Metabolic remodelling in heart failure

• Published in: Nature reviews cardiology 2018-08, Vol.15 (8), p.457-470
• Main Authors: Bertero, Edoardo, Maack, Christoph
• Format: Article
• Language: English
• Subjects: 631/443/319/333; 692/4019/592/75/230; Cardiac Imaging; Cardiac patients; Cardiac Surgery; Cardiology; Development and progression; Diabetes; Diabetes mellitus; Energy metabolism; Enzymes; Epigenetic inheritance; Fatty acids; Glucose metabolism; Health aspects; Heart; Heart cells; Heart failure; Medical tests; Medicine; Medicine & Public Health; Metabolism; Mitochondria; Oxidation; Oxidation-reduction reactions; Oxidative stress; Physiological aspects; Review Article
• ISSN: 1759-5002; 1759-5010
• DOI: 10.1038/s41569-018-0044-6

The heart consumes large amounts of energy in the form of ATP that is continuously replenished by oxidative phosphorylation in mitochondria and, to a lesser extent, by glycolysis. To adapt the ATP supply efficiently to the constantly varying demand of cardiac myocytes, a complex network of enzymatic and signalling pathways controls the metabolic flux of substrates towards their oxidation in mitochondria. In patients with heart failure, derangements of substrate utilization and intermediate metabolism, an energetic deficit, and oxidative stress are thought to underlie contractile dysfunction and the progression of the disease. In this Review, we give an overview of the physiological processes of cardiac energy metabolism and their pathological alterations in heart failure and diabetes mellitus. Although the energetic deficit in failing hearts — discovered >2 decades ago — might account for contractile dysfunction during maximal exertion, we suggest that the alterations of intermediate substrate metabolism and oxidative stress rather than an ATP deficit per se account for maladaptive cardiac remodelling and dysfunction under resting conditions. Treatments targeting substrate utilization and/or oxidative stress in mitochondria are currently being tested in patients with heart failure and might be promising tools to improve cardiac function beyond that achieved with neuroendocrine inhibition. In patients with heart failure, derangements of substrate utilization and intermediate metabolism, an energetic deficit, and oxidative stress are thought to underlie contractile dysfunction and disease progression. In this Review, Bertero and Maack describe the physiological processes of cardiac energy metabolism and their pathological alterations in heart failure and diabetes mellitus, and discuss promising treatments targeting substrate utilization or oxidative stress in mitochondria. Key points The healthy heart is metabolically flexible and can derive energy from various circulating substrates. Heart failure (HF) and diabetes mellitus are characterized by an increased reliance on ketone bodies and fatty acid oxidation, respectively, for cardiac ATP production. Metabolic inflexibility and accumulation of toxic intermediates, rather than unbalanced substrate utilization, might detrimentally affect cardiac function. Metabolic intermediates can operate as signalling factors, inducing post-translational and epigenetic modifications or activating intracellular signalling ca