The lowest VE/VCO2 ratio during exercise as a predictor of outcomes in patients with heart failure

Background: The lowest minute ventilation (VE) and carbon dioxide production (VCO2) ratio during exercise has been suggested to be the most stable and reproducible marker of ventilatory efficiency in patients with heart failure (HF). However, the prognostic power of this index is unknown. Methods and Results: A total of 847 HF patients underwent cardiopulmonary exercise testing (CPX) and were followed for 3 years. The associations between the lowest VE/VCO2 ratio, maximal oxygen uptake (peak VO2), the VE/VCO2 slope, and major events (death or transplantation) were evaluated using proportional hazards analysis; adequacy of the predictive models was assessed using Akaike information criterion (AIC) weights. There were 147 major adverse events. In multivariate analysis, the lowest VE/VCO2 ratio (higher ratio associated with greater risk) was similar to the VE/VCO2 slope in predicting risk (hazard ratios [HR] per unit increment 2.0, 95% CI 1.1-3.4, and 2.2, 95% CI 1.3-3.7, respectively; P < .01), followed by peak VO2 (HR 1.6, 95% CI 1.1-2.4, P = .01). Patients exhibiting abnormalities for all 3 responses had an 11.6-fold higher risk. The AIC weight for the 3 variables combined (0.94) was higher than any single response or any combination of 2. The model including all 3 responses remained the most powerful after adjustment for β-blocker use, type of HF, and after applying different cut points for high risk. Conclusions: The lowest VE/VCO2 ratio adds to the prognostic power of conventional CPX responses in HF.