FGF-23 IS A BIOMARKER OF RV DYSFUNCTION AND CONGESTION IN PATIENTS WITH HFREF

Aims: No biomarker reflecting right ventricular dysfunction in HFrEF patients is used in clinical practice. Our study aimed to search for circulating markers of RV dysfunction employing a quantitative proteomic strategy.

Methods and Results: The Olink Proteomics Multiplex panels (Cardiovascular Disease II, III, Cardiometabolic, and Inflammation Target Panels) identified FGF-23 to be most differentially abundant in blood plasma of HF patients with preserved RV function (n= 31) compared to those with severe RV dysfunction (n=30, more than 2-fold, p=0.07 for the adjustment on the number of performed tests).
A subsequent ELISA-based confirmatory 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 plasmatic FGF-23 level was most significantly 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 filtration rate (eGFR, p= 0.08), Table 1. Importantly, FGF-23 was associated with a degree of RV dysfunction in both sub-cohorts (i.e. patients with/without congestion, p<0.0001 for trend), Figure 1. The association between FGF-23 and RV-dysfunction remained significant after the adjustment for BNP (p= 0.01). On the contrary, when adjusted for BNP, FGF-23 was not associated with LV dysfunction (p=0.59). Cox proportional hazard model revealed that circulating FGF-23 was significantly associated with the adverse outcome even after adjustment 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.