title: Right ventricular and pulmonary vascular reserve in asymptomatic BMPR2 mutation carriers.
abstract: BACKGROUND
  Non-invasive estimates have suggested that asymptomatic BMPR2 mutation carriers may have an abnormal pulmonary vascular response to exercise and hypoxia. However, this has not been assessed with "gold standard" invasive measures.
  
  
  METHODS
  Eight controls and 8 asymptomatic BMPR2 mutation carriers underwent cardiac magnetic resonance imaging with simultaneous invasive pressure recording during bicycle exercise in normoxia, hypoxia and after sildenafil administration. Abnormal pulmonary vascular reserve was defined as an increase in mean pulmonary artery pressure relative to cardiac output (P/Q slope) >3 mm Hg/liter/min.
  
  
  RESULTS
  During normoxic exercise, BMPR2 mutation carriers had a similar P/Q slope when compared with healthy subjects. Only 1 of 8 BMPR2 mutation carriers had a P/Q slope >3 mm Hg/liter/min. During exercise in hypoxia, 3 of 8 BMPR2 mutation carriers had P/Q slopes >3 mm Hg/liter/min compared with none of the controls. Sildenafil decreased the P/Q slope both in controls and BMPR2 mutation carriers. The exercise-induced increase in right ventricular ejection fraction was similar between groups. None of the BMPR2 mutation carriers developed pulmonary arterial hypertension within 2 (range 1.3 to 2.8) years.
  
  
  CONCLUSIONS
  The presence of a BMPR2 mutation, per se, is not associated with an abnormal pulmonary vascular and right ventricular functional response to exercise in asymptomatic individuals. Longer follow-up will be required to determine whether a P/Q slope of >3 mm Hg/liter/min during exercise in normoxia or hypoxia is a sign of pre-clinical disease expression.
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium; University Hospitals Leuven, Leuven, Belgium. Electronic address: guido.claessen@uzleuven.be.
authors.forename: Guido
authors.initials: G
authors.lastname: Claessen
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium; Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Andre
authors.initials: A
authors.lastname: La Gerche
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium; University Hospitals Leuven, Leuven, Belgium.
authors.forename: Thibault
authors.initials: T
authors.lastname: Petit
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Hilde
authors.initials: H
authors.lastname: Gillijns
authors.affiliation: University Hospitals Leuven, Leuven, Belgium; Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Bogaert
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium; University Hospitals Leuven, Leuven, Belgium.
authors.forename: Mathias
authors.initials: M
authors.lastname: Claeys
authors.affiliation: University Hospitals Leuven, Leuven, Belgium; Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Dymarkowski
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Piet
authors.initials: P
authors.lastname: Claus
authors.affiliation: University Hospitals Leuven, Leuven, Belgium; Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Marion
authors.initials: M
authors.lastname: Delcroix
authors.affiliation: University of Hasselt and Heart Center, Jessa Hospital, Hasselt, Belgium.
authors.forename: Hein
authors.initials: H
authors.lastname: Heidbuchel
mesh_terms: D000328:Adult; D001784:Blood Gas Analysis; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics*; D002302:Cardiac Output / Q000502:physiology; D016022:Case-Control Studies; D005080:Exercise Test / Q000379:methods*; D005260:Female; D006579:Heterozygote; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis* / Q000235:genetics*; D019028:Magnetic Resonance Imaging, Cine / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology; D012016:Reference Values; D012189:Retrospective Studies; D012720:Severity of Illness Index; D000068677:Sildenafil Citrate / Q000008:administration & dosage*; D016278:Ventricular Function, Right / Q000502:physiology
chemical_list: D000068677:Sildenafil Citrate; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II
keywords: BMPR2; cardiac magnetic resonance imaging; exercise physiology; hypoxia; pulmonary vascular function; right ventricular function