Effects of respiratory exchange ratio on the prognostic value of peak oxygen consumption and ventilatory efficiency in patients with systolic heart failure

Objectives: The purpose of this analysis was to evaluate the prognostic characteristics of peak oxygen consumption (Vo₂) and the minute ventilation/carbon dioxide (VE/Vco₂) slope of different peak respiratory exchange ratios (RERs) obtained from cardiopulmonary exercise testing in patients with heart failure (HF). Background: For patients with HF, peak Vo₂ and the VE/Vco₂ slope are used for assessing prognosis. Peak Vo₂ is assessed in association with peak RER≥1.10, indicating maximal effort and prognostic sensitivity. Conversely, the VE/Vco₂ slope provides effort-independent prognostic discrimination. Methods: Patients with HF scheduled to undergo cardiopulmonary exercise testing were enrolled. Patients were subclassified by peak RER (RER<1.00, RER 1.00 to 1.04, RER 1.05 to 1.09, RER≥1.10) and followed for up to 3 years for major cardiac-related events (death, left ventricular assist device implantation, or cardiac transplantation). Results: Included were 1,728 patients with HF (75% males; 40% ischemic etiology; age: 55 ± 14 years; left ventricular ejection fraction: 28 ± 10%). Two hundred seventy major events occurred, with no proportional differences across the RER subgroups. Multivariate Cox regression analysis indicated that the VE/Vco₂ slope and peak Vo₂ remained prognostic within each subgroup; the VE/Vco₂ slope remained the strongest predictor. Receiver-operating characteristic analysis demonstrated equitable prognostic cutoffs for the VE/Vco₂ slope (range: 34.9 to 35.7; area under the curve [AUC] range: 0.69 to 0.75) and peak Vo₂ (range: 13.8 to 14.0 ml·kg^-1·min^-1; AUC range: 0.68 to 0.75). Conclusions: Peak Vo₂ provided a sensitive assessment of prognosis in patients with HF in all RER subgroups. The VE/Vco₂ slope provided greater prognostic discrimination in all RER subgroups. Clinical consideration may be warranted for patients with low RER, low peak Vo₂, and an elevated VE/Vco₂ slope.