Key result
SGLT2i use in severe AS is linked to reduced inflammatory and fibrocalcific remodeling in valve tissue.
Why the study?
SGLT2 inhibitors exert pleiotropic metabolic and anti-inflammatory effects, but their role in calcific aortic valve stenosis remains unclear.
Does SGLT2 inhibitor therapy improve molecular signatures of aortic valve remodeling in patients with severe calcific aortic valve stenosis undergoing surgical aortic valve replacement?
Observational (n=83)
Yes
Does SGLT2 inhibitor therapy improve molecular signatures of aortic valve remodeling in patients with severe calcific aortic valve stenosis undergoing surgical aortic valve replacement?
SGLT2 inhibitor therapy is associated with favorable molecular and metabolic reprogramming in the valvular microenvironment of patients with severe aortic stenosis, suggesting a potential disease-modifying role.
Sodium-glucose cotransporter 2 inhibitor (SGLT2i) exerts pleiotropic metabolic and anti-inflammatory effects, but its role in calcific aortic valve stenosis (CAVS) is unclear. In this multicenter prospective study, 83 patients with severe CAVS undergoing surgical aortic valve replacement were stratified by SGLT2i use. Explanted valve tissue and plasma were analyzed using transcriptomics, circulating biomarkers, and metabolomics, including MALDI-MSI. SGLT2i therapy was associated with reduced valvular expression of SGLT1/2, GLUT4, and NHE, increased PPARα, decreased PPARγ, attenuation of inflammatory signaling (lower NF-κB and IL-6), and oxidative stress response (higher SOD2). Extracellular matrix turnover and fibrocalcific remodeling enzymes (MMP-9 and MMP-12) were also reduced. Metabolomic profiling demonstrated distinct clustering, with enrichment of amino acid and redox pathways in SGLT2i users. These findings suggest that SGLT2i therapy is associated with coordinated molecular and metabolic reprogramming of the valvular microenvironment, supporting a potential disease-modifying role in CAVS.
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Paolisso et al. (2026) conducted an observational in Severe calcific aortic valve stenosis (n=83). SGLT2 inhibitors vs. No SGLT2 inhibitor use was evaluated on Molecular signatures of aortic valve remodeling (transcriptomics, circulating biomarkers, and metabolomics). SGLT2 inhibitor use in patients with severe aortic stenosis was associated with reduced inflammatory signaling, oxidative stress, and fibrocalcific remodeling enzymes in explanted valve tissue.
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