Differential Pathophysiological Mechanisms in Heart Failure With a Reduced or Preserved Ejection Fraction in Diabetes

State-of-the-art Review

Milton Packer, MD


JACC Heart Fail. 2021;9(7):535-549. 

In This Article


The totality of experimental and clinical evidence suggests that diabetes may promote the development of heart failure by effects on intracellular nutrient deprivation and surplus signaling and autophagy, by effects on sodium-hydrogen exchange in the heart and kidneys, and by effects on biological active adipose tissue depots, which—acting alone or in concert—may lead to the development of both HFrEF and HFpEF. Antagonism of these mechanisms may underlie the demonstrated ability of SGLT2 inhibitors to reduce the risk of serious heart failure events.