Ventilatory Efficiency During Exercise in CTEPH and PAH Pre- and Post-Treatment

Ventilatory inefficiency, assessed by the VE/VCO₂ slope during cardiopulmonary exercise testing (CPET), is a key physiological marker. However, differences in ventilatory efficiency between chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH), as well as their response to treatment, remain incompletely characterized. We retrospectively analyzed CPET data from 92 patients with CTEPH and 91 with PAH. Ventilatory efficiency (VE/VCO₂ slope) and peak oxygen uptake (peak VO₂) were compared at baseline and in treatment-naïve subgroups. Predictors of ventilatory efficiency were assessed using regression analyses. Longitudinal changes following treatment were evaluated in patients with serial CPETs. At baseline, ventilatory efficiency was significantly worse in CTEPH than in PAH (VE/VCO₂ slope median (IQR) 39.8 (34.3-47.5) versus 35.9 (31-41.5), p < 0.001), despite less severe hemodynamic impairment. This difference persisted in treatment-naïve patients. In both groups, pulmonary vascular resistance, mean pulmonary artery pressure, and peak VO₂ were independent predictors of the VE/VCO₂ slope. Following treatment, ventilatory efficiency improved significantly in CTEPH (ΔVE/VCO₂ slope -8, 95% CI - 13.3 to -4.2, p < 0.001), accompanied by an increase in peak VO₂. Improvements were most pronounced after pulmonary endarterectomy. Patients with PAH showed only modest changes after initiation of targeted therapy. Ventilatory inefficiency is more pronounced in CTEPH than in PAH despite less severe resting hemodynamics. Treatment, particularly pulmonary endarterectomy, leads to substantial improvement in ventilatory efficiency in CTEPH, whereas changes in PAH are less pronounced. CPET-derived ventilatory efficiency may serve as a useful non-invasive marker of treatment response in pulmonary hypertension, particularly in CTEPH.