Pulmonary arterial hypertension in the USA: an epidemiological study in a large insured pediatric population

Abstract

Pulmonary arterial hypertension (PAH) is rare in children and few data are available in a pediatric general population. This study aims to calculate the annual incidence and prevalence of PAH and to describe these children in a large US population of patients aged under 18 years. Using the US MarketScan claims database we identified 695 children with PAH in 2010–2013. We calculated annual incidence rates and prevalence overall, by age and PAH type (idiopathic and non-idiopathic) using Byar’s method. We also described characteristics, co-morbidities, treatment patterns, and diagnostic procedures for these children. In 2010–2013, the annual incidence rates of PAH per 1,000,000 children-years was in the range of 4.8–8.1; 0.5–0.9 for idiopathic PAH and 4.3–7.3 for non-idiopathic PAH. The annual prevalence of PAH was in the range of 25.7–32.6 per 1,000,000 children; 4.4–6.0 for idiopathic PAH and 21.3–27.0 for non-idiopathic PAH. Incidence rates and prevalence were highest in children under age 2 years. Around 36% of affected children were born prematurely. Most (75%) had some type of congenital heart defect and 13% had Down’s syndrome. Most patients received PAH monotherapy (83%), while 13% received dual therapy. Phosphodiesterase type 5 inhibitors were the most commonly used treatments. Around 92% had at least one echocardiogram and 37% a right heart catheterization. PAH is very rare in children especially in the absence of etiological factors such as congenital heart defects. A large proportion of diagnoses in children seem to be based on echocardiography rather than right heart catheterization.

Rare variants in SOX17 are associated with pulmonary arterial hypertension with congenital heart disease

“…Pulmonary arterial hypertension (PAH[MIM:178600]) is a rare disease characterized by distinctive changes in pulmonary arterioles that lead to progressive pulmonary arterial pressures, right-sided heart failure and a high mortality rate. Up to 30% of adult- [ 1 , 2 ] and 75% of pediatric-onset PAH cases [ 3 ] are associated with congenital heart disease (PAH-CHD), and due to improved treatments, the number of adults with PAH-CHD is rising [ 1 , 4 ]. Congenital heart defects can result in left-to-right (systemic-to-pulmonary) shunts leading to increased pulmonary blood flow and risk of PAH.…”

TMEM16A regulates the cell cycle of pulmonary artery smooth muscle cells in high‑flow‑induced pulmonary arterial hypertension rat model

“…The mean prevalence of CHD from 1970 to 2017 stood at 8.224 per 1,000 globally (1). Furthermore, the estimated incidence of sustained PH in all categories was reported at 5-8 cases per million children per year and 26-33 per million children in the USA (2). In particular, left-to-right shunt CHD is the most common form of CHD.…”

Treatment of pediatric pulmonary arterial hypertension: A focus on the NO‐sGC‐cGMP pathway

“…The most frequent causes of PAH in children are idiopathic (iPAH), heritable gene defects, and congenital heart disease (CHD); however, connective tissue disease, human immunodeficiency virus, drugs, and portopulmonary hypertension are rare causes in pediatric populations . The prevalence of iPAH has been determined as 2.1 to 4.4 cases per million children, with an incidence of 0.5 to 1‐2 cases per million children per year . PAH‐CHD was more common, comprising 75% of total PAH cases in an American study, with prevalence of 10.1 to 15.6 cases per million and incidence of 1.9 to 2.2 cases per million per year in European studies .…”

“…The prevalence of iPAH has been determined as 2.1 to 4.4 cases per million children, with an incidence of 0.5 to 1‐2 cases per million children per year . PAH‐CHD was more common, comprising 75% of total PAH cases in an American study, with prevalence of 10.1 to 15.6 cases per million and incidence of 1.9 to 2.2 cases per million per year in European studies . Importantly, hospitalizations for pediatric PH are increasing, particularly for children with non‐CHD‐related PH …”