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

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. In this Review, the authors describe the changes in metabolism that predispose individuals to developing atrial fibrillation (AF) and highlight the potential of available and emerging therapeutic strategies that target metabolic remodelling to treat AF. 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.