncope(HR=11.313,95%CI 4.860-26.332,P<0.001)were independent predictors of increased risk of death.All 3 kinds of cCW events were significantly associated with the significantly increased risk of death,and cCW2 was highly predictive to increased risk of death(HR=15.476,95%CI 4.346-37.576,P<0.001).Conclusions The overall long-term prognosis of CHD-PAH patients in this study is relatively good.cCW events and its components(NYHA classification deterioration,≥2 PAH symptoms occurrence/worsening,PAH-related hospitalization and syncope)have adverse influence on all-cause death in this patient cohort.