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Continued uptake of modified low-density lipoproteins (LDL) by the scavenger receptor, CD68, of activated macrophages is a crucial process in the development of atherosclerotic plaques and leads to the formation of foam cells. Eight-weeks-old male Apolipoprotein E-deficient (ApoE-/-) mice (n=6) were fed a high-fat diet for 12 weeks. C57BL/6J wildtype (WT) mice served as controls (n=6). Positron emission tomography (PET) with an acquisition time of 1800s (NanoPET/CT scanner; Mediso, Hungary & Bioscan, USA) was carried out 24h after intravenous tail vein administration of 50µl 64Cu-CD68-Fc (~20-30µg labeled protein/mouse containing approximately 10-12MBq 64Cu-CD68-Fc per mouse). Three days after PET/CT, all mice received an intravenous administration of 0.2 mmol/kg body weight of a gadolinium-based elastin-binding contrast agent to assess plaque burden and vessel wall remodeling. Two hours after injection, mice were imaged in a 3T clinical MR scanner (Philips Healthcare, Best, NL) using a dedicated single loop surface coil (23mm). Enhanced 64Cu-CD68-Fc uptake was found in the aortic arches of ApoE-/- compared to WT mice (ApoE-/- mice:10.5±1.5Bq/cm³ vs. WT mice: 2.1±0.3Bq/cm³; P=0.002). Higher gadolinium-based elastin-binding contrast agent uptake was also detected in the aortic arch of ApoE-/- compared to WT mice using R¹ maps (R¹=1.47±0.06 s-1 vs. 0.92±0.05 s-1; P <0.001). Radiolabeled scavenger receptor (64Cu-CD68-Fc) may help to target foam cell rich plaques with high content of oxidized LDL. This novel imaging biomarker tool may have potential to identify unstable plaques and for risk stratification. [ABSTRACT FROM AUTHOR]

Platelet-bound stromal cell-derived factor-1 (SDF-1) plays a crucial role in attachment of circulating CD34+ progenitor cells to the vascular wall, facilitating tissue healing after injury. However there is no evidence about expression of platelet-bound SDF-1 in patients with congestive heart failure (CHF). The aim of our study was to evaluate expression of platelet-bound SDF-1 and number of CD34+ progenitor cells in patients with CHF. Forty-eight patients with idiopathic dilated cardiomyopathy (DCM) and 61 patients with ischaemic cardiomyopathy (ICM) were consecutively enrolled into the study. Blood taken from 109 consecutive patients was studied for surface expression of platelet-bound SDF-1 and number of CD34+ progenitor cells by flow cytometry. The highest expression of platelet-bound SDF-1 was observed in patients with severe impairment of left ventricular systolic function compared with patients with mild or moderate impairment of left ventricular systolic function (mild vs. moderate vs. severe impairment of left ventricular systolic function: MFI ± SD: 35.6 ± 34 vs. 101.45 ± 73 vs. 124.86 ± 86.7, Kruskal-Wallis p < 0.001). Similar to platelet-bound SDF-1 number of CD34+ progenitor cells was the highest in severe impairment of left ventricular systolic function (mild vs. moderate vs. severe impairment of left ventricular systolic function: mean ± SD: 260.4 ± 177.5 vs. 580.7 ± 340.5 vs. 640.82 ± 370.6, Kruskal-Wallis p < 0.001). Platelet-bound SDF-1 expression was associated with number of circulating CD34+ progenitor cells ( r = 0.454, p < 0.001) in patients with CHF. Expression of platelet-bound SDF-1 and number of CD34+ cells were higher in patients with DCM compared with patients with ICM ( p < 0.001 for both) and inversely correlated with age and aspirin therapy. Platelet-bound SDF-1 and CD34+ progenitor cells are especially increased in patients with severe impairment of left ventricular systolic function in CHF. [ABSTRACT FROM AUTHOR]

