Integrated miRNA-cytokine profiling reveals a molecular signature of cachexia in patients with chronic heart failure.

Authors

Federica Tambaro, Giovanni Imbimbo, Carmen Gallicchio, Paolo Nardozi, Simona Orlando, Roberta Belli, Cesarina Ramaccini, Stefan D Anker, Alessio Molfino, Maurizio Muscaritoli

Published in

ESC heart failure. Volume 13. Issue 5. Aug 27, 2026.

Abstract

Cardiac cachexia (CC) complicates chronic heart failure (CHF). Circulating microRNAs (miRNAs) and cytokines, such as growth differentiation factor-15 (GDF-15) and fibroblast growth factor-21 (FGF-21), may reflect the catabolic-anabolic imbalance and structural remodelling associated with this syndrome. To define the circulating signature of CHF by profiling muscle and remodelling-related miRNAs alongside GDF-15 and FGF-21, and to assess their associations with cardiac function and clinical phenotypes.
Twenty-five CHF patients (median age 78.0 years, 40% male) and 10 controls (median age 56.8 years, 60% male) were studied. CC was defined as unintentional, non-oedematous weight loss ≥6% within 6 months. Circulating miRNAs were quantified by RT-qPCR, GDF-15 and FGF-21 by ELISA. CHF patients were classified as having reduced (HFrEF) or preserved ejection fraction (HFpEF). Associations with CC and clinical CHF phenotypes were evaluated.
Compared with controls, CHF patients showed lower levels of miR-15b, miR-29b, miR-133a, and miR-486 (all P < .01) and elevated GDF-15 levels (P < .001). FGF-21 was higher in patients with CC (P = .012), in HFrEF vs HFpEF (P = .039), and in NYHA III-IV vs I-II (P = .05). miR-29b levels were lower in CC (P = .019) and in HFrEF + CC vs HFpEF + nCC (P = .019). In CC, FGF-21 inversely correlated with miR-486 (ρ = -.69, P = .035), whereas GDF-15 inversely correlated with miR-21 (ρ = -.81, P = .007).
CHF is associated with miRNA suppression and elevated stress cytokine levels, amplified in CC. miR-29b and FGF-21 showed associations with CC, functional impairment, and structural remodelling, warranting validation in larger longitudinal cohorts.

PMID:
42853063
Bibliographic data and abstract were imported from PubMed on 09 Oct 2026.

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