Raised sympathetic nerve activity in heart failure and central sleep apnea is due to heart failure severity

Background-Congestive heart failure (CHF) patients with central sleep apnea (CHF-CSA) have elevated plasma norepinephrine (NE) compared with CHF patients without apnea (CHF-N). Patients with CHF-CSA also demonstrate higher mean pulmonary artery pressure (PAP), which is suggestive of worse cardiac function. Whether CSA contributes to chronic elevation of sympathetic nerve activity or is associated with more severe CHF remains unknown. We measured awake total body and cardiac NE spillover and related these to measurements of cardiac hemodynamics and apnea severity in CHF patients with CSA, with normal breathing, and with obstructive sleep apnea (CHF-OSA). Methods and Results-A total of 55 CHF patients underwent right heart catheterization and measurements of total body and cardiac NE spillover using NE radioisotope dilution methodology. After polysomnography, patients were grouped by apnea type: 19 were CHF-N, 15 were CHF-OSA, and 21 were CHF-CSA. Compared with the CHF-N and CHF-OSA groups, the CHF-CSA group had significantly higher total body NE spillover (4.62 +/- 0.56 versus 4.47 +/- 0.54 versus 6.95 +/- 0.89 nmol/min, respectively; P=0.03), cardiac NE spillover (0.25 +/- 0.05 versus 0.21 +/- 0.05 versus 0.42 +/- 0.06 nmol/min, respectively; P=0.02) and mean PAP (23.5 +/- 2.4 versus 21.2 +/- 0.8 versus 30.4 +/- 0.2 mm Hg, respectively; P<0.02). However, controlling for severity of CHF resulted in no significant differences in NE kinetics among the 3 groups. In a stepwise regression, only mean PAP independently correlated with total body (r=0.33, P=0.03) and cardiac NE spillover (r=0.44, P=0.002). Sleep apnea severity bore no relationship to markers of sympathetic nerve activity. Conclusion-Total body and cardiac sympathetic nerve activity are elevated in CHF-CSA compared with CHF-OSA and CHF-N patients and are related to heart failure not apnea severity.