title: The right ventricle explains sex differences in survival in idiopathic pulmonary arterial hypertension.
abstract: BACKGROUND
  Male sex is an independent predictor of worse survival in pulmonary arterial hypertension (PAH). This finding might be explained by more severe pulmonary vascular disease, worse right ventricular (RV) function, or different response to therapy. The aim of this study was to investigate the underlying cause of sex differences in survival in patients treated for PAH.
  
  
  METHODS
  This was a retrospective cohort study of 101 patients with PAH (82 idiopathic, 15 heritable, four anorexigen associated) who were diagnosed at VU University Medical Centre between February 1999 and January 2011 and underwent right-sided heart catheterization and cardiac MRI to assess RV function. Change in pulmonary vascular resistance (PVR) was taken as a measure of treatment response in the pulmonary vasculature, whereas change in RV ejection fraction (RVEF) was used to assess RV response to therapy.
  
  
  RESULTS
  PVR and RVEF were comparable between men and women at baseline; however, male patients had a worse transplant-free survival compared with female patients (P = .002). Although male and female patients showed a similar reduction in PVR after 1 year, RVEF improved in female patients, whereas it deteriorated in male patients. In a mediator analysis, after correcting for confounders, 39.0% of the difference in transplant-free survival between men and women was mediated through changes in RVEF after initiating PAH medical therapies.
  
  
  CONCLUSIONS
  This study suggests that differences in RVEF response with initiation of medical therapy in idiopathic PAH explain a significant portion of the worse survival seen in men.
authors.affiliation: Department of Pulmonology; Department of Pulmonology, Martini Hospital, Groningen, The Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: Jacobs
authors.affiliation: Department of Pulmonology.
authors.forename: Mariëlle C
authors.initials: MC
authors.lastname: van de Veerdonk
authors.affiliation: Department of Pulmonology.
authors.forename: Pia
authors.initials: P
authors.lastname: Trip
authors.affiliation: Department of Pulmonology.
authors.forename: Frances
authors.initials: F
authors.lastname: de Man
authors.affiliation: Department of Epidemiology and Biostatistics.
authors.forename: Martijn W
authors.initials: MW
authors.lastname: Heymans
authors.affiliation: Department of Physics and Medical Technology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Johannes T
authors.initials: JT
authors.lastname: Marcus
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Kawut
authors.affiliation: Department of Pulmonology.
authors.forename: Harm-Jan
authors.initials: HJ
authors.lastname: Bogaard
authors.affiliation: Department of Pulmonology.
authors.forename: Anco
authors.initials: A
authors.lastname: Boonstra
authors.affiliation: Department of Pulmonology. Electronic address: a.vonk@vumc.nl.
authors.forename: Anton
authors.initials: A
authors.lastname: Vonk Noordegraaf
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D005500:Follow-Up Studies; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000401:mortality* / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012189:Retrospective Studies; D012737:Sex Factors; D013318:Stroke Volume / Q000502:physiology; D015996:Survival Rate; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000502:physiology; D018497:Ventricular Dysfunction, Right / Q000473:pathology* / Q000503:physiopathology*