Abstract 9909: Selenium Supplementation Rescues Cardiac Function in Patients With Severe Heart Failure Who are Intractable to Renin-Angiotensin System Inhibitors and β-blockers

Abstract

Introduction: Increases in oxidative stress may be involved in the progression of heart diseases. Selenium (Se) is an integral part of the enzyme glutathione peroxidase (GSHPx), one of the central players of the heart’s antioxidant system. This study evaluated Se supplementation in patients with severe heart failure who were intractable to renin-angiotensin system (RAS) inhibitors and β-blockers. Methods: In order to confirm the activation of myocardial oxidative stress and the local deficiency of GSHPx, we examined immunohistochemical staining of endomyocardial biopsy specimens obtained from 24 dilated cardiomyopathy (DCM) patients and analyzed serum Se concentrations and GSHPx activities. We enrolled patients who had shown no functional improvements after RAS inhibitors and β -blockers (n = 11). The patients were supplied with 25 μg of Se chloride twice per day while their other medications remained unchanged. Results: Compared with patients with normal ventricular function (n = 30), the serum Se concentrations and GSHPx activities from the patients with DCM (n = 24) were decreased by 55% (0.167 μg/ml vs 0.076 μg/ml, p < 0.01), and by 33% (328 μmol/min/L vs 221 μmol/min/L, p < 0.01), respectively. Myocardial biopsy from DCM patients, but not control patients, uniformly showed marked reduction of GSHPx stains (24/24 vs 0/3, respectively) that was accompanied by positive staining for both 4-hydroxy-2nonenal (20/24 vs 1/3) and 8-hydroxy-2`-deoxyguanosine (16/24 vs 0/3). Left ventricular (LV) ejection fraction increased from 26% ± 8% to 34% ± 8%, 37% ± 12%, and 38% ± 11% at the 3-month follow-up, 6-month follow-up, and 12-month follow-up, respectively, and then maintained thereafter. Conclusions: Our study suggests that myocardial oxidative stress in chronic heart failure may be augmented at least in part by concomitant GSHPx deficiency, and that the administration of Se could rescue the exhaustion of this selenoprotein, resulting in improved LV function.