Cardiopulmonary exercise testing (CPET) is a frequently used tool in the differential diagnosis of dyspnoea. Ventilatory inefficiency, defined as high minute ventilation (V′E) relative to carbon dioxide output (V′CO2), is a hallmark characteristic of pulmonary vascular diseases, which contributes to exercise intolerance and disability in these patients. The mechanisms of ventilatory inefficiency are multiple and include high physiologic dead space, abnormal chemosensitivity and an altered carbon dioxide (CO2) set-point. A normal V′E/V′CO2 makes a pulmonary vascular disease such as pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) unlikely. The finding of high V′E/V′CO2 without an alternative explanation should prompt further diagnostic testing to exclude PAH or CTEPH, particularly in patients with risk factors, such as prior venous thromboembolism, systemic sclerosis or a family history of PAH. In patients with established PAH or CTEPH, the V′E/V′CO2 may improve with interventions and is a prognostic marker. However, further studies are needed to clarify the added value of assessing ventilatory inefficiency in the longitudinal follow-up of patients.

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