Pulmonary arterial hypertension (PAH) consists of a group of vascular abnormalities with elevated pulmonary arterial pressure and pulmonary vascular resistance. Idiopathic or familial PAH is progressive over several years and believed to be fatal without treatment. (1-2) The results of the Endothelin Antagonist tRial in mildly symptomatic PAH (EARLY) indicate that early diagnosis and treatment of PAH might improve time to clinical worsening and emphasize that PAH needs to be diagnosed and treated in the early stages. (3) Germline mutations of bone morphogenetic protein receptor (BMPR)-2, a member of the transforming growth factor (TGF)-β superfamily, have been found in familial and sporadic forms of idiopathic PAH,(4-6) and in appetite-suppressant PAH.(7) The BMPR-2 gene, on chromosome 2q33, has 13 exons. Exons 1-3 encode an extracellular domain, exon 4 encodes the transmembrane domain, exons 5-11 a serine/threonine kinase domain, and exons 12 and 13 a very large intracellular C-terminus of unknown function that appears to be unique to BMPR-2. (8) Mutations in familial PAH have been reported in all exons except for 5 and 13. (9) About 10-25% of sporadic cases of idiopathic PAH are thought to have BMPR-2 mutations (10) and rare cases of PAH associated with congenital heart disease, connective tissue disease and drug induced PAH were reported. (11-12) It is likely that genetic predispositions exist based on normal variations in genes that may influence the pulmonary circulation. However, the studies regarding prevalence of BMPR-2 gene mutations in Korean patients have not been performed.~In a previous study, family members of familial PAH patients showed an increased pulmonary artery systolic pressure (PASP) rise during exercise as assessed by echocardiography. (13-14) In other study, relatives of idiopathic/familial PAH patients displayed enhanced frequency of pulmonary hypertensive response during exercise and that this response is associated with mutations in the BMPR-2 gene. (15) These results suggest that asymptomatic gene carriers, in the absence of manifest pulmonary hypertension, might have enhanced PASP during exercise and more risk to develop resting pulmonary hypertension in the future compared with patients without gene mutations. Therefore, the treatment response by variable vasodilators (ex. calcium channel blockers, endothelin antagonist or prostacyclin analogues..) may be different based on the presence of BMPR-2 gene. In the present study, we want to investigate the prevalence of BMPR-2 gene mutations in the Korean PAH patients(Step-I) and to test that the PAH patients treated with iloprost inhalation solution (Ventavis®) would show hemodynamic response, especially assessed by exercise echocardiography (Step-II).
In the present study, the investigators want to investigate the prevalence of BMPR-2 gene mutations in the Korean PAH patients (Step-I) and to test that the PAH patients treated with iloprost inhalation solution (Ventavis®) would show hemodynamic response, especially assessed by exercise echocardiography (Step-II).