Modern cardiology is actively searching for effective approaches to the early diagnosis and prediction of heart failure, which remains a leading cause of disability and mortality. Alongside established markers of hemodynamic stress, such as B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide (NT-proBNP), interest is growing in myoglobin as a potential indicator of structural myocardial damage. The aim of this study was to assess the relationship between plasma myoglobin and NT-proBNP levels in patients with chronic heart failure (CHF) of various etiologies and to substantiate the concept of an integrated pathophysiological continuum linking myocardial damage and hemodynamic stress. This prospective, single-center, cross-sectional observational study included 138 participants, of whom 123 had CHF of various etiologies and 15 served as controls. Patients were stratified according to CHF etiology (valvular and non-valvular) and the presence of thromboembolic complications. Plasma myoglobin and NT-proBNP levels were measured by ELISA. Statistical analysis included nonparametric tests and correlation analysis. Patients with CHF had significantly higher myoglobin and NT-proBNP levels than controls. Myoglobin concentrations were highest in patients with non-valvular CHF , showing a 2.6-fold increase compared with controls, indicating persistent structural and metabolic myocardial stress. NT-proBNP levels were significantly elevated in all CHF groups, with the highest values observed in patients with combined valvular pathology. A significant positive correlation was found between plasma myoglobin and NT-proBNP levels (r = 0.397). ROC analysis demonstrated a statistically significant association between myoglobin levels and signs of heart failure defined by NT-proBNP concentrations >900 pg/ml (0.687; 95% CI: 0.581-0.792; P = 0.001), indicating a moderate discriminatory ability of the marker. The combined assessment of myoglobin and NT-proBNP reflects complementary aspects of CHF pathophysiology by integrating structural myocardial damage and hemodynamic stress. This two-marker approach represents a parsimonious yet pathogenetically grounded model that may improve risk stratification and facilitate the development of personalized diagnostic strategies in patients with CHF .