Micropartículas de pequeño tamaño como indicadores del estado agudo en la insuficiencia cardiaca sistólica / Small-size microparticles as indicators of acute decompensated state in ischemic heart failure

Introducción y objetivos. Las micropartículas son marcadores de la activación celular y la apoptosis y podrían aportar una información muy valiosa e inasequible con los datos clínicos. En este estudio se evalúa la relación clínica y biológica entre las micropartículas de pequeño tamaño presentes en diferentes formas de la insuficiencia cardiaca sistólica isquémica y los marcadores de la inflamación y la reparación. Métodos. Se compararon 49 pacientes con insuficiencia cardiaca aguda, 39 con insuficiencia cardiaca estable y 25 pacientes con enfermedad coronaria estable. Se cuantificaron las micropartículas de pequeño tamaño mediante citometría de flujo de alta resolución. Se analizaron también tres subpoblaciones monocitarias diferentes y su expresión de receptores barredores de la inflamación y la adhesión empleando un citómetro de flujo convencional. Resultados. El recuento de micropartículas CD144+ de origen endotelial mostró reducción en los grupos con insuficiencia cardiaca (p = 0,008). Se observó que el recuento de micropartículas unidas a anexina V aumentaban en la insuficiencia cardiaca (p = 0,024) y en los pacientes con peor clase funcional (p = 0,013). El recuento de micropartículas CD42b+ de origen plaquetario presentaron una correlación positiva con la fracción de eyección del ventrículo izquierdo (p = 0,006), y los de micropartículas unidas a anexina V presentaron correlación positiva con la concentración de interleucina 6 en la insuficiencia cardiaca estable (p = 0,034). En el estado agudo, el recuento de micropartículas unidas a anexina V mostró intensa correlación con la expresión del receptor toll-like-4 en todos los subgrupos de monocitos (p < 0,01 en todos los casos). Tres meses después del ingreso por insuficiencia cardiaca aguda, el recuento de micropartículas unidas a anexina V tenía correlación positiva con los receptores de interleucina 6, CD163 y CD204 (p < 0,05 en todos los casos). Conclusiones. El recuento de micropartículas unidas a anexina V es una valiosa característica distintiva del estado agudo descompensado en la insuficiencia cardiaca sistólica. La relación observada entre las micropartículas de pequeño tamaño unidas a anexina V y los receptores barredores respalda su intervención en la progresión de la respuesta aguda a la lesión y, por lo tanto, su contribución en la patogenia de la insuficiencia cardiaca aguda descompensada (AU)

Introduction and objectives. Microparticles are markers for cell activation and apoptosis and could provide valuable information that is not available from clinical data. This study assesses the clinical and biological relationship of small-sized microparticles in different forms of ischemic systolic heart failure and their relation to markers of inflammation and repair. Methods. We compared 49 patients with acute heart failure, 39 with stable heart failure and 25 patients with stable coronary artery disease. Small-size microparticles counts were determined by high-resolution flow cytometry. Moreover, 3 different monocyte subpopulations and their expression of inflammatory and adhesive scavenger receptors were analyzed using a conventional flow cytometer. Results. Endothelial CD144+ microparticle counts were decreased in heart failure groups (P = .008). Annexin V-binding microparticle counts were found increased in heart failure (P = .024) and in patients with lower functional class (P = .013). Platelet CD42b+ microparticle counts positively correlated with left ventricular ejection fraction (P = .006), and annexin V-binding microparticle counts with interleukin-6 levels in stable heart failure (P = .034). Annexin V-binding microparticle counts in the acute status strongly correlated with toll-like receptor-4 expression on all monocyte subsets (all P < .01). Three months after admission with acute heart failure, annexin V-binding microparticle counts were positively correlated with receptors for interleukin-6, CD163 and CD204 (all P < .05). Conclusions. Annexin V-binding microparticle counts constitute valuable hallmarks of acute decompensated state in systolic heart failure. The observed relationship between small-size annexin V-binding microparticles and scavenger receptors supports their involvement in the progression of the acute response to injury, and thus their contribution to the pathogenesis of acute decompensated heart failure (AU)

Small-size Microparticles as Indicators of Acute Decompensated State in Ischemic Heart Failure.

