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European Heart Journal Advance Access published online on December 14, 2004
European Heart Journal, doi:10.1093/eurheartj/ehi060
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European Heart Journal © The European Society of Cardiology 2004; all rights reserved.

Clinical research

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

Marco Guazzi 1*, Giuseppe Reina 2, Gabriele Tumminello 1, and Maurizio D. Guazzi 3

1 Cardiopulmonary Laboratory, Cardiology Division, University of Milano, San Paolo Hospital, Via A. di Rudinì, 8, 20142, Milano, Italy
2 Institute of Statistics and Biometry, University of Milano, Italy
3 Institute of Cardiology, University of Milano, Italy

* To whom correspondence should be addressed.
Marco Guazzi, E-mail: marco.guazzi{at}unimi.it


  Abstract

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/VCO2 slope determinants are the dead space-tidal volume (VD/VT) ratio and the arterial CO2 partial pressure (PaCO2). We aimed at defining the respective prognostic role of these two variables.

Methods and results One hundred and twenty-eight stable CHF patients (average left ventricular ejection fraction 34 ± 10%) underwent cardiopulmonary exercise testing and blood gas analysis. The prognostic relevance of the VE/VCO2 slope, VD/VT, and PaCO2 at peak exercise was evaluated by the Kaplan-Meier approach with log-rank testing and by multivariate Cox regression analysis. During a mean period of 31.3 ± 20 months, 24 patients died from cardiac causes. In univariate analysis, predictors of death included the use of anti-aldosterone drugs, low peak VO2, peak VE/VO2, peak PaCO2 and high VE/VCO2 slope, and peak VD/VT. Multivariate analysis identified a low peak PaCO2 (<35mmHg) 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/VCO2 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 role in the exercise ventilation inefficiency of CHF patients.

Keywords: Heart failure; PaCO2; Prognosis; Ventilation.
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