Combinational Biomarkers for Atrial Fibrillation Derived from Atrial Appendage and Plasma Metabolomics Analysis

Atrial fibrillation (AF) is one of the most common types of arrhythmias and often leads to clinical complications. The objectives of this study were to offer insights into the metabolites of AF and to determine biomarkers for AF diagnosis or prediction. Sixty atrial appendage samples (AF group: 30; non-AF group: 30) and 163 plasma samples (AF group: 48; non-AF group: 115) from 49 AF patients and 116 non-AF patients were subjected to liquid chromatography positive ion electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) metabolomics analysis. Consequently, 24 metabolites in atrial appendage samples and 24 metabolites in plasma samples were found to reflect metabolic differences between AF and non-AF patients (variable importance in projection (VIP) ≥ 1, P ≤ 0.05). Five identical metabolites including creatinine, D-glutamic acid, choline, hypoxanthine, and niacinamide (VIP ≥ 1.5, P < 0.01, FDR < 0.05) in atrial appendage and plasma samples were considered prominent features of AF patients, and the D-glutamine and D-glutamate metabolic pathway was also identified as a feature of AF patients. Finally, in plasma samples, the combination of D-glutamic acid, creatinine, and choline had an AUC value of 0.927 (95% CI: 0.875–0.979, P < 0.001) and displayed 90.5% sensitivity and 83.3% specificity; this group of metabolites was thus defined as a combinational biomarker for the recognition of AF and non-AF patients.