Pulmonary arterial hypertension (PAH) is a kind of heart and lung vascular disease with low incidence and poor prognosis. Genetic variants are the important factors of PAH. The mutations of activin receptor-like kinase-1 (ACVRL1) could cause pulmonary arteriole obstruction and occlusion in PAH patients. The ACVRL1 gene mutation and clinical characteristics of Chinese idiopathic or hereditary pulmonary hypertension (IPAH/HPAH) patients are still unclear. This study aimed to retrospective study the mutation characteristics of ACVRL1 gene in Chinese IPAH/HPAH patients and its effect on clinical prognosis. We analyzed the clinical, functional, hemodynamic and mutation characteristics of 12 IPAH/HPAH patients with ACVRL1 mutations, and compared with 94 IPAH/HPAH patients (27 patients carried bone morphogenetic protein receptor type 2 (BMPR2) mutations and 67 without mutations). All ACVRL1 mutations of 12 patients were single nucleotide missense mutations. The ratio of male to female in 12 patients was 1:1. The diagnosis age of ACVRL1 mutation patients was younger than that of BMPR2 mutation patients (13.6±11.3 years vs. 16.0±12.9 years), but higher than that of patients without mutations (13.6±11.3 years vs. 8.8±8.5years, P=0.006). IPAH/HPAH patients with ACVRL1 mutation have rapidly disease progresses, high overall mortality rate (approximately 50%) and no respond to the acute pulmonary vasodilation test. In conclusion, this is the first study to analyze the ACVRL1 gene mutation and clinical characteristics of Chinese IPAH/HPAH patients. It is beneficial to screen ACVRL1 gene mutation for IPAH/HPAH patients to facilitate genetic counseling and early prevention and treatment.

Pediatric patients with pulmonary arterial hypertension (PAH) are considered to be at risk for pulmonary hypertensive crisis (PHC) or even death during right heart catheterization (RHC). This retrospective study was designed to identify the risks and clinical characteristics associated with PHC in pediatric PAH patients. We included 163 consecutive procedures from 147 pediatric patients diagnosed with PAH who underwent diagnostic RHC in Beijing Anzhen Hospital between January 2007 and December 2020. The average patient age was 9.0 ± 4.7 years and 84 (51.5%) were females. Before RHC, over 20% of patients were in New York Heart Association (NYHA) class III-IV. Sedation or general intravenous anesthesia was used in 103 procedures (63.2%), with spontaneous breathing in 93.2%. PHC occurred in 19 patients (11.7%), 5 (3.1%) required cardiac compression, and 1 died (0.6%). Compared to patients without PHC, those who experienced PHC were more likely to be in NYHA class III-IV (p = 0.012) before RHC, require sedation (p = 0.011), had echocardiographic indices of higher peak tricuspid regurgitation velocity (p = 0.018), and right ventricle (RV) to left ventricle (LV) ratio (p < 0.001). Multivariate logistic regression for PHC identified the need for sedation and a higher RV/LV ratio as independent predictors. In conclusion, the risk of RHC remains significant in children with PAH, particularly in those with severe RV dilation who require sedation during cardiac catheterization. Comprehensive evaluation, close monitoring, and appropriate treatment before and during the procedure are essential for reducing mortality.

Background: Paediatric-onset idiopathic/hereditary pulmonary arterial hypertension (IPAH/HPAH) is partially linked to genetic factors that may also affect treatment response and outcome. The relation between clinical characteristics and pathogenicity of gene variants in childhood IPAH/HPAH is still not well understood. Methods: We retrospectively analyzed IPAH/HPAH paediatric patients aged between 3 months and 18 years under follow-up at a large tertiary referral center. Whole-exome sequencing focused on PAH high-risk genes was performed in all patients. Pathogenicity grading of gene variant sites was assessed using ClinVar and population frequencies. The association between gene variants and death was studied using Cox proportional multivariate models. Results: Overall, 129 patients (54.3% females; 91.5% on PAH therapy) with a median age at diagnosis of 6.8 (IQR 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, 3%) gene. Over a median follow-up period of 27.6 months, 26 children died. The presence of a likely pathogenic genetic variant was significantly associated with survival (HR: 3.56, p = 0.005) on multivariable Cox analysis. The number of PAH-specific drugs at presentation was associated with better survival in the cohort with pathogenic variants (p = 0.02). 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. Therefore, proactive medical therapy should be employed in this population.