INTRODUCTION AND OBJECTIVES: Microparticles are markers for cell activation and apoptosis and could provide valuable information that is not available from clinical data. This study assesses the clinical and biological relationship of small-sized microparticles in different forms of ischemic systolic heart failure and their relation to markers of inflammation and repair. METHODS: We compared 49 patients with acute heart failure, 39 with stable heart failure and 25 patients with stable coronary artery disease. Small-size microparticles counts were determined by high-resolution flow cytometry. Moreover, 3 different monocyte subpopulations and their expression of inflammatory and adhesive scavenger receptors were analyzed using a conventional flow cytometer. RESULTS: Endothelial CD144+ microparticle counts were decreased in heart failure groups (P=.008). Annexin V-binding microparticle counts were found increased in heart failure (P=.024) and in patients with lower functional class (P=.013). Platelet CD42b+ microparticle counts positively correlated with left ventricular ejection fraction (P=.006), and annexin V-binding microparticle counts with interleukin-6 levels in stable heart failure (P=.034). Annexin V-binding microparticle counts in the acute status strongly correlated with toll-like receptor-4 expression on all monocyte subsets (all P<.01). Three months after admission with acute heart failure, annexin V-binding microparticle counts were positively correlated with receptors for interleukin-6, CD163 and CD204 (all P<.05). CONCLUSIONS: Annexin V-binding microparticle counts constitute valuable hallmarks of acute decompensated state in systolic heart failure. The observed relationship between small-size annexin V-binding microparticles and scavenger receptors supports their involvement in the progression of the acute response to injury, and thus their contribution to the pathogenesis of acute decompensated heart failure.

Monocyte subsets in coronary artery disease and their associations with markers of inflammation and fibrinolysis.

AIMS: The multiple roles of monocytes in atherogenesis, including inflammation, angiogenesis and repair are attributed to the existence of different monocyte sub-populations. Scarce data are available on changes in phenotype and functional status of human monocyte subsets in patients with coronary artery disease (CAD), especially when monocytes are evaluated as three distinct subsets. METHODS AND RESULTS: Surface expression of receptors implicated in inflammation, repair and activation status (intracellular IKKß) of monocyte subsets was assessed by flow cytometry in 53 patients with CAD and compared to 50 age- and sex-matched healthy controls. Monocyte subsets were defined as CD14++CD16-CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2), and CD14+CD16++CCR2- (Mon3). Plasma levels of inflammatory cytokines (FACSArray) and fibrinolytic factors (ELISA) were measured in CAD. CAD was associated with reduced expression of CD14 on Mon1 (p = 0.02) and Mon3 (p = 0.036), higher expression of IL6 receptor on Mon1 (p = 0.025) and Mon2 (p = 0.015), CXCR4 on Mon1 (p = 0.035) and Mon3 (p = 0.003), and CD34 on all subsets (all p < 0.007). Monocyte CD163 expression correlated negatively with interleukin (IL)-6 levels (p < 0.01 for all subsets). Expression of vascular endothelial growth factor receptor-1 correlated positively with plasminogen activator inhibitor (PAI)-1 antigen levels (r = 0.47, p = 0.006). In vitro, monocyte subsets derived from CAD patients showed significantly altered responses to endotoxin stimulation compared to monocytes from healthy controls. CONCLUSIONS: There is a complex interplay between phenotype and activity of monocytes and plasma cytokines and fibrinolytic factors. These findings support the presence of unique roles for the three human monocyte subsets in atherogenesis and CAD pathogenesis.

Increased expression of cell adhesion molecule receptors on monocyte subsets in ischaemic heart failure.

The objective of this study was to evaluate the expression of cell adhesion molecule (CAM) receptors (integrins) on monocyte subsets in heart failure (HF) and examine their prognostic implication.Increased levels of soluble CAMs have been observed in patients with HF, but the precise mechanism of monocyte adhesion to the vascular endothelium remains unknown. Patients with acute HF (AHF, n=51) were compared to those with stable HF (SHF, n=42) and stable coronary artery disease (CAD, n=44) without HF. Expression of integrins-receptors to intercellular adhesion molecule-1 (ICAM-1R) and vascular CAM-1 (VCAM-1R) on monocyte subsets was assessed by flow cytometry. Monocyte subsets were defined as CD14++CD16-CCR2+ ('classical', Mon1), CD14++CD16+CCR2+ ('intermediate', Mon2), and CD14+CD16++CCR2- ('non-classical', Mon3). Compared to patients with SHF, those with AHF had significantly higher expression of ICAM-1R on Mon2 (p=0.01). Compared to those with stable CAD, patients with SHF had a significantly higher expression of ICAM-1R on Mon2 (p=0.025).Compared to SHF, patients with AHF had a similar expression of VCAM-1R on both Mon1 and Mon3 but significantly higher expression on Mon2 (p=0.019). There were no significant differences between SHF and CAD in monocyte expression of VCAM-1R. In multivariate Cox regression analysis, VCAM-1R expression on Mon2 was associated with adverse clinical outcome (death or rehospitalisation) in AHF [HR 1.07 (1.01-1.14), p=0.029]. In conclusion, HF is associated with increased monocyte expression of integrins-receptors to both ICAM-1 and VCAM-1, being particularly linked to Mon2 subset. Expression of VCAM-1R on Mon2 may have prognostic value in patients with AHF.

