Further studies are required to assess the extent to which these sex-related differences in the progression of systolic dysfunction and HF are generalizable to other types of cardiomyopathies (e.g., ischemic cardiomyopathy) and, whether they can be modulated by agents that alter renin, estrogen, mitochondrial function or other components of the RAAS or natriuretic peptide pathways to reduce HF and mortality. This evidence concerns the gene REN and hydrops fetalis.