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Plasma lipoproteins can be separated by ultracentrifugation based on their physical properties, without direct reference to their composition, with ‘high-density’ lipoproteins (HDL) comprising those with density greater than 1.063 g/ml. HDL lipoprotein particles should be explicitly distinguished from HDL-cholesterol, which is but one of the constituents of HDL. Apolipoprotein A-I is the major structural protein of HDL and comprises 70% of total HDL protein. In addition, there is a large number of protein constituents, the functions of which broadly span lipid transport, inflammation, immune function, hormone binding, haemostasis and antioxidant functions.1 Our appreciation of the context-specific roles of these proteins remains rudimentary, and tools to quantify their putative contributions still more so. On the other hand, measurement of HDL-cholesterol is relatively straightforward and has been undertaken widely. HDL has come to be regarded as atheroprotective, based on three lines of evidence: (1) the inverse relationship between cardiovascular event rates and HDL-cholesterol that is seen in epidemiological studies; (2) animal data showing that the administration of apolipoprotein AI and/or HDL particles reduce atherosclerosis and (favourably remodel atherosclerotic plaques); and (3) a small number of clinical trials suggesting that some drugs that elevate HDL-cholesterol also reduce cardiovascular events or result in plaque regression, assessed by ultrasound or MRI. These observations have raised the possibility that interventions that increase HDL-cholesterol might reduce cardiovascular risk. However, several recent findings have challenged this notion. First, alterations of HDL-cholesterol that are associated with naturally occurring, genetic polymorphisms allow the effects of changes in HDL-cholesterol due to Mendelian randomisation to be mapped to cardiovascular risk. Alterations in HDL-cholesterol by these means do not track with predicted cardiovascular risk. Secondly, niacin (nicotinic acid) is the most efficacious of clinically available drugs to elevate HDL-cholesterol. The AIM—HIGH trial of niacin in patients with low HDL-cholesterol was abandoned due to …

Myocardial infarction (MI) remains a major killer despite highly optimised systems for the delivery of primary percutaneous coronary intervention (PPCI), highlighting a need for novel therapeutics that could be administered in the days following the event. The healing myocardium undergoes a macrophage driven inflammatory response which is a compelling therapeutic target, though clinical exploration of this process has been limited because conventional imaging techniques cannot assess cellular inflammation in the heart. We hypothesised that the huge increases in signal-to-noise ratio provided by hyperpolarized MRI could provide a solution to this problem. In rodent models, hyperpolarized [1–13C]pyruvate MRI using a custom designed metabolite mapping sequence in vivo demonstrated that experimental MI caused intense [1–13C]lactate signal in healing myocardial segments at both day 3 (paralleling the maximal ‘inflammatory’ phase of the macrophage response) and also at day 7 (‘reparative’ phase), compared to sham operated controls. Monocyte/macrophage depletion using clodronate liposomes normalised the [1–13C]lactate signal at both timepoints. Gene expression analysis of monocytes/macrophages sorted from infarct tissue demonstrated regulation of key enzymes of glycolysis, suggesting that monocyte/macrophage recruitment and metabolic reprogramming of those cells underlies the high lactate signal detected. Hyperpolarized [1–13C]pyruvate MR spectroscopy in macrophage-like cell suspensions confirmed that cellular activation and polarisation almost doubles hyperpolarized lactate label flux rates in vitro; blockade of glycolysis with 2-deoxyglucose (2-DG) in activated macrophage-like cells normalised lactate label flux rates and also markedly inhibited production of key pro-inflammatory cytokines at both mRNA and protein level, without major cytotoxicity. Systemic administration of 2-deoxyglucose following rodent MI normalised hyperpolarized [1–13C]lactate signal in healing myocardial segments and also caused dose dependent improvement in IL-1β expression in infarct tissue, providing proof-of-concept of ‘MR visible’ immunomodulation. Furthermore, cine MRI demonstrated improvements in myocardial remodelling and systolic function in 2-DG treated rats at 3 months. Finally, we present initial human experience of cardiac hyperpolarized [1–13C]pyruvate MR, demonstrating unprecedented improvements in signal-to-noise ratio and highlighting the potential for rapid clinical translation of these findings. We conclude that hyperpolarized MRI provides a novel biomarker of cardiac inflammation and repair post-MI by detecting the induction of an immuno-metabolic pathway in cardiac macrophages which controls key inflammatory cytokine production and influences myocardial remodelling. In addition to a role in the development of novel therapeutics to improve remodelling post MI, hyperpolarized MRI may have broad applications in other inflammatory cardiovascular diseases.

