# Further Advances in Atrial Fibrillation Research: A Metabolomic Perspective
## 2 Application of Metabolomics in Atrial Fibrillation  
### Blood-Derived and Heart Tissue Biomarkers Analysis in Atrial Fibrillation  
After years of research and therapeutic interventions related to AF, scientists are still struggling to understand the causes and mechanisms of this condition. Blood-derived biomarkers, such as clotting markers, kidney function, inflammation, myocardial injury, and cardiovascular stress, have been associated with clinical events [19]. In this context, [PERSON] et al. [13] demonstrated the feasibility to use plasma metabolomics analysis to predict AF. They also found metabolic alterations in atrial appendage samples that allow the discrimination between patients with and without AF. They reported a combination of D-glutamic acid, creatinine, and choline as a potential biomarker for AF prediction. However, they recognized that is necessary to reproduce their results with a larger sample size, to validate their findings. Along with development and progression of AF, metabolite biomarkers could reflect its pathophysiological mechanisms. [PERSON] et al. [14] carried out a nondirected metabolomic analysis NMR to verify whether both \(\beta\)-hidroxibutirate and its ketogenic aminoacid, as well as glycine, were increased in myocardial blood samples of patients with persistent AF. \begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Study** & **Objective** & **Biological System** & **Sample** & **Metabolic Biomarkers** \\ \hline \multirow{8}{*}{[PERSON] et al. [14]} & Identify metabolic alterations correlated to the occurrence of AF & Human & Plasma & L-threonine, hypotaurine, L-leucine, L-3-amino-isobutyric acid, L-lysine, L-arginine, L-asparagine, \(\beta\)-alanine, L-kynurene, L-glutamic acid, saccharopine, L-methionine, 4-hydroxy pyrrolidine-2-carboxylic, and L-homoserine and L-histidine \\ \hline \multirow{8}{*}{[PERSON] et al. [15]} & Identify biomarkers for AF screening & Human & Plasma & 2-Methylbenzothiazole, 4-hydroxybenzoic acid, acetylcholine, adenine, adenosine 3’-monophosphate, adenosine-diphosphate, AMP, citruline, cysteine, D-arabinose-5-phosphate disodium salt, DL-beta-hydroxyburic acid, gamma-linolenic acid, guanosine 5’-monophosphate, hypoxanthine, isoleucine, O-acetylL-carnitine, oxidized glutathione, para-aminobenzzoic acid, proline, trigonelline, umbelliferone, uridine 5’-diphosphate, and uridine 5’-monophosphate \\ \hline \multirow{2}{*}{[PERSON] et al. [16]} & Predictive model for AF recurrence & Human & Serum and faecal samples & LysoPC(15:0), lysoPE(0:0/16:0), chenodeoxycholic acid, sebacic acid, lysoPE(0:0/20:0), corticosteroidsene, \(\alpha\)-linolenic acid, and uracil \\ \hline \multirow{2}{*}{[PERSON] et al. [17]} & Biomarkers for chronic AF in mitral valve disease & Human & Plasma & Sucrose, cellobiose, lactose, raffinose, galacintol, arachidonic acid, palmitic acid, and linoleic acid \\ \hline \multirow{2}{*}{[PERSON] et al. [6]} & Biomarkers for congestive heart failure induce AF & Dog & Left atrium & Alanine, glucose, glutamine, glutamate, taurine, \(\alpha\)-ketoacid, and \(\alpha\)-ketoisovale \\ \hline \multirow{4}{*}{[PERSON] et al. [18]} & Characterize the remodeling of energy metabolism during persistent AF & Sheep & Left atrium & Citrate, pyroglutamic acid, methionine, glycine, glutamic acid, proline, tyrosine, arginine, pyruvate, lactate, glycogen, and glucisamine \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Cont. In another study carried out by [PERSON] et al. [15], the plasma amino acid metabolic profile was analyzed in elderly patients, admitted to the cardiology unit of Xi'an Jiaotong University Affiliated Hospital, who were diagnosed with AF. Fasting venous blood collections were performed over 23 selected patients and 37 healthy controls, separating the plasma by centrifugation, and the amino acid profile was evaluated by GC/MS [15]. Quantification of 61 serum amino acids was performed, and the results were compared between groups.