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To determine the incidence, characteristics, and outcomes associated with geographical miss (GM) of plaque.GM describes plaques that are incompletely covered following stenting, with GM thought to be associated with worse clinical outcomes. However, the incidence and characteristics of intravascular ultrasound (IVUS)-defined GM plaques have never been studied and the relationship between GM with both short and long-term clinical events is unknown.One hundred and seventy patients with stable angina (n = 100) or myocardial infarction (MI) (n = 70) underwent virtual-histology IVUS (VH-IVUS) prior to, and following, percutaneous coronary intervention (PCI). GM was defined as three consecutive uncovered VH frames, either proximal or distal to the stented segment with plaque burden40%. MACE was defined as a composite of death, myocardial infarction, unplanned revascularization, or hospitalization for angina.In total, 245 plaques underwent PCI with 80 (32.7%) displaying evidence of GM (69 patients). GM was associated with increased plaque volume (p 0.001), % necrotic core, and dense calcium (both p 0.001) and VH-defined thin-cap fibroatheroma (VH-TCFA) (p = 0.01). GM was not associated with increased periprocedural MI (p = 0.15) or inflammatory cytokine release. At follow-up, 42 MACE occurred in 28 patients (median 1,115 days). MACE was attributable to 8/80 (10%) plaques with and 7/165 (4.2%) plaques without GM (log-rank p = 0.11). GM was associated with increased MACE in patients presenting with MI (p = 0.015), but not for those with stable angina (p = 0.94).GM is common after PCI and associated with more vulnerable plaque composition/subtype. GM may confer a worse prognosis in patients undergoing PCI for MI. © 2015 Wiley Periodicals, Inc.

Doping is one of the most important methods to control charge carrier concentration in semiconductors. Ideally, the introduction of dopants should not perturb the ordered microstructure of the semiconducting host. In some systems, such as modulation-doped inorganic semiconductors or molecular charge transfer crystals, this can be achieved by spatially separating the dopants from the charge transport pathways. However, in conducting polymers, dopants tend to be randomly distributed within the conjugated polymer, and as a result the transport properties are strongly affected by the resulting structural and electronic disorder. Here, we show that in the highly ordered lamellar microstructure of a regioregular thiophene-based conjugated polymer, a small-molecule p-type dopant can be incorporated by solid state diffusion into the layers of solubilizing side chains without disrupting the conjugated layers. In contrast to more disordered systems, this allows us to observe coherent, free-electron-like charge transport properties, including a nearly ideal Hall effect in a wide temperature range, a positive magnetoconductance due to weak localization and the Pauli paramagnetic spin susceptibility.

Transradial (TR) access for percutaneous coronary intervention (PCI) reduces bleeding compared with transfemoral (TF) access, and may reduce mortality in specific patient subsets. However, switching from TF to TR access is associated with a learning curve and it is unclear whether benefits observed in randomized trials translate into practice. We sought to characterize the trends in bleeding and mortality rates at our institution, as we changed from being a TF to predominantly TR center over a 5-year period.10,213 consecutive patients presenting for PCI were included (mean age 65.0 ± 11.6 years, 76.1% male, 48.0% PCI for acute coronary syndrome) over 5 years at a single center with PCI volume2,000 cases per annum. Patients were stratified by initial arterial access site (TR or TF) and outcome measures included temporal trends in TR procedural failure, 30-day bleeding complications and all-cause 1-year mortality. TR procedural failure fell to a consistently low rate within 1 year (11.8% in 2008 to 2.9% in 2009, P 0.001). As TR volume increased, the annual 30-day bleeding rate fell (1.64% in 2008 to 0.68% in 2012, P = 0.006). TR access predicted reduced 30-day bleeding (OR 0.17 [95%CI 0.07-0.38], P 0.001), but was not a predictor of 1-year survival (HR 0.78 [95%CI 0.58-1.05], P = 0.10).Successful transition from TF to TR PCI at our institution was rapid and associated with a reduction in 30-day bleeding. These data should encourage other centers considering the adoption of TR access.