Background Following acute myocardial infarction (AMI), monocytes are rapidly mobilised from the spleen to peripheral blood, from where they undergo transcriptional activation and infiltrate injured tissue, with potential to contribute to both injury and repair. The mechanism by which the injured myocardium signals splenic-monocyte mobilisation remains poorly understood. Recent work shows extracellular vesicles (EV, which carry proteins, microRNA/mRNA) are a means of rapid cell-to-cell communication, which, combined with knowledge of their composition and propensity to be taken up by other cells, suggests a possible role in signalling. Here we show that AMI results in a net increase in circulating endothelial cell (EC)-EV that induce splenic monocyte motility in vivo and cellular transcription. Methods Platelet-poor plasma was collected from patients with ST-segment elevation-AMI (STEMI) and mice subjected to AMI. EV were isolated by ultra-centrifugation and analysed for size/number by Nanoparticle Tracking Analysis, western blot (EV-markers: ALIX, TSG101, CD69, CD9 and Hsp70), ELISA for EC markers (CD31, ICAM-1, P-selectin, E-selectin and VCAM-1), electron microscopy and for EV-miRNAs. Human and mouse EC were used in vitro to evaluate EV release, injected into wild-type or CD68 GFP+ naive mice to assess bio-distribution, splenic-monocyte mobilisation, uptake by monocytes, cellular mRNA transcription and cell motility. Results Acutely (24 hours) after AMI there is a significant increase in circulating EV in humans (p In vitro pro-inflammatory cytokines significantly increase EV production by EC, whereas ‘anti-inflammatory’ IL-4 and IL-6 had no effect. Inflammatory-EC-EV displayed significant enrichment of VCAM-1 (p In-vitro labelled EC-EV accumulate in monocytes. Inflammatory-EC-EV significantly enhanced macrophage chemokineses (p in-vivo (p In conclusion (1) AMI surges plasma EV; (2) Plasma-EV protein composition is consistent with EC origin. (3) Injected EV localise to the spleen and (4) mobilise splenic monocytes. (5) In culture, EC increase EV release, enhance monocyte motility and (6) regulate genes that are important in cellular movement. These demonstrate a novel role for EC-derived EV in monocyte activation after AMI.

Aim Restoration of effective myocardial reperfusion by primary percutaneous coronary intervention (PPCI) in patients with STEMI is not predictable. A method to assess the likelihood of a suboptimal response to conventional pharmaco-mechanical therapies could be beneficial. We aimed to derive and validate a scoring system that can be used acutely at the time of coronary reopening to predict the likelihood of downstream microvascular impairment in patients with STEMI. Methods and Results A score estimating the risk of post-procedural microvascular injury defined by an index of microcirculatory resistance (IMR) > 40, was initially derived in a cohort of 85 STEMI patients (Derivation cohort). This score was then tested and validated in three further cohorts of patients (Retrospective (30 patients), Prospective (42 patients) and External (29 patients). The ATI score [Age ( > 50 = 1); pre-stenting IMR (> 40 and 40 in all the four cohorts (AUC:0.87; p 40, while no cases of final IMR >40 occurred in the presence of an ATI score Conclusions The ATI score appears to be a promising tool capable of identifying patients during PPCI that are at the highest risk of an adverse outcome following revascularisation.

