Abstract

The prognostic utility of the oxygen uptake efficiency slope (OUES) in heart failure with reduced ejection fraction is uncertain. In this post hoc analysis of the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial (n = 2,074), we tested for associations of OUES and peak oxygen uptake (VO₂) with heart failure hospitalization or cardiovascular death in multivariable Cox regression models, adjusting for minute ventilation/carbon dioxide production (VE/VCO₂) slope and other important confounders. Harrell's C-statistics assessed the discriminatory performance of OUES and peak VO₂. Lower OUES was associated with increased risk of the outcome (quartile 1 vs 4: hazard ratio 2.1 [1.5 to 2.9, p <0.001]). Peak VO₂ had greater discrimination than OUES in comparable models (e.g., C-statistic = 0.73 vs 0.70, p <0.001, respectively). In the subgroup with respiratory exchange ratio <1 (n = 358), peak VO₂ was associated with the outcome (p <0.001) but OUES was not (p = 0.96). In conclusion, whereas OUES was associated with clinical outcomes independently of VE/VCO₂ slope, its prognostic utility was inferior to that of peak VO₂, even when measured at submaximal effort.