title: Treatment of pulmonary arterial hypertension in congenital heart disease in Singapore versus the Netherlands: age exceeds ethnicity in influencing clinical outcome.
abstract: BACKGROUND
  Advanced treatment of pulmonary arterial hypertension (PAH) in congenital heart disease (CHD) is increasingly applied worldwide following the-mainly Western world based-international PAH-CHD guidelines. However, studies comparing clinical presentation and outcome after the initiation of PAH-specific treatment are lacking. We aimed to analyse this in a Singaporean and Dutch cohort of PAH-CHD patients.
  
  
  METHODS
  Adult CHD patients starting PAH-specific therapy, enrolled in two nationwide registries, were analysed. Patients received phosphodiesterase-type-5 inhibitors, endothelin receptor antagonists, or a combination. Change in six-minute walk test (6MWT) during follow-up was analysed using linear mixed model analysis. Determinants for mortality were assessed using Cox proportional hazard analyses.
  
  
  RESULTS
  A total of 74 patients, 45 Dutch (mean age 47 ± 14 years) and 29 Singaporean (mean age 41 ± 14 years) were analysed. Despite a lower 6MWT (312 versus 395 metres, p = 0.01) and peak VO2 (35 versus 49 % of predicted, p = 0.01) at baseline in Singaporean patients, the treatment effect was similar in the two populations. Age at initiation of therapy (per 5 year lower age, β = + 4.5, p = 0.017) was the strongest predictor of improvement in exercise capacity, corrected for ethnicity, baseline 6MWT, sex and CHD defect.
  
  
  CONCLUSIONS
  Patients from Singapore had a worse clinical performance at baseline compared with the PAH-CHD patients from the Netherlands. No relation between ethnicity and improvement in 6MWT after PAH-specific therapy was found. Age at initiation of PAH-specific therapy was the strongest predictor of treatment efficacy and mortality, emphasising the need for early initiation of treatment in these patients.
authors.affiliation: Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands. a.c.vanriel@amc.uva.nl.|ICIN - Netherlands Heart Institute, Utrecht, The Netherlands. a.c.vanriel@amc.uva.nl.
authors.forename: A C M J
authors.initials: ACMJ
authors.lastname: van Riel
authors.affiliation: Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Schuuring
authors.affiliation: Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: I D
authors.initials: ID
authors.lastname: van Hessen
authors.affiliation: Department of Cardiology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: A P J
authors.initials: APJ
authors.lastname: van Dijk
authors.affiliation: Department of Cardiology, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: E S
authors.initials: ES
authors.lastname: Hoendermis
authors.affiliation: Department of Cardiology, National University Heart Centre, Singapore, Singapore.
authors.forename: J W
authors.initials: JW
authors.lastname: Yip
authors.affiliation: Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands.|ICIN - Netherlands Heart Institute, Utrecht, The Netherlands.
authors.forename: B J M
authors.initials: BJM
authors.lastname: Mulder
authors.affiliation: Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands. b.j.bouma@amc.uva.nl.
authors.forename: B J
authors.initials: BJ
authors.lastname: Bouma
keywords: Advanced treatment; Clinical outcome; Congenital heart disease; Pulmonary arterial hypertension; Six minute walk test