title: Clinical implications of determining BMPR2 mutation status in a large cohort of children and adults with pulmonary arterial hypertension.
abstract: BACKGROUND
  Bone morphogenetic protein receptor type 2 (BMPR2) mutations occur in idiopathic and familial pulmonary arterial hypertension (IPAH, FPAH); however, the impact of these mutations on clinical assessment and disease severity remains unclear. We investigated the role of BMPR2 mutations on acute vasoreactivity and disease severity in IPAH/FPAH children and adults.
  
  
  METHODS
  BMPR2 mutation types were determined in 147 IPAH/FPAH patients. Hemodynamics were obtained at baseline and with acute vasodilator testing.
  
  
  RESULTS
  Of 147 patients (69 adults, 78 children; 114 with IPAH, 33 with FPAH), 124 (84%) were BMPR2 mutation-negative, and 23 (16%) were mutation-positive. BMPR2 mutation-positive patients were less likely to respond to acute vasodilator testing than mutation-negative patients (4% vs 33%; p < 0.003; n = 147). BMPR2 mutation-positive children also appeared less likely to respond to acute vasodilator testing than mutation-negative children. BMPR2-positive patients had lower mixed venous saturation (57 +/- 9% vs 62 +/- 10%; p < 0.05) and cardiac index (CI; 2.0 +/- 1.1 vs 2.4 +/- 1.5 liters/min; p < 0.05) than BMPR2-negative patients.
  
  
  CONCLUSIONS
  Patients with BMPR2 mutations are less likely to respond to acute vasodilator testing than mutation-negative patients and appear to have more severe disease at diagnosis. Determination of BMPR2 mutations appears to help identify IPAH/FPAH children and adults who are unlikely to respond to acute vasodilator testing and, thus, unlikely to benefit from calcium channel blockade (CCB) treatment.
authors.affiliation: Department of Pediatric Cardiology, Columbia University College of Physicians & Surgeons, New York, New York 10032, USA. esb14@columbia.edu
authors.forename: Erika B
authors.initials: EB
authors.lastname: Rosenzweig
authors.forename: Jane H
authors.initials: JH
authors.lastname: Morse
authors.forename: James A
authors.initials: JA
authors.lastname: Knowles
authors.forename: Kiran K
authors.initials: KK
authors.lastname: Chada
authors.forename: Amar M
authors.initials: AM
authors.lastname: Khan
authors.forename: Kari E
authors.initials: KE
authors.lastname: Roberts
authors.forename: Jude J
authors.initials: JJ
authors.lastname: McElroy
authors.forename: Nicole K
authors.initials: NK
authors.lastname: Juskiw
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Mallory
authors.forename: Stuart
authors.initials: S
authors.lastname: Rich
authors.forename: Beverly
authors.initials: B
authors.lastname: Diamond
authors.forename: Robyn J
authors.initials: RJ
authors.lastname: Barst
mesh_terms: D000328:Adult; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics*; D006328:Cardiac Catheterization; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics*; D008168:Lung / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012720:Severity of Illness Index; D014664:Vasodilation
chemical_list: D052006:Bone Morphogenetic Protein Receptors, Type II