PT39 - DISSECTING MIRNA, GDF-15, AND FGF-21 SIGNATURES IN CARDIAC CACHEXIA

PT39

DISSECTING MIRNA, GDF-15, AND FGF-21 SIGNATURES IN CARDIAC CACHEXIA

F. Tambaro^1,*, G. Imbimbo¹, P. Nardozzi¹, A. Molfino¹, M. Muscaritoli¹

¹Department of Translational and Precision Medicine, Sapienza University, Rome, Italy

Rationale: Cardiac cachexia (CC) affects approximately 10–15% of chronic heart failure (CHF) patients and has been associated with poor prognosis and mortality. CC among CHF is more common in patients with advanced myocardial dysfunction with reduced left ventricular ejection fraction (HFrEF) and might be driven by dysregulation of both microRNAs (miRNAs) and stress-induced cytokines. The aims of the present study were i) to evaluate circulating muscle-specific miRNAs, GDF-15 and FGF-21 in CHF patients and ii) to correlate them with changes in body composition and heart failure severity.

Methods: Diagnosis of cardiac cachexia (CC) was made based on Anker’s definition. HFrEF and preserved (HFpEF) were diagnosed according to the 2022 AHA/ACC/HFSA guideline. Circulating miRNAs were measured with RT-qPCR. GDF-15 and FGF-21 were quantified with ELISA assay.

Results: We observed downregulation of miR-15b (p<0.001), -29b (p<0.001), -133a (p=0.005) and -486 (p<0.001), along with higher serum levels of GDF-15 (p<0.001) in HF (n=25) vs C (n=10). In HF, GDF-15 significantly correlated with miR-486 (p=0.046, r=0.403). When considering HF patients with CC (CC) (n=10) vs without CC (nCC) (n=15), our data showed downregulation of miR-29b (p=0.019) and upregulation of FGF-21 (p=0.012) in HF with CC vs nCC. FGF-21 levels were higher in HFrEF (n=12) vs HFpEF (n=13) (p=0.046). Additionally, we observed a significant downregulation of miR-29b in HFrEF + CC (n=7) vs HFpEF + nCC (n=5) (p=0.030).

Conclusion: Our data highlight the modulations of specific miRNAs, GDF-15 and FGF- in CHF patients with CC, which may serve as potential indicators of disease progression and metabolic deterioration. Further investigations are warranted to clarify their diagnostic and pathogenic role in CC onset and progression.

Disclosure of Interest: None declared