Background The accurate diagnosis of acute myocarditis on cardiovascular MRI (CMR) often requires multiple modalities, including T2-weighted (T2W), early and late gadolinium imaging. Novel CMR techniques are now available, including bright-blood T2W-CMR, and T1-mapping which is also sensitive to changes in free water content. We hypothesised that these emerging methods can serve as new and potentially superior diagnostic criteria for myocarditis. Methods We studied 45 healthy controls and 34 patients with suspected acute myocarditis. All patients presented with acute chest pain, troponin I >0.04 µg/l and had unobstructed coronary arteries on angiogram or ruled out clinically (eg, young age Results All patients had a CMR diagnosis of acute myocarditis based on both positive T2-STIR and typical LGE pattern. Patients with an obvious alternate diagnosis (such as Takotsubo cardiomyopathy, hypertrophic cardiomyopathy) were excluded. Compared to controls, patients had significantly higher global myocardial T2 SI ratios by dark-blood T2W-CMR (1.81±0.28 vs 1.58±0.16, p Conclusions T1-mapping showed superior diagnostic performance compared to conventional dark-blood and newer bright-blood T2W-CMR in the detection of acute myocarditis. T1-mapping and bright-blood T2W-CMR may be used as novel diagnostic criteria for the assessment of acute myocarditis.

Adherence to secondary prevention medications following acute coronary syndrome (ACS) is disappointingly low, standing around 40–75% by various estimates. This is an inefficient use of the resources devoted to their development and implementation, and also puts patients at higher risk of poor outcomes post-ACS. Numerous factors contribute to low adherence including poor motivation, forgetfulness, lack of education about medications, complicated polypharmacy of ACS regimens, (fear of) adverse side effects and limited practical support. Using technology to improve adherence in ACS is an emerging strategy and has the potential to address many of the above factors—computer-based education and mobile phone reminders are among the interventions trialled and appear to improve adherence in patients with ACS. As we move into an increasingly technological future, there is potential to use devices such as smartphones and tablets to encourage patient responsibility for medications. These handheld technologies have great scope for allowing patients to view online medical records, education modules and reminder systems, and although research specific to ACS is limited, they have shown initial promise in terms of uptake and improved adherence among similar patient populations. Given the overwhelming enthusiasm for handheld technologies, it would seem timely to further investigate their role in improving ACS medication adherence.

Introduction Changes in myocardial tissue in acute ischaemia are dynamic and complex and the characteristics of myocardial tissue on cardiovascular magnetic resonance (CMR) in the acute setting are not fully defined. We investigated changes in oedema and late gadolinium enhancement (LGE) with serial imaging early after acute MI, relating these to global and segmental myocardial function at 6 months. Methods and Results CMR scans were performed on 30 patients with ST elevation MI (STEMI) treated by primary PCI at each of 4 time points: 12–48 h (TP1); 5–7 days (TP2); 14–17 days (TP3); and 6 months (TP4). All patients showed oedema at TP1. The mean volume of oedema (% LV) was 37±16 at TP1 and 39±17 at TP2 with a reduction to 24±13 (p Conclusions (1) Myocardial oedema was unchanged over the first week but decreased by 15 days; (2) a large majority of segments that were positive for oedema also showed LGE, assessed at 12–48 h; (3) In 46% of patients, LGE present on early scans had diminished in size by 6 months, (4) resolution of LGE was associated with improvement in function; (5) the reduction in LGE at the later time had a profound effect on the calculation of salvage index, which varied by up to ∼60%, depending on the time point used. (6) From a clinical perspective, the use of acute LGE may severely underestimate salvaged myocardium and should not be used to predict recovery of myocardial function.

Introduction Luminal stenosis is a poor predictor of the risk posed by any given atherosclerotic plaque, therefore current angiographic imaging techniques cannot reliably determine which patients are most likely to suffer future ischaemic events. However, MRI may be able to detect features of atherosclerotic plaque rupture that have been associated with an increased risk of recurrent atherothrombosis. Hypothesis 3T MRI of the carotid artery can identify atherosclerotic plaque rupture in patients presenting with TIA or minor stroke. Methods 81 patients with carotid artery disease were recruited; 41 presented acutely with TIA or minor stroke and 40 asymptomatic patients acted as the control group. Median time from symptom onset to MRI in the symptomatic group was 2.1 days (range 0.17–7.0). All patients underwent T1, T2 and proton density-weighted turbo spin echo MRI to 10 mm either side of the carotid. As part of a combined scan protocol, study participants then underwent diffusion-weighted imaging (DWI) and Fluid-Attenuated Inversion Recovery (FLAIR) imaging of the brain to assess acute and chronic injury, respectively. If physically able, patients underwent follow-up scanning a minimum of six weeks later. Plaques were graded according to the MRI modified American Heart Association (AHA) system by two independent reviewers blinded to the clinical status of the patient. Statistical analysis was performed using the Wilcoxon sign rank test and Fisher′s exact test to compare plaques, in addition to the Mann Whitney U test to compare cerebral injury. Results AHA type VI (ruptured) plaque was seen in 22/41(54%) in the symptomatic group vs 8/41(20%) in the asymptomatic group (p Conclusion Acute atherosclerotic plaque rupture can be visualised using 3T MRI. In particular, MRI can provide detailed information on plaque morphology that can predict downstream embolic injury, independent of the degree of luminal stenosis caused.

