A critical appraisal of the prognostic value of the VE/VCO2 slope in chronic heart failure

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Abstract
Increased ventilatory drive, reflected by the slope of increase of ventilation relative to carbon dioxide production (VE/VCO2 slope), has been shown to have a high prognostic value in patients with chronic heart failure (CHF). However, there is no consensus on how to calculate it, as the relation between VE and VCO2 becomes nonlinear near the end of exercise, when ventilation is driven both by CO2 output and by decrease in plasma pH. This may influence the results. Ninety-seven CHF patients with ejection fraction <45% (mean 27 +/- 9%), in NYHA class II-IV underwent a cardiopulmonary exercise test. VE/VCO2 slope was assessed by linear regression using all the data points (Sl), using only points before (Sli), or after (Slf) the non-linear part of the curve, and using only the first 3-min data (Sl3 min). Peak oxygen uptake (VO2), and circulatory power (VO2 x systolic arterial pressure) were also assessed. Death and transplantation were the end-points considered (mean follow-up 22 months). Mean value of VE/VCO2 overall slope was 39.3 +/- 11.6 (22-78). In 64% of the patients, two distinct slopes could be found: an initial, linear slope (31.8 +/- 7.5, 18-62) and a final, steeper slope (48.6 +/- 15.7, 24-101). Patients in whom no rupture of slope was observed were sicker. There was a relation between initial and overall VE/VCO2 slopes (r=0.915, P<10(-4)) and between overall and 3-min VE/VCO2 slopes (r=0.808, P<10(-4)). VE/VCO2 slope correlated with peak VO2 (r=-0.55, P<10(-4)) and peak circulatory power (r=-0.49, P<10(-4)). Univariate analysis showed that the prognostic value of overall VE/VCO2 slope (chi2 25.4, P<10(-4)) was greater than initial (chi2 22.8, P<10(-4)), 3-min (chi2 14.6, P<10(-4)) or final VE/VCO2 slopes (chi2 6.7, P=0.09). By multivariate analysis, the prognostic value of the peak circulatory power was similar to that of the VE/VCO2 overall slope. The VE/VCO2 slope should be computed from all the data points to have its highest prognostic value. Peak circulatory power also has similar prognostic value.