Abstract
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.
Highlights
Biomarkers associated with the recurrence and prognosis[10,11,12] or the initiation and maintenance[13] of Atrial fibrillation (AF) have previously been researched, including inflammatory factors[14], prothrombotic markers[15], and microRNAs16,17
The heart rate (HR) of AF group was higher than that of non-AF group (80.04 ± 11.87 vs. 73.24 ± 10.08, P < 0.001), and the left atrial diameter (LAD) was larger in the AF group than in the non-AF group (51.83 ± 13.33 mm vs. 38.77 ± 7.82 mm, P < 0.001), but the systolic pressure was lower in the AF group than in the non-AF group (118.85 ± 15.67 vs. 124.28 ± 16.94, P = 0.042)
The heart failure history of AF group was higher than that of non-AF group (19 (38.78) vs. 23 (19.83), P = 0.011), and the major adverse cardiac and cerebrovascular event (MACCE) incidence were higher in the AF group than in the non-AF group (11 (22.45) vs. 9 (7.76), P = 0.008, respectively) either
Summary
Biomarkers associated with the recurrence and prognosis[10,11,12] or the initiation and maintenance[13] of AF have previously been researched, including inflammatory factors[14], prothrombotic markers[15], and microRNAs16,17. A nuclear magnetic resonance (NMR) metabolomics technique was used to analyze atrial profibrillatory remodeling in a ventricular-tachypacing (VTP)-induced congestive heart failure (CHF) model in dogs[1] and in atrial appendage tissues in AF patients[18], but the results have not been replicated. The NMR technique has its own disadvantages, including low analytical resolution and insensitivity in comparison to mass spectrometry, it is very powerful in metabolite qualification[19,20]. In this study, untargeted LC-MS was utilized to investigate the different metabolites in atrial appendage and plasma samples. To distinguish altered metabolites in the samples and to discover metabolic biomarkers for AF diagnosis or prediction, comparative investigations were performed between AF patients and non-AF patients
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