Protein biomarkers associated with left bundle branch block in patients with heart failure and reduced ejection fraction
ESC Heart Failure, 2026
Ljung K., Vestman C., Reistam U., Braunschweig F., Zhao A., Lund L., Lang C., Voors A., Rullman E., Savarese G., Ståhlberg M.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
CVD | Pathophysiology | Plasma |  Olink Target 96 |
Abstract
Aims
Left bundle branch block (LBBB) is common in heart failure with reduced ejection fraction (HFrEF) and causes dyssynchrony, which accelerates cardiac remodeling. The biological mechanisms behind LBBB associated remodeling remain largely unknown. Therefore, we used an omics approach to test the hypothesis that LBBB is associated with plasma protein dysregulation aiming at defining a proteome that contributes to the specific disease driving phenotype in dyssynchronopathy.
Methods
Patients were selected from the BIOlogy Study to TAilored Treatment in Chronic Heart Failure database (n=4254). Patients with HFrEF and LBBB (HFrEF + LBBB) served as cases (n=268) and a matched control group (n=268) with HFrEF without LBBB (HFrEF – LBBB) was selected using propensity score matching. We compared relative plasma concentrations of 364 proteins between the two groups using proximity extension assay.
Results
HFrEF + LBBB was associated with up- or downregulation of 41 proteins out of 364 assessed, 11%, compared to HFrEF – LBBB. Fibroblast Growth Factor 2 (FGF2) decreased, Epidermal Growth Factor Receptor (EGFR) increased and several cytokines and proteins involved in extracellular matrix processing changed expression. Gene ontology pathways enriched among upregulated proteins were mainly involved in immune response and cell signaling and included the Mitogen-Activated Protein Kinase (MAPK) pathway.
Conclusions
In HFrEF, LBBB was associated with an altered circulating proteome. FGF2 and EGFR were highly dysregulated between the groups and the MAPK signaling pathway was affected, all of which may be pathophysiologically involved in the accelerated cardiac remodeling observed in these patients. These findings constitute a foundation for future studies of relevant LBBB related biomarkers, treatment targets and mechanisms behind the cardiac remodeling observed when LBBB is superimposed on HFrEF.