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Abstract BACKGROUND Right ventricular dysfunction (RVD) is a commonly accompanying condition in patients with heart failure with reduced ejection fraction (HFrEF), and is associated with poor prognosis. However, no specific biomarker of RVD is available for clinical routine. METHODS We performed a label-free proteomic analysis of myocardium from the left and right ventricles of HFrEF patients with and without RVD who underwent heart transplantation (n=20). Concentrations of two extracellular matrix proteins with highest myocardial upregulation in RVD – fibromodulin (FMOD) and fibulin-5 (FBLN5) - were assayed in the blood, compared to controls (n=65) and tested in separate large cohort of HFrEF patients (n=232) to test association of the two proteins with RV function and long-term outcome. RESULTS FMOD and FBLN5 plasma concentrations progressively increased with worsening RV function (p = 0.0001 and 0.004), while there was no association with LV dysfunction, BMI or kidney function. In survival analysis, plasma levels of both FMOD and FBLN5 were significantly associated with patient outcome (p = 0.005 and 0.0004). Using reclassification analysis, addition of plasma FBLN5 to right ventricle function assessment led to an improvement in AUC after 4 years compared to RV function assessment only. Similarly, adding plasma fibromodulin to the multi-parametric MAGGIC score showed a significantly higher AUC after 4 years. Importantly, the prognostic value of both biomarkers was additive. CONCLUSION Our study proposes that circulating levels of FMOD and FBLN5 may serve as a new biomarkers of RVD in HFrEF patients.
Běhounek et al. (Fri,) studied this question.