内膜和外膜的改变可能会导致心肌细胞逐渐受到压缩和固定，并且最终导致严重的僵硬，使得新形成的围绕心肌细胞和簇群的结构阻碍了正常舒张和收缩。这种现象被称为固定性间质性心脏纤维化（IICF）。解密心肌变化的分子和结构元素是理解心力衰竭发展的病因学基础的关键。研究包括69名患者。I组（n = 32）包括患有IICF的患者；II组（n = 37）为对照组。我们评估了患者的临床表现、疾病史、体格检查结果、患者的实验室和仪器检查以及尸检资料。在疾病史中，患有IICF的患者比对照组的患者更容易患病：心律失常和传导障碍（88％对19％，比值比（OR）：30.0；95％置信区间（CI）：7.918-113.7，P <0.001）、系统性结缔组织疾病（78％对5％，OR：62.5；95％CI：11.9-326.5，P <0.001）、病毒感染（包括严重急性呼吸综合症冠状病毒2型（SARS-CoV-2））（53％对19％，OR：4.86；95％CI：1.66-14.25，P = 0.003）、2型糖尿病（47％对8％，OR：10.0；95％CI：2.54-39.34，P <0.001）、纵隔淋巴瘤和其他肿瘤疾病的放射治疗（19％对0％，P = 0.008）、12个月内的局灶性感染（鼻窦炎、骨髓炎、牙周炎、肾炎、膀胱炎、肾盂肾炎、胸膜炎等）（31％对11％，P = 0.069）、慢性肾脏病（25％对8％，P = 0.097）和结核病（9％对0％，P = 0.095）。我们在两组之间发现了显着差异：纤维化区域的体积（17.5±9.2％对4.9±2.3％，P = 0.001）、Ⅰ型胶原蛋白的表达（1 mm2中的5,182±1,301对2,189±754，P = 0.0001）、Ⅲ型胶原蛋白（1 mm2中的7,562±1,405对2,320±541，P = 0.0001）、基质金属蛋白酶（MMP）-2（1 mm2中的12,850±6,200对9,501±7,145，P = 0.005）、MMP-9（1 mm2中的15,745±5,695对6,920±3,125，P = 0.0001）、连接蛋白-43（1 mm2中的25,689±14,871对37,523±12,561，P = 0.001）、纤维连接蛋白（1 mm2中的3,448±720对1,544±610，P = 0.0001）和转化生长因子β（TGF-β）（1 mm2中的5,121±1,243对2,531±1,489，P = 0.001）。IICF是一种独立的病理状态，也是慢性心力衰竭的主要原因之一。它是由心肌结缔组织的变化引起的，这些变化阻止了心肌的正常功能。版权所有2023年Shevchenko等人。

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.Copyright 2023, Shevchenko et al.