Receptors to interleukin-6 and adhesion molecules on circulating monocyte subsets in acute myocardial infarction.

The role of individual monocyte subsets in inflammation and recovery post-myocardial infarction (MI) is insufficiently understood. It was the objective of this study to evaluate the dynamics of monocyte expression of receptors to vascular cell adhesion molecule (VCAM-1r), intercellular adhesion molecule (ICAM-1r), and interleukin-6 (IL-6r) following MI and their relation to inflammatory cytokines, fibrinolytic factors and annexin V-binding microparticles. Expression of VCAM-1r, ICAM-1r, IL-6r on CD14++CD16-(Mon1), CD14++CD16+(Mon2), CD14+CD16++(Mon3) monocyte subsets were quantified by flow cytometry in patients with ST-elevation MI (STEMI, n=50), non-STEMI (n=48) and stable coronary artery disease (n=40). In STEMI, parameters were measured on days 1, 3, 7, 30. On admission with STEMI, VCAM-1r expression was reduced on Mon1 (p=0.007), Mon2 (p=0.036), Mon3 (p=0.005), whilst in NSTEMI there was significant up-regulation of expression by Mon2 (p=0.024) and Mon3 (p=0.049). VCAM-1r on Mon1 correlated positively with plasma IL-1ß levels (p=0.001). IL-6r was reduced on Mon2 in acute STEMI, with upregulation of the receptor on Mon1 and Mon2 during follow-up. IL-6r density correlated negatively with plasma levels of tissue-type plasminogen activator (p=0.0005 for Mon1, p=0.001 for Mon2 and Mon3), and positively with annexin V-binding microparticles (p=0.03 for Mon1, p=0.005 for Mon2 and p=0.005 for Mon3). There was no change in monocyte ICAM-1r expression. In conclusion, expression of IL-6r and VCAM-1r is reduced on circulating monocyte subsets involved in inflammatory responses in STEMI. This may represent a regulatory feed-back mechanism aiming to re-balance the marked inflammation which is typically present following acute MI or selective homing of monocytes with high receptor expression to damaged myocardium.

CXCR4 positive and angiogenic monocytes in myocardial infarction.

Limited data are available on the role of monocytes in cardiac repair. In the present study, we evaluated the dynamic alterations of monocytes with reparative and angiogenic potential in patients with myocardial infarction(MI). Reparative CXCR4+ monocytes, and CD34+ and KDR+ monocytes with angiogenic potential derived from individual monocyte subsets were quantified by flow cytometry in patients with ST-elevation MI (n=50) and stable coronary artery disease (CAD, n=40). Parameters were measured on days 1, 3, 7 and 30 post MI. Monocyte subsets were defined as CD14++CD16-CCR2+ ('classical', Mon1), CD14++CD16+CCR2+ ('intermediate', Mon2), CD14+CD16++CCR2- ('non-classical', Mon3). Plasma levels of inflammatory cytokines, fibrinolytic factors and microparticles (MPs) were assessed on day 1. CXCR4+ and KDR+ monocytes were increased following MI, being more prominently associated with Mon2 (median[IQR] of CXCR4+ Mon2 60[25-126] per µl in STEMI vs. 27[21-41] per µl in stable CAD). The counts of CXCR4+ Mon2 in STEMI significantly reduced by day 30 of follow-up (27[18-47], p<0.001). Expression of the pro-reparative scavenger receptor CD163 on Mon3 was reduced in acute MI (p=0.008), and on other subsets later during the follow-up with lowest levels at day 3 post-MI (p<0.001 for Mon1, p=0.02 for Mon2). CD204 expression on Mon1 correlated with tissue type plasminogen activator levels (r=0.46, p=0.001). Interleukin(IL)6 levels correlated with counts of Mon2-derived CXCR4+ and KDR+ cells. Interleukin-1ß correlated with KDR+ Mon2 counts. IL10 correlated with CXCR4+ Mon2 levels. Low count of CXCR4+ Mon2 and low CD163 expression by Mon2 were associated with higher ejection fraction six-weeks after MI. In conclusion, the Mon2 subset has the most prominent role in the observed changes in reparative monocytes in MI. The association of reparative monocytes with inflammatory/fibrinolytic markers indicates a complex interplay of these cells in the post-MI state.

