A Metabolomic Approach to Unexplained Syncope

<b>Background:</b> This study aims to identify a metabolomic signature that facilitates the classification of syncope and the categorization of the unexplained syncope (US) to aid in its management. <b>Methods:</b> We compared a control group (CTRL, <i>n</i> = 10) with a transient loss of consciousness (TLC) group divided into the OH group (<i>n</i> = 23) for orthostatic syncope, the NMS group (<i>n</i> = 26) for neuromediated syncope, the CS group (<i>n</i> = 9) for cardiological syncope, and the US group (<i>n</i> = 27) for US defined as syncope without a precise categorization after first- and second-level diagnostic approaches. <b>Results:</b> The CTRL and the TLC groups significantly differed in metabolic profile. A new logistic regression model has been developed to predict how the US will be clustered. Using differences in lysophosphatidylcholine with 22 carbon atom (C22:0-LPC) levels, 96% of the US belongs to the NMS and 4% to the CS subgroup. Differences in glutamine and lysine (GLN/LYS) levels clustered 95% of the US in the NMS and 5% in the CS subgroup. <b>Conclusions:</b> We hypothesize a possible role of C22:0 LPC and GLN/LYS in re-classifying US and differentiating it from cardiological syncope.