Outcome of children with pulmonary arterial hypertension in the era of antiproliferative medication

  • Rosa Laura van Loon, Department of Pediatric Cardiology, University Medical Center Groningen, Groningen, The Netherlands
  • Marc T Roofthooft, Department of Pediatric Cardiology, University Medical Center Groningen, Groningen, The Netherlands
  • Lennie van Osch-Gevers, Department of Pediatric Cardiology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands
  • Tammo Delhaas, Department of Pediatric Cardiology, University Hospital Maastricht, Maastricht, The Netherlands
  • A Derk-Jan ten Harkel, Center for Congenital Anomalies of the Heart, Amsterdam/Leiden, The Netherlands
  • Jan L Strengers, Department of Pediatric Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
  • Hans Hillege, Department of Cardiology and Epidemiology, University Medical Center Groningen, Groningen, The Netherlands
  • Rolf M Berger, Department of Pediatric Cardiology, University Medical Center Groningen, Groningen, The Netherlands

    • Objectives
    To investigate the outcome of children with pulmonary arterial hypertension (PAH) treated in the era of antiproliferative medication (prostanoids, endothelin-receptor-antagonists and 5-phosphodiesterase-inhibitors).
    Methods
    Fifty-two children with idiopathic (n=29) and systemic-to-pulmonary shunt associated PAH (n=23) underwent baseline and follow-up assessments at a national referral center for pediatric PAH. Treatment was initiated depending on functional class (WHOclass) and acute pulmonary vasoreactivity responder status.
    Observed survival was compared to expected survival using the NIH registry formula for PAH survival (D’Alonzo,1991). Potential baseline predictors for survival and effect of antiproliferative medication on clinical and laboratory follow-up assessments were evaluated.
    Results
    Median age was 6.1 years (range 0.04-17.4), WHOclass I/II/III/IV (n=1/13/26/12), median follow-up 3.2 years (range 0.02-14.2).
    Treatment (mono- and combination-) included calcium channel blockers (n=9), epoprostenol (n=10), bosentan (n=34) and sildenafil (n=11).
    Observed survival in the current era of antiproliferative medication was improved compared to expected survival (Figure).
    The following baseline variables were associated with decreased survival: higher WHOclass (p=0.02, HazardRatio2.2, 95%Confidence Interval 1.1-4.5), respiratory rate (p=0.02), pulmonary-to-systemic arterial pressure ratio (p=0.04); and lower blood pressure (p=0.02), cardiac index (p=0.04) and systemic venous saturation (p=0.05).
    After start of antiproliferative medication, 6-minute walk distance initially increased, but eventually decreased after longer follow-up. No changes were seen in transcutaneous oxygen saturation, body mass index or serum markers.
    Conclusions
    Current survival of pediatric PAH appeared improved compared to survival before the introduction of antiproliferative medication. After start of antiproliferative mediacation functional capacity improved during short-term, but declined during long-term follow-up.