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European Heart Journal Advance Access originally published online on December 14, 2004
European Heart Journal 2005 26(5):472-480; doi:10.1093/eurheartj/ehi060
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© The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: journals.permissions{at}oupjournals.org

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

Marco Guazzi1,*, Giuseppe Reina2, Gabriele Tumminello1 and Maurizio D. Guazzi3

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

Received 3 March 2004; revised 16 October 2004; accepted 28 October 2004; online publish-ahead-of-print 14 December 2004.

* Corresponding author. Tel/fax: +39 02 50323144. E-mail address: marco.guazzi{at}unimi.it

See page 426 for the editorial comment on this article (doi:10.1093/eurheartj/ehi141)

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 (<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/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.

Key Words: Heart failure • PaCO2 • Prognosis • Ventilation


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