Plaque erosion leads to exposure of subendothelial collagen, which may be targeted by glycoprotein VI (GPVI). We aimed to detect plaque erosion using 64Cu-labeled GPVI-Fc (fragment crystallized).Four-week-old male apolipoprotein E-deficient (ApoE-/-) mice (n=6) were fed a high-fat diet for 12 weeks. C57BL/6J wild-type (WT) mice served as controls (n=6). Another group of WT mice received a ligation injury of the left carotid artery (n=6) or sham procedure (n=4). All mice received a total activity of ≈12 MBq 64Cu-GPVI-Fc by tail vein injection followed by delayed (24 hours) positron emission tomography using a NanoPET/computed tomographic scanner (Mediso, Hungary; Bioscan, USA) with an acquisition time of 1800 seconds. Seventy-two hours after positron emission tomography/computed tomography, all mice were scanned 2 hours after intravenous administration of 0.2 mmol/kg body weight of a gadolinium-based elastin-specific MR contrast agent. MRI was performed on a 3-T clinical scanner (Philips Healthcare, Best, The Netherlands). In ApoE-/- mice, the 64Cu-GPVI-Fc uptake in the aortic arch was significantly higher compared with WT mice (ApoE-/-: 13.2±1.5 Bq/cm3 versus WT mice: 5.1±0.5 Bq/cm3; P=0.028). 64Cu-GPVI-Fc uptake was also higher in the injured left carotid artery wall compared with the intact right carotid artery of WT mice and as a trend compared with sham procedure (injured: 20.7±1.3 Bq/cm3 versus intact: 2.3±0.5 Bq/cm3; P=0.028 versus sham: 12.7±1.7 Bq/cm3; P=0.068). Results were confirmed by ex vivo histology and in vivo MRI with elastin-specific MR contrast agent that measures plaque burden and vessel wall remodeling. Higher R1 relaxation rates were found in the injured carotid wall with a T1 mapping sequence (injured: 1.44±0.08 s-1 versus intact: 0.91±0.02 s-1; P=0.028 versus sham: 0.97±0.05 s-1; P=0.068) and in the aortic arch of ApoE-/- mice compared with WT mice (ApoE-/-: 1.49±0.05 s-1 versus WT: 0.92±0.04 s-1; P=0.028).64Cu-GPVI-Fc positron emission tomographic imaging allows identification of exposed subendothelial collagen in injured WT and high-fat diet-fed ApoE-/- mice. [ABSTRACT FROM AUTHOR]

Platelet collagen receptor glycoprotein VI (pGPVI) is elevated in patients with acute coronary syndrome (ACS) and ischemic stroke. Recently, we developed a novel bead-based sandwich immunoassay to determine soluble GPVI (sGPVI), which has been validated in ACS patients. This study aimed to evaluate the plasma levels of sGPVI and pGPVI expression in patients with suspected stroke. We consecutively evaluated 176 patients, who were admitted to the stroke unit. Surface expression of pGPVI was determined by flow cytometry, sGPVI concentrations were determined using our sandwich immunoassay. Unlike patients with TIA, patients with stroke showed significantly decreased plasma levels of sGPVI compared to patients with non-ischemic (NI) events (TIA: mean [µg/L] ± standard deviation): 6.1 ± 2.1 vs. NI: 8 ± 4; p = 0.192; stroke: 5.9 ± 2.3 vs. NI; p = 0.013), whereas for pGPVI, patients with TIA and ischemic stroke revealed a significantly increased platelet surface expression compared to NI patients (TIA: mean fluorescence intensity [MFI] ± standard deviation): 20.9 ± 5.4 vs. NI: 17.6 ± 5.2; p = 0.021; stroke: 20.3 ± 6.2 vs. NI; p = 0.016). Using logistic regression analysis, both sGPVI (p = 0.002) and pGPVI (p = 0.012) are independently associated with ischemic stroke compared to other laboratory markers. To predict the individual risk for ischemic stroke using the plasma levels of sGPVI, receiver operating characteristic (ROC) analysis determined an optimal cutoff value of sGPVI at 6.5 µg/l, thus, patients with decreased plasma levels (<6.5 µg/l) have a 1.5-fold adjusted odds ratio (95%confidence interval, 1.4-2.7). Lower plasma levels of sGPVI are associated with the slightly elevated risk of stroke and may be a promising novel biomarker. [ABSTRACT FROM AUTHOR]

