Neuro-Hormonal Activation Predicts Ventilatory Response to Exercise and Functional Capacity in Patients with Heart Failure

BACKGROUND: Heart failure (HF) is characterised by reduced tolerance to effort, associated with progressive fatigue and dyspnoea. Neuro-hormonal activation is a hallmark of HF and influences its clinical evolution. AIM: To evaluate the relationship between neuro-hormonal activation, exercise capacity and ventilatory efficiency. METHODS AND RESULTS: 154 HF patients (127 males, 62 +/- 1 years) underwent cardiopulmonary exercise testing and resting blood sampling for assay of plasma brain natriuretic peptide (BNP), NT-proBNP, norepinephrine, epinephrine, aldosterone and plasma renin activity (PRA). BNP and NT-proBNP levels correlated with peak oxygen consumption (VO2) (both R = -0.53, p < 0.001), VE/VCO2 slope (R = 0.56; p < 0.001 and R = 0.58; p < 0.001, respectively) and maximum workload (R = -0.49; p < 0.001 and R = -0.47; p < 0.001, respectively). Norepinephrine correlated slightly less with peak VO2 (R = -0.38, p < 0.001), VE/VCO2 (R = 0.45; p < 0.001) and maximum workload (R = -0.35; p < 0.001). There was a significant inverse correlation between left ventricular ejection fraction and BNP (R = -0.48, p < 0.001), NT-proBNP (R = -0.42; p < 0.001) and norepinephrine (R = -0.43; p < 0.001). Weaker correlations were found for PRA, exercise parameters and ejection fraction. ROC curves showed that BNP was able to identify patients with peak VO2 < 14 ml/min/kg (cut-off 98 pg/ml, AUC 0.775) and a VE/VCO2 > 35 (cut-off 183 pg/ml, AUC 0.797), as well as NT-proBNP (cut-off 537 pg/ml, AUC 0.799 and cut-off 1010 pg/ml, AUC 0.768, respectively) and norepinephrine (cut-off 454 pg/ml, AUC 0.716 and cut-off 575 pg/ml, AUC 0.783, respectively). CONCLUSION: Haemodynamic impairment (as indicated by BNP and NT-proBNP plasma values) and sympathetic activation predict exercise capacity and ventilatory efficiency in HF patients.