CD11b expression on monocytes and data of inflammatory parameters after Transcatheter Aortic Valve Implantation in dependence of early mortality.

An inflammatory systemic reaction is common after Transcatheter Aortic Valve Implantation (TAVI). We recently reported about an involvement of Mon2-monocytes, the CD11b expression on monocytes and parameters of systemic inflammation before TAVI correlating with early mortality after TAVI. Here, we provide data of monocyte subpopulations, CD11b expression and parameters of a systemic inflammation in dependence of three-month mortality after TAVI. With this, we provide further insights into inflammatory mechanism after TAVI. The data were collected by flow-cytometric quantification analyses of peripheral blood in 120 consecutive patients who underwent TAVI (on day 1 and 7 after TAVI). Monocyte-subsets were identified by their CD14 and CD16 expression and monocyte-platelet-aggregates (MPA) by CD14/CD41 co-expression. The extent of monocyte activation was determined by quantification of CD11b-expression (activate epitope). Additionally, pro-inflammatory cytokines such as interleukin (IL)-6, IL-8, C-reactive protein, procalcitonin were measured using the cytometric bead array method or standard laboratory tests. Additionally, we report procedural outcomes in dependence of three-month mortality. Furthermore, correlations of CD11b-expression on monocytes with parameters of platelet activation or further inflammatory parameters are presented. For further interpretation of the presented data, please see the research article "Mon2-Monocytes and Increased CD-11b Expression Before Transcatheter Aortic Valve Implantation are Associated with Earlier Death" by Pfluecke et al.[1].

Mon2-monocytes and increased CD-11b expression before transcatheter aortic valve implantation are associated with earlier death.

BACKGROUND: In the first three months after Transcatheter aortic valve implantation (TAVI), a remarkable number of patients have an unfavorable outcome. An inflammatory response after TAVI is suspected to have negative effects. The exact mechanisms remain unclear. We examined the influence of monocyte subpopulations on the clinical outcome, along with the degree of monocyte activation and further parameters of inflammation and platelet activation. METHODS: Flow-cytometric quantification analyses of peripheral blood were done in 120 consecutive patients who underwent TAVI (one day before TAVI and on day 1 and 7 after TAVI). Monocyte-subsets were defined by their CD14 and CD16 expression, monocyte-platelet-aggregates (MPA) by CD14/CD41 co-expression. The extent of monocyte activation was determined by quantification of CD11b-expression (activation epitope). Additionally, pro-inflammatory cytokines such as interleukin (IL)-6, IL-8, C-reactive protein were measured with the cytometric bead array method or standard laboratory tests. RESULTS: Elevated Mon2 (CD14++CD16+) - monocytes (38 vs. 62 cells/µl, p < 0.001) and a high expression of CD11b prior to TAVI (MFI 50.1 vs. 84.6, p < 0.05) were independently associated with death 3 months after TAVI. Mon2 showed the highest CD11b-expression and CD11b correlated with platelet activation and markers of systemic inflammation. Even CRP and IL-8 before TAVI were associated with death after TAVI. In contrast, a systemic inflammation response shortly after TAVI was not associated with early death. CONCLUSIONS: Elevated Mon2-monocytes and a high level of monocyte activation before TAVI are associated with early mortality after TAVI. Chronic inflammation in aging patients seems to be an important risk factor after TAVI.

Lipoprotein apheresis influences monocyte subpopulations.

BACKGROUND: Monocytes can be differentiated into subpopulations depending on their expression profile of CD14 and CD16. CD16-positive monocytes are associated with coronary artery disease. Up to now, no data exist about the effect of lipoprotein apheresis (LA) on the distribution of monocyte subpopulations. METHODS: 80 patients who underwent LA at the University Hospital Dresden were included in the study. 8 out of the 80 LA patients received LA for the first time at the time point of blood analysis. Six different methods of LA were used (H.E.L.P. n = 8; Liposorber D n = 10; LF n = 14; DALI n = 17; MONET n = 11; Therasorb® LDL n = 12). Blood samples were taken immediately before and after LA and analyzed for CD14 and CD16 expression on monocytes. A total of 42 patients with cardiovascular risk factors but no indication for LA served as control group. RESULTS: The composition of monocyte-population was analyzed in regard to the 3 subpopulations. After LA, an increase in classical monocytes (CD14++CD16-) (93.3% vs. 93.9%, p < 0.01) and a decrease in non-classical monocytes (CD14+CD16+) (1.5% vs 1.0%; p < 0.001) were observed. LA did not change the amount of intermediate monocytes (CD14++CD16+) (5.3% vs. 5.1%). Two methods (MONET and Therasorb® LDL) did not influence the distribution of monocyte subpopulations. Interestingly, patients with LDL-C above 2.5 mmol/l prior LA showed increased amounts of intermediate monocytes. CONCLUSION: The distribution of monocyte populations is influenced by LA but depends on the distinct method of LA. Influences of LA were mainly observed in the content of classical and non-classical monocytes, whereas the intermediate monocyte population remained unaltered by LA.

Intra-aortic balloon pump (IABP) counterpulsation improves cerebral perfusion in patients with decreased left ventricular function.