Increased formation of monocyte-platelet aggregates in ischemic heart failure.

BACKGROUND: Cross-talk between monocytes and platelets is reflected by the formation of monocyte-platelet aggregates (MPAs). It is not known whether MPAs are affected in heart failure (HF), and we examined differences in patients with acute HF (AHF), stable HF (SHF), stable coronary artery disease (CAD) without HF, and healthy controls (HCs). METHODS AND RESULTS: MPAs were analyzed by flow cytometry for the 3 monocyte subsets (CD14++CD16-CCR2+ [Mon1], CD14++CD16+CCR2+ [Mon2] and CD14+CD16++CCR2- [Mon3]) in patients with AHF (n=51), SHF (n=42), stable CAD (n=44), and HCs (n=40). Counts of total MPA and MPAs associated with Mon1 and Mon2 were significantly higher in AHF compared with SHF, CAD, and HCs (P<0.001 for all). The proportion of Mon1 aggregated with platelets was increased in AHF compared with SHF (P=0.033), CAD (P<0.001), and HCs (P<0.001). A higher percentage of Mon3 aggregated with platelets was also seen in AHF compared with SHF (P=0.012) and HCs (P<0.001) but not compared with CAD (P=0.647). MPAs associated with Mon2 were significantly lower in patients who experienced adverse clinical outcomes of death or rehospitalization compared with those who remained free of events (P=0.03). Mon2 count remained an independent negative predictor of combined death and rehospitalization after adjustment for age, left ventricular ejection fraction, creatinine, and brain natriuretic peptide (hazard ratio, 0.58 [95% CI, 0.34-0.98]; P=0.043). CONCLUSIONS: MPA formation in patients with both acute and stable HF is increased and seems to be confined to monocytes from Mon1 and Mon2 subsets. MPAs associated with Mon2 seem to be negatively predictive of a worse prognosis in AHF.

CD14++CD16+ monocytes in patients with acute ischaemic heart failure.

BACKGROUND: Monocytes play important roles in inflammation, angiogenesis and tissue repair and may contribute to the pathophysiology of heart failure (HF). OBJECTIVES: We examined differences in monocyte subset numbers and expression of cell surface markers of activation (CD14) and chemotaxis (CCR2) in patients with acute HF (AHF), stable HF (SHF), and controls and evaluated their impact on clinical outcomes. METHODS: Three monocyte subsets [CD14++CD16-CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2) and CD14+CD16++CCR2- (Mon3)] were analysed by flow cytometry in 51 patients with AHF, 42 patients with SHF, 44 patients with stable coronary artery disease and without HF (CAD) and 40 healthy controls (HC). The prognostic impact of monocyte subsets was examined in AHF. RESULTS: Patients with AHF had significantly higher Mon1 counts compared to the three control groups (P < 0·001 for all). Similarly, Mon2 levels were increased in AHF compared to SHF (P = 0·004) and CAD (P < 0·001) and increased in SHF vs. CAD (P = 0·009). There were no differences in Mon3 counts between the groups. Twenty patients (39·2%) with AHF reached the primary end-point of death or re-hospitalisation, and after adjustment for confounders, Mon2 count remained negatively associated with a combined end-point of death and re-hospitalisation [hazard ratio (per 10 cells/µL): 0·79; confidence interval: 0·66-0·94; P = 0·009]. CONCLUSIONS: Mon2 counts are increased in patients with both acute and stable HF, with enhanced expression of surface markers of activation (CD14) and chemotaxis (CCR2). This subset was also associated with an adverse prognosis in patients with AHF.

A contemporary view on endothelial function in heart failure.

