Heart failure with reduced ejection fraction (HFrEF) is common in the developed world and results in significant morbidity and mortality. Accurate risk assessment methods and prognostic variables are therefore needed to guide clinical decision making for medical therapy and surgical interventions with the ultimate goal of decreasing risk and improving health outcomes. The purpose of this review is to examine the role of cardiopulmonary exercise testing (CPET) and its most commonly used ventilatory gas exchange variables for the purpose of risk stratification and management of HFrEF. We evaluated five widely studied gas exchange variables from CPET in HFrEF patients based on nine previously used systematic criteria for biomarkers. This paper provides clinicians with a comprehensive and critical overview, class recommendations and evidence levels. Although some CPET variables met more criteria than others, evidence supporting the clinical assessment of variables beyond peak V̇O2 is well-established. A multi-variable approach also including the V̇E-V̇CO2 slope and EOV is therefore recommended.
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