He Yuan, Li Qiangqiang, Zhang Chen, Keller Bradley B, Shen Yiping, Gu Hong
Department of Pediatric Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Cincinnati Children's Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Respir Res. 2025 Jul 2;26(1):231. doi: 10.1186/s12931-025-03249-y.
This study aims to analyze the genetic characteristics, genotype-phenotype correlation and long-term prognosis of children with idiopathic/hereditary pulmonary arterial hypertension (IPAH/HPAH) in a Chinese tertiary medical center.
A retrospective review was conducted for all children with IPAH/HPAH treated at Beijing Anzhen Hospital over the past 15 years. All patients underwent genetic testing.
In total, 170 children with IPAH/HPAH were included in the study (females n = 95, 56%), with a median age of diagnosis 6.46 (3.80, 10.70) years. The study population presented with severe conditions at baseline, with 77 patients assessed as clinically high-risk. Genetic testing identified pathogenic variants in 110 patients (64%), with BMPR2, ACVRL1, and TBX4 accounted for the main causal genes. Compared to non-carriers, carriers of pathogenic variants had a higher clinical risk at baseline (54% vs. 30%, p = 0.04). After targeted therapy, carriers experienced greater clinical deterioration (p = 0.008). The overall follow-up duration was 2.68 (1.60, 4.98) years, with the survival rate at 1-, 3-, and 5-year was 93.4%, 86.7%, and 68.6%, respectively. The prognosis of carriers was significantly worse than that of non-carriers (Log-rank p < 0.001). Multivariate Cox regression analysis indicated that pathogenic variants and higher pulmonary vascular resistance index (PVRI) and were associated with a higher risk of death.
We uncovered a higher rate of pathogenic variants in Chinese pediatric PAH, while targeted therapy improves the overall prognosis of children with PAH, patients with pathogenic variants presented with poorer response to therapy and poorer prognosis.
本研究旨在分析中国一家三级医疗中心特发性/遗传性肺动脉高压（IPAH/HPAH）患儿的遗传特征、基因型-表型相关性及长期预后。
对过去15年在北京安贞医院接受治疗的所有IPAH/HPAH患儿进行回顾性研究。所有患者均接受了基因检测。
本研究共纳入170例IPAH/HPAH患儿（女性95例，占56%），诊断时的中位年龄为6.46（3.80，10.70）岁。研究人群在基线时病情严重，77例患者被评估为临床高危。基因检测在110例患者（64%）中发现了致病变异，其中BMPR2、ACVRL1和TBX4是主要的致病基因。与非携带者相比，致病变异携带者在基线时具有更高的临床风险（54%对30%，p = 0.04）。经过靶向治疗后，携带者的临床恶化程度更高（p = 0.008）。总随访时间为2.68（1.60，4.98）年，1年、3年和5年生存率分别为93.4%、86.7%和68.6%。携带者的预后明显比非携带者差（对数秩检验p < 0.001）。多因素Cox回归分析表明，致病变异以及较高的肺血管阻力指数（PVRI）与较高的死亡风险相关。
我们发现中国儿童PAH的致病变异率较高，而靶向治疗改善了PAH患儿的总体预后，但致病变异患者对治疗的反应较差且预后较差。
