SIRT1 and hydrops fetalis: As SIRT1 downregulation and SASP amplification underpin fibroblast activation, extracellular matrix remodeling, and diastolic dysfunction — key hallmarks of HF with preserved ejection fraction (1, 18) — these metabolites may exacerbate cardiomyocyte-fibroblast crosstalk, promoting myocardial stiffening and metabolic inflexibility.