CaMKII inhibition in heart failure makes jump to human.

In this issue of Circulation Research, Sossalla et al1 show that acute inhibition of Ca /calmodulin-dependent protein kinase (CaMK)II in failing human myocardium causes functional improvement in contractility by restoring a positive force–frequency relationship (FFR) in cardiac trabeculae. The loss of this normal positive FFR (and often an induction of a negative FFR) is a functional hallmark of failing human myocardium2 and has been seen as an intrinsic limitation of the failing heart to enhance contractility appropriately at higher heart rates. This failure of positive FFR also constitutes a reduction in functional cardiac reserve. So, why might CaMKII inhibition be beneficial in heart failure (HF)?