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Rationale: Hunter-Cheyne-Stokes breathing with central sleep apnea (CSA) is prevalent in some patients with heart failure with reduced ejection fraction (HFrEF). Theoretical models of Hunter-Cheyne-Stokes breathing predict that a low metabolic rate (MR) predisposes one to CSA. Objectives: In this study, we examined the role of MR in the pathogenesis of CSA. Methods: A physiological study was conducted in a sleep laboratory at a U.S. Department of Veterans Affairs medical center. Patients were 28 consecutive male Veterans with stable HFrEF. After an adaptation night, polysomnography, left ventricular ejection fraction, pulmonary function tests, carbon dioxide production (VCO2), and arterial blood samples were obtained under strict standardized conditions. Physiological variables were then entered into regression models to examine the association with CSA. Results: Body mass index varied from 20 to 40 kg/m², and VCO2 ranged from 167 to 434 ml/min. In the final regression model, low VCO2 and low body mass index were associated with CSA index. VCO2 had the strongest association (95% confidence interval, 20.36 to 20.06; P=0.007). Conclusions: In patients with HFrEF, a low MR and related low VCO2, but not low oxygen consumption, were associated with CSA. Mechanistically, in the face of low MR and VCO2, a given change in ventilation results in large swings in partial pressure of CO2, thus promoting CSA. To our knowledge, this is the first study in humans that shows this association. [ABSTRACT FROM AUTHOR]

Rationale: Hunter-Cheyne-Stokes breathing with central sleep apnea (CSA) is prevalent in some patients with heart failure with reduced ejection fraction (HFrEF). Theoretical models of Hunter-Cheyne-Stokes breathing predict that a low metabolic rate (MR) predisposes one to CSA. Objectives: In this study, we examined the role of MR in the pathogenesis of CSA. Methods: A physiological study was conducted in a sleep laboratory at a U.S. Department of Veterans Affairs medical center. Patients were 28 consecutive male Veterans with stable HFrEF. After an adaptation night, polysomnography, left ventricular ejection fraction, pulmonary function tests, carbon dioxide production ([Formula: see text]), and arterial blood samples were obtained under strict standardized conditions. Physiological variables were then entered into regression models to examine the association with CSA. Results: Body mass index varied from 20 to 40 kg/m 2 , and [Formula: see text] ranged from 167 to 434 ml/min. In the final regression model, low [Formula: see text] and low body mass index were associated with CSA index. [Formula: see text] had the strongest association (95% confidence interval, -0.36 to -0.06; P  = 0.007). Conclusions: In patients with HFrEF, a low MR and related low [Formula: see text], but not low oxygen consumption, were associated with CSA. Mechanistically, in the face of low MR and [Formula: see text], a given change in ventilation results in large swings in partial pressure of CO 2 , thus promoting CSA. To our knowledge, this is the first study in humans that shows this association.