Improvement in exercise capacity by exercise training associated with favorable clinical outcomes in advanced heart failure with high B-Type natriuretic peptide level

Background: The efficacy of exercise training (ET) programs and its relationship with long-term clinical outcomes in advanced heart failure (HF) patients with high levels of B-type natriuretic peptide (BNP) remain uncertain. Methods and Results: We studied 340 consecutive HF patients with ejection fraction (EF) <45% who completed a 3-month ET program. Patients with BNP ≥200 pg/mL (High-BNP, n=170) had more advanced HF characteristics, including lower EF (25.0±8.6% vs. 28.1±8.0%, P=0.0008), than those with BNP <200 pg/mL. In the High-BNP patients, peak oxygen uptake (VO₂) was significantly increased by 8.3±16.2% during the ET program, and changes in peak VO₂ inversely correlated with changes in BNP (R=−0.453, P<0.0001) and changes in ventilatory efficiency (VE/VCO₂ slope) (R=−0.439, P<0.0001). During a median follow-up of 46 months, patients in the upper tertile of changes in peak VO₂ (≥13.0%), compared with those in the lower tertile (<1.0%), had lower rates of the composite of all-cause death or HF hospitalization (37.9% vs. 54.4%, P=0.036) and all-cause death (8.6% vs. 24.6%, P=0.056). In the multivariate analysis, change in peak VO₂ was a significant independent predictor of the composite outcome and all-cause death. Conclusions: Even among advanced HF patients with high BNP level, an ET program significantly improved exercise capacity, and a greater improvement in exercise capacity was associated with greater decreases in BNP level and VE/VCO₂ slope and more favorable long-term clinical outcomes.