The Role of High-Mobility Group Box 1/Toll-Like Receptor 4 in Pericardial Fibrosis and Postoperative Low Cardiac Output Syndrome in Constrictive Pericarditis

Abstract

Background: It has remained unclear about the factors that are involved in the pericardial fibrotic process and the occurrence of postoperative low cardiac output syndrome (LCOS) in constrictive pericarditis. This study aimed to analyze the role of toll-like receptor 4 (TLR4) and high-mobility group box 1 (HMGB1) in pericardial fibrosis, and their impact on the development of postoperative LCOS in patients with constrictive pericarditis.

Methods: This retrospective study enrolled 24 constrictive pericarditis patients who underwent isolated pericardiectomy at our department from May 2023 to April 2025. Pericardial tissues were subjected to immunohistochemistry to detect the expression of TLR4, HMGB1, α-smooth muscle actin (α-SMA) and collagen III. Mean optical density (MOD) was used for quantitative analysis of immunohistochemical staining. Pearson correlation analysis was performed to assess associations between TLR4, HMGB1 and fibrotic markers, while receiver operating characteristic (ROC) curves were used to evaluate their potential predictive value for postoperative LCOS.

Results: Of the 24 patients, seven (29.2%) patients developed postoperative LCOS. TLR4 was expressed in 21 (87.5%) specimens, and HMGB1 was expressed in all specimens. Pearson correlation analysis showed positive correlations between TLR4 and α-SMA (r = 0.529, P = 0.008), HMGB1 and α-SMA (r = 0.516, P = 0.010), and TLR4 and HMGB1 (r = 0.844, P < 0.001). MOD values of TLR4 and HMGB1 were significantly higher in patients with postoperative LCOS (P = 0.028 and P < 0.001, respectively). ROC curve suggested that TLR4 (area under the curve (AUC) = 0.790, 95% confidence interval (CI), 0.516–1.000) and HMGB1 (AUC = 0.941, 95% CI, 0.853–1.000) had potential predictive value for postoperative LCOS.

Conclusions: TLR4 and HMGB1 were involved in the pericardial fibrosis and were significantly associated with the occurrence of postoperative LCOS in constrictive pericarditis.