Exercise ventilation inefficiency and cardiovascular mortality in heart failure : the critical independent prognostic value of the arterial CO2 partial pressure

Aims In chronic heart failure (CHF) patients, the ventilation (VE) needed to eliminate metabolically produced CO2 during exercise (i.e. the VE/VCO2 slope) is a strong prognosticator. VE/Vco(2) slope determinants are the dead space-tidal volume (VD/VT) ratio and the arterial CO2 partial pressure (Paco(2)). We aimed at defining the respective prognostic role of these two variables. Methods and results One hundred and twenty-eight stable CHIF patients (average left ventricular ejection fraction 34 &PLUSMN; 10%) underwent cardiopulmonary exercise testing and blood gas analysis. The prognostic relevance of the VE/Vco(2) slope, VD/VT, and Paco(2) at peak exercise was evaluated by the Kaptan-Meier approach with Log-rank testing and by multivariate Cox regression analysis, During a mean period of 31.3 &PLUSMN; 20 months, 24 patients died from cardiac causes. In univariate analysis, predictors of death included the use of anti-aldosterone drugs, low peak Vo(2), peak Ve/Vo(2), peak Paco(2) and high VE/VCO2 slope, and peak VD/VT. Multivariate analysis identified a low peak Paco(2) (< 35 mmHg) as the strongest independent prognostic indicator [hazard ratio 4.65, 95% confidence interval (CI) (1.695 12.751), P = 0.003] that primarily accounts for the VE/Vco(2) slope prognostic power. Conclusion These findings imply that regulatory mechanisms involved in the tight control of ventilatory command and blood gas tension, rather than lung function abnormalities, play a critical pathophysiological. rote in the exercise ventilation inefficiency of CHF patients.