Metabolic Dysregulation in Heart Failure
Summary
Heart failure is increasingly recognised as a disorder of cardiac energy metabolism as much as of pump function. Under normal conditions the myocardium flexibly switches between fatty acids, glucose and ketone bodies to meet fluctuating energy demands. In the failing heart this flexibility is lost: mitochondrial biogenesis and function become impaired, fatty acid oxidation declines, glucose utilisation is disrupted and reliance on alternative substrates may emerge. At the same time, neurohormonal activation and systemic inflammation drive insulin resistance, endothelial dysfunction and maladaptive remodelling. The net result is a mismatch between energy supply and demand, progressive contractile failure and worsening clinical status. Understanding these pathways has revealed new targets—from therapies that restore mitochondrial health to agents that improve insulin sensitivity and optimise substrate choice.
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Metabolic Dysregulation in Heart Failure publication trend
The graph below shows the total number of articles in metabolic dysregulation in heart failure across all publications each year (not limited to Nature Index journals).
Technical terms
Metabolic dysregulation: Impaired control of energy production and substrate utilisation by cells in the failing heart.
Insulin resistance: Reduced responsiveness of tissues to insulin, leading to impaired glucose uptake and hyperinsulinaemia.
Heart failure with preserved/reduced ejection fraction (HFpEF/HFrEF): Clinical syndromes defined by normal (≥50%) or reduced (<50%) left ventricular ejection fraction, respectively.
Multiple hormonal and metabolic deficiency syndrome (MHDS): Concurrent deficiencies in two or more endocrine or metabolic pathways in chronic heart failure.
Substrate utilisation: The selection and oxidation of energy sources, such as fatty acids, glucose or ketone bodies, by cardiac myocytes.
References
- The Negative Impact of Insulin Resistance/Hyperinsulinemia on Chronic Heart Failure and the Potential Benefits of Its Screening and Treatment. Biomedicines (2023).
- Prediabetes and insulin resistance in a population of patients with heart failure and reduced or preserved ejection fraction but without diabetes, overweight or hypertension. Cardiovascular Diabetology (2022).
- Multiple hormonal and metabolic deficiency syndrome predicts outcome in heart failure: the T.O.S.CA. Registry. European Journal of Preventive Cardiology (2021).
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