Dislodged Coronary Artery Stent Retrieved With an Endovascular Snare.

Advances in stent design and technology have made stent loss during percutaneous coronary intervention rare. When stent loss occurs, the risk of life-threatening procedural complications is high. We describe the use of an endovascular snare system to retrieve a dislodged stent from the proximal right coronary artery of a 54-year-old man during percutaneous coronary intervention after other conventional retrieval techniques had failed.

Biostial iatrogenic coronary artery stenosis: a rare complication of aortic valve surgery successfully treated with percutaneous coronary stenting.

A 66-year-old woman presented 4 months after conventional surgical aortic valve replacement with an acute coronary syndrome resulting from rare iatrogenic biostial left main and right coronary artery stenoses, which were successfully treated with percutaneous coronary stenting, optimized by intracoronary imaging.

Initial experience of a large, self-expanding, and fully recapturable transcatheter aortic valve: The UK & Ireland Implanters' registry.

OBJECTIVES: The UK & Ireland Implanters' registry is a multicenter registry which reports on real-world experience with novel transcatheter heart valves. BACKGROUND: The 34 mm Evolut R transcatheter aortic valve is a self-expanding and fully recapturable transcatheter aortic valve, designed to treat patients with a large aortic annulus. METHODS: Between January 2017 and April 2018, clinical, procedural and 30-day outcome data were prospectively collected from all patients receiving the 34 mm Evolut R valve across 17 participating centers in the United Kingdom and Ireland. The primary efficacy outcome was the Valve Academic Research Consortium-2(VARC-2)-defined endpoint of device success. The primary safety outcome was the VARC-2-defined composite endpoint of early safety at 30 days. RESULTS: A total of 217 patients underwent attempted implant. Mean age was 79.5 ± 8.8 years and Society of Thoracic Surgeons Predicted Risk of Mortality Score 5.2% ± 3.4%. Iliofemoral access was used in 91.2% of patients. Device success was 79.7%. Mean gradient was 7.0 ± 4.6 mmHg and effective orifice area 2.0 ± 0.6 cm2 . Paravalvular regurgitation was more than mild in 7.2%. A new permanent pacemaker was implanted in 15.7%. Early safety was demonstrated in 91.2%. At 30 days, all-cause mortality was 3.2%, stroke 3.7%, and major vascular complication 2.3%. CONCLUSIONS: Real-world experience of the 34 mm Evolut R transcatheter aortic valve demonstrated acceptable procedural success, safety, valve function, and incidence of new permanent pacemaker implantation.

Incidental finding of giant pericardial lipoma.

We describe a patient with an incidental finding of a large mass adjacent to the heart detected on a screening CT scan. The differential diagnosis included primary and secondary tumours of the heart. Subsequent investigation with trans-thoracic echocardiogram and cardiac MRI confirmed a diagnosis of a giant pericardial lipoma, one of the common benign primary cardiac tumours.

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)

Free Light Chains in patients with acute coronary syndromes: Relationships to inflammation and renal function.

AIMS: We assessed changes of serum combined free immunoglobulin light chains (cFLC) levels, which are associated with increased all-cause mortality, in ST-elevation myocardial infarction (STEMI) in relation to inflammation and renal function indices. METHODS: cFLC were measured in 48 patients with STEMI on days 1, 3, 7 and 30 with assessment of their relationships with monocyte subsets, high sensitivity C-reactive protein (hsCRP), and cystatin C. Day 1 levels in STEMI patients were compared to 40 patients with stable coronary artery disease, and 37 healthy controls. RESULTS: There were no significant differences in cFLC levels between the study groups. In STEMI patients, cFLC values peaked on day 7 post-MI and remained elevated on day 30 (p<0.001 vs. day 1 for both). hsCRP concentrations peaked on day 3 of STEMI followed by their gradual reduction to the levels seen in the controls (p<0.001). In STEMI cFLC correlated with cystatin C (r=0.55, p<0.001), and negatively correlated with counts of CD14++CD16- monocytes (r=-0.55, p<0.001). On multivariate Cox regression analysis, cFLC concentrations were associated with increased need for future percutaneous coronary intervention (PCI) (p=0.019). CONCLUSION: cFLC levels increase during STEMI with peak values on day 7 after presentation and predict the need for future PCI.