Calculating high stress concentration within carotid atherosclerotic plaques has been shown to be complementary to anatomical features in assessing vulnerability. Reliability of stress calculation may depend on the constitutive laws/strain energy density functions (SEDFs) used to characterize tissue material properties. Different SEDFs, including neo-Hookean, one-/two-term Ogden, Yeoh, 5-parameter Mooney–Rivlin, Demiray and modified Mooney–Rivlin, have been used to describe atherosclerotic tissue behavior. However, the capacity of SEDFs to fit experimental data and the difference in the stress calculation remains unexplored. In this study, seven SEDFs were used to fit the stress–stretch data points of media, fibrous cap, lipid and intraplaque hemorrhage/thrombus obtained from 21 human carotid plaques. Semi-analytic solution, 2D structure-only and 3D fully coupled fluid-structure interaction (FSI) analyses were used to quantify stress using different SEDFs and the related material stability examined. Results show that, except for neo-Hookean, all other six SEDFs fitted the experimental points well, with vessel stress distribution in the circumferential and radial directions being similar. 2D structural-only analysis was successful for all seven SEDFs, but 3D FSI were only possible with neo-Hookean, Demiray and modified Mooney–Rivlin models. Stresses calculated using Demiray and modified Mooney–Rivlin models were nearly identical. Further analyses indicated that the energy contours of one-/two-term Ogden and 5-parameter Mooney–Rivlin models were not strictly convex and the material stability indictors under homogeneous deformations were not always positive. In conclusion, considering the capacity in characterizing material properties and stabilities, Demiray and modified Mooney–Rivlin SEDF appear practical choices for mechanical analyses to predict the critical mechanical conditions within carotid atherosclerotic plaques.

Objective Although certain morphological features depicted by high resolution, multi-contrast magnetic resonance imaging (hrMRI) have been shown to be different between culprit and non-culprit middle cerebral artery (MCA) atherosclerotic lesions, the incremental value of hrMRI to define culprit lesions over stenosis has not been assessed. Methods Patients suspected with MCA stenosis underwent hrMRI. Lumen and outer wall were segmented to calculate stenosis, plaque burden (PB), volume (PV), length (PL) and minimum luminal area (MLA). Results Data from 165 lesions (112 culprit and 53 non-culprit) in 139 individuals were included. Culprit lesions were larger and longer with a narrower lumen and increased PB compared with non-culprit lesions. More culprit lesions showed contrast enhancement. Both PB and MLA were better indicators than stenosis in differentiating lesion types (AUC were 0.649, 0.732 and 0.737 for stenosis, PB and MLA, respectively). Combinations of PB, MLA and stenosis could improve positive predictive value (PPV) and specificity significantly. An optimal combination of stenosis ≥ 50 %, PB ≥ 77 % and MLA ≤ 2.0 mm2 produced a PPV = 85.7 %, negative predictive value = 54.1 %, sensitivity = 69.6 %, specificity = 75.5 %, and accuracy = 71.5 %. Conclusions hrMRI plaque imaging provides incremental information to luminal stenosis in identifying culprit lesions. Key points • High resolution MRI provides incremental information in defining culprit MCA atherosclerotic lesions. • Both plaque burden and minimum luminal area are better indicators than stenosis. • An optimal combination includes stenosis ≥ 50 %, PB ≥ 77 % and MLA ≤ 2.0 mm2. Electronic supplementary material The online version of this article (doi:10.1007/s00330-015-4008-5) contains supplementary material, which is available to authorized users.

Invasive imaging modalities, in particular intravascular ultrasound (IVUS) and optical coherence tomography (OCT), have become established tools for the in vivo study of coronary atherosclerosis. Their use in clinical studies has confirmed histopathological observations that certain important plaque features, such as thin fibrous caps and large lipid cores, are associated with plaque rupture, the precipitating event for the majority of myocardial infarctions. Serial imaging studies have also successfully been used for the evaluation of potential disease modifying pharmacological agents. Recent prospective IVUS studies have confirmed specific baseline imaging features associated with subsequent adverse clinical outcomes, although absolute event rates were too low for clinical utility. Development of hybrid IVUS-OCT imaging or integration of novel techniques, including near-infrared spectroscopy, plaque structural and endothelial shear stress, have great potential to improve our current ability to identify and stratify atheromatous plaques at risk of rupture.

