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  • Review Article
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Metabolic remodelling in atrial fibrillation: manifestations, mechanisms and clinical implications

Abstract

Atrial fibrillation (AF) is a continually growing health-care burden that often presents together with metabolic disorders, including diabetes mellitus and obesity. Current treatments often fall short of preventing AF and its adverse outcomes. Accumulating evidence suggests that metabolic disturbances can promote the development of AF through structural and electrophysiological remodelling, but the underlying mechanisms that predispose an individual to AF are aetiology-dependent, thus emphasizing the need for tailored therapeutic strategies to treat AF that target an individual’s metabolic profile. AF itself can induce changes in glucose, lipid and ketone metabolism, mitochondrial function and myofibrillar energetics (as part of a process referred to as ‘metabolic remodelling’), which can all contribute to atrial dysfunction. In this Review, we discuss our current understanding of AF in the setting of metabolic disorders, as well as changes in atrial metabolism that are relevant to the development of AF. We also describe the potential of available and emerging treatment strategies to target metabolic remodelling in the setting of AF and highlight key questions and challenges that need to be addressed to improve outcomes in these patients.

Key points

  • Metabolic disorders, such as diabetes mellitus and obesity, can increase the risk of atrial fibrillation (AF); current treatments for these metabolic diseases often fail to prevent AF, highlighting a treatment gap.

  • Metabolic stress and metabolic remodelling can increase susceptibility to AF.

  • AF alters glucose, lipid and ketone metabolism, mitochondrial function and myofibrillar energetics, which together affect atrial function.

  • The mechanisms underlying AF in patients with metabolic disorders are aetiology-dependent, emphasizing the need for tailored therapeutic strategies to treat the arrhythmia.

  • Established cardiometabolic drugs show promise for the management of AF in specific patient groups; emerging strategies targeting atrial metabolism suggest novel treatment possibilities.

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Fig. 1: Cascade of metabolic disturbances leading to AF.
Fig. 2: Metabolic remodelling in AF.
Fig. 3: Molecular mechanisms underlying atrial remodelling associated with diabetes and obesity.

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Acknowledgements

D.B. is supported by the German Center for Cardiovascular Research (DZHK 81 × 3100215). G.G.S. is supported by the Deutsche Forschungsgemeinschaft (DFG, SFB-1470–A02), the German Center for Cardiovascular Research (DZHK 81 × 3100210) and by the European Research Council (StG 101078307). N.V. is supported by the Deutsche Forschungsgemeinschaft (DFG, VO 1568/3-1, VO 1568/4-1, SFB-1002–A13 and under Germany’s Excellence Strategy (EXC 2067/1-390729940)) and by the German Center for Cardiovascular Research (DZHK SE181 and 81 × 4300102 ‘DNAfix’).

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Bode, D., Pronto, J.R.D., Schiattarella, G.G. et al. Metabolic remodelling in atrial fibrillation: manifestations, mechanisms and clinical implications. Nat Rev Cardiol (2024). https://doi.org/10.1038/s41569-024-01038-6

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