Effect of Metformin on Oxidative Stress and Left Ventricular Geometry in Nondiabetic Heart Failure Patients: A Randomized Controlled Trial.

Introduction: There is an increasing interest in using metformin in cardiovascular diseases and its potential new roles. Only two randomized controlled trials investigated the effect of metformin in nondiabetic heart failure (HF) patients. However, none of these studies assess the role of metformin in reducing oxidative stress. We hypothesized that metformin might improve oxidative stress and left ventricular remodeling in nondiabetic HF patients with reduced ejection fraction (HFrEF). Methods and Methods: Seventy HFrEF patients (EF 37% ± 8%; median age 66 years) were randomized to metformin (n = 35) or standard of care (SOC) for HF (n = 35) for 6 months in addition to standard therapy. Outcomes included the difference in the change (Δ) in total antioxidant capacity (TAC) and malondialdehyde (MDA), both assessed colorimetrically and left ventricular mass index (LVMI) assessed through transthoracic echocardiography. Results: Compared with the SOC, metformin treatment increased TAC [Δ = 0.12 mmol/L, confidence intervals (95% CIs): 0.03-0.21; P = 0.007]. TAC increased significantly only in the metformin group (0.90 ± 0.08 mmol/L at baseline vs. 1.04 ± 0.99 mmol/L at 6 months, P < 0.05). Metformin therapy preserved LVMI (Δ = -23 g/m2, 95% CI: -42.91 to -4.92; P = 0.014) and reduced fasting plasma glucose (Δ = -6.16, 95% CI: -12.31 to -0.02, P = 0.047) compared with the SOC. Results did not change after adjusting for baseline values. Changes in MDA left ventricular ejection fraction (LVEF) and blood pressure were not significantly different between groups. Conclusion: Metformin treatment in HF patients with reduced LVEF improved TAC and prevented the increase in LVMI compared with the SOC. These effects of metformin warrant further research in HF patients without diabetes to explore the potential benefits of metformin. Trial Registration Number: This protocol was registered in ClinicalTrials.gov under the number NCT05177588.

Total Antioxidant Capacity and Prediabetes Are Associated with Left Ventricular Geometry in Heart-Failure Patients with Reduced Ejection Fraction: A Cross-Sectional Study.

Introduction: Few studies explored the association between total antioxidant capacity (TAC) and left ventricular (LV) geometry in patients with heart failure and reduced ejection fraction (HFrEF). The current study aimed to assess factors associated with LV geometry in HFrEF patients with particular emphasis on oxidative stress and glycemic status. Methods: A cross-sectional study was conducted from July 2021 to September 2022. All consecutive patients with HFrEF who were stabilized on optimal or maximally tolerated heart failure medications were recruited. Patients were classified into tertiles based on TAC and malondialdehyde for correlation with other parameters. Results: TAC was significantly associated with LV geometry (P = 0.01), with higher TAC levels observed in patients with normal LV geometry (0.95 ± 0.08) and concentric hypertrophy (1.01 ± 0.14) than in patients with eccentric hypertrophy (EH) (0.90 ± 0.10). There was a significant positive trend in the association between glycemic state and LV geometry (P = 0.002). TAC showed a statistically significant positive correlation with EF (r = 0.29, P = 0.0064) and a negative correlation with LV internal diameter at end diastole (r = -0.26, P = 0.014), LV mass index (r = -0.25, P = 0.016), and LV mass (r = -0.27, P = 0.009). After adjusting for multiple confounders, prediabetes [odds ratio (OR) = 4.19, P = 0.032] and diabetes (OR = 7.47, P = 0.008) were associated with higher odds of EH than normoglycemic patients. A significant inverse trend was also observed in the association between TAC tertile and the odds of LV geometry (OR = 0.51, P = 0.046). Conclusions: TAC and prediabetes are significantly associated with LV geometry. TAC can be used as an additional marker in HFrEF patients to reflect the severity of the disease. Interventions aimed at managing oxidative stress might be useful in HFrEF patients to reduce oxidative stress and improve LV geometry and quality of life. Trial Registration Number: This study is part of an ongoing randomized clinical trial (ClinicalTrials.gov identifier NCT05177588).