RESUMEN
Atrial fibrillation (AF) is well known for being a major risk factor of thromboembolic stroke. We could recently demonstrate an association of monocyte-platelet aggregates (MPAs) with the degree of thrombogenicity in patients with AF. This study investigated platelet activation markers, as potential biomarkers for the presence of left atrial (LA) thrombus in patients with AF. One hundred and eight patients with symptomatic AF underwent transesophageal echocardiography (TEE) before scheduled cardioversion or pulmonary vein isolation. In order to determine the content of MPAs by flow-cytometric quantification analyses, blood was drawn on the day of TEE. The soluble CD40 Ligand (sCD40L) and soluble P-selectin (sP-selectin) were obtained by Cytometric Bead Arrays (CBA). D-dimer levels were detected by quantitative immunological determination of fibrin degradation products. Clinical, laboratory, and echocardiographic standard parameters were obtained from all patients, including the determination of the flow in the left atrial appendage (LAA). Patients with detected LA thrombus (n = 28) compared with patients without thrombus (n = 80) showed an increased number of common risk factors, such as age, diabetes, heart failure, and coronary artery disease (CAD). The presence of LA thrombus was associated with significantly increased levels of MPAs (147 ± 12 vs. 304 ± 29 per µl; p < 0.00), sCD40L (106.3 ± 31.0 vs. 33.5 ± 2.1 pg/ml, p = 0.027), and D-dimer (0.13 ± 0.02 vs. 0.69 ± 0.21 mg FEU/l, p = 0.015). In contrast, sP-selectin showed no association with LA thrombus. A multivariate regression analysis showed that MPAs, sCD40L as well as D-dimers were independent indicators for the existence of LA thrombus. MPAs above 170 cells/µl indicated LA thrombus with a high sensitivity of 93% and a specificity of 73% (OR 62, 95% CI. 6.9-557.2, p < 0.001) in patients with AF, whereas the D-dimer lost their quality as independent indicator by using the conventional cut-off of 0.5 mg/l within the regression analysis. MPAs, as well as the D-dimer, correlated significantly negatively with the flow in the LAA measured during TEE. The content of MPAs, sCD40L, and D-dimer, but not sP-selectin showed an increased dependence on LA thrombus in patients with AF. In our study group, MPAs showed the best diagnostic test accuracy of the compared platelet markers. The different results of the examined platelet activation markers could be an indication of diverse mechanisms of LA thrombus in AF. Further studies should evaluate whether determination of MPAs in clinical routine may suffice to indicate the presence of LA thrombus in patients with AF.
Asunto(s)
Fibrilación Atrial/complicaciones , Plaquetas/metabolismo , Cardiopatías/diagnóstico , Cardiopatías/etiología , Activación Plaquetaria , Trombosis/diagnóstico , Trombosis/etiología , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/etiología , Biomarcadores , Ligando de CD40/metabolismo , Ecocardiografía Transesofágica , Femenino , Productos de Degradación de Fibrina-Fibrinógeno , Atrios Cardíacos/patología , Atrios Cardíacos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Selectina-P/sangre , Agregación Plaquetaria , Curva ROCRESUMEN
Aims: It is hypothesized that inflammation could promote structural and electrical remodelling processes in atrial fibrillation (AF). Atrial infiltration of monocytes and granulocytes has been shown to be dependent on CD11b expression. The aim of this study was to investigate whether treatment of AF by pulmonary vein isolation (PVI) may lead to reduced inflammation, as indicated by a decrease of CD11b expression on monocytes and granulocytes. Methods and results: Flow-cytometric quantification analysis and determination of systemic inflammatory markers of peripheral blood were performed in 75 patients undergoing PVI 1 day before and 6 months after PVI. The extent of activation of monocytes and granulocytes was measured by quantifying the cell adhesion molecule CD11b. The mean expression of CD11b on monocytes (20.9 ± 2.5 vs. 10.2 ± 1.4; P < 0.001) and granulocytes (13.9 ± 1.6 vs. 6.8 ± 0.5; P < 0.001), as well as the relative count of CD11b-positive monocytes (P < 0.05) and CD11b-positive granulocytes (P < 0.01) were significantly reduced when comparing the identical patients before and 6 months after PVI. Systemic inflammatory parameters showed only a declining tendency after 6 months. Patients with unsuccessful PVI and ongoing AF on the day of follow-up showed no decrease in CD11b expression. Conclusions: A significant reduction of CD11b expression on monocytes and granulocytes, as a sign of reduced cellular inflammation, was achieved by treatment of AF using PVI. These data strongly support that AF is not only a consequence of but also a cause for inflammatory processes, which, in turn, may contribute to atrial remodelling.