The assessment of different aspects of endothelial dysfunction in cardiovascular medicine in general and in heart failure (HF) has been the focus of intense research, and includes vasomotor, haemostatic, antioxidant, and inflammatory activities. Differences also exist in the pattern of endothelial dysfunction depending on aetiology, severity, and stability of HF in individual patients. In the majority of patients with ischaemic aetiology of HF, endothelial dysfunction is systemic in its nature and involves both arteries and veins, conductance vessels and microvascular beds, coronary, pulmonary, and peripheral vessels. The pattern of endothelial dysfunction is more heterogeneous in non-ischaemic HF, with fewer features of systemic abnormalities. Indeed, many subjects with non-ischaemic HF have a functionally preserved endothelium in peripheral arteries, with endothelial dysfunction seen only in coronary vessels. Endothelial dysfunction has significant prognostic value in HF, but its clinical application is hampered by methodological limitations in its assessment. Various medications (including angiotensin-converting enzyme inhibitors and statins) and regular physical activity have been shown to improve endothelial function in HF. However, there are still no pharmaceutical agents specifically targeting the vascular endothelium. Despite the large number of studies, the pathophysiological role of the vascular endothelium and its clinical potential as a therapeutic target has not yet been sufficiently developed and undoubtedly awaits further exploration.

Anticoagulation versus placebo for heart failure in sinus rhythm.

BACKGROUND: Patients with chronic heart failure (heart failure) are at risk of thromboembolic events, including stroke, pulmonary embolism and peripheral arterial embolism, whilst coronary ischaemic events also contribute to the progression of heart failure. Long-term oral anticoagulation is established in certain groups, including patients with heart failure and atrial fibrillation, but there is wide variation in the indications and use of oral anticoagulation in the broader heart failure population. OBJECTIVES: To determine whether long-term oral anticoagulation reduces total deaths and/or major thromboembolic events in patients with heart failure. SEARCH METHODS: We updated the searches in February 2010 on CENTRAL on The Cochrane Library (Issue 1, 2010), MEDLINE (2000 to February 2010) and EMBASE (1998 to February 2010). Reference lists of papers and abstracts from national and international cardiovascular meetings were studied to identify unpublished studies. Relevant authors were contacted to obtain further data. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing oral anticoagulants with placebo in adults with heart failure, and with treatment duration at least one month. Non-randomised studies were also included for assessing side-effects. Inclusion decisions were duplicated, disagreement resolved by discussion or a third party. DATA COLLECTION AND ANALYSIS: Four review authors independently assessed trials for inclusion and assessed the risks and benefits from antithrombotic therapy using relative measures of effects, such as odds ratio, accompanied with 95% confidence intervals. MAIN RESULTS: Two RCTs were identified. One compared warfarin, aspirin and no antithrombotic therapy and the second compared warfarin with placebo in patients with idiopathic dilated cardiomyopathy. Three small prospective controlled studies of warfarin in heart failure were also identified, but were over 50 years old with methods not considered reliable by modern standards. In both WASH 2004 and HELAS 2006, there were no significant differences in the incidence of myocardial infarction, non-fatal stroke and death between patients taking oral anticoagulation and placebo. Four retrospective non-randomised cohort analyses and four observational studies of oral anticoagulation in heart failure included differing populations of heart failure patients and reported contradictory results. AUTHORS' CONCLUSIONS: Based on the two major randomised trials (HELAS 2006; WASH 2004), there is no convincing evidence that oral anticoagulant therapy modifies mortality or vascular events in patients with heart failure and sinus rhythm. Although oral anticoagulation is indicated in certain groups of patients with heart failure (for example atrial fibrillation), the data available does not support its routine use in heart failure patients who remain in sinus rhythm. A large randomised trial of warfarin in heart failure patients in sinus rhythm is currently in progress and data from this trial will be a useful addition to this topic.

Fibrinolytic status in acute coronary syndromes: evidence of differences in relation to clinical features and pathophysiological pathways.

Limited data are available on the role of innate fibrinolysis in acute coronary syndromes (ACS). In the present study we evaluated the dynamic alterations of fibrinolytic markers in patients presenting with ACS. Tissue-type-(tPA) and urokinase type-(uPA) plasminogen activators, plasminogen activator inhibitor (PAI-1) antigen and activity and thrombin activatable fibrinolysis inhibitor (TAFI) were analysed in 50 patients with ST elevation myocardial infarction (STEMI), 47 non-STEMI patients (NSTEMI), 40 patients with stable coronary artery disease (CAD) and 39 controls. The parameters were measured on day 1 and days 3, 7 and 30. Counts of monocyte subsets, monocyte-platelet aggregates and plasma inflammatory cytokines were assessed on admission. On day 1, TAFI was higher in NSTEMI vs. STEMI (p<0.001) while PAI-1 activity was higher in STEMI (p<0.001). In STEMI, uPA activity levels was low on day 1 but significantly increased on day 30 (p<0.001). TAFI levels were increased in NSTEMI on day 1 and gradually reduced by day 30 (p<0.05). In STEMI, TAFI levels peaked at day 7 (p<0.05) and dropped significantly by day 30 (p<0.05). CD14++CD16+ monocytes were independently associated with PAI-1 activity in ACS (p=0.03). Monocyte-platelet aggregates rather than platelet-free monocytes were an independent determinant of tPA, PAI-1 antigen and TAFI on a multivariate analysis (p<0.05). There are significant differences in fibrinolytic activity between patients with STEMI and NSTEMI. These changes could reflect the role of these factors in post-MI myocardial healing. Monocyte-platelet interactions are independently associated with the regulation of the fibrinolytic status in ACS.

