The role of HMGB1/TLR4 in pericardial fibrosis and postoperative low cardiac output syndrome in constrictive pericarditis

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 TLR4 and 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-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 predictive value for postoperative LCOS. Results Of the 24 patients, 7 (29.2%) 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 (AUC = 0.790, 95%CI: 0.516–1.000) and HMGB1 (AUC = 0.941, 95%CI: 0.853–1.000) had potential predictive value for postoperative LCOS. Conclusion TLR4 and HMGB1 were involved in the pericardial fibrosis and were significantly associated with the occurrence of postoperative LCOS in constrictive pericarditis.