Abstract 15114: Intensive Immunosuppressive Therapy Improves Pulmonary Hemodynamics in Patients with Pulmonary Arterial Hypertension Associated with Connective Tissue Disease
Background: Pulmonary arterial hypertension (PAH) still remains a serious disease characterized by elevated pulmonary artery pressure (PAP) and increased pulmonary vascular resistance (PVR), leading to right-sided heart failure and death. Among the several forms of PAH, PAH associated with connective tissue disease (CPAH) has the worse prognosis due to resistance to conventional vasodilator therapy. Since immunological mechanisms should be involved in the pathogenesis of CPAH, we hypothesized that intensive immunosuppressive therapy could improve pulmonary hemodynamics in CPAH.
Methods and Results: In our PAH cohort study with 136 PH patients, we evaluated 13 consecutive patients with CPAH who received immunosuppressive therapy (mean age 44.8±7.7 [SD] years, 12 females and 1 male, systemic lupus erythematosus in 7, Sjogren syndrome in 4, mixed connective tissue disease in 1 and systemic sclerosis in 1). They were intensively treated with cyclphosphamide (500 mg/month IV for more than 6 months) and glucocorticosteroids (1 mg/kg/day PO for more than a month), in addition to the conventional vasodilator therapy with calcium channel blocker, prostacyclin, bosentan, and/or phosphodiesterase-5 inhibitors. They were closely followed up every half to one year by cardiac catheterization. The intensive immunosuprressive therapy effectively decreased mean PAP (mPAP) (from 39.5±9.1 to 28.9±11.0 mmHg, P<0.01 vs. the historical controls, n=4) (Figure) and tended to decrease PVR (from 700±434 to 481±418 dyn*sec/cm5, P=0.07), while cardiac index was maintained (from 2.8±0.7 to 2.9±1.4 L/min/m2, n.s.). Importantly, in 6 out of the 13 patients (46%), mPAP was almost normalized (<25 mmHg) and stabilized for more than a year (16.5±11.4 months).
Conclusions: These results suggest that the intensive immunosuppressive therapy with the combination of cyclophosphamide and glucocorticosteroids improves pulmonary hemodynamics in patients with CPAH.
- © 2010 by American Heart Association, Inc.