Oxidative stress contributes to heart failure (HF) progression by mechanisms that go beyond hemodynamic overload, including mitochondrial dysfunction, endothelial injury, inflammation, and fibrotic remodeling. This review evaluates the relationship between redox imbalance, Galectin-3 (Gal-3), fibrosis, and imaging findings in HF. Reactive oxygen species (ROS) generated by mitochondria, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, and xanthine oxidase may disturb calcium handling, impair mitochondrial function, activate fibroblasts, and promote ferroptosis. Biomarkers of oxidative injury and antioxidant reserve, including malondialdehyde (MDA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and circulating thiols, provide information complementary to natriuretic peptides. Experimental evidence supports a context-dependent role of Gal-3 in fibro-inflammatory remodeling, whereas circulating Gal-3 should be regarded as a complementary biomarker rather than as a direct measure of myocardial fibrosis. Echocardiography assesses functional remodeling through diastolic indices, myocardial deformation, and right ventricular–pulmonary arterial (RV–PA) coupling, while cardiac magnetic resonance characterizes focal scar and diffuse interstitial remodeling using late gadolinium enhancement, native T1 mapping, and extracellular volume fraction. Therapeutic strategies are increasingly shifting from nonspecific antioxidant supplementation toward targeting ROS sources and downstream pathways, with SGLT2 inhibitors emerging as clinically relevant agents with indirect redox-modulating effects. Integrated redox, fibro-inflammatory, hemodynamic, and imaging phenotyping may refine risk stratification, although prospective validation is required before routine implementation.

Background/Objectives: Oxidative stress and galectin-3-related fibro-inflammatory processes contribute to heart failure pathophysiology, but their concurrent relationships with natriuretic peptides and structural/cardiorenal parameters remain incompletely characterized. We evaluated baseline associations of serum peroxide burden and galectin-3 with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and related phenotypic parameters in chronic heart failure. Methods: This cross-sectional analysis included 57 patients from a prospective single-center cohort. Serum peroxides were quantified using the ferrous oxidation–xylenol orange assay and expressed as nmol H₂O₂ equivalents/mL. Associations were assessed using Spearman correlation and linear regression with ln-transformed NT-proBNP. Benjamini–Hochberg correction was applied to eight secondary/exploratory correlations. Results: Serum peroxide burden correlated with NT-proBNP (ρ = 0.387, p = 0.0095; n = 44) and remained significantly associated after adjustment for age, sex, and left ventricular ejection fraction (B = 0.1756, p = 0.0420; n = 43). After additional estimated glomerular filtration rate (eGFR) adjustment, the effect estimate remained similar, although statistical significance was not reached (B = 0.1646, p = 0.0525; n = 39). Galectin-3 correlated with NT-proBNP, left ventricular end-diastolic volume index (LVEDVi), and serum uric acid; all associations remained significant after false-discovery-rate correction. Serum peroxide burden and galectin-3 were not significantly correlated. In an exploratory joint model (n = 29), both biomarkers remained significantly associated with ln(NT-proBNP) (adjusted R² = 0.4294). Conclusions: Serum peroxide burden and galectin-3 showed different cross-sectional association patterns with NT-proBNP and selected structural/cardiorenal parameters. Given the limited sample size, missing data, and exploratory nature of the joint model, these findings should be considered hypothesis-generating and do not establish biological independence or incremental clinical value.