NR3C2 and heart failure: The best known example is probably heart failure after Pitt and coworkers demonstrated mortality reduction with a rather low dose of spironolactone given on top of standard of care among patients with severe heart failure in the RALES landmark trial (Pitt et al. 1999); the actual MR ligand in these patients is cortisol, rather than aldosterone, reflecting the absence of the cortisol-converting enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) in cardiomyocytes (Funder 2005).