INTRODUCTION: Up to 10% of patients presenting with chest pain and elevated troponin levels demonstrate non-obstructive coronary arteries on angiography, posing a clinical challenge in diagnosis, prognosis and management. The final diagnosis has important implications for the patient, including prescription for treatment and fitness for permissible activities, occupation and medical insurance. Cardiovascular magnetic resonance (CMR) is superior to other cardiac imaging modalities in tissue characterisation. We hypothesised that CMR, when performed early using conventional and novel tissue characterisation techniques, can determine the cause of acute myocardial injury in these patients and provide a diagnosis. METHODS: One hundred and twenty (n = 120) patients (mean age 50 ± 17 yrs; 50% female) presenting with chest pain, positive troponin I (normal 60 μg/L) and non-obstructive coronaries were prospectively recruited.Early CMR at 1.5T (median 3 days, IQR 1-6 days) included cine, T2W (dark-blood STIR), T1-mapping (ShMOLLI) and LGE imaging. Findings were compared to 50 controls matched for age and gender distributions.Image analysis included: the detection of oedema comparing T2 signal intensity of myocardium to skeletal muscle (>2.0) or remote myocardium (>2 SD); myocardial T1 times (areas of injury defined as an area of ≥40 mm2 with T1 >990 ms as validated for detecting oedema); and presence of LGE. RESULTS: When CMR was performed early using only conventional techniques (cine, T2W and LGE), there was a high diagnostic yield of 95%. Oedema was detected in 79% and LGE in 61% of patients.Based on CMR findings, including the type, pattern and regional distribution of injury, the commonest diagnosis was myocarditis (37%), followed by Takotsubo cardiomyopathy (23%), myocardial infarction (18%), acute regional stunning (9%; wall motion abnormality with oedema but no LGE), dilated cardiomyopathy (4%), hypertrophic cardiomyopathy (3%), and missed pulmonary embolism (1%). In 11/21 (52%) of patients with MI, a patent foramen ovale (PFO) was demonstrated on echocardiography with agitated saline contrast, suggesting these patients may have suffered a paradoxical coronary embolism. The remaining 5.0% (n = 6) of patients had no findings on T2W and LGE imaging. However, T1 mapping localised areas of injury in 4 out of the remaining 6 patients, improving the detection rate to 98%. CONCLUSIONS: Early CMR using conventional and novel T1-mapping techniques has a high diagnostic yield in patients presenting with acute chest pain, positive troponins but non-obstructive coronaries. T1 mapping detected additional areas of abnormality when conventional CMR was "normal", improving the detection rate to 98%. Early multiparametric CMR is able to localise areas of affected myocardium and is useful in the further management or diagnostic workup in this patient cohort.

