ABSTRACT
Heart failure with reduced ejection fraction (HFrEF) is a complex collection of disease entities, all resulting in impairment of myocardial contraction such that cardiac output can no longer meet peripheral tissue demands. The list of etiologies is extensive but can all be conceptualized as occurring after one or more index event(s) either directly damaging the myocardium or preventing cardiomyocytes from contracting normally. In order to maintain cardiac output, cascades of neurohormonal, structural (remodeling), and energetic changes are simultaneously triggered, perpetuating the vicious cycle that characterizes the progression of HFrEF. These mechanisms form the basis of our current understanding of heart failure pathophysiology and serve as targets for established and novel therapies.
