Frailty is associated with chronic inflammation and pro-inflammatory monocyte subpopulations.

AIM OF THE STUDY: Frail patients with high grade aortic valve stenosis (AS) undergoing Transcatheter Aortic Valve Implantation (TAVI) have an increased mortality. A connection between frailty and inflammation has been suggested. Monocyte subpopulations are associated with both cardiovascular diseases and chronic inflammatory diseases. This study investigates the association of frailty with monocyte subpopulations and systemic inflammatory parameters in elderly patients undergoing TAVI. METHODS: A total of 120 patients with symptomatic AS was examined. Before TAVI implantation, frailty was assessed by a bedside evaluation (eyeball test). In all patients a flow cytometry analysis has been performed. Monocyte subpopulations were defined as follows: classical (CD14++CD16-), intermediate (CD14++CD16+) and non-classical (CD14+CD16++). Expression of CD11b was measured as a marker for monocyte activation. Pro-inflammatory cytokines such as interleukin IL-8, as well as CRP were measured with Cytometric Bead Array or standard laboratory methods. RESULTS: 28 out of 120 patients were frail. These patients showed both, signs of elevated chronic systemic inflammation reflected by elevated CRP (3.7 (1.4-5.4) vs. 5.9 (3.7-29.1), p = 0.001) and an elevated level of intermediate monocytes (37 (24-54) vs. 53 (47-63), p = 0.001). At 6 months after TAVI, 19 of 120 patients died, primarily without relevant dysfunction of the implanted aortic valve. Mortality was significantly higher in the frail as compared with non-frail patients (9 of 28 frail patients vs. 10 of 92 non frail patients, p < 0.001). A binary logistic regression analysis validated frailty and intermediate monocytes as independent predictors for early mortality after TAVI. CONCLUSION: Chronic systemic inflammation and increased levels of intermediate monocytes are associated with frailty in old patients with severe aortic valve stenosis. Both the syndrome of frailty and elevated intermediate monocytes showed an association with early mortality after TAVI.

[Cardiac arrhythmias in patients with chronic autoimmune diseases]. / Rhythmusstörungen bei chronischen Autoimmunerkrankungen.

Chronic inflammation due to autoimmune diseases is associated with a higher rate of supraventricular and ventricular arrhythmias leading to an increased risk for cardiovascular morbidity and mortality. Involvement of the cardiac conduction system is common in patients with chronic autoimmune diseases, although the penetrance of clinical signs and symptoms is variable and complete heart block with need for therapy is rare. The combination of the increased prevalence of structural cardiovascular disease and the direct impact of inflammatory mechanisms on cardiac electrophysiology seems to be responsible for the higher rate of tachyarrhythmias. In particular, fibroblast activation, gap junction impairment via changes in connexin composition and abnormalities in intracellular calcium-handling are mentioned. Electrocardiographic markers of an increased arrhythmogenic potential in patients with chronic autoimmune disorders may include prolonged P­wave duration as well as abnormal QTc interval and reduced heart rate variability. Thus, minimizing the inflammatory burden through tight control of disease activity may help reduce the arrhythmic load.

Atrial fibrillation is associated with high levels of monocyte-platelet-aggregates and increased CD11b expression in patients with aortic stenosis.

A growing body of evidence suggests a pivotal role of inflammatory processes in AF in a bidirectional manner. Infiltrating leukocytes seem to promote both structural and electrical remodelling processes in patients with AF. Monocyte-platelets-aggregates (MPAs) are sensitive markers of both platelets and monocyte activation. So far it is not clear whether the content of MPAs is affected by AF. The present study examined the content of MPAs and the activation of monocytes in elderly patients with an aortic stenosis in dependence of AF. These patients are known to have a high prevalence of AF. Flow-cytometric quantification analysis demonstrated that patients with AF have an increased content of MPAs (207 ± 13 cells/µl vs 307 ± 21 cells/µl, p< 0.001), and enhanced expression of CD11b on monocytes (p< 0.001), compared to patients in stable sinus rhythm (SR). The number of CD14+/CD16+ monocytes were only slightly elevated in patients with AF. These findings were seen in patients with permanent AF. But also patients with paroxysmal AF, even when presenting in SR, the MPAs were increased by 50 % (p< 0.05) as well as the CD11b expression, which was twice as high (p< 0.05) compared to stable SR. These results demonstrate for the first time a dependency of MPAs and CD11b expression on monocytes in the presence of AF and support the notion of a close relationship between AF, thrombogenesis and inflammation. The content of MPAs and the extent of activation on monocytes appear promising as biomarkers for paroxysmal AF and as possible future targets for developing novel pharmacological therapeutic strategies.

Monocyte-platelet aggregates and CD11b expression as markers for thrombogenicity in atrial fibrillation.

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.