The alterations in the endomysium and perimysium might cause compaction and gradual mechanical compression of cardiomyocytes resulting in their immobilization. This process finally leads to severe stiffening, so that the newly formed frame around individual cardiomyocytes and their clusters hinders normal diastole, and later systole. This phenomenon is referred to as immobilizing interstitial cardiac fibrosis (IICF). Deciphering the molecular and structural elements of myocardial changes is the key to understanding the pathogenetic foundations of heart failure development.The study included 69 patients. Group I (n = 32) included patients with IICF; group II (n = 37) was comparison group. We evaluated the clinical picture, anamnesis of the disease, the results of physical examination, laboratory and instrumental examination of patients and autopsy data.In the anamnesis, patients with IICF were more likely to have diseases than patients in the control group: arrhythmia and impaired conductivity (88% vs. 19%, odds ratio (OR): 30.0; 95% confidence interval (CI): 7.918 - 113.7, P < 0.001), systemic connective tissue diseases (78% vs. 5%, OR: 62.5; 95% CI: 11.9 - 326.5, P < 0.001), viral infections (including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) (53% vs. 19%, OR: 4.86; 95% CI: 1.66 - 14.25, P = 0.003), type 2 diabetes mellitus (47% vs. 8%, OR: 10.0; 95% CI: 2.54 - 39.34, P < 0.001), radiation therapy for mediastinal lymphoma and other oncological diseases (19% vs. 0%, P = 0.008), focal infections (sinusitis, osteomyelitis, periodontitis, nephritis, cystitis, pyelonephritis, pleurisy, etc.) within 12 months (31% vs. 11%, P = 0.069), chronic kidney disease (25% vs. 8%, P = 0.097), and tuberculosis (9% vs. 0%, P = 0.095). We have identified a statistically significant difference between the groups: the volume of the fibrosis zone (17.5±9.2% vs. 4.9±2.3%, P = 0.001), the expression of type I collagen (5,182 ± 1,301 vs. 2,189 ± 754 in 1 mm2, P = 0.0001), type III collagen (7,562 ± 1,405 vs. 2,320 ± 541 in 1 mm2, P = 0.0001), matrix metalloproteinase (MMP)-2 (12,850 ± 6,200 vs. 9,501 ± 7,145 in 1 mm2, P = 0.005), MMP-9 (15,745 ± 5,695 vs. 6,920 ± 3,125 in 1 mm2, P = 0.0001), connexin-43 (25,689 ± 14,871 vs. 37,523 ± 12,561 in 1 mm2, P = 0.001), fibronectin (3,448 ± 720 vs. 1,544 ± 610 in 1 mm2, P = 0.0001), and transforming growth factor β (TGF-β) (5,121 ± 1,243 vs. 2,531 ± 1,489 in 1 mm2, P = 0.001).IICF is a separate pathological condition and one of the main causes of chronic heart failure. It is induced by changes in the myocardial connective tissue that prevent normal functioning of the myocardium.