Background Available data on the use of the ABSORB bioresorbable vascular scaffold (BVS) (Abbott Vascular, Santa Clara, CA) in real-world patients is limited. The aim of this study was to assess the mid-term clinical outcomes in a real-world population treated with ABSORB BVS. Methods and materials We retrospectively evaluated all patients treated with ABSORB at Papworth Hospital, Papworth Everard, UK between July 2012 and July 2014. A total of 108 patients (126 lesions) were identified. Clinical follow-up was performed on all subjects by clinic visit or telephone interview. Results Most patients were male (91.7%) with a relative high incidence of previous myocardial infarction (MI) (40.7%). Clinical presentation was equally divided between stable angina and acute coronary syndrome (ACS) (51.8% vs. 48.2%, p = 0.59). Of the ACS patients, 26.9% presented with ST-elevation myocardial MI. Intravascular imaging was used in all cases. Predilatation (92.9%) and postdilatation (82.5%) were frequently performed. Major adverse cardiac event (MACE) rates defined as the composite of all-cause death, follow-up MI and target vessel revascularization were 2.5% at 6-month and 4.5% at 1-year. The 1-year target lesion failure rate, defined as the composite of cardiac death, target-vessel MI and target lesion revascularization was 1.9%. There was 1 case of subacute stent thrombosis. Conclusions The use of ABSORB BVS in real-world patients appears to be associated with good mid-term clinical outcomes when guided by intravascular imaging. Larger studies are required to evaluate further the role of BVS in routine clinical practice and examine how this compares to metallic devices. Summary Available data on the use of the ABSORB BVS in real-world patients is limited. We retrospectively evaluated all patients treated with ABSORB BVS between July 2012 and July 2014. A total of 108 patients (126 lesions) were identified. Clinical presentation was equally divided between stable angina and acute coronary syndrome (51.8% vs. 48.2%, p = 0.59). Predilatation (92.9%) and postdilatation (82.5%) were frequently performed. Estimated MACE rates at 6-month and 1-year were 2.5% and 4.5% respectively, with a 1-year TLF rate of 1.9%. These results suggest that the use of ABSORB BVS use in the real-world is associated with good mid-term clinical outcomes when guided by intravascular imaging.

Objective Utilising a novel study design, we evaluated serial measurements of the index of microcirculatory resistance (IMR) in patients undergoing primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) to assess the impact of device therapy on microvascular function, and determine what proportion of microvascular injury is related to the PPCI procedure, and what is an inevitable consequence of STEMI. Design 41 patients undergoing PPCI for STEMI were randomised to balloon angioplasty (BA, n=20) or manual thrombectomy (MT, n=21) prior to stenting. Serial IMR measurements, corrected for collaterals, were recorded at baseline and at each stage of the procedure. Microvascular obstruction (MVO) and infarct size at 24 h and 3 months were measured by troponin and cardiac MRI (CMR). Results IMR did not change significantly following PPCI, but patients with lower IMR values (

Mechanical analysis has the potential to provide complementary information to aneurysm morphology in assessing its vulnerability. Reliable calculations require accurate material properties of individual aneurysmal components. Quantification of extreme extensibility and ultimate material strength of the tissue are important if rupture is to be modelled. Tissue pieces from 11 abdomen aortic aneurysm (AAA) from patients scheduled for elective surgery and from 8 normal aortic artery (NAA) from patients who scheduled for kidney/liver transplant were collected at surgery and banked in liquid nitrogen with the use of Cryoprotectant solution to minimize frozen damage. Prior to testing, specimen were thawed and longitudinal and circumferential tissue strips were cut from each piece and adventitia, media and thrombus if presented were isolated for the material test. The incremental Young’s modulus of adventitia of NAA was direction-dependent at low stretch levels, but not the media. Both adventitia and media had a similar extreme extensibility in the circumferential direction, but the adventitia was much stronger. For aneurysmal tissues, no significant differences were found when the incremental moduli of adventitia, media or thrombus in both directions were compared. Adventitia and media from AAA had similar extreme extensibility and ultimate strength in both directions and thrombus was the weakest material. Adventitia and media from AAA were less extensible compared with those of NAA, but the ultimate strength remained similar. The material properties, including extreme extensibility and ultimate strength, of both healthy aortic and aneurysmal tissues were layer-dependent, but not direction-dependent.

