title: Survival differences in pediatric pulmonary arterial hypertension: clues to a better understanding of outcome and optimal treatment strategies.
abstract: OBJECTIVE
  In order to describe survival and treatment strategies in pediatric pulmonary arterial hypertension (PAH) in the current era of PAH-targeted drugs and to identify predictors of outcome, we studied uniformly defined contemporary patient cohorts at 3 major referral centers for pediatric PAH (New York [NY], Denver, and the Netherlands [NL]).
  
  
  BACKGROUND
  In pediatric PAH, discrepancies exist in reported survival rates between North American and European patient cohorts, and robust data for long-term treatment effects are lacking.
  
  
  METHODS
  According to uniform inclusion criteria, 275 recently diagnosed consecutive pediatric PAH patients who visited the 3 referral centers between 2000 and 2010 were included.
  
  
  RESULTS
  Unadjusted survival rates differed between the center cohorts (1-, 3-, and 5-year transplantation-free survival rates: 100%, 96%, and 90% for NY; 95%, 87%, and 78% for Denver; and 84%, 71%, and 62% for NL, respectively; p < 0.001). Based on World Health Organization (WHO) functional class and hemodynamic parameters, disease severity at diagnosis differed between the center cohorts. Adjustment for diagnosis, WHO functional class, indexed pulmonary vascular resistance, and pulmonary-to-systemic arterial pressure ratio resolved the observed survival differences. Treatment with PAH-targeted dual and triple therapy during the study period was associated with better survival than treatment with PAH-targeted monotherapy.
  
  
  CONCLUSIONS
  Survival rates of pediatric PAH patients differed between 3 major referral centers. This could be explained by differences between the center cohorts in patients' diagnoses and measures of disease severity, which were identified as important predictors of outcome. In this study, treatment with PAH-targeted combination therapy during the study period was independently associated with improved survival.
authors.affiliation: Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Willemijn M H
authors.initials: WMH
authors.lastname: Zijlstra
authors.affiliation: Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Douwes
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Erika B
authors.initials: EB
authors.lastname: Rosenzweig
authors.affiliation: Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Sandor
authors.initials: S
authors.lastname: Schokker
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Usha
authors.initials: U
authors.lastname: Krishnan
authors.affiliation: Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Marcus T R
authors.initials: MTR
authors.lastname: Roofthooft
authors.affiliation: Children's Hospital Colorado, Aurora, Colorado.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Miller-Reed
authors.affiliation: Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Hans L
authors.initials: HL
authors.lastname: Hillege
authors.affiliation: Children's Hospital Colorado, Aurora, Colorado.
authors.forename: D Dunbar
authors.initials: DD
authors.lastname: Ivy
authors.affiliation: Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. Electronic address: r.m.f.berger@umcg.nl.
authors.forename: Rolf M F
authors.initials: RMF
authors.lastname: Berger
mesh_terms: D000293:Adolescent; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005060:Europe / Q000453:epidemiology; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000401:mortality* / Q000503:physiopathology; D008297:Male; D017410:Practice Guidelines as Topic; D011379:Prognosis; D012042:Registries; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D014655:Vascular Resistance / Q000502:physiology*
chemical_list: D000959:Antihypertensive Agents
keywords: pediatrics; pulmonary hypertension; survival