Cardiopulmonary variables, particularly peak oxygen consumption (peak VO(2)) corrected for total and lean body weight, have been confirmed to predict prognosis in patients with chronic systolic heart failure (HF). Only limited data are available on the prognostic ability of maximal oxygen (O(2)) pulse, an indicator of stroke volume and arteriovenous O(2) difference, especially when corrected for lean body mass. Cardiopulmonary exercise tests were performed in 209 consecutive patients with mild-to-moderate HF (mean ejection fraction 23%), followed for 19 +/- 12 months to determine the impact of maximal O(2) pulse in relation to other cardiopulmonary variables on major clinical events (13 cardiovascular deaths and 15 urgent transplantations). Compared with patients with clinical events, those without major events had a higher peak O(2) pulse (11.4 +/- 4.1 vs 9.2 +/- 2.3 ml/beat, p <0.0001) and body fat-adjusted peak O(2) pulse (15.6 +/- 5.6 vs 11.9 +/- 3.4 ml/beat, p <0.0001). In multivariate analysis, a low peak O(2) pulse was the strongest independent predictor of clinical events (chi-square 10.5, p <0.01). Although peak O(2) pulse was a stronger predictor for clinical events than any other exercise cardiopulmonary variable, including peak VO(2), peak VO(2) lean (defined as the VO(2) corrected for lean body mass), and percentage of predicted peak VO(2), this relation was further strengthened by correcting peak O(2) pulse for percent body fat (chi-square 12.4, p <0.001). In most subgroups (including women, obese subjects, those receiving beta blockers, and those with class III HF), peak O(2) pulse lean was similar to or superior to peak VO(2) lean for predicting major clinical events. Especially in patients who were class III HF and who were receiving beta blockers, peak VO(2) (cutoff 14 ml/kg/min) poorly predicted prognosis; risk stratification was best with peak O(2) pulse lean (cutoff 14 ml/beat). These data indicate the potential usefulness of peak O(2) pulse and lean body mass-adjusted O(2) pulse for predicting prognosis in patients with systolic HF.