BACKGROUND: The current goal of treatment after acute ischemic stroke is the increase of cerebral blood flow (CBF) in ischemic brain tissue. Intra-aortic balloon pump (IABP) counterpulsation in the setting of cardiogenic shock is able to reduce left ventricular afterload and increase coronary blood flow. The effects of an IABP on CBF have not been sufficiently examined. We hypothesize that the use of an IABP especially enhances cerebral blood flow in patients with pre-existing heart failure. METHODS: In this pilot study, 36 subjects were examined to investigate the effect of an IABP on middle cerebral artery (MCA) transcranial Doppler (TCD) flow velocity change and relative CBF augmentation by determining velocity time integral changes (ΔVTI) in a constant caliber of the MCA compared to a baseline measurement without an IABP. Subjects were divided into two groups according to their left ventricular ejection fraction (LVEF): Group 1 LVEF >30% and Group 2 LVEF ≤30%. RESULTS: Both groups showed an increase in CBF using an IABP. Patients with a LVEF ≤30% showed a significantly higher increase of ΔVTI in the MCA under IABP augmentation compared to patients with a LVEF >30% (20.9% ± 3.9% Group 2 vs.10.5% ± 2.2% Group 1, p<0,05). The mean arterial pressure (MAP) increased only marginally in both groups under IABP augmentation. CONCLUSIONS: IABP improves cerebral blood flow, particularly in patients with pre-existing heart failure and highly impaired LVEF. Hence, an IABP might be a treatment option to improve cerebral perfusion in selected patients with cerebral misperfusion and simultaneously existing severe heart failure.

High rates of prasugrel and ticagrelor non-responder in patients treated with therapeutic hypothermia after cardiac arrest.

INTRODUCTION: After cardiac arrest due to acute coronary syndromes (ACS) therapeutic hypothermia (HT) is the standard care to reduce neurologic damage. Additionally, the concomitant medical treatment with aspirin and a P2Y12 receptor inhibitor like clopidogrel (Cl), prasugrel (Pr) or ticagrelor (Ti) is mandatory. The platelet inhibitory effect of these drugs under hypothermia remains unclear. METHODS: 164 patients with ACS were prospectively enrolled in this study. 84 patients were treated with HT, 80 patients were under normothermia (NT). All patients were treated with aspirin and one of the P2Y12 receptor inhibitors Cl, Pr or Ti. 24h after the initial loading dose the platelet reactivity index (PRI/VASP-index) was determined to achieve the platelet inhibitory effect. RESULTS: In the HT-group the PRI/VASP-index was significantly higher compared to the NT-group (54.86%±25.1 vs. 28.98%±22.8; p<0.001). In patients under HT receiving Cl, the platelet inhibition was most markedly reduced (HT vs. NT: 66.39%±19.1 vs. 33.36%±22.1; p<0.001) compared to Pr (HT vs. NT: 37.6%±25.0 vs. 27.04%±25.5; p=0.143) and Ti (HT vs. NT: 41.5%±21.0 vs. 17.83%±14.5; p=0.009). The rate of non-responder defined as PRI/VASP-index>50% was increased in HT compared to NT (60.7% vs. 22.5%; p<0.001) with the highest rates in the group receiving Cl (CL: 82% vs. 26%, p<0.001; Pr: 32% vs. 23%; n.s.; Ti: 30% vs. 8%, n.s.). CONCLUSION: The platelet inhibitory effect in patients treated with HT after cardiac arrest is significantly reduced. This effect was most marked with the use of Cl. The new P2Y12-inhibitors Pr and Ti improved platelet inhibition in HT, but could not completely prevent non-responsiveness.

Combined immunosuppressive therapy including a TNF-alpha blocker induces remission in a difficult to treat patient with Takayasu arteriitis and coronary involvement.

A 40 year old woman presented with symptoms of a systemic inflammatory disease and obstruction of the left subclavian artery. Takayasu arteriitis (TA) was clinically diagnosed and confirmed by MR angiography and FDG-PET scan showing inflammation of the aortic arch and the left subclavian artery. Immunosuppression with glucocorticoids and methotrexate resulted in immediate clinical improvement and normalization of systemic markers of inflammation. Despite that the patient developed chest pain on exertion suggesting coronary involvement, which was confirmed by dobutamine stress echocardiography. After adding the TNF-alpha blocker infliximab coronary symptoms gradually improved and a clinically stable situation could be achieved for more than 6 months. Coronary angiography and aortography showed an occluded main stem of the left coronary artery, an occluded left subclavian artery, and stenoses of the brachiocephalic trunk and the left common carotid artery. Revascularization of the coronary artery and the aortic arch and its branches was performed. The patient returned to work two months after the operation. Immunosuppressive therapy with infliximab and methotrexate is continued, glucocorticoids were stopped after one year of treatment. This case shows that vascular progress in TA patients may occur even when systemic inflammation is controlled, therefore patients have to be carefully observed for new vascular manifestations. TNF-alpha blockers may be an additional treatment option in otherwise difficult to treat TA patients allowing to perform revascularization after a stable disease state has been achieved.