Implantation of the everolimus-eluting bioresorbable vascular scaffold (BVS) requires accurate vessel sizing, lesion preparation and device optimization. Intravascular imaging may assist in all such stages, but its benefits over angiographic guidance alone have not been tested. We analyzed

Real-time quantitative PCR (qPCR) is the standard method for determination of relative changes in mRNA transcript abundance. Analytical accuracy, precision and reliability are critically dependent on the selection of internal control reference genes. In this study, the authors have identified optimal reference genes that can be utilised universally for qPCR analysis of CHO cell mRNAs. Initially, transcriptomic datasets were analysed to identify eight endogenous genes that exhibited high expression stability across four distinct CHO cell lines sampled in different culture phases. The relative transcript abundance of each gene in 20 diverse, commonly applied experimental conditions was then determined by qPCR analysis. Utilizing GeNorm, BestKeeper and NormFinder algorithms, the authors identified four mRNAs (Gnb1, Fkbp1a, Tmed2 and Mmadhc) that exhibited a highly stable level of expression across all conditions, validating their utility as universally applicable reference genes. Whilst any combination of only two genes can be generally used for normalisation of qPCR data, the authors show that specific combinations of reference genes are particularly suited to discrete experimental conditions. In summary, the authors report the identification of fully validated universal reference genes, optimised primer sequences robust to genomic mutations and simple reference gene pair selection guidelines that enable streamlined qPCR analyses of mRNA abundance in CHO cells with maximum accuracy and precision.

Transient gene expression (TGE) in CHO cells is utilized to produce material for use in early stage drug development. These systems typically utilize the cytomegalovirus (CMV) promoter to drive recombinant gene transcription. In this study, we have mechanistically dissected CMV-mediated TGE in CHO cells in order to identify the key regulators of this process. An in silico analysis of the promoter composition of transcription factor regulatory elements (TFREs) and the CHO cell repertoire of transcription factors identified eight TFREs as likely effectors of CMV activity. We determined the regulatory function of these elements by preventing their cognate transcription factors from binding at the CMV promoter. This was achieved by both scrambling promoter binding site sequences and using decoy molecules to sequester intracellular transcription factors. We determined that the vast majority of CMV activity is mediated by just two discrete TFREs, showing that simultaneous inhibition of NF-κB and CRE-mediated transactivation reduced CMV-driven transient secreted alkaline phosphatase (SEAP) production by over 75%. Further, we identified a mechanism by which CMV-mediated TGE is negatively regulated in CHO cells, showing that inhibition of YY1-mediated transrepression increased SEAP production 1.5-fold. This work enables optimization and control of CMV-mediated TGE in CHO cells, in order to improve transient protein production yields.

Optical coherence tomography (OCT) provides unparalleled image resolution but quantitative assessment and plaque classification, particularly when defining thin-capped fibroatheroma (TCFA) may be prone to inter-observer error. We sought to assess the reproducibility of several OCT plaque imaging

Using deformable models to register medical images can result in problems of initialization of deformable models and robustness and accuracy of matching of inter-subject anatomical variability. To tackle these problems, a novel model is proposed in this paper by compounding local invariant features and global deformable geometry. This model has four steps. First, a set of highly-repeatable and highly-robust local invariant features, called Key Features Model (KFM), are extracted by an effective matching strategy. Second, local features can be matched more accurately through the KFM for the purpose of initializing a global deformable model. Third, the positional relationship between the KFM and the global deformable model can be used to precisely pinpoint all landmarks after initialization. And fourth, the final pose of the global deformable model is determined by an iterative process with a lower time cost. Through the practical experiments, the paper finds three important conclusions. First, it proves that the KFM can detect the matching feature points well. Second, the precision of landmark locations adjusted by the modeled relationship between KFM and global deformable model is greatly improved. Third, regarding the fitting accuracy and efficiency, by observation from the practical experiments, it is found that the proposed method can improve 6~8% of the fitting accuracy and reduce around 50% of the computational time compared with state-of-the-art methods.

Graphical abstract Fibrous cap and media in the carotid atherosclerotic plaques are much stiffer than either lipid, intraplaque haemorrhage or thrombus., Computational modelling to calculate the mechanical loading within atherosclerotic plaques has been shown to be complementary to defining anatomical plaque features in determining plaque vulnerability. However, its application has been partially impeded by the lack of comprehensive knowledge about the mechanical properties of various tissues within the plaque. Twenty-one human carotid plaques were collected from endarterectomy. The plaque was cut into rings, and different type of atherosclerotic tissues, including media, fibrous cap (FC), lipid and intraplaque haemorrhage/thrombus (IPH/T) was dissected for uniaxial extension testing. In total, 65 media strips from 17 samples, 59 FC strips from 14 samples, 38 lipid strips from 11 samples, and 21 IPH/T strips from 11 samples were tested successfully. A modified Mooney–Rivlin strain energy density function was used to characterize the stretch–stress relationship. The stiffnesses of media and FC are comparable, as are lipid and IPH/T. However, both media and FC are stiffer than either lipid or IPH/T. The median values of incremental Young’s modulus of media, FC, lipid and IPH/T at λ = 1 are 290.1, 244.5, 104.4, 52.9, respectively; they increase to 1019.5, 817.4, 220.7 and 176.9 at λ = 1.1; and 4302.7, 3335.0, 533.4 and 268.8 at λ = 1.15 (unit, kPa; λ, stretch ratio). The material constants of each tissue type are suggested to be: media, c1 = 0.138 kPa, D1 = 3.833 kPa and D2 = 18.803; FC, c1 = 0.186 kPa, D1 = 5.769 kPa and D2 = 18.219; lipid, c1 = 0.046 kPa, D1 = 4.885 kPa and D2 = 5.426; and IPH/T, c1 = 0.212 kPa, D1 = 4.260 kPa and D2 = 5.312. It is concluded that all soft atherosclerotic tissues are non-linear, and both media and FC are stiffer than either lipid or IPH/T.

