Histopathological Features of Aspirated Thrombi after Primary Percutaneous Coronary Intervention in Patients with ST-Elevation Myocardial Infarction

BACKGROUND: Plaque disruption with superimposed thrombus is the predominant mechanism responsible for the onset of acute coronary syndromes. Studies have shown that plaque disruption and thrombotic occlusion are frequently separated in time. We established the histopathological characteristics of material aspirated during primary percutaneous coronary intervention (PCI) in a large consecutive ST-elevation myocardial infarction (STEMI) population. METHODOLOGY/PRINCIPAL FINDINGS: Thrombus aspiration during primary PCI was performed in 1,362 STEMI patients. Thrombus age was classified as fresh (<1 day), lytic (1-5 days), or organized (>5 day). Further, the presence of plaque was documented. The histopathological findings were related to the clinical, angiographic, and procedural characteristics. Material could be aspirated in 1,009 patients (74%). Components of plaque were found in 395 of these patients (39%). Fresh thrombus was found in 577 of 959 patients (60%) compared to 382 patients (40%) with lytic or organized thrombi. Distal embolization was present in 21% of patients with lytic thrombus compared to 12% and 15% of patients with fresh or organized thrombus. CONCLUSIONS/SIGNIFICANCE: Material could be obtained in 74% of STEMI patients treated with thrombus aspiration during primary PCI. In 40% of patients thrombus age is older than 24 h, indicating that plaque disruption and thrombus formation occur significantly earlier than the onset of symptoms in many patients

Oral vaccination with heat inactivated Mycobacterium bovis activates the complement system to protect against tuberculosis

Tuberculosis (TB) remains a pandemic affecting billions of people worldwide, thus stressing the need for new vaccines. Defining the correlates of vaccine protection is essential to achieve this goal. In this study, we used the wild boar model for mycobacterial infection and TB to characterize the protective mechanisms elicited by a new heat inactivated Mycobacterium bovis vaccine (IV). Oral vaccination with the IV resulted in significantly lower culture and lesion scores, particularly in the thorax, suggesting that the IV might provide a novel vaccine for TB control with special impact on the prevention of pulmonary disease, which is one of the limitations of current vaccines. Oral vaccination with the IV induced an adaptive antibody response and activation of the innate immune response including the complement component C3 and inflammasome. Mycobacterial DNA/RNA was not involved in inflammasome activation but increased C3 production by a still unknown mechanism. The results also suggested a protective mechanism mediated by the activation of IFN-γ producing CD8+ T cells by MHC I antigen presenting dendritic cells (DCs) in response to vaccination with the IV, without a clear role for Th1 CD4+ T cells. These results support a role for DCs in triggering the immune response to the IV through a mechanism similar to the phagocyte response to PAMPs with a central role for C3 in protection against mycobacterial infection. Higher C3 levels may allow increased opsonophagocytosis and effective bacterial clearance, while interfering with CR3-mediated opsonic and nonopsonic phagocytosis of mycobacteria, a process that could be enhanced by specific antibodies against mycobacterial proteins induced by vaccination with the IV. These results suggest that the IV acts through novel mechanisms to protect against TB in wild boar

Group‑wise ANOVA simultaneous component analysis for designed omics experiments

Modern omics experiments pertain not only to the measurement of many variables but also follow complex experimental designs where many factors are manipulated at the same time. This data can be conveniently analyzed using multivariate tools like ANOVA-simultaneous component analysis (ASCA) which allows interpretation of the variation induced by the different factors in a principal component analysis fashion. However, while in general only a subset of the measured variables may be related to the problem studied, all variables contribute to the final model and this may hamper interpretatio

Histopathology of Aspirated Thrombus and Its Association With ST-Segment Recovery in Patients Undergoing Primary Percutaneous Coronary Intervention With Routine Thrombus Aspiration

