Clinical significance of reactive oxidative metabolites in patients with heart failure with reduced left ventricular ejection fraction

Abstract

We investigated the clinical significance of the derivative of reactive oxygen metabolites (DROM), a new marker of reactive oxygen species (ROS), in patients with heart failure (HF) with reduced left ventricular ejection fraction (LVEF) (HFrEF). Serum DROM concentrations were measured in 201 consecutive patients with HFrEF (EF < 50%) in stable condition. DROM values were significantly higher in patients with HFrEF than in risk-matched patients without HF (P < 0.01). They also correlated significantly with high-sensitivity C-reactive protein and B-type natriuretic peptide. Kaplan-Meier analysis demonstrated significantly higher probabilities of HF-related events in the high-DROM group than in the low-DROM group (log-rank test, P < 0.01). Multivariable Cox hazard analysis revealed that DROM were independent and significant predictors of cardiovascular events. In a subgroup analysis, DROM levels were also measured at the aortic root and coronary sinus in 49 patients. The transcardiac gradient of DROM values was significantly higher in patients with HFrEF than in patients without HF (P = 0.04), indicating an association between DROM production in the coronary circulation and HFrEF development. Changes in DROM following optimal therapy were significantly associated with LVEF improvement (r = 0.34, P = 0.04). The higher levels of DROM and their association with cardiovascular events suggest the clinical benefit of DROM measurements in the risk stratification of patients with HFrEF.