State of the art: Pulmonary hypertension in children

Professor of Pediatrics, Division of Pediatric Cardiology,
Columbia University, College of Physicians & Surgeons,
New York, USA
Robyn J. Barst

Treatment for idiopathic pulmonary arterial hypertension in children has included calcium channel blockade for acute responders with vasodilator drug testing, and chronic intravenous epoprostenol for nonresponders. Our approach to the child with idiopathic pulmonary arterial hypertension has been to stratify by response status to acute vasodilator testing and functional class. Acute responders in functional class II or III were considered for chronic oral calcium channel blockade. In contrast, chronic intravenous epoprostenol was recommended for nonresponders, functional class IV patients, and children who clinically and hemodynamically failed chronic calcium channel blockade therapy. Noninvasive studies obtained prior to initiating therapy, as well as periodically thereafter, may be useful in guiding changes in therapeutic regimens, particularly in light of recent advances with various novel therapeutic agents. Serial follow up is necessary to maintain an “optimal therapeutic regimen” for children based on overall risk: benefit considerations. This is a pivotal time for the treatment of idiopathic pulmonary arterial hypertension, as there are a number of very promising new drugs, e.g. prostacyclin analogues, including treprostinil administered by chronic subcutaneous or intravenous infusion, and inhaled iloprost; endothelin receptor antagonists, such as oral bosentan; and inhaled nitric oxide. Clinical investigation is ongoing with additional agents, including inhaled treprostinil, selective ETA receptor antagonists such as oral sitaxsentan and oral ambrisentan, as well as phosphodiesterase inhibitors such as oral sildenafil. Whether these new agents will replace intravenous epoprostenol in selected children remains unknown. Clinical trials are also ongoing with combination therapy, based on the rationale that combining epoprostenol or another prostacyclin analogue with an endothelin receptor antagonist as well as possibly with a phosphodiesterase inhibitor, to further improve the overall risk: benefit profile for medical regimens remains to be determined. However, we hope that by increasing the understanding of the pathobiology of idiopathic pulmonary arterial hypertension, one day this disease will be prevented or “cured”, as opposed to our currently only being able to provide palliative therapy.