Non-invasive screening using ventilatory gas analysis to distinguish between chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension

Background and objective Clinical presentations associated with chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) at rest are highly similar. Differentiating between CTEPH and PAH using non-invasive techniques remains challenging. Thus, we examined whether analysis of ventilatory gas in response to postural changes can be useful as a non-invasive screening method for pulmonary hypertension (PH), and help differentiate CTEPH from PAH. Methods We prospectively enrolled 90 patients with suspected PH and performed right heart catheterization, ventilation/perfusion scan and ventilatory gas analysis. Various pulmonary function parameters were examined in the supine and sitting postures, and postural changes were calculated (Delta(supine - sitting)). Results In total, 25 patients with newly diagnosed PAH, 40 patients with newly diagnosed CTEPH and 25 non-PH patients were included. Delta End-tidal CO2 pressure (PETCO2) was significantly lower in patients with CTEPH and PAH than in non-PH patients (both P < 0.001). Delta PETCO2 < 0 mm Hg could effectively differentiate PH from non-PH (area under the curve (AUC) = 0.969, sensitivity = 89%, specificity = 100%). Postural change from sitting to supine significantly increased the ratio of ventilation to CO2 production (VE/VCO2) in the CTEPH group (P < 0.001). By contrast, VE/VCO2 significantly decreased in the PAH group (P = 0.001). Notably, CTEPH presented with higher Delta VE/VCO2 than PAH, although no differences were observed in haemodynamic and echocardiographic parameters between the two groups (P < 0.001). Furthermore, Delta VE/VCO2 > 0.8 could effectively differentiate CTEPH from PAH (AUC = 0.849, sensitivity = 78%, specificity = 88%). Conclusion Postural changes in ventilatory gas analysis are useful as a non-invasive bedside evaluation to screen for the presence of PH and distinguish between CTEPH and PAH.