Paediatric Pulmonary Arterial Hypertension in China During 2006-18: Insights from a Longitudinal Registry Study

Abstract

Background: Little is known about paediatric pulmonary arterial hypertension (PAH) in low- and middle-income countries (LMICs). We sought to investigate clinical characteristics, treatment patterns and survival statistics for paediatric PAH in China between 2006 and 2018.

Methods: We collected and analyzed data from a registry which consecutively recruited newly diagnosed PAH patients aged 3 months to 18 years between 2006 and 2016 from 2 major national referral centers in China, and followed them through 2018. The main outcome was the time from diagnosis to the occurrence of death or lung transplantation.

Findings: 348 patients (median age 10·6 years, 60·1% female) were followed-up for a median of 6·3 years. Among them, PAH associated with congenital heart disease (APAH-CHD) was confirmed in 208 (59·8%) patients; 62 (57.9%) with unrepaired APAH-CHD had not been identified as having CHD before the diagnosis of PAH. In patients with repaired defects, the defects were closed at a median age of 7·0 (3·8-14·3) years. The 5- and 10-year transplantation-free survival for all patients was 75·4 ± 2·4% and 60·9 ± 3·6%. The survival rates were lowest in idiopathic/heritable PAH (IPAH/HPAH) (5-year 58·2 ± 5·2%, 10-year 29·4% ± 8·2% with median survival of 5·7 years), followed by APAH-CHD (5-year 82·3 ± 2·7%, 10-year 69·2 ± 4·5), and positive responders (5-year 96·0 ± 3·9%, 10-year 96·0 ± 3·9%) (P<0·001 at 5-year, 10-year, respectively). From 2006-2011 and from 2012-2016, children received incrementally more aggressive targeted therapies for PAH treatment (initial traditional therapy: 23.2% vs 8.0%; initial targeted combination therapy: 23.2% vs 57.7%, both P<0.001), however, parenteral prostanoids were only used in 4.9% of patients. These trends in targeted therapy were consistent with the upward trends of survival during study period: PAH diagnosed after 2011 (vs 2006-2011, Hazard Ratio 0·49, [95% CI 0·28-0·85], P=0·01) was an independent predictor for improved transplantation-free survival.

Interpretation APAH-CHD was a heavy burden in China, attributed to significantly delayed diagnosis and poor management of CHD in childhood. A clear improvement of overall transplantation-free survival was observed for patients diagnosed after 2011, possibly due to the more aggressive targeted therapy treatment. Findings from this study should provide an important basis for policy making of priority areas for the medical care of pediatric PAH in LMICs.

Funding: This study was supported by the National Key Research and Development Program of China (2016YFC0901502, 2016YFC0901500), the Key Program of Beijing Municipal Natural Science Foundation (7181009), National Science Fund for Distinguished Young Scholars (81425002), CAMS Innovation Fund for Medical Sciences (2016-I2M-1-002, 2017-I2M-1-004, 2017-I2M-2-001), the Key Program of National Natural Science Foundation of China (81630003).

Declaration of Interests: We declare no competing interests.

Ethical Approval Statement: This study was approved by the local Ethics Committees. Written informed consent was obtained from parents or legal guardians.

Keywords: paediatric, pulmonary arterial hypertension, registry, low- and middle-income countries, transplantation-free survival