Biomarkers of RV Dysfunction in HFrEF Identified by Direct Tissue Proteomics: Extracellular Proteins Fibromodulin and Fibulin-5.

Summary

Direct myocardial proteomics identified FMOD and FBLN5 as upregulated in RVD; their plasma levels associated with RV function across assessment methods and with outcomes in an HFrEF cohort. These biomarkers were not associated with LV dysfunction or systemic comorbidities, highlighting RV-specific signal.

Key Findings

• Tissue proteomics (RVD vs non-RVD, n=10 each) identified FMOD and FBLN5 as top upregulated ECM proteins in RV dysfunction.
• Plasma FMOD and FBLN5 levels were independently associated with RV function across assessment methods in HFrEF (validation cohort n=232).
• No association with LV dysfunction, cardiac index, BMI, diabetes, or kidney function, supporting RV specificity.
• Plasma levels of FMOD and FBLN5 were significantly associated with patient outcomes (details per study).

Clinical Implications

FMOD and FBLN5 could be developed for RV-focused risk stratification in HFrEF, complementing LV-centric metrics; validation and assay standardization are required before routine adoption.

Limitations

• Small discovery sample size (n=20 hearts) and observational validation design limit causal inference
• External validation in diverse populations and assay standardization are needed before clinical adoption

Future Directions

Prospective multicenter validation, threshold definition, incremental prognostic value over imaging/hemodynamics, and exploration of therapeutic modulation of FMOD/FBLN5 pathways.