Prognostic value of cardiopulmonary exercise testing in pulmonary arterial hypertension

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-naïve patients with idiopathic, heritable, drug/toxins-induced, and connective tissue disease-associated PAH between 2010 and 2022 were analysed. Correlations between CPET and haemodynamic and right ventricular (RV) 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 RV function than 6MWD. The CPET score included peak oxygen uptake (peak VO 2 ), the slope relating ventilation to carbon dioxide production (VE/VCO 2 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 VO 2 and oxygen pulse 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.