BACKGROUND: High-risk percutaneous coronary intervention (PCI) procedures are being performed in greater numbers, in older patients with multiple comorbidities, and increasingly in the setting of acute coronary syndromes. Estimating inpatient PCI mortality and MACE risk (mortality, Q-wave myocardial infarction, urgent coronary artery bypass grafting and stroke) is essential in informing decision-making, consent, and operator and institutional benchmarking. There are a number of currently available risk scores that are often applied interchangeably. We investigated if there was concordance between contemporary risk scoring systems for inpatient mortality and MACE following PCI in patients at low, moderate or high-risk in a 'real life' cohort, depending upon method of presentation (elective, urgent, emergency). METHODS: We retrospectively identified 1,404 consecutive patients treated by PCI within a 6-month period in 2013. The New York risk score (NY) and National Cardiovascular Data Registry score (NCDR) were calculated for each patient to predict inpatient mortality risk and the Northwestern Quality Improvement score (NWQIP) and the Mayo Clinical Risk Score (MCRS) were calculated to predict inpatient MACE risk. Using the NY score as the reference for inpatient mortality and the NWQIP score as the reference for inpatient MACE, patients were divided into three risk groups (low < 1%; moderate 1-5%; high > 5%) and stratified into elective, urgent and emergency clinical presentations. Concordance was estimated using the Intraclass Correlation Coefficient (ICC) calculated with respect to each risk score and stratified by patient group. RESULTS: 757 patients were identified as low-risk (461 elective, 280 urgent, 16 emergency), 497 patients as moderate-risk (73 elective, 197 urgent, 227 emergency) and 150 patients as high-risk (4 elective, 43 urgent, 103 emergency) for inpatient mortality. 607 patients were identified as low-risk (382 elective, 225 urgent, 0 emergency), 594 patients as moderate-risk (97 elective, 237 urgent, 260 emergency) and 203 patients as high-risk (14 elective, 66 urgent, 123 emergency) for inpatient MACE events. The ICC indicated that risk scores correlated well for low-risk groups however were poorly concordant for high-risk groups (Table 1) and that this was true regardless of mode of clinical presentation (Table 2). heartjnl;100/Suppl_3/A41-b/T1F1T1 Abstract 71 Table 1 heartjnl;100/Suppl_3/A41-b/T2F2T2 Abstract 71 Table 2 CONCLUSIONS: Currently available PCI risk scores for both inpatient mortality and MACE are broadly concordant in low risk patient groups. However in patients at higher risk with multiple co-morbid factors, current tools are poorly concordant in predicting mortality and MACE. This has important implications for consent, and benchmark analysis of operator and institutional performance. Better understanding of choice of risk score for use in clinical practice is needed particularly as case mix and complexity evolve.

Introduction Patients presenting with chest pain, raised troponin but non-obstructive coronary arteries pose a clinical challenge in diagnosis, prognosis and management. We hypothesised that early cardiovascular magnetic resonance (CMR) imaging can provide a diagnosis and comprehensive characterisation for acute myocardial injury of indeterminate aetiology. Methods and results 120 patients presenting with chest pain, positive troponin (TnI>0.04 µg/l) and non-obstructive coronary arteries prospectively underwent early CMR (median 3 days, range 0–14 days) at 1.5 T, including cine imaging for function, T2-weighted imaging for oedema and late gadolinium enhancement (LGE) imaging for myocardial necrosis/scarring. The mean age=50±17 years (50% female); median TnI=3.99 ug/l (0.07–60 µg/l); mean left ventricular ejection fraction=64±12%. There was a high CMR diagnostic yield of 95%. Significant oedema was detected in 79% and LGE in 61%. The commonest diagnosis was myocarditis (37.5%), followed by Takotsubo cardiomyopathy (22.5%), myocardial infarction (17.5%), acute regional stunning (9.2%; wall motion abnormality with oedema but no LGE), dilated cardiomyopathy (4.2%), hypertrophic cardiomyopathy (3.3%), and missed pulmonary embolism (0.8%). Eleven of the 21 patients with MI (52%) had a patent foramen ovale (PFO) demonstrated on transthoracic echocardiography with agitated saline contrast and presumably suffered a paradoxical embolism to a coronary artery. The remaining 5.0% of patients had no clear diagnosis identified. Conclusions CMR has a high diagnostic yield (95%) in patients presenting with troponin-positive chest pain but non-obstructive coronary arteries when performed early (median 3 days). This study highlights the importance and usefulness of early access to CMR in this group of patients. When no apparent cause is identified, early conventional CMR was able to exclude myocardial infarction, wall motion abnormality, significant oedema or scarring.

