Advances in pediatric pulmonary arterial hypertension

Abstract

Purpose of review: Pulmonary arterial hypertension (PAH) is an important cause of morbidity and mortality in children. Approved medications for the treatment of adult PAH have been used to treat children, but evidence-based treatment algorithms for children are lacking.

Recent findings: Pediatric PAH registries have begun to define the incidence and prevalence of idiopathic PAH and PAH associated with congenital heart disease. A pediatric-specific classification of pulmonary hypertensive vascular disease has been proposed. Furthermore, the first randomized placebo-controlled trial of type-5 phosphodiesterase therapy in treatment-naïve children with PAH has been completed and reported. This trial highlights the importance of the difficulties of performing clinical trials in children with targeted PAH therapy as well as the importance of long-term follow-up of adverse events.

Summary: Classification, clinical trials, and therapy for children with PAH must take into account the unique aspects of PAH in children.

Figure 1

Annual incidence rates for pediatric pulmonary hypertension in the Netherlands. PH indicates pulmonary hypertension; PAH, pulmonary arterial hypertension; PAH-CHD, PAH associated with congenital heart defects; and iPAH, idiopathic PAH. Source: [7] Van Loon RL, et al. Circulation. 2011 Sep 26;124:1755-64.

Figure 2

Survival curves for idiopathic pulmonary arterial hypertension (IPAH) and associated pulmonary arterial hypertension (APAH) cases censored for time in the study and for transplantation. There was no significant difference between the two groups. B. Survival curves for the subgroups within the associated pulmonary arterial hypertension (APAH) group. The number in each group (brackets) and the predicted survival out of a possible 5 years are shown. CT: Connective Tissue. Source: [9] Haworth, SG et al. Heart 2009;95:312-317

Figure 2

Survival curves for idiopathic pulmonary arterial hypertension (IPAH) and associated pulmonary arterial hypertension (APAH) cases censored for time in the study and for transplantation. There was no significant difference between the two groups. B. Survival curves for the subgroups within the associated pulmonary arterial hypertension (APAH) group. The number in each group (brackets) and the predicted survival out of a possible 5 years are shown. CT: Connective Tissue. Source: [9] Haworth, SG et al. Heart 2009;95:312-317

Figure 3

Treatment algorithm in children with severe pulmonary arterial hypertension. Source: [14] Tissot C, et al. J Pediatr. 2010;157:528-532

Figure 4

Evidence-based treatment algorithm for pulmonary arterial hypertension adults (for group 1 patients only). APAH: associated pulmonary arterial hypertension; BAS: balloon atrial septostomy; CCB: calcium channel blocker; ERA: endothelin receptor antagonist; IPAH: idiopathic pulmonary arterial hypertension; PAH: pulmonary arterial hypertension; PDE-5 I: phosphodiesterase type-5 inhibitor; s.c.: subcutaneously; WHO-FC: World Health Organization functional class. ^#: to maintain arterial blood O₂ pressure >60 mmHg; ^¶: under regulatory review in the European Union; ⁺: IIa-C for WHO-FC II. Source: [16] Galie N et al Eur Heart J. 2009;30(20):2493-2537.

Figure 5

A. Unadjusted survival rate curves (with 95% CIs) by treatment with advanced therapies in adults with Eisenmenger syndrome (AT (n=287). P value refers to Cox model. B. Adjusted survival rate curves, based on the propensity score–adjusted Cox model, of patients within the third propensity score quartile, with and without advanced therapy. Source: [52] Dimopoulos K et al; Circulation. 2010;121:20-25

Figure 6

Placebo-adjusted percent change in peak VO₂ by cardiopulmonary exercise after 16 weeks of sildenafil or placebo in a randomized, double-blind, placebo-controlled, dose-ranging study of oral sildenafil citrate in treatment-naive children with pulmonary arterial hypertension. Source: [9] Barst RJ, Ivy DD, et al. Circulation. 2011;In Print.