Abstract
PURPOSE: Cheyne-Stokes respiration during sleep is associated with increased mortality in heart failure. The magnitude of oxidative stress is a marker of disease severity and a valuable predictor of mortality in heart failure. Increased oxidative stress associated with periodic breathing during Cheyne-Stokes respiration may mediate increased mortality in these patients. We hypothesized that the presence of Cheyne-Stokes respiration is associated with oxidative stress by increasing the formation of reactive oxygen species in patients with heart failure. METHODS AND RESULTS: Twenty-three patients with heart failure [left ventricular ejection fraction 30.2 ± 9% (mean ± standard deviation)] and 11 healthy controls underwent nocturnal polysomnography. Subjects with obstructive sleep apnea were excluded. The majority (88%) of patients with heart failure had Cheyne-Stokes respiration during sleep. The intensity of oxidative stress in neutrophils was greater in patients with heart failure (4,218 ± 1,706 mean fluorescence intensity/cell vs. 1,003 ± 348 for controls, p < 0.001) and correlated with the duration of Cheyne-Stokes respiration. Oxidative stress was negatively correlated with SaO(2) nadir during sleep (r = -0.43, p = 0.039). The duration of Cheyne-Stokes respiration predicted severity of oxidative stress in patients with heart failure (beta = 483 mean fluorescence intensity/cell, p < 0.02). CONCLUSIONS: Levels of oxidative stress are increased in patients with heart failure and Cheyne-Stokes respiration during sleep compared with healthy controls. The duration of Cheyne-Stokes respiration predicts the magnitude of oxidative stress in heart failure. Increased oxidative stress may mediate increased mortality associated with Cheyne-Stokes respiration in patients with heart failure.