Hemodynamic and Clinical Correlates of Endothelin-1 in Chronic Thromboembolic Pulmonary Hypertension

• Published in: Circulation Journal Vol. 70; no. 8; pp. 1058 - 1063
• Main Authors: Reesink, Herre J, Meijer, Ronald C, Lutter, René, Boomsma, Frans, Jansen, Henk M, Kloek, Jaap J, Bresser, Paul
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Circulation Society 2006
• Subjects: Adolescent; Adult; Aged; Chronic thromboembolic pulmonary hypertension; Endarterectomy; Endothelin-1; Endothelin-1 - blood; Endothelin-1 - physiology; Female; Hemodynamics - physiology; Humans; Hypertension, Pulmonary - blood; Hypertension, Pulmonary - etiology; Hypertension, Pulmonary - physiopathology; Male; Middle Aged; Pulmonary Artery - physiopathology; Pulmonary Embolism - blood; Pulmonary Embolism - complications; Pulmonary Embolism - physiopathology; Pulmonary Embolism - surgery; Pulmonary endarterectomy; Sensitivity and Specificity; Severity of Illness Index; Treatment Outcome; Vascular Resistance - physiology
• ISSN: 1346-9843; 1347-4820
• DOI: 10.1253/circj.70.1058

Background In non-thromboembolic pulmonary hypertension, endothelin (ET)-1 levels are increased and correlate with the hemodynamic severity of the disease. Whether such correlations exist in chronic thromboembolic pulmonary hypertension (CTEPH) is unknown, nor whether ET-1 levels correlate with hemodynamic outcome after pulmonary endarterectomy (PEA). Methods and Results ET-1 levels were determined by ELISA. ET-levels were increased in 35 CTEPH patients (1.62±0.21 pg/ml) compared with healthy controls (n=11: 0.75±0.06 pg/ml, p<0.02). ET-1 levels correlated (all p<0.0001) with mean pulmonary artery pressure (mPAP) (r=0.70), cardiac index (r=-0.76), total pulmonary resistance (r=0.72), mixed venous oxygen saturation (r=-0.87), and the distance walked in the 6-min walk test (r=-0.59; p<0.005; n=23). Three months after PEA, ET-1 levels had decreased (p<0.002), and were similar between patients with and without residual pulmonary hypertension (p=0.4). Preoperative ET-1 levels, however, were higher in patients with bad postoperative outcome; that is, patients who either died because of persistent pulmonary hypertension or had residual pulmonary hypertension after PEA (2.68±0.48 pg/ml, and 1.13±0.15 pg/ml, respectively; p<0.002). The levels also correlated with hemodynamic outcome after PEA (mPAP: r=0.67, p<0.0001). By receiver-operator characteristic curve analysis, ET-1 >1.77 pg/ml detected a bad postoperative outcome with a sensitivity and specificity of 79% and 85%, respectively, and a likelihood ratio of 5.2. Conclusion ET-1 levels in CTEPH closely correlated with the hemodynamic and clinical severity of disease in a large cohort of patients. Preoperative ET-1 levels may be useful for better identification of patients at risk for persistent pulmonary hypertension after PEA. (Circ J 2006; 70: 1058 - 1063)