Vascular lesion formation and collagen presentation are key events leading to the development of vulnerable plaques. Glycoprotein VI (GPVI) significantly contributes to plaque-associated collagen binding and thrombus formation. The aim of this study was to image endothelial injury using fluorescence-labelled GPVI-Fc (Fc, fragment crystallized), a soluble form of GPVI that was generated by cloning and fusing GPVI to an Fc-domain, in an ex-vivo rabbit model. This study serves as a proof-of-principle study to demonstrate that GPVI-Fc is a useful tool for detecting endothelial damage. The carotid and femoral arteries and the aorta abdominalis were isolated from rabbits and perfused with phosphate buffered saline (PBS) to remove all blood, and a catheter was placed into the vessels in situ. Endothelial damage was achieved by pulling an inflated balloon approximately 1 inch through the vessels, while control vessels were not balloon-treated. After balloon deflation, the catheter was removed. Fluorescence-labelled GPVI-Fc (50 µg/mL) was injected into the injured and control intact vessels, and the opened vessels were sealed by clamps. After incubation, the vessels were rinsed with PBS, and optical imaging was performed to measure GPVI-Fc binding to injured endothelium. The optical data corresponding to the mean detected optical signal of the regions of interest were corrected by subtracting the mean data of the background fluorescence (arbitrary units). After denudation, fluorescence was enhanced in injured femoral and carotid arteries when compared to intact femoral (41.1 ± 17.5 vs. 14.6 ± 6.5; P == 0.021) and carotid (30.2 ± 7.6 vs. 7.9 ± 3.9; P == 0.005) arteries. This preclinical GPVI-Fc-based vascular lesion imaging approach may be the first step towards a method that allows identification of vascular lesions in vivo. [ABSTRACT FROM AUTHOR]

Abstract: Background: The purpose of the study was to test whether an elevated surface expression of platelet collagen receptor glycoprotein VI (GPVI) is an appropriate marker for the diagnosis of the acute coronary syndrome (ACS), especially when the electrocardiogram (ECG) is ambiguous. Methods: Between 2007 to 2008, we consecutively evaluated 378 patients with ACS and ambiguous ECG on hospital admission. In all patients, GPVI surface expression was determined by flow cytometry. In addition, the myocardial necrosis markers troponin-I (Tn-I) and creatine kinase-MB (CKMB) were measured. Results: We found that in patients with ACS and unclear ECG in whom GPVI levels (mean fluorescence intensity (MFI) ≥18.6) were elevated, the relative risk for ACS was 2.6-fold enhanced. Binary logistic regression analysis revealed that an elevated platelet GPVI level is indicating an ACS independent of biomarkers of myocardial necrosis including Tn-I, creatine kinase (CK), CKMB (GPVI: p =0.011; Tn-I: p =0.180; CKMB: p =0.250; CK: p =0.127). Patients with evident T-wave inversion and/or ST-depression showed a strong association between ACS and GPVI expression. Conclusions: Platelet GPVI surface expression is enhanced in patients with ACS with unclear ECG findings and is strongly associated with myocardial ischemia. Additional to the classical markers of myocardial necrosis Tn-I and CK, GPVI is an early biomarker for the diagnosis of ACS, especially when the ECG is ambiguous. [Copyright &y& Elsevier]

