Clinical utility of ventilatory and gas exchange evaluation during low-intensity exercise for risk stratification and prognostication in pulmonary arterial hypertension

Background and objective: Peak oxygen consumption (pVO₂ ), determined from CPET, provides a valuable indication of PAH severity and patient prognosis. However, CPET is often contraindicated in severe PAH and frequently terminated prior to achievement of a sufficient exercise effort. We sought to determine whether in PAH low-intensity [i.e. freewheeling exercise (FW)] exercise reveals abnormal V_E /VCO₂ and P_ET CO₂ responses that are associated with pVO₂ and serve as indices of PAH risk stratification and mortality.

Methods: Retrospective analysis of CPET from 97 PAH patients and 20 age-matched controls was undertaken. FW V_E /VCO₂ and P_ET CO₂ were correlated with pVO₂ % age-predicted. Prognostication analysis was conducted using pVO₂ > 65% age-predicted, as known to represent a low mortality risk. Primary outcome was mortality from any cause.

Results: FW P_ET CO₂ was correlated with pVO₂ (P < 0.0001; r = 0.52), while FW V_E /VCO₂ was not (P = 0.13; r = -0.16). ROC curve analyses showed that FW P_ET CO₂ (AUC = 0.659), but not FW V_E /VCO₂ (AUC = 0.587), provided predictive information identifying pVO₂ > 65% age-predicted (best cut-off value of 28 mm Hg). By Cox analysis, FW P_ET CO₂ < 28 mm Hg remained a predictor of mortality after adjusting for age and PAH aetiology (HR: 2.360, 95% CI: 1.144-4.866, P = 0.020).

Conclusion: Low P_ET CO₂ during FW is associated with reduced pVO₂ in PAH and provides predictive information for PAH risk stratification and prognostication.