Prognostic value of cardiopulmonary exercise testing in connective tissue disease-associated pulmonary arterial...

Pulmonary arterial hypertension (PAH) is a severe complication of connective tissue disease (CTD) and a leading cause of mortality in affected patients. Although the COMPERA 2.0 model is widely used for risk stratification in PAH, its ability to discriminate prognosis among low-risk patients remains limited. This study aimed to explore the prognostic predictive role of cardiopulmonary exercise testing (CPET) in CTD-PAH patients classified as low or intermediate-low risk by COMPERA 2.0.

This ambispective cohort included 33 CTD-PAH patients confirmed by right heart catheterization (RHC) and classified as low or intermediate-low risk via COMPERA 2.0 after standardized therapy. All patients underwent CPET. According to the 2022 ESC/ERS criteria, participants were stratified by peak oxygen uptake (PeakVO₂) and ventilatory equivalent for carbon dioxide (VE/VCO₂) slope. The primary endpoint was a composite of clinical deterioration, analyzed using Kaplan-Meier survival curves.

The non-attainment group presented with significantly worse baseline and follow-up characteristics, including reduced exercise tolerance, higher N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and more impaired echocardiographic and hemodynamic parameters compared to the attainment group. Over a mean follow-up of 23.7 ± 12.3 months, the non-attainment group had significantly poorer event-free survival (p = 0.031).

CPET provides additional prognostic information beyond COMPERA 2.0, identifying CTD-PAH patients with greater disease severity and a higher risk of adverse outcomes, even within the low and intermediate-low risk strata. Failure to achieve CPET thresholds was independently associated with increased disease burden and reduced event-free survival. Key Points • This study demonstrates that cardiopulmonary exercise testing (CPET) offers significant prognostic value beyond the COMPERA 2.0 risk stratification model in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) classified as low or intermediate-low risk. • Patients failing to meet CPET criteria (PeakVO₂ > 15 mL/min/kg and VE/VCO₂ slope < 36) exhibited more severe disease, including worse hemodynamics, right ventricular dysfunction, and higher NT-proBNP levels, despite similar COMPERA 2.0 risk categories. • The CPET non-attainment group had significantly lower event-free survival, underscoring the utility of CPET in identifying high-risk patients who might otherwise be underestimated by conventional risk assessment tools. • Inadequate use of immunosuppressive therapy in the non-attainment group suggests that optimizing management of the underlying connective tissue disease may be critical for improving cardiopulmonary outcomes in CTD-PAH.