Background: Alzheimer's disease (AD) and atherosclerosis share common vascular risk factors such as arterial hypertension and hypercholesterolemia. Adipocytokines and CD34+ progenitor cells are associated with the progression and prognosis of atherosclerotic diseases. Their role in AD is not adequately elucidated. Methods and Findings: In the present study, we measured in 41 patients with early AD and 37 age- and weight-matched healthy controls blood concentrations of adiponectin and leptin by enzyme linked immunoabsorbent assay and of CD34+ progenitor cells using flow cytometry. We found significantly lower plasma levels of leptin in AD patients compared with the controls, whereas plasma levels of adiponectin did not show any significant differences (AD vs. control (mean6SD): leptin:8.9±5.6 ng/mL vs.16.3±15.5 ng/mL;P = 0.038; adiponectin:18.5±18.1 μg/mL vs.16.7±8.9 mg/mL;P = 0.641). In contrast, circulating CD34+ cells were significantly upregulated in AD patients (mean absolute cell count6SD:253651 vs. 203637; P = 0.02) and showed an inverse correlation with plasma levels of leptin (r =20.248; P = 0.037). In logistic regression analysis, decreased leptin concentration (P = 0.021) and increased number of CD34+ cells (P = 0.036) were both significantly associated with the presence of AD. According to multifactorial analysis of covariance, leptin serum levels were a significant independent predictor for the number of CD34+ cells (P = 0.002). Conclusions: Our findings suggest that low plasma levels of leptin and increased numbers of CD34+ progenitor cells are both associated with AD. In addition, the results of our study provide first evidence that increased leptin plasma levels are associated with a reduced number of CD34+ progenitor cells in AD patients. These findings point towards a combined involvement of leptin and CD34+ progenitor cells in the pathogenesis of AD. Thus, plasma levels of leptin and circulating CD34+ progenitor cells could represent an important molecular link between atherosclerotic diseases and AD. Further studies should clarify the pathophysiological role of both adipocytokines and progenitor cells in AD and possible diagnostic and therapeutic applications. [ABSTRACT FROM AUTHOR]

Platelets have been regarded as static cells that do not move once they adhere to a matrix. The present study explored, whether platelets are able to migrate. In contrast to the current opinion, we found that platelets were mobile, able to migrate over a surface, and transmigrate through a transwell membrane and endothelium toward a source of stromal cell-derived factor 1 (SDF-1). Platelet migration was stimulated by SDF-1, which led to the downstream activation and phosphorylation of Wiskott-Aldrich syndrome protein. SDF-1 signaling and subsequent platelet migration could be inhibited by CXCR4-receptor blocker AMD3100, pertussis toxin, inhibition of phosphoinositol 3-kinase (PI3 kinase) with LY294002 or wortmannin, and disruption of actin polymerization with cytochalasin B. The potential of platelets to migrate in an SDF-1-mediated fashion may redefine the role of platelets in the pathophysiology of vascular inflammation, subsequent atherosclerotic degeneration, and vascular regeneration. [ABSTRACT FROM AUTHOR]

Thrombocytopenia, fever, and acute renal failure are characteristic features of nephropathia epidemica, the predominant hantavirus infection in Europe. However, clinical presentation and blood cell counts may point to other disorders, such as a hematologic disease, particularly when impairment of renal function is not evident. This differential diagnosis often results in further extensive and unnecessary testing. We describe 3 patients with hantavirus infection with no renal failure, in whom a hematologic disorder was initially suspected. Serologic testing of hantavirus finally unraveled the mystery, and outcome of the patients was excellent, It is conceivable that similar cases often remain undiagnosed. Thus, testing for hantavirus should always be considered in cases of thrombocytopenia and fever of unknown origin, especially in areas endemic for the infection. [ABSTRACT FROM AUTHOR]

Background: Type-2 diabetes is accompanied by a prothrombotic state influenced by endothelial dysfunction, inflammatory condition and platelet hyperreagibility. We aimed to characterize the relationship of inflammation and residual platelet aggregability (RPA) under antiplatelet therapy with regard to prognosis in an unselected PCI-cohort of diabetics. Methods: In a first step, a consecutive collective of 75 type 2 diabetics compared to 153 non-diabetic controls was evaluated at the time of PCI. Inflammatory markers, Interleukin 6 and C-reactive protein were measured by immunoassays. ADP and Aspirin assays were performed by multiple electrode aggregometry. Then, we consecutively evaluated ADP-induced RPA in 542 diabetics and 1,161 non-diabetics undergoing PCI and treated by standard antiplatelet therapy. Major CV-events were assessed at 30 days after PCI. Results: Inflammatory markers were significantly increased in diabetics with peri-interventional hyperglycemic state and inversely correlated with responsiveness to clopidogrel and aspirin. In a large scale cohort, diabetics showed a higher RPA compared to non-diabetics (median 38.1 vs. 28.8%; p < 0.001). After adjustment for relevant co-factors, diabetes remained a strong predictor for increased RPA (OR 4.39; 95% CI 1.95-6.83; p < 0.001). Furthermore, diabetics with high RPA had an increased risk for 30-day MI and CV-death than diabetics with low RPA (adjusted HR 1.05; 95% CI 1.02-1.07; p < 0.001). Conclusions: We demonstrate that peri-interventional inflammatory degree and glycaemic control correlate with decreased antiplatelet drug responsiveness in diabetics. In addition, we identified high RPA as strong predictor for short-term CV-events in this group. Therefore, approaches to treat these entities are needed to improve outcome in diabetics undergoing PCI. [ABSTRACT FROM AUTHOR]

