Long-term outcome of children with newly diagnosed pulmonary arterial hypertension: results from the global TOPP registry

Abstract

Background and aims: The Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension (TOPP) registry is a global network established to gain insights into the disease course and long-term outcomes of paediatric pulmonary arterial hypertension (PAH). Previously published cohorts in paediatric PAH are obscured by survival bias due to the inclusion of both prevalent (previously diagnosed) and incident (newly diagnosed) patients. The current study aims to describe long-term outcome and its predictors in paediatric PAH, exclusively of newly diagnosed patients.

Methods and results: Five hundred thirty-one children with confirmed pulmonary hypertension, aged ≥3 months and <18 years, were enrolled in the real-world TOPP registry at 33 centres in 20 countries, from 2008 to 2015. Of these, 242 children with newly diagnosed PAH with at least one follow-up visit were included in the current outcome analyses. During long-term follow-up, 42 (17.4%) children died, 9 (3.7%) underwent lung transplantation, 3 (1.2%) atrial septostomy, and 9 (3.7%) Potts shunt palliation (event rates: 6.2, 1.3, 0.4, and 1.4 events per 100 person-years, respectively). One-, three-, and five-year survival free from adverse outcome was 83.9%, 75.2%, and 71.8%, respectively.Overall, children with open (unrepaired or residual) cardiac shunts had the best survival rates. Younger age, worse World Health Organization functional class, and higher pulmonary vascular resistance index were identified as independent predictors of long-term adverse outcome. Younger age, higher mean right atrial pressure, and lower systemic venous oxygen saturation were specifically identified as independent predictors of early adverse outcome (within 12 months after enrolment).

Conclusion: This comprehensive analysis of survival from time of diagnosis in a large exclusive cohort of children newly diagnosed with PAH describes current-era outcome and its predictors.

Keywords: Outcome; Paediatric pulmonary arterial hypertension; Prognosis; Survival.

Figure 1

Flow chart of patient inclusion. A total of 531 patients with PH were enrolled in TOPP between 2008 and 2015. Of these, 242 incident patients with pulmonary arterial hypertension (PAH, PH Group 1 according to the World Symposium on Pulmonary Hypertension classification) were included in the current evaluation. One hundred forty-five had idiopathic or heritable PAH, 85 had PAH associated with congenital heart disease [*53 with open shunts (unrepaired or residual shunts) and 32 without open shunts (either fully repaired or never shunt)], and 12 had PAH associated with other conditions (^†3 chronic liver disease, 3 connective tissue disease, 3 pulmonary veno-occlusive disease, 2 hereditary haemorrhagic telangiectasia, and 1 other). TOPP indicates Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension Registry; PH, pulmonary hypertension; PAH, pulmonary arterial hypertension; IPAH, idiopathic PAH; HPAH, heritable PAH; APAH-CHD, PAH associated with congenital heart disease; APAH-other, PAH associated with other conditions.

Figure 2

Causes of death stratified by early [<1 year from diagnostic right-heart catheterization (RHC)] and late (>1 year from diagnostic RHC) deaths. PH indicates pulmonary hypertension; RV, right ventricular; HC, heart catheterization; ARDS, acute respiratory distress syndrome; CVL, central venous line.

Figure 3

Survival displayed as Kaplan–Meier survival curves. Data are shown for (A) the total cohort of incident PAH patients and (B) stratified by aetiology subgroups. PAH indicates pulmonary arterial hypertension; IPAH, idiopathic PAH; HPAH, heritable PAH; APAH-CHD, PAH associated with congenital heart disease; APAH-other, PAH associated with other conditions.

Figure 4

Survival free of adverse outcomes (death, lung transplantation, atrial septostomy, or Potts shunt palliation). Data are shown for (A) the total cohort of incident PAH patients and (B) stratified by aetiology subgroups. PAH indicates pulmonary arterial hypertension; IPAH, idiopathic PAH; HPAH, heritable PAH; APAH-CHD, PAH associated with congenital heart disease; APAH-other, PAH associated with other conditions.