Characteristics and Mechanisms of Septal Myocardial Injury and Repair Following Left Bundle Branch Area Pacing

Objective This study aimed to evaluate the impact of deep screwing attempts on septal myocardial injury and repair and to explore the underlying mechanisms. Methods Prospective LBBAP implantation was performed in 41 patients with bradycardia. Serum creatine kinase–MB (CK-MB) and left ventricular (LV) global longitudinal strain (GLS) were used to evaluate myocardial damage. Mechanisms of septal damage were explored in 24 LBBAP canines using histopathological and molecular changes. Results Compared to patients with ≤ 3 attempts, those with >3 attempts had a higher incidence of CK-MB elevation (6 vs. 44%, *P* =0.004), a less negative LV endocardial (-17.9 vs. -13.6 %, P<0.001), and mid-myocardial GLS (-15.3 vs. -12.4 %, P<0.001). In animal study, molecular changes associated with >3 attempts featured amplified HMGB1-centered sterile inflammation and enhanced CD206 + macrophage-mediated profibrotic remodeling. Canines with >3 attempts were characterized by three markedly thickened concentric reparative layers around the lead—inner thrombus layer, middle fibrous sheath layer, and outer reactive fibrotic layer. Interestingly, removal of the pacing lead after >3 attempts resulted in only mild scattered fibrosis, with markedly attenuated CD206 + macrophage-mediated profibrotic pathway. Conclusions LBBAP with >3 deep septal screwing attempts was associated with a higher risk of septal myocardial injury and markedly thickened concentric reparative layers, underpinned by more pronounced sterile inflammation, profibrotic remodeling, and foreign body reaction.