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. 2025 Aug 22;66(2):2402026.
doi: 10.1183/13993003.02026-2024. Print 2025 Aug.

Prognostic value of cardiopulmonary exercise testing in pulmonary arterial hypertension

Andrea Baccelli  1 , Rocco F Rinaldo  2 , Gulammehdi Haji  3 , Rachel J Davies  3 , Francesco Lo Giudice  3 , Wendy Gin-Sing  3 , Beatrice Vigo  4 , Stefano Centanni  5 , J Simon R Gibbs  6 , Luke S Howard  7   6
Affiliations

Prognostic value of cardiopulmonary exercise testing in pulmonary arterial hypertension

Andrea Baccelli et al. Eur Respir J. .

Abstract

Background: Current guidelines recommend a four-strata model based on World Health Organization Functional Class (WHO FC), 6-min walk distance (6MWD) and serum levels of brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP) for risk stratification in patients with pulmonary arterial hypertension (PAH) during follow-up. We explored the relevance of using cardiopulmonary exercise testing (CPET) as the exercise parameter in place of 6MWD at first reassessment after treatment initiation in PAH.

Methods: Incident treatment-naive patients with idiopathic, heritable, drug/toxin-induced and connective tissue disease-associated PAH between 2010 and 2022 were analysed. Correlations between CPET and haemodynamic and right ventricular function parameters were explored, and those which were significant were carried forward to assess association with survival. Independent predictors were used to derive a four-strata CPET score.

Results: 262 patients were included. CPET parameters showed better correlations with haemodynamics and right ventricular function than 6MWD. The CPET score included peak oxygen uptake (peak V̇ O2 ), the slope relating minute ventilation to carbon dioxide production (V̇ E/V̇ CO2 slope) and peak oxygen pulse. The four-strata model based on WHO FC, BNP and CPET score predicted survival at the time of the first re-evaluation, with better accuracy than the model including 6MWD (C-index 0.81 versus 0.71). The CPET score on its own also performed well (C-index 0.82) with a greater spread between categories. Treatment-associated changes in peak V̇ O2 predicted survival, while changes in 6MWD did not.

Conclusions: A simplified four-strata CPET score either alone or included with BNP and WHO FC accurately predicts survival at follow-up in PAH.

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Conflict of interest statement

Conflict of interest: G. Haji reports payment or honoraria for lectures, presentations or educational events, and support for attending meetings from Janssen. R.J. Davies reports payment or honoraria for lectures, presentations or educational events, and support for attending meetings from Janssen. F. Lo Giudice reports payment or honoraria for lectures, presentations or educational events, and support for attending meetings from Janssen. W. Gin-Sing reports consulting fees from Roivant and Liquidia, payment for lectures, presentations or manuscript writing from Janssen, Gossamer Bio and MSD, and support for attending meetings from Janssen. J.S.R. Gibbs reports consulting fees from Acceleron/Merck, Actelion/Janssen/Johnson & Johnson, Aerovate, LG Chem and United Therapeutics, participation on data safety monitoring boards or advisory boards with Actelion/Janssen/Johnson & Johnson, Gossamer Bio, Keros, Merck and Pulmovant, and a leadership role as Functional Committee Chair with ERN-LUNG. L.S. Howard reports payment or honoraria for lectures, presentations or educational events from Janssen, MSD and Aerovate, payment for expert testimony from Janssen, support for attending meetings from Gossamer Bio and Janssen, participation on a data safety monitoring board or advisory board with Janssen, MSD, Gossamer Bio, Altavant, Liquidia, Morphic and Apollo, and stock or stock options with ATXA, iOWNA, Circular and Calibre Bio. The remaining authors have no potential conflicts of interest to disclose.

Figures

None
A four-strata risk stratification model that includes World Health Organization Functional Class (WHO FC), brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP) and cardiopulmonary exercise testing (CPET) score accurately predicts survival in pulmonary arterial hypertension (PAH). V̇O2: oxygen uptake; V̇E/V̇CO2: minute ventilation/carbon dioxide production.
FIGURE 1
FIGURE 1
Flow diagram showing the study population and excluded patients. PAH: pulmonary arterial hypertension; CPET: cardiopulmonary exercise testing; BNP: brain natriuretic peptide; 6MWD, 6-min walk distance; WHO FC: World Health Organization Functional Class.
FIGURE 2
FIGURE 2
Relations between cardiopulmonary exercise testing parameters and haemodynamic variables: a) correlation between peak oxygen uptake (V̇O2) and cardiac index, b) correlation between peak V̇O2 and mixed venous oxygen saturation (SvO2), c) correlation between minute ventilation/carbon dioxide production (V̇E/V̇CO2) slope and cardiac index, d) correlation between V̇E/V̇CO2 slope and SvO2, e) correlation between oxygen pulse and cardiac index, and f) correlation between oxygen pulse and pulmonary vascular resistance (PVR).
FIGURE 3
FIGURE 3
Kaplan–Meier survival curves at first follow-up. a) Transplant-free survival according to the four-strata cardiopulmonary exercise testing (CPET) score risk groups at follow-up. b) Transplant-free survival according to the four-strata ESC/ERS6MWT and ESC/ERSCPET risk categories at follow-up. ESC/ERS: European Society of Cardiology/European Respiratory Society; 6MWT: 6-min walk test.
FIGURE 4
FIGURE 4
Receiver operating characteristic curves and areas under the curve (AUC) of the cardiopulmonary exercise testing (CPET) score, ESC/ERS6MWT and ESC/ERSCPET risk stratification models. The AUC for the CPET score was 0.82 (95% CI 0.77–0.86), for the ESC/ERSCPET was 0.82 (95% CI 0.78–0.86) and for the ESC/ERS6MWT was 0.73 (95% CI 0.69–0.77). ESC/ERS: European Society of Cardiology/European Respiratory Society; 6MWT: 6-min walk test.
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References

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