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.

Small-size circulating microparticles in acute coronary syndromes: relevance to fibrinolytic status, reparative markers and outcomes.

BACKGROUND: Recent evidence suggests that circulating microparticles (MPs) contribute to inflammation, coagulation and vascular injury. Majority of MPs have usually not been included into prior analyses due their small size and limited resolution of conventional equipment. Our aim was to assess levels of MPs of different cellular origin sized below 0.5 µm polystyrene beads, denoted as small-size microparticles (sMP), their relation to markers of cardiovascular repair and their impact on prognosis in patients with acute coronary syndromes (ACS). METHODS: In a cross-sectional study, we initially compared levels of sMP between patients with ST-segment elevation myocardial infarction (STEMI, n = 50), non-STEMI (n = 47), stable coronary artery disease (CAD, n = 40) and healthy individuals (HC, n = 40). In a separate study, the prognostic value of sMP was assessed in patients with non-STEMI (n = 160). Annexin V-binding sMP (sAMP), platelet CD42b(+) sMPs (sPMP), endothelial CD144(+) sMP (sEMP) and monocyte CD14(+) sMP (sMMP) were quantified using high resolution flow cytometry. Endothelial progenitor cells (EPCs) and monocyte expression of scavenger receptors was quantified by flow cytometry. Fibrinolytic factors were measured by ELISA. RESULTS: Counts of sAMP and sEMP were lower in STEMI after PCI (p < 0.001 and p = 0.025, respectively) but not in non-STEMI vs. CAD. sAMP was positively correlated with EPCs in non-STEMI (p < 0.001). Likewise, plasminogen activators negatively correlated with sAMP in non-STEMI and STEMI (p = 0.02 and p = 0.002, respectively). In non-STEMI patients, sEMP and sMMP were independently predictive for future admissions related to heart failure (p = 0.034 and 0.013, respectively) and sPMP for major bleedings (p = 0.002). The sAMP/EPCs ratio was higher in patients (before PCI) compared to STEMI patients. CONCLUSIONS: Small-size MPs could be potentially implicated in the modulation of the post-ACS reparative response to injury, with prognostic implications. Besides, the sAMP/EPCs ratio could reflect a change in the apoptotic/reparative potential, being a putative indicator for vascular repair.

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.

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.

Ethnic differences in macrovascular and microvascular function in systolic heart failure.

BACKGROUND: Endothelial dysfunction is implicated in the pathophysiological features of heart failure (HF), and ethnic differences in the presentation of cardiovascular disease are evident, with an excess seen among South Asians (SAs). However, data on ethnic differences in endothelial function in HF are limited. METHODS AND RESULTS: In a cross-sectional study, we recruited 128 subjects with systolic HF: 50 SAs, 50 whites, and 28 African Caribbeans (ACs). In addition, SAs with systolic HF were compared with 40 SAs with coronary artery disease without HF ("disease controls") and 40 SA healthy controls. Macrovascular endothelial function was assessed by measurement of flow-mediated dilation (FMD) in response to hyperemia, arterial stiffness was assessed by the pulse-wave velocity, and microvascular endothelial function was assessed by forearm laser Doppler flowmetry. CD144-expressing endothelial microparticles were measured by flow cytometry. When compared with disease controls and healthy controls, SAs with HF had an impaired microvascular response to acetylcholine (P=0.001) and reduced FMD (P<0.001). In comparing ethnic groups, SAs with HF had an impaired response to acetylcholine (123±95.5%) compared with whites (258±156%) and ACs (286±173%, P<0.001 for both). Whites had a higher FMD (8.49±4.63%) than SAs (4.76±4.78%, P<0.001) and ACs (4.55±3.56%, P=0.01). No difference in endothelial-independent response was observed between study groups or in pulse-wave velocity. Ethnicity remained associated with microvascular endothelial function even after adjustment for age, presence of hypertension and diabetes mellitus, blood pressure, and glucose levels (P=0.003). There were no differences in numbers of endothelial microparticles. CONCLUSIONS: The SAs with HF have impaired microvascular and macrovascular endothelial function but preserved arterial elastic properties. Significant ethnic differences in endothelial function are evident in subjects with HF, with ethnicity being associated with microvascular endothelial dysfunction in this disorder.

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.