Diagnosis, Evaluation and Treatment of Pulmonary Arterial Hypertension in Children

Abstract

Pulmonary Hypertension (PH), the syndrome of elevated pressure in the pulmonary arteries, is associated with significant morbidity and mortality for affected children. PH is associated with a wide variety of potential underlying causes, including cardiac, pulmonary, hematologic and rheumatologic abnormalities. Regardless of the cause, for many patients the natural history of PH involves progressive elevation in pulmonary arterial resistance and pressure, right ventricular dysfunction, and eventually heart failure. In recent years, a number of pulmonary arterial hypertension (PAH)-targeted therapies have become available to reduce pulmonary artery pressure and improve outcome. A growing body of evidence in both the adult and pediatric literature demonstrates enhanced quality of life, functional status, and survival among treated patients. This review provides a description of select etiologies of PH seen in pediatrics and an update on the most recent data pertaining to evaluation and management of children with PH/PAH. The available evidence for specific classes of PAH-targeted therapies in pediatrics is additionally discussed.

2019 updated consensus statement on the diagnosis and treatment of pediatric pulmonary hypertension: The European Pediatric Pulmonary Vascular Disease Network (EPPVDN), endorsed by AEPC, ESPR and ISHLT

“…Pulmonary hypertension (PH) and associated pulmonary vascular disease (PVD) are characterized by pulmonary vascular remodeling leading to elevated pulmonary arterial pressure and, over time, right ventricular (RV) dysfunction, underfilling/compression of the left ventricle, and terminal heart failure. 1−3 PH-associated mortality has been decreasing over the last 2 decades in children 4 and adults, 5 likely because of increased awareness of this condition and its multiple etiologies, more accurate diagnosis, better risk stratification, and early initiation of combination pharmacotherapy. 3,5−7 Nevertheless, transplant-free survival of children and adults with idiopathic pulmonary arterial hypertension (IPAH), heritable pulmonary arterial hypertension (HPAH), and other forms of World Health Organization (WHO) Group 1 PH, such as Eisenmenger syndrome and persistent pulmonary arterial hypertension (PAH) after repair of congenital heart disease (CHD) (PAH-CHD) remains poor.…”

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

“…Endogenous prostacyclin (prostaglandin I 2 ) activates prostacyclin receptors in pulmonary vascular smooth muscle cells and other tissues, increasing production of cyclic adenosine monophosphate, which induces pulmonary vasodilation as well as antithrombotic, antiproliferative, antimitogenic, and immunomodulatory effects . Prostacyclin levels are reduced in patients with PAH, providing a rationale for treatment with prostacyclin analogs (prostanoids) .…”

“…Biomarkers, such as brain natriuretic peptide (BNP) and N ‐terminal prohormone of BNP (NT‐proBNP), are correlated with hemodynamics and right ventricular function and can be used to assess disease severity and prognosis, and to define treatment goals . The prognosis of pediatric PAH varies widely depending on etiology, with better survival in iPAH than in associated PAH . For example, the UK Pulmonary Hypertension Service for Children reported 5‐year survival rates of 71.9% in iPAH and 56.9% in associated PAH .…”

“…For example, the UK Pulmonary Hypertension Service for Children reported 5‐year survival rates of 71.9% in iPAH and 56.9% in associated PAH . Patients with CHD whose PAH persists after surgical repair have very poor survival . However, a review of 134 children with CHD found no survival difference between four groups of patients with PAH‐CHD (Eisenmenger syndrome; left‐to‐right shunts; coincidental CHD; postoperative PAH) .…”

Pulmonary Hypertension Secondary to Scurvy in a Developmentally Typical Child

“…A thorough search for an underlying cause is essential in all new cases of PH. 1,2 In this instance, several physical examination clues led to his diagnosis: bruising, petechiae, gum bleeding, and corkscrew leg hairs. Consistent with prior reports, PH rapidly improved after vitamin C supplementation.…”