Further, pharmacologic MR antagonism with spironolactone (Spiro) prevented obesity-associated diastolic dysfunction in female mice [6] consistent with a recent post hoc analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial suggesting greater benefit of MR blockade in obese female HFpEF patients compared to males [43]. The gene discussed is NR3C2; the disease is obesity due to melanocortin 4 receptor deficiency.