Background Measures of ventilatory efficiency during cardiopulmonary exercise testing (CPX), such as the V_E/VCO₂ slope and ventilatory equivalent for CO₂ at anaerobic threshold (EqCO₂_AT), are increasingly being used as prognostic markers in heart failure and pulmonary arterial hypertension (PAH). Little is known about whether these measures can be applied to all forms of PH, in particular chronic thromboembolic pulmonary hypertension (CTEPH), where thrombotic vascular occlusion may an impact on gas exchange through increased dead space fraction.

Methods and results 127 patients, 77 with CTEPH and 50 with PAH, underwent incremental CPX. Ventilatory dead space fraction (V_D/V_T) measured at peak exercise with arterial blood gas analysis was higher in CTEPH than PAH (52.9 vs 41.8, p<0.001).The V_E/VCO₂ slope was higher in CTEPH patients than in PAH patients (50.7 vs 44.4, p=0.024) and was mirrored by similar changes in EqCO₂_AT (47.7 vs 42.0 p=0.008). Multivariate analysis demonstrated disease subtype to be a powerful independent predictor of V_D/V_T (p<0.001), V_E/VCO₂ slope (p=0.003) and EqCO₂_AT (p<0.001). These three measures could distinguish between WHO functional classes I/II and III/IV in PAH, but not CTEPH (Abstract S98 Figure 1). As a result of increased ventilatory inefficiency in CTEPH, breathing reserve was lower at peak exercise compared with PAH (29.0 vs 38.8, p=0.003) despite similar peak VO₂ and heart rate reserves.

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Abstract S98 Figure 1

Conclusion Significant differences in gas exchange exist between CTEPH and PAH, possibly due to differences in V_D/V_T as a result of vascular occlusion due to thromboembolic disease. These findings increase our understanding of the mechanisms of exercise limitation in subtypes of pulmonary hypertension, with increased dependence on gas exchange and ventilatory capacity in CTEPH. Furthermore these differences in gas exchange dissociate measures of ventilatory efficiency from disease severity in CTEPH. Caution should be applied in using common prognostic end-points from CPX in all forms of pulmonary hypertension.