Background 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. Methods 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. Results 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). Conclusions 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.<Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec colname="c1" colnum="1" /> <colspec colname="c2" colnum="2" /> <tbody> <row> <entry align="left" nameend="c2" namest="c1"> 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. </entry> </row> </tbody> </tgroup> </Table>

Prognostic value of cardiopulmonary exercise testing in connective tissue disease-associated pulmonary arterial hypertension at low and intermediate-low risk

期刊论文
发表日期：

2026年3月31日

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Yixin Zhang,
Linwei Shan,
Jiayi Dai,
Zhangdi Zhou,
Yanrong Liu,
Qin Shen,
Xiaoxuan Sun,
Qiang Wang,
Lei Zhou

摘要

Background

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.

Methods

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.

Results

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).

Conclusions

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.