Growing evidence supports a major role of chronic inflammation and platelet activation in the development of atherosclerosis and cardiovascular (CV) disease. Because CV dysfunction is, at least in part, reversible, identifying these early stages may enhance the development of new therapeutic and preventive interventions. Technological advances have led to appreciation of underlying pathophysiology in vivo via targeted clinical readouts by soluble markers and noninvasive imaging. Integration of these readouts in early phases of development of novel drug candidates may provide a key addition to translational steps toward robust evidence. New paradigms of drug discovery may lead to earlier and more targeted interventions at reversible stage of disease. [Copyright &y& Elsevier]

Previous studies suggested that the adipocytokines, adiponectin and leptin, are associated with the progression and prognosis of coronary artery disease (CAD). The aim of this study was to differentially evaluate plasma levels of adiponectin and leptin in patients with CAD and their association with conventional laboratory parameters and markers of platelet activation. We consecutively evaluated 220 patients, who presented with a symptomatic CAD. Among these 83 (37.7%) presented with an acute coronary syndrome (ACS) and 137 (62.3%) with a stable angina pectoris (SAP). All patients have received coronary angiography. Baseline concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Lower detection limits of the assay were 0.079 ng/mL for total adiponectin and 15.6 pg/mL for leptin. Patients with ACS showed significantly enhanced plasma levels of adiponectin and leptin compared with SAP (ACS vs. SAP (mean ± SD): adiponectin: 9.9 ± 7.6 µg/mL vs. 7.2 ± 5.7 µg/mL; P = 0.008; leptin: 20.9 ± 16.4 ng/mL vs. 15.2 ± 10.9 ng/mL; P = 0.012). However, a correlation between plasma total adiponectin and leptin levels has not been observed ( r = 0.038; P = 0.706). Plasma levels of total adiponectin and leptin positively correlated with C-reactive protein (adiponectin: r = 0.277; P = 0.001; leptin: r = 0.248; P = 0.007) and troponin-I (adiponectin: r = 0.219; P = 0.001; leptin: r = 0.190; P = 0.025). Plasma levels of both adipocytokines have shown an inverse correlation with markers of platelet activation such as platelet glycoprotein VI (adiponectin: r = −0.120; P = 0.048; leptin: r = −0.205; P = 0.036), and in a negative trend with P-selectin (adiponectin: r = −0.116; P = 0.073; leptin: r = −0.172; P = 0.078). To support our findings, we determined high-molecular-weight adiponectin in a subgroup of 37 patients, which showed similar results. Increased concentrations of total adiponectin and leptin were associated with ACS. Intriguingly, high plasma levels of both adipocytokines seem to modulate platelet activation. Further studies should elucidate the adipocytokine regulation in CAD. [ABSTRACT FROM AUTHOR]

