Elevated serum matrix metalloproteinase-2 levels in heart failure patients with reduced ejection fraction and Cheyne-Stokes respiration

Study Objectives Cheyne-Stokes respiration (CSR), a kind of central sleep apnea, is referred to as a poor prognostic factor in heart failure patients with reduced ejection fraction (HFrEF). Matrix metalloproteinase (MMP) and B-type natriuretic peptide (BNP) play important roles in HFrEF patients and are markers of poor prognosis. However, there is no literature mentioning the changes in MMP and BNP in HFrEF patients with CSR. Methods From June 2018 to June 2019, 41 adult patients with stable heart failure and left ventricular ejection fraction < 50% were enrolled from the cardiology clinic. After history-taking and medication review to exclude possible central nervous system- or medication-related central sleep apnea, an overnight polysomnography study was performed, and CSR was identified. The morning serum MMP-2, MMP-9, and BNP levels were determined using enzyme-linked immunosorbent assay and fluorescence immunoassay techniques. A positive airway pressure device was applied to 7 patients for 3 months. Results The serum MMP-2 and BNP levels were significantly higher in HFrEF patients with CSR than in patients without CSR. In addition, elevated serum MMP-2 levels correlated well with the severity of sleep apnea and intermittent hypoxia, which were represented as the apnea-hypopnea index and the oxygen desaturation index. No positive correlation was found between those markers and left ventricular ejection fraction. Finally, the treatment of sleep apnea with continuous positive airway pressure for 3 months tended to reduce the elevated serum MMP-2 levels. Conclusions Higher serum MMP-2 and BNP levels were found in HFrEF patients with CSR. Elevated MMP-2 levels were correlated with the severity of sleep apnea and intermittent hypoxia.