LAUSR

RATIONALE Hunter-Cheyne-Stokes breathing (HCSB) with central sleep apnea (CSA) is prevalent in some patients with heart failure and reduced ejection fraction (HFrEF). Theoretical models of HCSB predict that a low metabolic rate (MR) predisposes one to CSA. OBJECTIVES This study examines the role of MR in the pathogenesis of CSA. METHODS A physiological study was conducted in a sleep laboratory at a 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 fraction tests, CO2 production, and arterial blood samples were obtained under strict standardized conditions. Physiological variables were then entered into regression models to examine association with CSA. RESULTS BMI varied from 20 to 40 kg/m2 and CO2 production ranged from 167 to 434 ml/min. In the final regression model, low CO2 production and low BMI were associated with CSA index. CO2 production had the strongest association (95% CI [-0.36, -0.06], p=0.007). CONCLUSIONS In patients with HFrEF, a low MR and related low CO2 production, but not low oxygen consumption, were associated with CSA. Mechanistically, in the face of low MR and CO2 production, a given change in ventilation results in large swings in PCO2, thus promoting CSA. To our knowledge, this is the first study in humans that shows this association.