McLeod, Thomas G.

Aim. Thromboembolic presentation (stroke, mesenteric or limb ischemia) in non-valvular atrial fibrillation may occur randomly or may identify unique subpopulations of patients with this dysrhythmia. The aim of this study was to determine whether future major adverse cardiovascular event rates (myocardial infarction, stroke, peripheral arterial embolism, death) differ between patients with peripheral embolism (AFPE) compared to those suffering stroke (AFS). Methods. An inception cohort (1995–2005) with AFPE (n=216) were compared to randomly selected AFS patients (n=241). Results. Patients with AFPE were older than AFS patients (79±10 vs 73±13 years; p<0.001) with a greater percentage of women (71% vs 45%; p<0.001). The most common presentation of AFPE patients was limb ischemia (90%). Except for prior stroke, all CHADS-2 variables were more prevalent in AFPE (Table ). During 3.3±3.6 years of follow up, survival was lower in AFPE compared to either AFS (p<0.001) or age/gender matched controls (p<0.001; Figure ). AFPE patients had lower survival free from recurrent embolization compared to AFS (82% vs 100%; p=0.005). Recurrence free survival for MI and stroke were similar. Conclusions. Patients with peripheral embolization represent a unique subset of non-valvular atrial fibrillation with an increased risk of recurrence and high mortality rates compared to those suffering stroke. Comparison of clinical and echocardiographic characteristics

Background and Aim: Cardioembolic stroke from non-valvular atrial fibrillation (NVAF) begins with the development of left atrial appendage thrombus (LAAT). Although nearly 15% of patients with NVAF have LAAT by transesophageal echocardiography, the annual stroke rate is 5% on average. The overall aim of this project is to identify variables associated with embolic propensity of LAAT. Materials and Methods: LAAT specimens were obtained during cardiac surgery (MAZE procedure; n=26). Embolized thrombi (n=51) were obtained during surgical embolectomy from lower (n=36) and upper extremities (n=11) and mesenteric arteries (n=4). Platelet-rich regions within sectioned thrombi were sampled by punch biopsy from which total RNA was extracted and analyzed for expression of 5 platelet specific genes: A1 domain of factor XIII, (F13A1); integrin α 2b β 3 (ITGA2B); glycoprotein IX (GP9), platelet factor 4 (PF4), glycoprotein Ib (GP1BB). Gene expression was quantified using TaqMan MGB-probe based quantitative real-time polymerase chain reaction normalized to β 2 macroglobulin using cDNAs reverse transcribed from total RNA. Results: Factor XIII gene expression (Figure ) was significantly lower in embolic (mean fold change 0.08) compared to left atrial thrombi in situ (mean fold change 0.28; p=0.03). Expression of other genes did not show significant change by embolic status. Conclusions: Variable Factor XIII gene expression in thrombi generated during NVAF may in part explain the propensity to embolization. Whereas Factor XIII stabilizes thrombi by crosslinking fibrin without influencing atrial attachment, this data suggests that embolization occurs through fragmentation.

Objective— Left atrial blood stasis is associated with increased risk for left atrial appendage thrombus (LAAT) and stroke in atrial fibrillation (AF). Von Willebrand factor (VWF) is associated with thromboembolism in AF. VWF thrombogenic activity is proportional to multimer size, which is regulated by VWF-cleaving protease (ADAMTS13). Methods and Results— To assess the association between left atrial blood stasis and VWF-ADAMTS13 system, plasma VWF antigen (VWF:Ag), VWF activity (VWF:Act), and ADAMTS13 activity were measured in 414 consecutive patients with nonvalvular AF (age 63±13 years; 25% women) and in 100 patients (age 64±14 years; 39% women) with normal sinus rhythm. Spontaneous echocardiographic contrast (SEC), left atrial appendage emptying velocity, and LAAT were assessed by transesophageal echocardiography. Presence and intensity of SEC varied directly with VWF:Ag and VWF:Act but not with ADAMTS13 activity. AF patients with LAAT had higher VWF:Ag (200±61 versus 155±52, P =0.0006) and VWF:Act (179±57 versus 141±51 P =0.0026) compared with those without LAAT. VWF:Ag and VWF:Act were independent predictors of LAAT after adjustment for CHADS 2 score ( P =0.0179 and P =0.0497, respectively). Conclusion— The association between VWF and SEC may explain the thrombotic propensity in AF. Elevated VWF:Ag may help identify AF patients at risk for LAAT.