Twenty-year experience and outcomes in a national paediatric pulmonary hypertension service
Authors: Constantine A , Dimopoulos K , Muthurangu V , Haworth S , Moledina S 
Published: October 2021

Abstract

Background/Introduction
Paediatric pulmonary hypertension (PH) is an important cause of childhood morbidity and mortality, but there are limited data on the range of associated diseases (including several paediatric-specific aetiologies), contributions of different PH subtypes, therapeutic strategies and clinical outcomes in paediatric patients.

Purpose
In this study, we report the 20-year experience of a UK National Paediatric Pulmonary Hypertension Service focusing on the aetiology, management and outcomes of children with PH.

Methods
Consecutive patients presenting to the service between January 2001 and January 2021 were included in this retrospective study. Other inclusion criteria were: age ≤18 years at diagnosis and diagnosis of PH following specialist assessment. Only incident patients (without pre-existing PH) were entered in the survival analysis.

Results
A total of 1104 (81.5%) PH patients were included during the study period: 51% female, median age 2.6 [0.8–8.2] years. The most common PH diagnosis was group 1 (pulmonary arterial hypertension, PAH) in 532 (48.2%) patients, followed by group 3 PH (due to lung disease) in 358 (32.4%), group 2 (101, 9.1%), group 5 (93, 8.4%), and group 4 disease (20, 1.8%). The most common PAH subgroup was PAH associated with congenital heart disease (CHD, 63.3%), followed by idiopathic PAH (22.4%). One quarter of patients (23.6%) had multiple contributory factors for PH, fitting more than one diagnostic group.
Resolution of PH, defined as normalisation of pulmonary artery pressures following cessation of PAH therapy, occurred in 172 (15.6%) patients at a median age of 3.7 [2.1–5.7] years and was more common in group 3 than other PH groups (33.5% vs. 9.1% at 5 years post-diagnosis, p&lt;0.0001).
Overall, 909 (82.3%) patients received PAH therapy. Patients with group 3 PH were as likely to receive PAH therapy as an initial treatment strategy as group 1 patients (86.6% vs. 82.3%, p=0.11), but were more likely to receive sildenafil monotherapy (p=0.002) and less likely to be offered triple therapy (p&lt;0.0001). During follow-up, maintenance or escalation to triple therapy was required in 103 (9.3%) patients and was far more common in idiopathic compared to other PAH subgroups (37.7% vs. 7.8%, p&lt;0.0001).
Transplant-free survival was 86.7% (95% CI: 84.5–88.9%) at 1 year, 74.2% (95% CI: 71.1–77.5%) at 5 years, and 68.9% (95% CI: 65.1–73%) at 10 years (Figure 1). PAH related to CHD had the highest transplant-free survival (HR 0.62, 95% CI: 0.46–0.84, p=0.002). Group 2 had the lowest transplant-free survival (HR 2.09, 95% CI: 1.42–3.09, p=0.0002) whereas groups 3,4 and 5 did not differ significantly from PAH (Figure 2).

Conclusions
In this large, national cohort of paediatric PH patients, the most common type of PH was PAH, followed by group 3 PH. Multiple contributory causes for PH are common and PH resolution was not uncommon, especially in group 3 patients. Despite widespread use of PAH therapy, the prognosis remains guarded.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Dr Constantine has received a PhD grant from Janssen-Cilag Ltd. as the CHAMPION PhD Fellow. Figure 1Figure 2