Left bundle branch area pacing (LBBAP) has shown effectiveness in dyssynchronous heart failure (DHF) and can be categorized into two types: left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP). However, the basic mechanisms are unknown. Here, we performed proteomic profiling of the myocardium from 3 control, 3 DHF, 2 LBBP and 2 LVSP canines. Subsequently, targeted proteomics were employed to further validate several biomarkers in 6 control, 6 DHF, 6 LBBP and 6 LVSP canines. This study revealed that LBBP reversed the expression of proteins associated with contraction process, while LVSP reversed expression of proteins associated with adhesion process. This study provides new insights into mechanisms behind the superior outcomes of LBBP.