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Objectives: The prevalence of chronic heart failure and a reduced ejection fraction (CHF-REF) has increased over the last decade. The cardiopulmonary exercise test (CPET) is an established tool for managing these patients. For patients who are administered beta-blockers, its predictive value is debated. The aim of this study was to assess the prognostic values of several parameters in patients with CHF-REF who were on beta-blockers. Study design: 390 patients with CHF-REF underwent CPET after cardiac rehabilitation and were followed for two years. Results: The primary endpoints were all-cause mortality, cardiac- related mortality and major cardiovascular events (hospitalization for HF, heart transplantation and acute coronary syndrome or arrhythmia). The mean beta-blockers dosage was 68.9% of the target dose. The two-year mortality rate was 13%, while the mean age of the population was 57.1 years. In addition, most of the patients were men (85.5% vs. 14.5%). The resting LVEF was 35.7+-9.4 and the maximal oxygen uptake (peak VO2) was 19.5 ml/kg/min. The peak VO2, VE/ VCO2 slope and circulatory power were significant predictors of risk. The prognosis was better when the initial linear VE/VCO2 slope was lower than 30, and the final steeper VE/ VCO2 slope was lower than 32. There was no difference between the two slopes. The oxygen uptake efficiency slope, oxygen uptake, heart rate recovery, VE/VCO2/VO2 index and ventilatory threshold had no prognostic value. Conclusion: The peak VO2, circulatory power and VE/VCO2 slope were prognostic indicators for patients with CHF-REF who were on beta-blockers.