These findings provide an explanation for the cardiac hypertrophy observed in pre-clinical models upon treatment with rosiglitazone (and PPARγ agonists in general) without affecting cardiac PPARγ and possibly for the increased cardiovascular risk observed in clinical trials, particularly heart failure, associated with rosiglitazone treatment that led, depending on the country, to drug bans or restrictions for prescription [57]. Here, PPARG is linked to heart failure.