Clinical Outcomes of Pulmonary Arterial Hypertension in Carriers of BMPR2 Mutation

• Published in: American journal of respiratory and critical care medicine Vol. 177; no. 12; pp. 1377 - 1383
• Main Authors: Sztrymf, Benjamin, Coulet, Florence, Girerd, Barbara, Yaici, Azzedine, Jais, Xavier, Sitbon, Olivier, Montani, David, Souza, Rogerio, Simonneau, Gerald, Soubrier, Florent, Humbert, Marc
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 15.06.2008; American Lung Association; American Thoracic Society
• Subjects: Adult; Age of Onset; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Bone Morphogenetic Protein Receptors, Type II - genetics; Clinical outcomes; Female; France - epidemiology; Genetic Predisposition to Disease; Germ-Line Mutation; Hemodynamics; Humans; Hypertension, Pulmonary - epidemiology; Hypertension, Pulmonary - genetics; Hypertension, Pulmonary - mortality; Intensive care medicine; Male; Medical sciences; Middle Aged; Phenotype; Pneumology; Point Mutation; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; Sequence Deletion; Survival Rate; France; Intensive care; Prognosis; genetics; bone morphogenetic protein receptor 2; Respiratory disease; Cardiovascular disease; Hemodynamics; Mutation; Survival; pulmonary arterial hypertension; Pulmonary hypertension; Resuscitation
• ISSN: 1073-449X; 1535-4970; 1535-4970
• DOI: 10.1164/rccm.200712-1807OC

Germline mutations in the gene encoding for bone morphogenetic protein receptor 2 (BMPR2) are a cause of pulmonary arterial hypertension (PAH). We conducted a study to determine the influence, if any, of a BMPR2 mutation on clinical outcome. The French Network of Pulmonary Hypertension obtained data for 223 consecutive patients displaying idiopathic or familial PAH in whom point mutation and large size rearrangements of BMPR2 were screened for. Clinical, functional, and hemodynamic characteristics, as well as outcomes, were compared in BMPR2 mutation carriers and noncarriers. Sixty-eight BMPR2 mutation carriers (28 familial and 40 idiopathic PAH) were compared with 155 noncarriers (all displaying idiopathic PAH). As compared with noncarriers, BMPR2 mutation carriers were younger at diagnosis of PAH (36.5 +/- 14.5 vs. 46.0 +/- 16.1 yr, P < 0.0001), had higher mean pulmonary artery pressure (64 +/- 13 vs. 56 +/- 13 mm Hg, P < 0.0001), lower cardiac index (2.13 +/- 0.68 vs. 2.50 +/- 0.73 L/min/m(2), P = 0.0005), higher pulmonary vascular resistance (17.4 +/- 6.1 vs. 12.7 +/- 6.6 mm Hg/L/min/m(2), P < 0.0001), lower mixed venous oxygen saturation (59 +/- 9% vs. 63 +/- 9%, P = 0.02), shorter time to death or lung transplantation (P = 0.044), and younger age at death (P = 0.002), but similar overall survival (P = 0.51). BMPR2 mutation carriers with PAH present approximately 10 years earlier than noncarriers, with a more severe hemodynamic compromise at diagnosis.