Background Due to the recent progress of vasodilators for pulmonary arterial hypertension (PAH), the prognosis of PAH has been getting better for the past 10 years. Among them, idiopathic PAH (IPAH) well improved but PAH associated with connective tissue disease (CTD-PAH) especially scleroderma (SSc-PAH) have poorer prognosis than IPAH.
Objectives This study intended to clarify the clinical features and prognosis of CTD-PAH in modern era when multiple PAH drugs are available, in addition, compare between SSc-PAH and PAH associated with other CTD-PAH (non SSc-PAH).
Methods Fifty-seven consecutive CTD-PAH patients were enrolled to this study, who received hemodynamic examination with right heart catheterization between 2004 and 2016. Thirty of 57 patients were SSc-PAH patients and other 27 patients were non SSc-PAH patients (11 mixed connective tissue disease, 8 systemic lupus erythematosus, 5 primary sjogren syndrome, 1 polymyositis, 1 rheumatoid arthritis and 1 Still's disease were included). We retrospectively analyzed the relationship between clinical parameters at baseline and the prognosis of CTD-PAH patients.
Results Mean age at entry were 65.3±10.3 and 48.3±15.5 years old each other (SSc-PAH vs non SSc-PAH P<0.001). Twenty-eight SSc-PAH (93%) and 26 non SSc-PAH patients (96%) took at least one vasodilator, among them, 18 SSc-PAH (60%) and 13 non-SSc-PAH (48%) patients took multiple vasodilators at the end of follow-up period. Comparing the baseline clinical parameters between two groups, vital capacity and diffusing capacity of the lung for carbon monoxide (DLCO) were significantly lower in SSc-PAH patients than non SSc-PAH patients and brain natriuretic peptide and creatinine level were higher in SSc-PAH patients than non SSc-PAH patients (P<0.05). However, there were no significant differences in hemodynamic indices between two groups. During a mean follow-up period of 42.5±31.5 months, 22 patients (18 SSc-PAH and 4 non SSc-PAH) died or received lung transplantation. The SSc-PAH patients had worse prognosis than non SSc-PAH patients (figure: P<0.001). Only 6 of 18 SSc-PAH patients and 1 of 4 non SSc-PAH patient died of PH related cardiovascular event and other principal causes of death included interstitial lung disease (ILD), neoplasm and infection. Applying multivariate Cox-proportional hazard regression, mean pulmonary arterial pressure, right atrial pressure, creatinine level and %DLCO were extracted as the independent risk for all-cause mortality.
Conclusions SSc-PAH patients had poor prognosis among CTD-PAH patients despite the progression of PAH drugs. As well as the report from REVEAL registry, not only PAH severity but also respiratory dysfunction may predict the prognosis of CTD-PAH patient. Scleroderma is multiorgan disease affected by complex pathology of vasoconstriction (ischemia), proliferation, inflammation, autoimmune disorder and fibrosis. Our data suggest that vasodilator alone is not enough to improve the prognosis of CTD-PAH patients. Comprehensive therapeutic strategy for scleroderma is needed.
Chung L.et al. Unique predictors of mortality in patients with pulmonary arterial hypertension associated with systemic sclerosis in the REVEAL registry. Chest 2014;146(6):1494–1504.
Disclosure of Interest H. Maki: None declared, M. Hatano Grant/research support from: Ministry of Health, Labour and Welfare, Bayer Japan, Nippon Shinyaku Co,.Ltd, GlaxoSmithKline K.K., Speakers bureau: Actelion pharmaceuticals Japan Ltd, Bayer Japan, S. Minatsuki: None declared, T. Inaba: None declared, I. Komuro Grant/research support from: Actelion pharmaceuticals Japan Ltd, Y. Asano Grant/research support from: Ministry of Health, Labour and Welfare, S. Sato Grant/research support from: Ministry of Health, Labour and Welfare