Noninvasive Gas Exchange Determinants of Exercise Hemodynamics in Non-Severe Pulmonary Hypertension Associated With...

Level 3 cardiopulmonary exercise testing (CPET) can unmask the dynamic burden of pulmonary vascular disease (PVD), while submaximal exercise testing offers a simpler, noninvasive alternative. Emerging markers such as a gas-exchange derived estimate of pulmonary vascular capacitance (GXCAP) and ventilatory efficiency (VE/VCO₂) may reflect PVD and correlate with invasive hemodynamics. Level 3 CPET has been used to stratify PH-ILD patients into those with exercise-induced increases in pulmonary vascular resistance (PVR_D) and those with static PVR (PVR_S). This study evaluated whether GXCAP and VE/VCO₂ measured during submaximal testing could identify non-severe PH-ILD patients with exercise-induced increases in PVR. GXCAP and VE/VCO₂ were retrospectively analyzed in 16 non-severe PH-ILD patients who underwent both submaximal exercise testing and invasive Level 3 CPET. Patients were previously categorized as having dynamic (PVR_D) or stable (PVR_S) PVR responses. Between-group differences were assessed using unpaired t-tests, and receiver operating characteristic (ROC) analysis evaluated the ability of each variable to identify the PVR_D phenotype. Among the 16 patients included in the analysis, 6 were classified as PVR_S and 10 as PVR_D. Baseline characteristics, including peak VO₂, were similar between groups. Mean GXCAP was significantly higher in PVR_S (471 ± 85 mL·mmHg) than in PVR_D (311 ± 38 mL·mmHg, p < 0.01), while VE/VCO₂ was lower in PVR_S (33 ± 2 vs 37 ± 2.5, p < 0.01). ROC analysis demonstrated excellent discriminatory performance for GXCAP (AUC 0.98) and good discrimination for VE/VCO₂ (AUC 0.90). The GXCAP/VE/VCO₂ ratio performed similarly (AUC 0.98). These findings suggest that GXCAP and VE/VCO₂ obtained during submaximal testing may serve as practical, noninvasive tools for identifying exercise-induced pulmonary vascular impairment and aiding risk stratification in patients with non-severe PH-ILD. However, validation in larger prospective cohorts is needed.