# Further Advances in Atrial Fibrillation Research: A Metabolomic Perspective
## 1 Introduction  
Atrial fibrillation (AF) is one of the most common types of arrhythmia [1, 2]. In this pathology, the electric signals that come from the atria (two small chambers of the heart) are sent in a very fast and uncontrolled way, which produces vibration in the atria instead of contraction, and the electric signals reach to the ventricles irregularly (Figure 1) [3]. When the contract of the auricles is not effective, blood can accumulate or clot. If one of these clots is placed in a cerebral artery, it can lead to stroke [4].  
This is a pathology with a substantial effect on the morbidity and mortality of the patients with cardiovascular conditions (around 15% of strokes occur in people with AF). It has a prevalence of 0.7% in patients between 55 and 59 years old, and its incidence increases to 17.8% after 85 years old [5, 6].  
For the treatment of AF drugs such as as aspirine, warfarine and other medicines for the heart may be used [7]. However, over the last several decades, it has been proved that traditional cardiovascular disease risk control does not seem to reduce AF in a significant way due to a series of specific factors that influence it, such as age, high blood pressure, congenital heart failure, stroke, obesity, and diabetes [8].  
One of the proposed approaches to know the factors that affect AF and reduce its prevalence is the application of metabolomics, the systematic study of the chemical process involving metabolites in a particular tissue or biofluid [9]. Metabolites are the small moleculeintermediates and products of cell metabolism. However, up to now metabolomics research about heart arrythmias, specifically on AF, has been limited. Most published studies have examined the metabolic profile of auricular tissue from AF patients or from animal models, such as a canine model. Despite this, as far as we know, no prospective evaluations of the metabolomic profile associated with risk of AF have been published. To address this gap, it was proposed to explore the association of molecules identified through indirected metabolomic associated with newly diagnosed AF risk in a subset of participants in the Atherosclerosis Risk in Communities (ARIC) study [10; 11].  
Thus, the application of metabolomics in the study of AF has so far been limited. Phenotypic changes in AF seem to point to changes in metabolites induced by environmental factors [6]. Therefore, understanding and defining all the molecules involved in these processes and their interactions is one of the great current challenges. Compared to genomics and proteomics, metabolomics are more closely related to phenotypic expression and influential environmental factors and therefore can better reflect the state of the human body and help to achieve a better understanding of AF. In this review, our aim is to compile and summarize the studies carried out so far to identify new biomarkers of AF (Table 1), focusing on the two most used metabolomic: Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS).  
\begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Study** & **Objective** & **Biological System** & **Sample** & **Metabolic Biomarkers** \\ \hline \multirow{3}{*}{[PERSON] et al. [12]} & AF diagnosis or & & & \begin{tabular}{c} Betaine, choline, creatinine, D-glutamic \\ acid, glycerophosphocholine, \\ hypoxanthine, L-valine, \\ and niacinamide \\ \end{tabular} \\ \cline{1-1}  & \
\begin{tabular}{c} Metabolic adaptation \\ to persistent AF \\ \end{tabular} & Human & Atrial appendages &
\begin{tabular}{c} Beta-hydroxybutyrate, tyrosine, \\ and glycine \\ \end{tabular} \\ \hline \hline \end{tabular}
\end{table}
Table 1: Proposed metabolic biomarkers for AF in human patients and animal models.  
Figure 1: Cardiac electric signals in normal and AF heart.