Asunto(s)
Fibrilación Atrial/cirugía , Antígeno CD11b/metabolismo , Ablación por Catéter , Granulocitos/metabolismo , Mediadores de Inflamación/metabolismo , Monocitos/metabolismo , Venas Pulmonares/cirugía , Potenciales de Acción , Anciano , Fibrilación Atrial/inmunología , Fibrilación Atrial/metabolismo , Fibrilación Atrial/fisiopatología , Remodelación Atrial , Antígeno CD11b/inmunología , Ablación por Catéter/efectos adversos , Regulación hacia Abajo , Femenino , Granulocitos/inmunología , Frecuencia Cardíaca , Humanos , Mediadores de Inflamación/inmunología , Masculino , Persona de Mediana Edad , Monocitos/inmunología , Venas Pulmonares/fisiopatología , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
Atrial fibrillation (AF) is known to cause platelet activation. AF and its degree of thrombogenesis could be associated with monocyte-platelet aggregates (MPAs). We investigated on whether the content of MPAs or other platelet activation markers is associated with the recurrence of AF after pulmonary vein isolation (PVI). A total of 73 patients with symptomatic AF underwent PVI. After 6 months, all patients were evaluated for episodes of AF recurrence. At the same time, flow-cytometric quantification analyses were performed to determine the content of MPAs. Further platelet activation parameters were detected by using either cytometric bead arrays or quantitative immunological determination. Patients with recurrent AF (n = 20) compared to individuals without AF relapse (n = 53) were associated with an increased content of MPAs (43 ± 3% vs. 33 ± 2%, p = 0.004), as well as an increased CD41 expression on monocytes (191 ± 20 vs. 113 ± 6, p = 0.001). The level of the soluble platelet activation markers such as D-dimer, sCD40L, and sP-selectin did not differ between these groups. The content of MPAs correlated weakly with the level of sCD40L (r = 0.26, p = 0.03), but not with sP-selectin and D-dimer, whereas sP-selectin and sCD40L correlated with each other (r = 0.38, p = 0.001). Only the cellular marker of platelet activation, the content of MPAs, was increased in patients with recurrent AF after PVI. In contrast, soluble markers remained unaltered. These data indicate a distinct mechanism and level of platelet activation in AF. The clinical relevance of MPAs in identifying AF recurrence or in guiding the therapy with anticoagulants remains to be elucidated.
Asunto(s)
Fibrilación Atrial/etiología , Activación Plaquetaria/fisiología , Venas Pulmonares/fisiopatología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , RecurrenciaRESUMEN
BACKGROUND: A strong interdependence is known between atrial fibrillation (AF), inflammation and thrombogenesis. Monocyte-platelet aggregates (MPAs) are sensitive markers of platelets and monocyte activation. It is not known whether MPAs are associated with thrombogenicity in AF. Therefore, we examined differences in the content of MPAs and CD11b expression in patients with AF in dependence of the presence of atrial thrombus formation. METHODS: 107 patients with symptomatic AF underwent transesophageal echocardiography (TEE) before planned cardioversion or pulmonary vein isolation. Flow-cytometric quantification analysis was done on the day of performed TEE to determine the content of MPAs and the expression of CD11b on monocytes and granulocytes. RESULTS: Compared to patients without thrombus (n = 80) those with an echocardiographic proven left atrium (LA) thrombus (n = 27) showed an increased extent of the risk factors age, diabetes and heart failure. The content of MPAs (147 ± 12 vs. 311 ± 29 cells/µl, p < 0.001) as well as the CD11b expression on monocytes (p < 0.05) and granulocytes (p < 0.05) were strongly associated with the existence of a LA thrombus. The content of MPAs and the CD11b expression remained independent predictors for LA thrombus after adjustment in logistic regression analysis and negatively correlated with left atrial appendage flow velocity. MPAs above 170 cells/µl (OR 34.2, p = 0.01) had a sensitivity of 96 % and a specificity of 73 % for predicting LA-thrombus. CONCLUSIONS: The content of MPAs and the CD11b expression on monocytes and granulocytes are increased in AF-patients with proven thrombus formation. They seem to be appropriate biomarkers for stratification of thromboembolic risk in patients with AF.