Background-Recent studies suggest that acute pulmonary congestion induces hyperventilation and that hyperventilationrelated hypocapnia leads to ventilatory control instability and central sleep apnea. Whether chronic pulmonary congestion due to congestive heart failure (CHF) is associated with central apnea is unknown. We hypothesized that CHF patients with central apnea would have greater pulmonary capillary wedge pressure (PCWP) than patients without central apnea and that PCWP would correlate with central apnea severity. Methods and Results-Seventy-five stable CHF patients underwent right heart catheterization and, on the basis of overnight sleep studies, were divided into central apnea (nϭ33)

Given that the apnea-ventilation cycle length during central sleep apnea (CSA) with congestive heart failure (CHF) is approximately 70 s, we hypothesized that rapidly responsive peripheral CO(2) ventilatory responses would be raised in CHF-CSA and would correlate with the severity of CSA. Sleep studies and single breath and rebreathe hypercapnic ventilatory responses (HCVR) were measured as markers of peripheral and central CO(2) ventilatory responses, respectively, in 51 subjects: 12 CHF with no apnea (CHF-N), 8 CHF with obstructive sleep apnea (CHF-OSA), 12 CHF-CSA, 11 CSA without CHF ("idiopathic" CSA; ICSA), and 8 normal subjects. Single breath HCVR was equally elevated in CHF-CSA and ICSA groups compared with CHF-N, CHF-OSA, and normal groups (0.58 +/- 0.09 [mean +/- SE] and 0. 58 +/- 0.07 versus 0.23 +/- 0.06, 0.25 +/- 0.04, and 0.27 +/- 0.02 L/min/PET(CO(2)) mm Hg, respectively, p < 0.001). Similarly, rebreathe HCVR was elevated in both CHF-CSA and ICSA groups compared with CHF-N, CHF-OSA, and normal groups (5.80 +/- 1.12 and 3.53 +/- 0. 29 versus 2.00 +/- 0.25, 1.44 +/- 0.16, and 2.14 +/- 0.22 L/min/PET(CO(2)) mm Hg, respectively, p < 0.001). Furthermore, in the entire CHF group, single breath HCVR correlated with central apnea-hypopnea index (AHI) (r = 0.63, p < 0.001) and percentage central/total apneas (r = 0.52, p = 0.022). Rebreathe HCVR correlated with awake Pa(CO(2)) (r = -0.61, p < 0.001), but not with central AHI or percentage central/total apneas independent of its relationship with single breath HCVR. In conclusion, in subjects with CHF, raised central CO(2) ventilatory response predisposes to CSA promoting background hypocapnia and exposing the apnea threshold to fluctuations in ventilation, whereas raised and faster-acting peripheral CO(2) ventilatory response determines the periodicity and severity of CSA.

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. 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 (rϭ0.33, Pϭ0.03) and cardiac NE spillover (rϭ0.44, Pϭ0.002). 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.