Abstract 4370227: Acute Rhythm Change Reveals Atrial-Specific Metabolomic and Lipidomic Alterations in Atrial Fibrillation

Introduction: Arterio-venous (AV) gradients across tissue beds provide insights into the metabolic activity by measuring the net uptake or release of lipids and metabolites. In the heart, these gradients can reflect real-time changes in myocardial substrate utilization in disease states like atrial fibrillation (AF). Aims: We aimed to explore the lipidomic and metabolic alterations due to acute rhythm changes in AF patients. Methods: Blood samples were collected from the left atrium (LA), coronary sinus (CS), and the vein of Marshall (VOM) during AF ablation procedures, representing the arterial and venous sides of the whole myocardial and atrial tissue, respectively. Samples were collected in the presenting rhythm (SR or AF), after which patients were either cardioverted or underwent AF induction before any ablation delivery. Sampling was repeated 5 minutes after the onset of the new rhythm (Panel A). Blood samples were analyzed for lipid species and metabolites using the Sciex Lipidyzer system and LC-MS metabolite analysis, respectively. Results: We analyzed 16 arterio-venous blood samples (8 in AF, 8 in SR) to measure 1,561 lipid species across 18 lipid classes and 29 metabolites, including those specific to the heart and atria. Oxygen saturation in the VOM was lower in AF (median 53%, IQR 40–58%) compared to SR (58%, IQR 46–68%; P=0.021), indicating greater oxygen extraction in AF by the atria (Panel B). However, there was no significant difference in oxygen saturation in the CS samples: AF (median 56%, IQR 44–63%) and SR (median 57%, 42– 62%; P=0.1). Differences in AV gradients between AF and SR were assessed in both whole-heart and atrial-specific samples. In whole-heart samples, there was a general balance between lipid import and export. However, atrial-specific samples showed a clear shift toward net lipid import in AF (Panel C). For metabolites, we found a mismatch between atrial and ventricular metabolism in AF. Specifically, glucose, valine, and isoleucine showed net export from the whole heart, but net import at the atrial level (Panel D). Conclusion: Atrial-specific metabolic alterations, characterized by increased lipid and amino acid uptake, altered glucose utilization, and increased oxygen extraction were observed with AF compared to SR. These findings point to an acute metabolic shift, with increased energetic demand in atrial tissue, and potential atrial–ventricular metabolic desynchrony during AF.