Outcome of pediatric patients with pulmonary arterial hypertension in the era of new medical therapies.
Little is known about the effects of "second-generation drugs" (prostanoids, endothelin receptor antagonists, 5-phosphodiesterase inhibitors) in children with pulmonary arterial hypertension (PAH). This study describes the outcome of a national cohort of children with PAH in an era when these drugs became available. From 1993 to 2008, 52 consecutive children with idiopathic PAH (n = 29) or systemic-to-pulmonary shunt-associated PAH (n = 23) underwent baseline and follow-up assessments. Treatment was initiated depending on functional class, acute pulmonary vasoreactivity response, and drug availability. Observed survival was evaluated depending on time of diagnosis in relation to second-generation drug availability and subsequently compared to calculated predicted survival. Children for whom second-generation drugs were available had improved survival compared to their predicted survival (1-, 3-, and 5-year survival rates 93%, 83%, and 66% vs 79%, 61%, and 50%, respectively). However, this improved survival was observed only in patients for whom second-generation drugs became available during their disease course. No improved survival was observed in patients for whom drugs were available already at diagnosis. Baseline variables associated with decreased survival included higher functional class, higher pulmonary-to-systemic arterial pressure ratio, lower cardiac index, and higher serum levels of N-terminal pro-brain natriuretic peptide and uric acid. After start of second-generation drugs, functional class, 6-minute walking distance, and N-terminal pro-brain natriuretic peptide improved but gradually decreased after longer follow-up. In conclusion, survival of pediatric PAH seemed improved since the introduction of second-generation drugs only in selected patients for whom these drugs became available during their disease course. Start of second-generation drugs initially induced clinical improvements, but these effects decreased after longer follow-up.
van Loon
Rosa Laura E
RL
Department of Pediatric Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
Roofthooft
Marcus T R
MT
Delhaas
Tammo
T
van Osch-Gevers
Magdalena
M
ten Harkel
Arend D J
AD
Strengers
Jan L M
JL
Backx
Ad
A
Hillege
Hans L
HL
Berger
Rolf M F
RM
D000293:Adolescent; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D065128:Endothelin Receptor Antagonists; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D007223:Infant; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D011453:Prostaglandins / Q000627:therapeutic use; D017466:Receptors, Endothelin / Q000627:therapeutic use; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D010726:Phosphodiesterase Inhibitors; D011453:Prostaglandins; D017466:Receptors, Endothelin