Fibrillazione atriale nell’anziano: dalla valutazione clinica alle indagini dimetabolomica. Un approccio multidimensionale per lo studio di un’aritmia complessa. Atrial fibrillation in the elderly: From multidimensional assessment to a metabolomic insight. A complex approach for a complex arrhythmia.

Atrial fibrillation (AF) is the most common type of arrhythmia among the elderly and it is characterized by a disordered electrical activity of the atria which causes ineffective atrial contraction. The major riskes posed by AF are the occurrence of stroke, worsen ing heart failure, and dementia. Its pathophysiology is complex and multifaceted and several aspects remain not completely understood. Our project aimed at exploring the molecular characteristics of AF patients with an untargeted metabolomics approach fol lowed by a more in-depth analysis focused on the lipidomics profile, acylcarnitine and amino acids concentrations. In parallel, patients’ frailty was evaluated with the tools from the Geriatric Multidimensional Assessment and the CHA2DS2-VASc score, and key markers of inflammation including IL-6 and OPG were measured to assess the link between low-grade inflammation and AF development and progression. All these data were analyzed and integrated to have a comprehensive understanding of the interplay between all the factors included in the study. A difference in BMI between patients and healthy controls emerged and this may represent a surrogate marker of sarcopenia. With the cluster analysis applied to metabolomics data, a cluster with higher IL-6 levels, higher CHA2DS2-VASc score, and lower physical function was detected, meaning that metabolomics could group patients according to their overall clinical profile and the subjects with the arrhythmia presenting the worse metabolic profile could represent the frailest ones. An association between IL-6 and medium- long-chain acylcarnitines emerged from the analysis shedding light on the complex interplay between low-grade inflammation and acylcarnitines which can alter the heart electrophysiology and thus contribute to the establishment of a favourable substrate for AF development. Addi tionally, a decrease in arginine levels according to age and progression of disease was found and this could represent a marker of endothelial dysfunction. All these findings, linking bench with bedside experience, could be useful to guide the clinical manage ment of patients with AF according to age. In particular, these data may help in the choice between rate and rhythm control therapy of the arrhythmia and could be the basis to understand the correlation between AF and frailty.