Protein biomarkers associated with left bundle branch block in patients with heart failure and reduced ejection fraction

TY - JOUR

T1 - Protein biomarkers associated with left bundle branch block in patients with heart failure and reduced ejection fraction

AU - Ljung, Karin

AU - Vestman, Christian

AU - Reistam, Ulrika

AU - Braunschweig, Frieder

AU - Zhao, Allan

AU - Lund, Lars H.

AU - Lang, Chim

AU - Voors, Adriaan A.

AU - Rullman, Eric

AU - Savarese, Gianluigi

AU - Ståhlberg, Marcus

N1 - Publisher Copyright: © The Author(s) 2026. Published by Oxford University Press on behalf of the European Society of Cardiology.

PY - 2026/2/3

Y1 - 2026/2/3

N2 - INTRODUCTION: Left bundle branch block (LBBB) is common in heart failure with reduced ejection fraction (HFrEF) and causes dyssynchrony, which accelerates cardiac remodelling. The biological mechanisms behind LBBB-associated remodelling 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 with 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 signalling and included the mitogen-activated protein kinase (MAPK) pathway. CONCLUSION: In HFrEF, LBBB was associated with an altered circulating proteome. FGF2 and EGFR were highly dysregulated between the groups and the MAPK signalling pathway was affected, all of which may be pathophysiologically involved in the accelerated cardiac remodelling observed in these patients. These findings constitute a foundation for future studies of relevant LBBB-related biomarkers, treatment targets, and mechanisms behind the cardiac remodelling observed when LBBB is superimposed on HFrEF.

AB - INTRODUCTION: Left bundle branch block (LBBB) is common in heart failure with reduced ejection fraction (HFrEF) and causes dyssynchrony, which accelerates cardiac remodelling. The biological mechanisms behind LBBB-associated remodelling 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 with 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 signalling and included the mitogen-activated protein kinase (MAPK) pathway. CONCLUSION: In HFrEF, LBBB was associated with an altered circulating proteome. FGF2 and EGFR were highly dysregulated between the groups and the MAPK signalling pathway was affected, all of which may be pathophysiologically involved in the accelerated cardiac remodelling observed in these patients. These findings constitute a foundation for future studies of relevant LBBB-related biomarkers, treatment targets, and mechanisms behind the cardiac remodelling observed when LBBB is superimposed on HFrEF.

KW - Biomarkers

KW - Dyssynchrony

KW - Heart failure

KW - Left bundle branch block

KW - Proteomics

KW - Remodelling

UR - https://www.scopus.com/pages/publications/105030633383

U2 - 10.1093/eschf/xvag009

DO - 10.1093/eschf/xvag009

M3 - Article

C2 - 41711715

SN - 2055-5822

VL - 13

JO - ESC Heart Failure

JF - ESC Heart Failure

IS - 1

M1 - xvag009

ER -