Considering the strong correlation between the extent of collagen cross-linking with impairment of cardiac function and with a poor prognosis in HF patients, the enzymes catalyzing covalent cross-links between polypeptide chains of adjacent fibrils, lysyl oxidase (LOX), and lysyl oxidase homolog 2 (LOXL2), could be of major interest as therapeutic target. This evidence concerns the gene LOX and hydrops fetalis.