Clinical implications of determining BMPR2 mutation status in a large cohort of children and adults with pulmonary arterial hypertension.
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.
Rosenzweig
Erika B
EB
Department of Pediatric Cardiology, Columbia University College of Physicians & Surgeons, New York, New York 10032, USA. esb14@columbia.edu
Morse
Jane H
JH
Knowles
James A
JA
Chada
Kiran K
KK
Khan
Amar M
AM
Roberts
Kari E
KE
McElroy
Jude J
JJ
Juskiw
Nicole K
NK
Mallory
Nicole C
NC
Rich
Stuart
S
Diamond
Beverly
B
Barst
Robyn J
RJ
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
D052006:Bone Morphogenetic Protein Receptors, Type II