Noninvasive Gas Exchange Determinants of Exercise Hemodynamics in Non-Severe Pulmonary Hypertension Associated With Interstitial Lung Disease

Chebly Dagher, Niala Moallem, Garrett Fiscus, Brett Carollo, Kristen Swanson, Harrison W. Farber, Raj Parikh

https://doi.org/10.1002/pul2.70358 

Abstract

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 (PVRD) and those with static PVR (PVRS). 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 (PVRD) or stable (PVRS) 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 PVRD phenotype. Among the 16 patients included in the analysis, 6 were classified as PVRS and 10 as PVRD. Baseline characteristics, including peak VO2, were similar between groups. Mean GXCAP was significantly higher in PVRS (471 ± 85 mL·mmHg) than in PVRD (311 ± 38 mL·mmHg, p < 0.01), while VE/VCO2 was lower in PVRS (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.

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