Variation of PetCO₂ during incremental exercise and severity of IPAH and CTEPH

End-tidal PCO₂ (PetCO₂) patterns during exercise testing as well as ventilatory equivalents for CO₂ have been reported for different pulmonary vascular diseases but seldomly for the significant differences in exercise response depending on the etiology of pulmonary hypertension. We aimed to compare PetCO₂ change pattern in IPAH and CTEPH with varying severity during incremental cardiopulmonary exercise testing (CPET).

164 IPAH patients and 135 CTEPH patients referred to Shanghai Pulmonary Hospital between 2012 and 2019 were retrospectively recruited into the study. All patients performed CPET and also underwent right-heart catheterization (RHC). Forty-four healthy subjects also performed CPET and were included as controls.

PetCO₂ was significantly lower in IPAH and CTEPH patients as compared to normal subjects. Moreover, the PetCO₂ did not rise, in fact fell from rest to anaerobic threshold (AT), then further decreased until peak in both IPAH and CTEPH. PetCO₂ value at rest, unloaded, AT and peak were proportionately reduced as the World Health Organization functional class (WHO-Fc) increased in both IPAH and CTEPH patients. The PETCO₂ in IPAH patients had significant differences during all phases of exercise between WHO-Fc I-II and III-IV subgroup. CTEPH also demonstrated significant difference except for PetCO₂ at peak. PetCO₂ values were significantly higher in IPAH during all phases of exercise as compared to CTEPH patients (all P < 0.001). PeakVO₂%pred correlated significantly with PetCO₂ at rest (r = 0.477, P < 0.001), AT (r = 0.609, P < 0.001) and peak exercise (r = 0.576, P < 0.001) in IPAH. N-terminal natriuretic peptide type-B (NT-proBNP) also correlated markedly with PetCO₂, with a correlation coefficient of - 0.326 to - 0.427 (all P < 0.001). Additionally, PetCO₂ at rest, at AT and at peak correlated positively with peakVO₂%pred and showed an inverse correlation with NT-proBNP in CTEPH patients (all P < 0.05).

PetCO₂ during exercise in IPAH and CTEPH patients was significantly different from normal subjects. Moreover, PetCO₂ values were significantly higher in IPAH during all phases of exercise as compared to CTEPH patients (all P < 0.001). PetCO₂ was progressively more abnormal with increasing disease severity according to peakVO₂%pred and WHO-Fc.