Abstract 17987: Structural and Senescence Changes in the Atria of Lone Atrial Fibrillation Patients

Abstract

Introduction: Hypertension and structural heart disease (SHD) are the most frequent causes of Atrial Fibrillation (AF). Hemodynamic overload and inflammation are key mediators of the arrhythmogenic substrate, at least partly by triggering accelerated senescence. Remarkably, up to one third of AF patients have no associated SHD (lone AF), and their arrhythmogenic substrate is largely unknown. We sought to compare structural and senescence changes in AF patients with or without SHD. Methods: Atrial appendage samples from four groups of patients were analyzed; patients with no SHD (AF_lone, n=10), AF patients with SHD (AF_Card, n=14), controls with no AF but with other cardiovascular diseases (CVD) (C_CVD, n=18) and controls with no CVD (C_Healthy, n=5). The percentage of intramyocardial collagen deposition was quantified by sirius red staining and morphometric analysis, and connexin-43 was analyzed by immunohistochemistry. Tissue senescence was evaluated with telomere length quantification and mRNA levels of a family of proteins involved in cellular senescence (Sirtuin-1, -2, -3 and -6). Results: There were no differences in age (overall mean 60 ± 2 years) and the percentage of male gender (overall 67%) between groups of patients. AF patients had a marked increase in atrial fibrosis, with no differences between AF_lone and AF_Card (Figure A). Connexin-43 quantification and distribution was similar in AF patients with or without SHD. Nevertheless, telomeres were longer in AF_lone than in AF_Card patients (Figure B). Also, AF_lone samples had higher mRNA levels of sirtuin-2 and -3 compared to AF_Card samples with no changes in sirtuin-1 and -6. Conclusions: Even though a similar degree of structural remodelling was found, AF_Card patients presented an accelerated atrial senescence when compared to AF_lone patients. These results could have important implications in the prognosis and therapeutic options of AF_lone patients.