儿童特发性/遗传性肺动脉高压患者靶向药物治疗时期的生存情况分析  

Outcomes of pediatric patients with idiopathic/hereditary pulmonary arterial hypertension during periods of targeted therapies

作　　者：徐茁原 顾虹[1] XU Zhuoyuan;GU Hong(Department of Pediatric Cardiology,Beijing Anzhen Hospital,Capital Medical University,Beijing Institute of Heart,Lung and Blood Vessel Diseases,Beijing 100029,China)

机构地区：[1]首都医科大学附属北京安贞医院小儿心脏中心,100029

出　　处：《心肺血管病杂志》2023年第12期1238-1242,共5页Journal of Cardiovascular and Pulmonary Diseases

摘　　要：目的:儿童期发病的特发性/遗传性肺动脉高压(idiopathic/hereditary pulmonary arterial hypertension,I/HPAH)的遗传因素,影响治疗反应和预后结局。方法:回顾性分析了2008年至2021年,于北京安贞医院小儿心脏中心就诊的发病年龄在3个月~18岁,129例不明原因动脉型肺动脉高压(pulmonary arterial hypertension,PAH)患者,所有患者完善了全外显子测序。收集患者基线资料,并对基线、随访资料进行统计学分析,采用Kaplan-Meier生存曲线分析,描述患者生存情况。结果:共纳入儿童I/HPAH患者129例(52.7%,女性;91.5%接受了PAH靶向药物治疗),确诊时中位年龄为6.8(3.4,10.7)岁。95例患者(73.6%)被检测到携带目前已知的PAH相关风险基因变异。在本研究检测到的最常见的变异基因是BMPR2(43例,33.3%)。中位随访时间为27.6个月,26例患者死亡(20.2%)。I/HPAH儿童患者诊断后1、3和5年无终点事件的整体生存率分别为94.2%、78.8%和75.9%。结论:儿童I/HPAH患者携带致病/可能致病的基因变异的比例较高,预后结局较差。积极的治疗,可不同程度地改善包括携带BMPR2致病变异的患者在内的I/HPAH患者,短期到中期的生存情况。Objective:Paediatric-onset idiopathic/hereditary pulmonary arterial hypertension(I/HPAH)is partially linked to genetic factors that may also affect treatment response and outcome.We aimed to describe the association of genotype with clinical characteristics and prognosis based on the biggest Chinese paediatric IPAH/HPAH cohort with whole exome sequencing(WES)where all patients were followed at a large tertiary paediatric PAH centre with standardized PAH therapy protocols.Methods:We retrospectively analyzed I/HPAH paediatric patients aged between 3 months and 18 years under follow-up at a large tertiary referral centre.WES focused on PAH high-risk genes was performed in all patients.The follow-up data were statistically analyzed,and Kaplan-Meier survival curves were used to describe the survival rate.Results:Overall,129 patients(52.7%females;91.5%on PAH therapy)with a median age at diagnosis of 6.8(3.4,10.7)years were included.A relevant PAH gene variant was detected in 95 patients(73.6%).The most common variants were in the BMPR2(n=43,33.3%)gene.Over a median follow-up period of 27.6 months,26 children died(20.2%).In this study,the overall survival rates at 1 year,3 years and 5 years after the diagnosis of I/HPAH children were 94.2%,78.8%and 75.9%,respectively.Conclusions:Pathogenic/likely pathogenic genetic variants are prevalent in children with PAH and are related to a worse prognosis irrespective of other recognized risk factors in this population.Combination PAH therapy was associated with superior prognosis in children with pathogenic variants or BMPR2 variants.

关 键 词：肺动脉高压 特发性/遗传性 儿童 预后 

分 类 号：R54[医药卫生—心血管疾病]