FGF-23 is a Biomarker of RV Dysfunction and Congestion in Patients with HFrEF

Aims: There is no biomarker re ecting right ventricular dysfunction in HFrEF patients used in clinical practice.
 We have aimed to look for a circulating marker of RV dysfunction employing a quantitative proteomic strategy.
 Methods and Results: The Olink Proteomics Multiplex panels (Cardiovascular Disease II, III, Cardiometabolic,
 and In ammation Target Panels) identi ed FGF-23 to be the most differentially abundant (more than 2.5-fold)
 in blood plasma of HF patients with severe RV dysfunction (n=30) compared to those with preserved RV
 function (n= 31).  A subsequent ELISA-based con rmatory analysis of circulating FGF-23 in a large cohort of
 patients (n= 344, 72.7% NYHA III/IV, LVEF 22.5%, 54.1% with moderate/severe RV dysfunction), followed by
 multivariable regression analysis, revealed that the plasma FGF-23 level was most signi cantly associated with
 RV dysfunction grade (p= 0.0004) and congestion in the systemic circulation (p= 0.03), but not with LV-ejection
 fraction (p= 0.69) or estimated glomerular ltration rate (eGFR, p= 0.08). FGF-23 was associated with the
 degree of RV dysfunction in both sub-cohorts (i.e. in patients with and without congestion, p<0.0001). The
 association between FGF-23 and RV-dysfunction remained signi cant after the adjustment for BNP (p= 0.01).
 In contrast, when adjusted for BNP, FGF-23 was no longer associated with LV dysfunction (p=0.59). The Cox
 proportional hazard model revealed that circulating FGF-23 was signi cantly associated with adverse
 outcomes even after adjusting for BNP, LVEF, RV dysfunction grade and eGFR.
 Conclusion: Circulating FGF-23 is a biomarker of right ventricular dysfunction in HFrEF patients regardless of
 congestion status