Exercise oscillatory breathing and increased ventilation to carbon dioxide production slope in heart failure: An unfavorable combination with high prognostic value

Background Increased slope of exercise ventilation to carbon dioxide production (VE/VCO(2)) is an established prognosticator in patients with heart failure. Recently, the occurrence of exercise oscillatory breathing (EOB) has emerged as an additional strong indicator of survival. Objective The aim of this study is to define the respective prognostic significance of these variables and whether excess risk may be identified when either respiratory disorder is present. Methods In 288 stable chronic HF patients (average left ventricular ejection fraction, 33 +/- 13%) who underwent cardiopulmonary exercise testing, the prognostic relevance of VE/VCO(2) slope, EOB, and peak Vo(2) was evaluated by multivariate Cox regression. Results During a mean interval of 28 +/- 13 months, 62 patients died of cardiac reasons. Thirty-five percent presented with EOB. Among patients exhibiting EOB, 54% had an elevated VE/VCO(2) slope. The optimal threshold value for the VE/VCO(2) slope identified by receiver operating characteristic analysis was <36.2 or >= 36.2 (sensitivity, 77%; specificity, 64%; P < .001). Univariate predictors of death included low left ventricular ejection fraction, low peak Vo(2), high VE/VCO(2) slope, and EOB presence. Multivariate analysis selected EOB as the strongest predictor (X(2), 46.5;. P < .001). The VE/VCO(2) slope (threshold, <36.2 or >= 36.2) was the only other exercise test variable retained in the regression (residual X(2), 5.9; P = .02). The hazard ratio for subjects with EOB and a VE/VCO(2) slope >= 36.2 was 11.4 (95% confidence interval, 4.9-26.5; P < .001). Conclusion These findings identify EOB as a strong survival predictor even more powerful than VE/VCO(2) Slope. Exercise oscillatory breathing presence does not necessarily imply an elevated VE/VCO(2) slope, but combination of either both yields to a burden of risk remarkably high.