Background: Platelet collagen receptor glycoprotein VI (GPVI) plays a critical role in acute coronary thrombosis. This prospective study examined the predictive value of GPVI for acute coronary syndromes (ACS) in a large consecutive group of patients with symptomatic coronary artery disease to identify the high-risk cohort with imminent coronary events. Methods: We evaluated 1,003 patients with symptomatic coronary artery disease, verified by coronary angiography, and determined the surface expression of GPVI using flow cytometry. In a subgroup of 471 patients, who were treated with aspirin plus clopidogrel for coronary stenting, adenosine disphosphate (20 μmol/L)–induced platelet aggregation was evaluated. Results: Patients with ACS (n = 485) showed a significantly enhanced GPVI expression compared to patients with stable angina pectoris (SAP; n = 518) (mean fluorescence intensity for ACS 19.8 ± 5.9; SAP 18.7 ± 8.5, P = .01). Patients with elevated GPVI levels on admission (GPVI cutoff value ≥18.6 mean fluorescence intensity) had a 1.4-fold relative risk for ACS. Logistic regression analysis showed that an elevated platelet GPVI level may indicate ACS independent of biomarkers of myocardial necrosis including troponin, creatine kinase, and creatine kinase-MB. Patients with increased platelet activation (GPVI expression level ≥18.6) showed significant enhanced residual platelet aggregation despite dual antiplatelet therapy compared to patients with low GPVI levels (P = .028). Conclusions: Surface expression of GPVI is enhanced in patients with ACS and indicates an imminent acute coronary event before irreversible myocardial necrosis is evident. High GPVI levels are associated with increased residual platelet aggregation despite antiplatelet therapy. Therefore, GPVI is useful to identify the subgroup of patients with a high risk for coronary stent thrombosis and thromboischemic events. [Copyright &y& Elsevier]

Several lines of evidence suggest a viral infection as the initiating event for the development of myocarditis (MC). Especially enteroviruses like coxsackie B3 virus have been shown to induce MC in humans and strains of MC-prone mice after an infection. The further course of the disease is, however, determined not only by the viral infection but also by the host’s immune system. Both the humoral and the cellular immune system can modify the extent of the damage caused by the disease. The humoral immune system mounts an anti-viral immune response immediately after the infection; however, during the course of the disease, autoantibodies against a variety of different autoantigens emerge. The epitopes recognized by the anti-viral antibodies and those of several autoantibodies have been identified using synthetic peptides. The human disease could be transferred into SCID mice using peripheral blood leukocytes of patients, suggesting a pathophysiological significance of the autoimmune reaction. However, the significance of the humoral immune responses needs to be tested in randomized, prospective studies using immunoadsorption of autoantibodies in patients with inflammatory cardiomyopathy. [ABSTRACT FROM AUTHOR]

Background: Right ventricular (RV) function is a known predictor of adverse events in heart failure and following acute myocardial infarction (AMI). While right atrial (RA) involvement is well characterized in pulmonary arterial hypertension, its relative contributions to adverse events following AMI especially in patients with heart failure and congestion need further evaluation. Methods: In this cardiovascular magnetic resonance (CMR)-substudy of AIDA STEMI and TATORT NSTEMI, 1235 AMI patients underwent CMR after primary percutaneous coronary intervention (PCI) in 15 centers across Germany (n = 795 with ST-elevation myocardial infarction and 440 with non-ST-elevation MI). Right atrial (RA) performance was evaluated using CMR myocardial feature tracking (CMR-FT) for the assessment of RA reservoir (total strain εs), conduit (passive strain εe), booster pump function (active strain εa), and associated strain rates (SR) in a blinded core-laboratory. The primary endpoint was the occurrence of major adverse cardiac events (MACE) 12 months post AMI. Results: RA reservoir (εsp = 0.061, SRs p = 0.049) and conduit functions (εep = 0.006, SRe p = 0.030) were impaired in patients with MACE as opposed to RA booster pump (εap = 0.579, SRa p = 0.118) and RA volume index (p = 0.866). RA conduit function was associated with the clinical onset of heart failure and MACE independently of RV systolic function and atrial fibrillation (AF) (multivariable analysis hazard ratio 0.95, 95% confidence interval 0.92 to 0.99, p = 0.009), while RV systolic function and AF were not independent prognosticators. Furthermore, RA conduit strain identified low- and high-risk groups within patients with reduced RV systolic function (p = 0.019 on log rank testing). Conclusions: RA impairment is a distinct feature and independent risk factor in patients following AMI and can be easily assessed using CMR-FT-derived quantification of RA strain. [ABSTRACT FROM AUTHOR]

The article provides information on the results of a research on the differention of human CD34+ progenitor cells into foam cells and endothelial cells induced by platelets. It was found that modified low density lipoprotein is picked up by platelets and accumulated in organelles containing mepacrine. It says that platelets affixed with Dil-AcLDL are fastly internalized into foam cells as presented by electron and fluorescence microscopy.

