The potentially novel primary findings of this study are the following: (a) there was a resident cardiac ATRA decline in HF patients and a guinea pig model of HF, despite adequate tissue reserves of retinol; (b) remodeling of the retinoid metabolic program differed between human and guinea pig HF, with implications for a therapeutic strategy based on normalizing cardiac ATRA levels; and (c) inhibition of the CYP26 family of the cytochrome p450 hydroxylases with talarozole inhibited myocyte hypertrophy in vitro. This evidence concerns the gene CYP26A1 and hydrops fetalis.