Supplementary Material for: Cardiopulmonary Exercise Testing to Detect Chronic Thromboembolic Pulmonary Hypertension in Patients with Normal Echocardiography

<b><i>Background:</i></b> Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious complication of pulmonary embolism (PE). Taking into account the reported incidence of CTEPH after acute PE, the number of patients with undiagnosed CTEPH may be high. <b><i>Objectives:</i></b> We aimed to determine if cardiopulmonary exercise testing (CPET) could serve as complementary tool in the diagnosis of CTEPH and can detect CTEPH in patients with normal echocardiography. <b><i>Methods:</i></b> At diagnosis, we analyzed the data of CPET parameters in 42 patients with proven CTEPH and 51 controls, and evaluated the performance of two scores. <b><i>Results:</i></b> VE/VCO<sub>2</sub> slope, EQO<sub>2</sub>, EQCO<sub>2</sub>, P(A-a)O<sub>2</sub>, end-tidal partial pressure of CO<sub>2</sub> at anaerobic threshold (PETCO<sub>2</sub>) and capillary to end-tidal carbon dioxide gradient [P(c-ET)CO<sub>2</sub>] were significantly different between patients with CTEPH and controls (p < 0.001). P(c-ET)CO<sub>2</sub> was the single parameter with the highest sensitivity (85.7%) and specificity (88.2%). A score combining VE/VCO<sub>2</sub> slope, P(A-a)O<sub>2</sub>, P(c-ET)CO<sub>2</sub>, PETCO<sub>2</sub> [4-parameter-CPET (4-P-CPET) score] reached a sensitivity of 83.3% and a specificity of 92.2% after cross-validation. In 42 patients with CTEPH, echocardiography identified PH in 29 patients (69%), but it was normal in 13 patients (31%). All patients with normal or unmeasurable right ventricular systolic pressure had a pathological CPET. Twelve of the 13 patients (92%) were detected by both CPET scores. <b><i>Conclusion:</i></b> CPET is a useful noninvasive diagnostic tool for the detection of CTEPH in patients with suspected PH but normal echocardiography. The 4-P-CPET score provides a high sensitivity with the highest specificity.