Elevated Factor VIIa-antithrombin Complexes Are Associated with Spontaneous Echo Contrast in Atrial Fibrillation: The Impact of Heart Failure

Abstract Elevated factor VIIa–antithrombin (FVIIa-AT) complex levels reflect enhanced tissue factor (TF)-driven coagulation activation and have been reported in atrial fibrillation (AF) recently. We hypothesized that elevated FVIIa-AT levels characterize patients with spontaneous echo contrast (SEC). We studied 131 AF patients (median age: 70 years; median CHADS-VASc score: 4 [2–5]); all but one were anticoagulated. Transesophageal echocardiography was performed to assess SEC and left atrial appendage thrombus (LAAT). FVIIa-AT complexes, fibrin clot permeability (K s), clot lysis time (CLT), and endogenous thrombin potential (ETP) were measured. SEC was detected in 35 patients (27%), including eight (6%) with concomitant LAAT. The patients with SEC had 30% higher FVIIa-AT levels, compared with the remainder (p < 0.0001). FVIIa-AT levels correlated positively with AF duration (r = 0.38), CLT (r = 0.41), and ETP (r = 0.34; all p < 0.0001), but not with demographic, stroke risk or other clinical variables, except for permanent AF (+15%, p < 0.0001) and heart failure (HF; +11%, p = 0.02). Eighty-two percent of patients with SEC were in the highest FVIIa-AT quartile (≥178 pM), characterized by higher plasminogen activator inhibitor-1 (+14%) levels, reduced K s (−12%), and prolonged CLT (+33%; all p ≤ 0.02). In multivariable analysis, HF (OR: 9.00, 95% CI: 1.81–44.67) and FVIIa-AT concentration (OR per 10 pM increase: 2.40, 95% CI: 1.66–3.47) independently predicted SEC. This study is the first to link elevated FVIIa-AT levels, reflecting TF-pathway activation, with SEC and/or LAAT in anticoagulated AF patients, particularly in the presence of HF, suggesting a potential contribution of TF-mediated coagulation activation and impaired fibrinolysis in this phenomenon.