Introduction Targeting particles to sites of inflammation is of considerable interest for molecular imaging and drug delivery. We and others have described micron-sized particles of iron oxide (MPIO) that can be directed using specific ligands to bind to mediators of vascular inflammation in vivo. Since leukocyte binding to these molecules can induce changes in the target cell, an outstanding question is whether the binding of imaging particles induces biologically significant changes in the endothelial cells, potentially initiating or propagating inflammation. We address this by looking for changes in human aortic endothelial cells (HAEC) following binding of contrast agent. Methods 1 µm MPIO dual-targeted to E-selectin and VCAM were prepared by labelling with specific antibodies, and cellular responses to binding events assessed. Calcium flux was monitored using the calcium indicator Fluo-4 and fluorescent microscopy for analysis. Production of reactive oxygen species was investigated using a nitroblue tetrazolium blue (NBT) assay. Real-time RT-PCR was used to assess gene expression of several endothelial markers of inflammation. Antibody staining of cell surface proteins and flow cytometry analysis monitored protein levels presented by HAEC. Results Binding of E+V-MPIO did not cause calcium flux in HAEC; normalised fluorescence intensity of Fluo-4 dropped to 0.81 (SEM ±0.02) of baseline 60 seconds post MPIO binding and to 0.64 (SEM±0.02) with vehicle only, whilst a significant increase in Fluo-4 fluorescence to 1.96 (SEM±0.48) was seen following THP-1 binding indicating endothelial calcium flux post-leukocyte binding (P Conclusions Our experiments demonstrate that whilst antibody-targeted microparticles mimic the binding capability of leukocytes to inflamed endothelium, they do not trigger the same cellular responses and do not appear to initiate or compound inflammation. These properties are desirable for targeted therapeutic and diagnostic agents.

Background Acute myocardial infarction (AMI) results in both systemic inflammation and recruitment of leukocytes to injured myocardium. Additionally, myocardium remote to the infarct zone, also becomes inflamed and is associated with adverse LV remodelling. Renal ischaemic syndromes have been associated with remote organ inflammation and impaired function. We therefore tested the hypothesis thatAMI results in acute inflammation at remote sites which may contribute to organ dysfunction. Methods Female C57BL/6J mice underwent AMI by surgical coronary artery ligation or sham procedure. At 24 hours, mice underwent transthoracic echocardiography prior to sacrifice (n=8/group). The inflammatory response in peripheral blood, injured and remote myocardium, and kidneys was studied. Results At 24 hours, in comparison to sham operated mice, AMI resulted in increased circulating neutrophils and monocytes (P Conclusion (1) AMI induces a local inflammatory response, characterised by infiltration of leukocytes and increased expression of mRNA for inflammatory cytokines; (2) cytokines are upregulated in myocardium that is remote from the site of ischaemic injury; (3) AMI is associated with systemic inflammation, reflected in increased peripheral blood neutrophils and monocytes; (4) AMI is also associated with remote organ inflammation evidenced by (i) increased expression of mRNA for inflammatory cytokines, (ii) marked upregulation of VCAM-1 in renal glomeruli and (iii) by the recruitment and infiltration of leukocytes in the kidney.

Introduction Although in-vivo multicontrast MRI is capable of characterizing atherosclerotic plaques in carotid arteries, its non-quantitative nature and the need for extensive post-acquisition interpretation limit its widespread clinical application. Quantitative T2 mapping is a promising alternative since it can provide an absolute physical measure of plaque components that can be standardised among different MRI systems and widely adopted in multi-centre studies. The purpose of this pilot study is to seek the potential of in-vivo T2 mapping and its correlation with different plaque components ex-vivo on histology. Methods 3T-MRI : 15 asymptomatic patients (11 males, 71±10 years) and 13 patients scheduled for endarterectomy (9 males, 70±17 years) were imaged at 3T using the conventional multicontrast protocol and Multiple-Spin-Echo (Multi-SE). T2 maps were generated by mono-exponential fitting to the series of images acquired by Multi-SE using non-linear least-squares regression. Two reviewers independently classified plaque types according to the MRI-modified AHA scheme, one using T2 maps+TOF images, the other using multicontrast MRI. Histology Carotid plaques were freshly obtained at time of endarterectomy. Plaques were divided at the level of maximal stenosis and 4mm-segments on either side of the cut were processed for formalin-fixed, paraffin-embedded (FFPE) sections and cryosections, respectively. FFPE sections were stained for H&E and Masson’s trichrome, while cryosections were used for Oil-Red-O/adipophilin (foam cells marker) staining to visualize lipid. MRI-histology matching was performed for each segment using the carotid bifurcation as the common anatomical landmark. AHA plaque type was determined by an independent reviewer. Results In the 15 asymptomatic patients, AHA plaque type classified on multicontrast MRI and on T2 maps (+TOF) showed good agreement (76% of matching classifications and Cohen’s κ=0.68). 4 of the 13 patients scheduled for endarterectomy were excluded due to severe MRI motion artefacts. AHA type classification of the remaining 9 plaques using T2 maps (+TOF) vs. histology is presented in Table 1. Figure 1 shows a type VI and Figure 2 a type IV-V plaque. T2 maps were able to differentiate lipid-rich necrotic core (LRNC), fibrous tissue, calcification, and recent intraplaque-haemorrhage (IPH). Conslusions These preliminary results show the potential of in-vivo T2 mapping for atherosclerotic plaque characterization. Agreement between AHA plaque types classified by T2 maps (+TOF) and by conventional multicontrast MRI was good. The ability of T2 maps to discriminate LRNC, fibrous tissue and recent IPH was confirmed by histology. Further prospective quantitative validation study is now underway.