Purpose of Review: The purpose of this paper is to review the latest advancements and developments in non-invasive coronary magnetic resonance (MR) and hybrid positron emission tomography (PET)/MR imaging. Recent Findings: Coronary MRI has advanced in recent years in different aspects, especially regarding technical developments, scan protocols, and molecular probes. Recently introduced hybrid PET/MR scanners have already demonstrated great potential in improving cardiovascular imaging. Summary: Coronary atherosclerosis and acute myocardial infarction remain major threats to physical health worldwide. Several techniques, from invasive intravascular imaging to non-invasive imaging methods, are studied extensively to identify patients with vulnerable plaques at risk for adverse coronary events. While imaging of vulnerable plaques is getting more and more sophisticated, the clinical impact of molecular plaque imaging on prognosis and disease management still has to be fully defined. [ABSTRACT FROM AUTHOR]

An abstract on quantification of the ischemic burden on cardiac magnetic resonance perfusion maps by perfusion threshold analysis is presented.

An abstract of the article "Quantitative assessment of magnetic resonance derived perfusion measurements using advanced techniques: comparison with microspheres in an explanted pig heart system," by Andreas Schuster and colleagues is presented.

An abstract to the article "The intra-observer reproducibility of cardiovascular magnetic resonance myocardial feature tracking strain assessment is independent of field strength," by Andreas Schuster, Geraint Morton, Shazia T. Hussain, Roy Jogiya, Shelby Kutty, and colleagues presented.

An abstract of the conference paper "Direct comparison of MR and CT perfusion utilizing a myocardial perfusion phantom," by James Otton and colleagues is presented.

An abstract of the conference paper "Cardiac magnetic resonance imaging of isolated perfused pig hearts in a 3T clinical MR scanner," by Eike Nagel, and colleagues is presented.

An abstract of the conference paper "Cardiac magnetic resonance myocardial feature tracking detects quantitative wall motion during dobutamine stress," by Andreas Schuster and colleagues is presented.

An abstract of the conference paper "Quantification of transmural perfusion gradients by high-resolution MR versus fractional flow reserve for the assessment of coronary artery stenosis," by Amedeo Chiribiri and colleagues is presented.

An abstract of the conference paper "Transmural perfusion gradient analysis by high resolution MR versus fractional flow reserve for the assessment of coronary artery stenosis," by Amedeo Chiribiri and colleagues is presented.

An abstract of the conference paper "Cardiac magnetic resonance myocardial feature tracking correlates with natural radial strain and corresponds to inotropic stimulation," by Andreas Schuster and colleagues is presented.

A letter to the editor is presented in response to the article "Effects of CYP2C19 Genotype on Outcomes of Clopidogrel Treatment," by G. Paré and colleagues in the October 28, 2010 issue.

Background: Recently, a novel left atrioventricular coupling index (LACI) has been introduced providing prognostic value to predict cardiovascular events beyond common risk factors in patients without cardiovascular disease. Since data on cardiovascular magnetic resonance (CMR)-derived LACI in patients following acute myocardial infarction (AMI) are scarce, we aimed to assess the diagnostic and prognostic implications of LACI in a large AMI patient cohort. Methods: In total, 1046 patients following AMI were included. After primary percutaneous coronary intervention CMR imaging and subsequent functional analyses were performed. LACI was defined by the ratio of the left atrial end-diastolic volume divided by the left ventricular (LV) end-diastolic volume. Major adverse cardiac events (MACE) including death, reinfarction or heart failure within 12 months after the index event were defined as primary clinical endpoint. Results: LACI was significantly higher in patients with MACE compared to those without MACE (p < 0.001). Youden Index identified an optimal LACI cut-off at 34.7% to classify patients at high-risk (p < 0.001 on log-rank testing). Greater LACI was associated with MACE on univariate regression modeling (HR 8.1, 95% CI 3.4–14.9, p < 0.001) and after adjusting for baseline confounders and LV ejection fraction (LVEF) on multivariate regression analyses (HR 3.1 95% CI 1.0–9, p = 0.049). Furthermore, LACI assessment enabled further risk stratification in high-risk patients with impaired LV systolic function (LVEF ≤ 35%; p < 0.001 on log-rank testing). Conclusion: Atrial-ventricular interaction using CMR-derived LACI is a superior measure of outcome beyond LVEF especially in high-risk patients following AMI. Trial registration ClinicalTrials.gov, NCT00712101 and NCT01612312 [ABSTRACT FROM AUTHOR]

