Thromboembolism or Atherothromboembolism in Atrial Fibrillation?

Abstract

Atrial fibrillation (AF) is associated with increased morbidity, mortality, and ischemic stroke,1 and these ischemic strokes are almost always severe.2 Thrombus formation in the left atrium with ensuing embolism in the cerebral circulation is deemed to be the cause.2 Article see p 1168 According to the Virchow’s triad, hypercoagulability, endothelial dysfunction, and venous stasis should be prerequisite for thrombus formation in the left atrium.3 Several markers of clotting and platelet activation have been detected in AF patients, including high-plasma levels of the prothrombin fragment F1+2, a marker of thrombin generation, and P-selectin, a marker of clotting activation.3 The existence of a prothrombotic state may predispose to vascular disease. In a prospective study performed in 231 AF patients, we showed that plasma levels of CD40L, a marker of platelet activation, was associated with and predicted vascular outcomes, such as ischemic stroke and myocardial infarction (MI), during a follow-up period of 2 years.4 Endothelial dysfunction has been documented by measuring von Willebrand factor, which has been found to be elevated in AF patients and associated with poor vascular outcomes.5 The rate of endothelial damage seems temporarily related to AF duration because the highest levels have been observed in patients with permanent compared with those with paroxysmal or persistent AF.5 Venous stasis is the third component; it is supposed to be related not only to arrhythmia but also to AF-induced atrium remodeling, which could further lower contractility via several mechanisms, including low Ca2+ mobilization and impaired myosin phosphorylation.3 Furthermore, AF-related remodeling of left atrium may have a negative impact on the cardiac circulation as it is associated with downregulation of atrial NO, a molecule with vasodilator and antiaggregating properties.6 It is still unclear, however, whether remodeling-related venous stasis per se is actually …