Metabolic remodelling of the failing heart: beneficial or detrimental?

The failing heart is characterized by alterations in energy metabolism, including mitochondrial dysfunction and a reduction in fatty acid (FA) oxidation rate, which is partially compensated by an increase in glucose utilization. Together, these changes lead to an impaired capacity to convert chemical energy into mechanical work. This has led to the concept that supporting cardiac energy conversion through metabolic interventions provides an important adjuvant therapy for heart failure. The potential success of such a therapy depends on whether the shift from FA towards glucose utilization should be considered beneficial or detrimental, a question still incompletely resolved. In this review, the current status of the literature is evaluated and possible causes of observed discrepancies are discussed. It is cautiously concluded that for the failing heart, from a therapeutic point of view, it is preferable to further stimulate glucose oxidation rather than to normalize substrate metabolism by stimulating FA utilization. Whether this also applies to the pre-stages of cardiac failure remains to be established.