In cardiorenal syndrome (CRS), heart failure and renal failure are pathophysiologically closely intertwined by the reciprocal relationship between cardiac and renal injury. Type 1 CRS is most common and associated with acute heart failure. A preexistent chronic kidney disease (CKD) is common and contributes to acute kidney injury (AKI) in CRS type 1 patients (acute cardiorenal syndrome). The remaining CRS types are found in patients with chronic heart failure (type 2), acute and chronic kidney diseases (types 3 and 4), and systemic diseases that affect both the heart and the kidney (type 5). Establishing the diagnosis of CRS requires various tools based on the type of CRS, including non-invasive imaging modalities such as TTE, CT, and MRI, adjuvant volume measurement techniques, invasive hemodynamic monitoring, and biomarkers. Albuminuria and Cystatin C (CysC) are biomarkers of glomerular filtration and integrity in CRS and have a prognostic impact. Comprehensive "all-in-one" magnetic resonance imaging (MRI) approaches, including cardiac magnetic resonance imaging (CMR) combined with functional MRI of the kidneys and with brain MRI are proposed for CRS. Hospitalizations due to CRS and mortality are high. Timely diagnosis and initiation of effective adequate therapy, as well as multidisciplinary care, are pertinent for the improvement of quality of life and survival. In addition to the standard pharmacological heart failure medication, including SGLT2 inhibitors (SGLT2i), renal aspects must be strongly considered in the context of CRS, including control of the volume overload (diuretics) with special caution on diuretic resistance. Devices involved in the improvement of myocardial function (e.g., cardiac resynchronization treatment in left bundle branch block, mechanical circulatory support in advanced heart failure) have also shown beneficial effects on renal function. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To assess endothelial injury and repair using fluorescence-labeled glycoprotein VI (GPVI)-Fc in a murine model. Materials and methods: Three 4-week-old male ApoE-deficient (ApoE−/−)-mice were fed with a 1.25% cholesterol diet over 16 weeks and compared to three wild type (WT) C57BL/6J-mice in a wire-induced vascular injury model. Another group of WT mice (n =10) were mechanically injured by carotid ligation. Fluorescence-labeled GPVI-Fc (150μg/mouse) was administered and assessed by optical imaging 24h after injury and compared to another group (n =3) which was injected two days after injury and sacrificed another day later. Results: After denudation, all injured carotids of WT mice showed a higher mean fluorescence signal than the corresponding intact carotids of the same animals (48.4±18.9 vs. 10.4±1.0; P =0.028). Injection of unlabeled GPVI-Fc 20h and 3h before injecting GPVI-Fc-FITC significantly reduced the fluorescence signal in injured carotids to 14.6±4.6, while intact carotids showed a signal of 9.2±1.1; P =0.046. Ligation injury resulted with an increased GPVI-Fc-binding to injured carotids compared to intact carotids (31.53±6.18 vs. 16.48±5.15; P =0.039). Three days after injury and 24h after GPVI-Fc-FITC injection, differences between intact and injured carotids have vanished (12.51±2.76 vs. 14.76±1.59; P =0.519). Conclusions: A GPVI-based plaque imaging system could help to identify vascular lesions and to take a precautionary measure as necessary. [Copyright &y& Elsevier]