Gas Exchange and Ventilatory Efficiency During Exercise in Pulmonary Vascular Diseases

Ventilatory inefficiency (high V'_E/V'CO₂) and resting hypocapnia are common in pulmonary vascular disease and are associated with poor prognosis. Low resting PaCO₂ suggests increased chemosensitivity or an altered PaCO₂ set-point. We aimed to determine the relationships between exercise gas exchange variables reflecting the PaCO₂ set-point, exercise capacity, hemodynamics and V'_E/V'CO₂.

Pulmonary arterial hypertension (n=34), chronic thromboembolic pulmonary hypertension (CTEPH, n=19) and pulmonary veno-occlusive disease (PVOD, n=6) patients underwent rest and peak exercise arterial blood gas measurements during cardiopulmonary exercise testing. Patients were grouped according to resting PaCO₂: hypocapnic (PaCO₂ ≤34mmHg) or normocapnic (PaCO₂ 35-45mmHg). The PaCO₂ set-point was estimated by the maximal value of end-tidal PCO₂ (maximal P_ETCO₂) between the anaerobic threshold and respiratory compensation point.

The hypocapnic group (n=39) had lower resting cardiac index (3.1±0.8 vs. 3.7±0.7L/min/m², p<0.01), lower peak V'O₂ (15.8±3.5 vs. 20.7±4.3mL/kg/min, p<0.01), and higher V'_E/V'CO₂ slope (60.6±17.6 vs. 38.2±8.0, p<0.01). At peak exercise, hypocapic patients had lower PaO₂, higher V_D/V_T and higher P_(a-ET)CO₂. Maximal P_ETCO₂ (r=0.59) and V_D/V_T (r=-0.59) were more related to cardiac index than PaO₂ or PaCO₂ at rest or peak exercise. Maximal P_ETCO₂ was the strongest correlate of V'_E/V'CO₂ slope (r=-0.86), peak V'O₂ (r=0.64) and peak work rate (r=0.49).

Resting hypocapnia is associated with worse cardiac function, more ventilatory inefficiency and reduced exercise capacity. This could be explained by elevated chemosensitivity and lower PaCO₂ set-point. Maximal P_ETCO₂ may be a useful non-invasive marker of PaCO₂ setpoint and disease severity even with submaximal effort.