Background: In patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) with thrombus aspiration, the histopathology of aspirated thrombus was previously related to long-term mortality. In this study, we sought to investigate the association between histopathology of aspirated thrombus and ST-segment recovery, a marker of microvascular dysfunction, immediately at the end of the PCI procedure. Methods: We included 892 STEMI patients who underwent primary PCI with routine thrombus aspiration and for whom combined data on histopathology of aspirated thrombus and ST-segment recovery were available. Patients were categorized according to histopathology of aspirated thrombus: fresh only ( 1 day), or no material aspirated. ST-segment recovery was defined as incomplete if <50%. Results: Incomplete ST-segment recovery occurred in 134 of 363 patients (37%) with fresh thrombus, in 104 of 238 patients (44%) with older thrombus, and in 142 of 291 patients (49%) with no material. Unadjusted odds ratios for incomplete ST-segment recovery of patients with older thrombus and no material, when compared with patients with fresh thrombus, were 1.33 (95% CI, 0.95-1.85; P = 0.097) and 1.63 (95% CI 1.19-2.23; P = 0.002), respectively. Both associations were unchanged after multivariable adjustment for clinical predictors of ST-segment recovery. ST-segment recovery was a strong predictor of long-term mortality, independent of the histopathology of aspirated thrombus. Conclusions: This study shows that ST-segment recovery immediately at the end of the PCI procedure was a significant prognosticator, independent of the histopathology of aspirated thrombus. We found that the histopathology of aspirated thrombus (fresh, older, no material) was associated with ST-segment recovery in STEMI patients undergoing primary PCI with thrombus aspiration. (C) 2010 Wiley-Liss, In

A pattern of disperse plaque microcalcifications identifies a subset of plaques with high inflammatory burden in patients with acute myocardial infarction

Inflammation plays a crucial role in plaque vulnerability. Calcifications can be detected by means of in vivo imaging techniques. The study purpose is to assess a potential association between tissue localization of calcifications and the inflammatory biomarkers, C-reactive protein (CRP), osteopontin and lipoprotein-associated phospholipase A2 (Lp-PLA2), in plaque tissue of patients with acute myocardial infarction (AMI). Thrombectomy materials obtained from patients with electrocardiographically documented ST-segment elevation type of AMI (STEMI) were histologically screened for presence of thrombus, plaque tissues and calcifications. Size of calcifications was measured morphometrically, and their colocalization with the inflammatory biomarkers macrophages, CRP, osteopontin and Lp-PLA2 was assessed with immunostaining. A total of 171 samples containing plaque tissues were obtained from 562 thrombectomy procedures. Calcifications were observed in 67 (39%) plaque fragments, with diameters ranging from 4 to 170 μm. Plaque tissues with calcifications contained more frequently extracellular CRP and intracellular CRP in macrophages than those without calcifications (85%, 59% vs. 64%, 32%, P=0.012 and 0.005 respectively). Similar results were obtained with osteopontin immunostaining (98%, 76% vs. 56%, 40%; P <0.001 both). Furthermore, samples with calcifications were immunostained for CRP more intensely than those without calcifications (P=0.001). Finally, 96% of the plaque tissues stained positively for Lp-PLA2, but there was no association with presence of microcalcifications. A pattern of disperse microcalcifications is positively associated with presence of the inflammatory biomarkers macrophages, CRP and osteopontin in thrombectomy materials of STEMI patients. Based on these findings, we speculate that such microcalcifications could have the potential to serve as a surrogate marker for plaques with high inflammatory burde

Predictors and prognostic consequence of gastrointestinal bleeding in patients with ST-segment elevation myocardial infarction

