Update on targeted therapies in pediatric pulmonary arterial hypertension

Abstract

Treatment of pediatric pulmonary arterial hypertension (PAH) has dramatically changed with the recent availability of specific oral drugs. These new treatments have been exclusively approved in PAH that should be differentiated from other causes of pulmonary hypertension particularly frequent in intensive care unit (ICU) patients. In pediatrics, data assessing efficacy and safety of these drugs do not exist in other settings than PAH. Consistently, these drugs are not recommended in persistent pulmonary hypertension of the newborn or during the postoperative course of cardiac surgery, even if routinely used. Treatment of PAH associated with congenital heart diseases represents a major concern and designing trials is challenging due to the possible benefits for children. Endothelin receptor antagonists and phosphodiesterase-5 (PDE-5) inhibitors have been approved in Europe for children use. Prostanoids including epoprostenol are largely used in the ICU, mostly by intravenous route. Specific PAH drugs may be used alone or in combination. Several trials are ongoing to test the best combination strategy with preliminary hopeful results suggesting significant improvement for the future. Creation of right-to-left shunts (atrioseptotomy and Potts’ anastomosis) as well as lung transplantation should be indicated when children’s clinical situation worsen despite optimal PAH pharmacological management.