Introduction Nicotinic acid (NA) has been known to exert favourable effects on plasma lipoproteins. It regresses atherosclerosis in human imaging studies and reduces atherosclerosis in mice, mediated by its receptor GPR109a on myeloid cells, independent of its lipoprotein effect. Since GPR109a is expressed by human monocytes, we hypothesized that NA may drive cholesterol efflux from human macrophage-derived foam cells. Methods THP-1 cells were induced into foam cells by acetylated LDL. After treatment with NA, GW1929 (a PPARγ agonist) and vehicle controls, cholesterol efflux was assessed using HDL3 and apo-AI as cholesterol acceptors. qRT-PCR was performed using primers for genes responsible for inflammation and reverse cholesterol transport (RCT). ELISA9s for PPARγ activity and cAMP response were performed to investigate NA9s putative cellular mechanisms of action. Fluorescence immunohistochemistry on ex-vivo human carotid atherosclerotic plaques was carried out against CD68, adipophilin (a foam cells marker), as well as GPR109a. Immediately adjacent sections were stained with Oil-red-O to visualized lipid content and distribution. Results In basal THP-1 cells, NA suppressed LPS-induced mRNA transcription of MCP-1 by 76.6±12.2% (P Conclusions This study shows that despite NA9s anti-inflammatory effect on human macrophages, it does not appear to enhance cholesterol efflux in foam cells, which is at least partially ascribed to GPR109a down-regulation upon foam cell transformation. This implies that direct NA-promotion of cholesterol efflux from foam cells may not contribute to atherosclerosis regression, which has been demonstrated with this drug.

Introduction Cardiovascular magnetic resonance (CMR) is the gold standard technique to assess myocardial viability (using late gadolinium enhancement (LGE)) and reversible injury (using T2-Weighted (T2W) for oedema imaging) in acute myocardial infarction (MI). However, both LGE and T2W are hampered by methodological issues such as threshold-based method for post-processing with scope for error and the need for MR contrast agent. The interpretation of CMR is also challenged by the dynamic changes occurring in the acutely ischaemic tissue as part of the healing process. Pre-contrast T1-mapping can overcome these limitations by providing voxel-based quantitative tissue characterisation. In acute MI patients, we sought to investigate whether pre-contrast T1-mapping11 (1) detects acute myocardial injury, (2) allows for quantification of the severity of damage when compared to standard techniques such as LGE and T2W, and (3) has the ability to predict long term functional recovery. Methods 41 patients with acute MI (30% non-ST elevation MI (NSTEMI)) underwent 3T CMR including T2W, T1 mapping and LGE, 12–48 h after chest pain onset and at 6 months. Patients with ST elevation MI (STEMI) underwent primary PCI first. Acute mean segmental T1values, acute and chronic regional and global function and segmental damaged fraction by T2W and LGE were assessed. Results The diagnostic performance of acute T1-mapping was at least as good as that of T2W CMR for detecting myocardial injury; however, in NSTEMI it was significantly higher than T2W oedema imaging. Also, T1 values could define the segmental damaged fraction, as assessed by either by LGE or T2W (p Conclusions In patients with acute MI, pre-contrast T1 mapping allows to delineate the extent of myocardial injury and to predict functional recovery at 6 months. Further investigations will be needed to determine whether T1 mapping can distinguish oedema from necrosis in acute MI.