Fig. 1.

Factors affecting cardiac energy supply and demand [26]. In heart failure, the balance between cardiac demands and supply for energy is tipped such that the supply does not meet the demand. Inadequate myocardial energy production occurs during myocardial ischemia either at rest or following episodes of increased energy demand, causing left ventricular diastolic dysfunction. Reduced energy supply also accompanies HFrEF or HFpEF. Abnormalities in mitochondrial ultrastructure, dynamics, and enzymatic activities of key complexes of the electron transfer chain are common in the failing myocardium and are responsible, in large part, for the reduction in ATP production. Next-generation therapies can improve on existing standard-of-care therapies by bolstering mitochondrial energy production Adapted with permission from [26]. Abbreviations: ACEi angiotensin-converting enzyme inhibitor, ARB angiotensin II receptor blocker, ETC electron transport chain, HFpEF heart failure with preserved ejection fraction, HFrEF heart failure with reduced ejection fraction, ROS reactive oxygen species