Circulating Neuropeptide Y Dynamics and Performance During Exercise in Heart Failure Patients with Contemporary Medical and Device Therapy

High cardiac sympathetic drive and release of the sympathetic cotransmitter neuropeptide Y (NPY) are significant features of congestive heart failure (CHF), in which resting venous NPY levels are known to be associated with mortality. However, whether circulating NPY levels increase during exercise in CHF when they are already elevated is controversial. We sought to establish the dynamics of circulating NPY levels in CHF patients treated with contemporary medical therapy and devices in relationship to indices of performance linked to long-term prognosis. CHF patients (n = 15) underwent cardiopulmonary exercise testing with venous blood sampling at rest, peak exercise and recovery. These patients had significantly higher resting venous NPY levels compared with an age- and sex-matched control group of patients (n = 16) with normal left ventricular function (40 ± 6.9 vs. 9.0 ± 4.6 pg/mL, respectively; P < 0.0001). In CHF patients, NPY levels increased significantly from baseline to peak exercise (to 93.5 ± 42.1 pg/mL; P = 0.0004) and remained elevated during recovery (86.8 ± 44.6 pg/mL; P = 0.0018). The peak (r = 0.58, P = 0.0222) and recovery (r = 0.56, P = 0.0304) NPY levels and the ability to increase NPY from baseline (r = 0.53, P = 0.0427) showed significant positive correlations with heart rate recovery at 1 min, but not with peak oxygen consumption. In CHF patients, the ability to increase NPY levels on exertion is correlated with heart rate recovery, a known prognostic indicator for mortality. These findings suggest that NPY dynamics during exercise might provide valuable insights into sympathetic responses and prognosis in CHF patients.