Limited data are available on the predictors and implications of gastrointestinal (GI) bleeding in ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PPCI) and dual antiplatelet therapy. Predictors of and clinical outcome after GI bleeding were assessed in 2002 STEMI patients undergoing PPCI between 1-1-2003 and 31-07-2008. 139 patients suffered GI bleeding during a median follow-up of 4.9 years. Predictors of GI bleeding were age, history of bleeding, anemia, baseline thrombocytopenia, previous coronary artery bypass grafting, cardiogenic shock, anterior infarction and the use of GP IIb/IIIa inhibitor. By multivariable analysis, a first occurrence of GI bleeding was associated with a twofold increase in risk of subsequent GI bleeding (hazard ratio (HR) 2.19; 95% confidence interval (CI) 1.15-4.17). GI bleeding was not significantly associated with subsequent major adverse cardiac events (HR 1.33; 95% CI 0.98-1.79), cardiac (HR 1.40; 95% CI 0.97-2.02) and all-cause mortality (HR 1.34; 95% CI 0.96-1.85), recurrent MI (HR 0.97; 95% CI 0.58-1.63), stroke (HR 1.26; 95% CI 0.57-2.79) or stent thrombosis (HR 0.71; 95% CI 0.33-1.69). Among STEMI patients undergoing PPCI, the risk of GI bleeding is related to a number of risk factors, including advanced age, previous (GI) bleeding, GP IIB/IIIA inhibitors, anterior infarction and anemia. GI bleeding does not substantially increase the risk of subsequent recurrent ischemic events in STEMI patients undergoing PPCI, whereas the risk of GI bleeding after a first occurrence is more than double

Presence of Older Thrombus Is an Independent Predictor of Long-Term Mortality in Patients With ST-Elevation Myocardial Infarction Treated With Thrombus Aspiration During Primary Percutaneous Coronary Intervention

Background-Routine thrombus aspiration is frequently used during primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction to prevent distal embolization. Recently, evidence of clinical benefit was published. In 50% of the ST-elevation myocardial infarction patients with an onset of symptoms 1 day old. This observation illustrates that plaque rupture and coronary occlusion are significantly separated in time. In the present study, we correlate the presence of fresh versus older thrombus with long-term mortality. Methods and Results-Thrombus aspiration was performed in 1315 patients treated with primary percutaneous coronary intervention with 3 devices (Rescue, Export, and Proxis). Aspirated material was fixed in formalin and processed for histopathology. If possible, thrombus age was classified as either fresh only ( 1 day). We identified fresh thrombus in 552 patients and older thrombus in 372 patients. The cumulative Kaplan-Meier estimate of all-cause mortality at 4 years was significantly higher in patients with older thrombus (16.0%) compared with patients with fresh thrombus (7.4%), with a hazard ratio of 1.82 (95% confidence interval, 1.17 to 2.85; P=0.008). Multivariate analysis identified the presence of older thrombus, in addition to other established predictors, as an independent predictor (hazard ratio, 1.83; 95% confidence interval, 1.14 to 2.93; P=0.01) of long-term mortality. Conclusion-Our study demonstrates that the presence of older thrombus, in addition to other established predictors, is an independent predictor of long-term mortality in patients with ST-elevation myocardial infarction treated with thrombus aspiration during primary percutaneous coronary intervention. (Circulation. 2008; 118: 1810-1816.

Anxiety levels of patients undergoing coronary procedures in the catheterization laboratory

High levels of anxiety are associated with worse outcomes in coronary artery disease patients. Little is known about anxiety levels in patients undergoing coronary procedures. Our objective is to examine the levels of anxiety in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) during the different phases of hospital stay and to evaluate which patient characteristics are associated with increased anxiety. Patients undergoing CAG or PCI between April 2009 and April 2010 were included in this prospective cohort study. Anxiety levels were measured using the self reported Visual Analogue Scale (VAS) of Anxiety, ranging from 0 to 100. VAS anxiety scores were obtained at hospital intake, pre- and post-procedure, and at hospital discharge. Multivariate linear regression analyses were performed to assess correlations between baseline characteristics and anxiety levels at the different time points. In total 2604 patients were included, with 70.4% male participants with a mean age of 65±12years. VAS anxiety scores were highest pre-procedure (44.2±27.0mm). Female patients reported a significantly higher pre procedure VAS anxiety score (50.4±26.5) compared to males (41.5±26.8, p=0.02). Other factors associated with higher levels of anxiety at different time points were age <65years, low level of education and an acute primary PCI. In the largest cohort to date, we examined anxiety among patients undergoing PCI or CAG was highest immediately around the procedure, particularly in patients aged <65years, of female gender, undergoing primary PCI, or with a lower level of education. Better pre-procedural information or pharmacological strategies may reduce anxiety in these patient