FOXO3 and hydrops fetalis: Using a combination of molecular and biochemical analyses of clinical samples, knockout models, in vivo Igfbp7 knockdown in cardiac myocytes and monoclonal antibody (mAb)-mediated blockade, this study reveals that IGFBP7 directly regulates pathological cardiac remodeling, senescence and fibrosis by suppressing the FOXO3a-mediated pro-longevity pathway, thereby accelerating the progression of HF.