Relationship between baseline ET-1 plasma levels and outcome in patients with idiopathic pulmonary hypertension treated with bosentan

Objectives: To address if baseline endothelin-1 (ET-1) plasma levels might predict clinical worsening (CW) in patients with idiopathic pulmonary hypertension (IPAH) treated with bosentan. Methods: Forty-four consecutive patients with IPAH (WHO classes II–III) were included in this study. After an initial assessment (clinical status, pulmonary hemodynamics, samples for adrenomedullin (ADM), ET-1 and brain natriuretic peptide (BNP) plasma levels), patients were treated with bosentan and followed-up for CW. Results: WeobservedCWin 24 patients. Actuarial rates of freedom fromCWwere 74% at 1 year, 56% at 2 years, and 43% at 3 years. Patients with CW had a worseWHO functional class (II/III; no-CW 14/6 vs CW5/19, p=0.002), sixminute walk-test distance (no-CW 439+94 mvsCW385+82 m, p=0.04), mean pulmonary artery pressure (no- CW47.4+10.6 mmHg vs CW56+12.6 mmHg, p=0.02) and pulmonary vascular resistance (PVR no-CW12.5+ 4.8 WU vs CW 16.4+6.3 WU, p=0.03) than the no-CW group. Moreover ET-1 (no-CW 14.1+4.2 pg/ml vs CW 21.3+6.3 pg/ml, p=0.0001), ADM (no-CW 14.9+7 pg/ml vs CW 21.5+10.4 pg/ml p=0.002) and BNP (no- CW 82.8+35.3 pg/ml vs CW 115.4+39.6 pg/ml, p=0.007) plasma levels were significantly higher in the CW group than in the no-CW group. The multivariate Cox proportional hazards model identified WHO class III (RR 4.6, 95%CI 14.6–1.45), ET-1 plasma levels (RR 1.1, 95%CI 2.05–1.01) and PVR (RR 1.2, 95%CI 1.3–1.03) as independent risk factors for CW. Conclusions: These data confirm the high rate of CW in patients with IPAH treated with bosentan and document the impact of the endothelin system on CW of these patients.