The effects of exercise and diurnal variation on monocyte subsets and monocyte-platelet aggregates.

BACKGROUND: Monocytes are important mediators in the pathophysiology of cardiovascular disease, but only scarce data are available on biological and methodological factors affecting their levels. DESIGN: Three monocyte subsets, CD14(++) CD16(-) CCR2+ (Mon1), CD14(++) CD16(+) CCR2(+) (Mon2), CD14(+) CD16(+) CCR2(-) (Mon3), and monocyte-platelet aggregates (MPAs) were analysed by flow cytometry. The effects of treadmill exercise were assessed on 12 healthy volunteers. Diurnal variation was evaluated in 16 healthy volunteers, and the effects of delayed blood processing were measured in 12 samples. RESULTS: Mon1 were increased when measured 15 min after exercise followed by a reduction at 1 h (P < 0·05 for both). MPAs were significantly reduced at 15 min and 1 h (P < 0·05 for both). There was significant diurnal variation in the numbers of Mon2, which were highest at 6 pm and lowest at 6 am. There were also significant diurnal variations in phagocytic activity of Mon1 and Mon2, which were highest at 12 pm and lowest at 12 am. Monocyte counts remained stable up to 2 h after venipuncture. MPAs were significantly increased at 2 h and increased further by 4 h after sampling. CONCLUSIONS: Monocyte subset Mon2 and monocyte phagocytic activity undergo significant diurnal variation. A single bout of exercise causes a temporal increase in monocytes and a reduction in MPAs. Monocyte subset counts should be analysed within 2 h of blood sampling, whereas measurement of MPAs and monocyte CD14 and CD16 expression should be performed within 1 h.

The role of monocytes and inflammation in the pathophysiology of heart failure.

There is growing evidence to support an important role of inflammation in the underlying pathophysiology of heart failure (HF). Indeed, inflammatory cytokine levels are well recognized to be increased in patients with left ventricular dysfunction and appear to have prognostic implications. Monocytes play a pivotal role in the inflammatory cascade and are a major source of both pro- and anti-inflammatory cytokines. They are intimately involved in tissue damage and repair and an imbalance of these processes may have detrimental consequences for the failing myocardium. Importantly, monocytes comprise of distinct subsets with different cell surface markers and functional characteristics and this heterogeneity may be important in understanding their specific role in HF. In HF, monocyte activation involves interplay between pattern recognition molecules, endotoxins, cytokines, and acute phase proteins. Activated monocytes migrate to the myocardium in response to powerful chemokines, where they must then attach to the endothelial wall before infiltrating into the myocardium itself. This review article aims to discuss the role of monocytes and inflammation in HF, focusing on monocyte activation, mobilisation, recruitment and endothelial adherence, as well as the effects they may have on myocardial performance. The therapeutic modulation of inflammation and monocyte activation in HF treatment will also be reviewed.

Antithrombotic therapy in anticoagulated patients with atrial fibrillation presenting with acute coronary syndromes and/or undergoing percutaneous coronary intervention/stenting.

The management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary inter vention/stenting cannot be done according to a regimented common protocol, and stroke and bleeding risk stratification schema should be employed to individualize treatment options. A delicate balance is needed between the prevention of thromboembolism, against recurrent cardiac ischemia or stent thrombosis, and bleeding risk. New guidance from a consensus document of the European Society of Cardiology Working Group on Thrombosis, endorsed by the European Heart Rhythm Association and the European Association of Percutaneous Cardiovascular Interventions on the management of Antithrombotic Therapy in Atrial Fibrillation Patients Presenting with Acute Coronary Syndrome and/or Undergoing Percutaneous Coronary Intervention/Stenting has sought to clarify some of the major issues and problems surrounding this practice, and will allow clinicians to make much more informed decisions when faced with treating such patients.