Background: Derivative of reactive oxygen metabolites (DROM), reflecting blood hydroperoxide levels, is a new marker of reactive oxygen species (ROS). We investigated the role of DROM in HFrEF.
Methods: We measured DROM in consecutive 204 HFrEF patients at the stable condition, and followed them until the occurrence of cardiovascular events (CVE). In a subgroup analysis, DROM levels were also measured at the aortic root and coronary sinus in 49 patients.
Results: DROM values were significantly higher in HFrEF patients (n=112) compared to risk-matched non-HF patients (n=112) (p=0.04). Moreover, DROM was associated with the severity of HF (p<0.01). DROM was independently associated with the severity of HF by multivariate logistic regression analysis (odds ratio 1.01, p<0.01). Furthermore, DROM values significantly correlated with other biomarkers (high-sensitivity C-reactive protein and B-type natriuretic peptide [BNP]), and echo-parameters in HFrEF (left ventricular ejection fraction [LVEF] and tricuspid regurgitation pressure gradient). In multivariate Cox-proportional-hazard analysis, DROM (hazard ratio: 1.01, 95% confidence interval: 1.00-1.02, p=0.03), BNP values (P=0.03), and the presence of ischemic heart disease (P=0.01) were independently associated with CVE in HFrEF. Kaplan-Meier analysis demonstrated significant higher probabilities of CVE in high-DROM group (>351 U.CARR; median value of DROM) than in low-DROM group (<351 U.CARR) in HFrEF (log-rank test, P<0.01). After HFrEF patients were divided into 4 groups according to a combination of DROM and BNP values, high-DROM and high-BNP group had a highest probability of CVE among 4 groups (log-rank test, p<0.001) Additionally, the transcardiac gradient of DROM values was significantly higher in HFrEF than in non-HF patients (p=0.04), indicating an association between DROM production in the coronary circulation and HFrEF development. Moreover, changes in DROM following optimal therapy were significantly associated with LVEF improvement in HFrEF patients (p=0.04).
Conclusion: The higher levels of DROM in HFrEF patients and their association with future CVE suggest the clinical benefit of DROM measurements in the risk stratification of HFrEF.