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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.

We have characterized the humoral and cellular immune responses of BALB/c mice immunized with HIV-1 Nef regulatory protein encapsulated in poly(DL-lactide-co-glycolide) PLG particles. Three groups of mice were immunized with Nef PLG, Nef in the presence of complete Freund's adjuvant (CFA) or Nef alone in PBS. When titers were compared 7 months after the last injection, anti-Nef titers in mice immunized with Nef PLG were still close to the maximum, whereas a significant decrease was observed in mice immunized with Nef alone (five times lower) or with Nef in CFA (three times lower). These results indicate that Nef PLG is at least a similar or better vector/adjuvant than Nef in CFA concerning the duration of the humoral immune response. The analysis of cytokine profiles (IL-5 and IL-10) and the isotypic patterns of anti-Nef antibodies (predominantly IgG1), in the three groups of mice, indicated a predominant Th2 immune response. Using synthetic peptides covering the entire sequence of Nef, we identified at least three linear epitopes within sequences 32-64, 118-167 and 185-205 in the sera of mice immunized with Nef PLG or Nef CFA. In contrast, anti-Nef antibodies against Nef alone failed to recognize synthetic peptides, indicating that the majority of anti-Nef antibodies were primarily directed against conformational epitopes. We then examined the ability of Nef PLG to prime for the antigen-specific proliferative responses in vitro. The data obtained indicate the presence of both B-cell and T-cell epitopes in the C-terminal fragment of the protein after immunization of mice with Nef encapsulated in PLG particles.