Randomised trials have shown that direct stenting (DS) is associated with improved markers of reperfusion during primary percutaneous coronary intervention (PPCI) for ST elevation myocardial infarction (STEMI). However, data evaluating its impact on long-term clinical outcomes are lacking. We set out to evaluate the effect of DS on mortality in a contemporary population of patients undergoing PPCI for STEMI.Consecutive patients undergoing PPCI for STEMI at two high-volume UK heart attack centres between September 2008- December 2010 (n=1562) were included in the analysis. Local databases were analysed for patient demographics, as well as details on PPCI strategy, including use of DS versus predilatation (PD) followed by stenting, manual thrombus aspiration (MT) and glycoprotein IIb/IIIa inhibitors (GPIs). National databases were interrogated for in-hospital, 30-day and one-year mortality. To determine the impact of PPCI strategy on one-year survival, multivariate logistic analysis was performed.Altogether 489 patients underwent DS (31.3%) and 1073 (68.7%) received PD prior to stenting. Patients receiving DS had reduced mortality at 30 days (2.04 versus 4.66%, p=0.01) and one year (3.27 versus 8.48%, p=0.0001). After multivariate adjustment, PD remained an independent predictor of one-year mortality (odds ratio 2.42, 95% confidence interval 1.08-5.45, p=0.032) along with age, cardiogenic shock, number of diseased vessels, and left main or proximal left anterior descending artery intervention. However, neither GPI use nor MT improved survival in either univariate or multivariate analyses.In a contemporary, unselected population of patients undergoing PPCI for STEMI, DS - when compared with stenting after PD - is independently predictive of improved 30-day and one-year survival.

We describe for the first time the creation of a library of 140 synthetic promoters specifically designed to regulate the expression of recombinant genes in CHO cells. Initially, 10 common viral promoter sequences known to be active in CHO cells were analyzed using bioinformatic sequence analysis programs to determine the identity and relative abundance of transcription factor regulatory elements (TFREs; or transcription factor binding sites) they contained. Based on this, 28 synthetic reporters were constructed that each harbored seven repeats of a discrete TFRE sequence upstream of a minimal CMV core promoter element and secreted alkaline phosphatase (SEAP) reporter gene. After evaluation of the relative activity of TFREs by transient expression in CHO-S cells, we constructed a first generation library of 96 synthetic promoters derived from random ligation of six active TFREs inserted into the same reporter construct backbone. Comparison of the sequence and relative activity of first generation promoters revealed that individual TFRE blocks were either relatively abundant in active promoters (NFκB, E-box), equally distributed across promoters of varying activity (C/EBPα, GC-box) or relatively abundant in low activity promoters (E4F1, CRE). These data were utilized to create a second generation of 44 synthetic promoters based on random ligation of a fixed ratio of 4 TFREs (NFκB 5: E-box 3: C/EBPα 1: GC-box 1). Comparison of the sequence and relative activity of second generation promoters revealed that the most active promoters contained relatively high numbers of both NFκB and E-box TFREs in approximately equal proportion, with a correspondingly low number of GC-box and C/EBPα blocks. The most active second generation promoters achieved approximately twice the activity of a control construct harboring the human cytomegalovirus (CMV) promoter. Lastly, we evaluated the function of a subset of synthetic promoters exhibiting a broad range of activity in different CHO cell host cell lines (CHO-S, CHO-K1, and CHO-DG44) and across extended fed-batch transient expression in CHO-S cells. In general, the different synthetic promoters both maintained their relative activity and the most active promoters consistently and significantly exceeded the activity of the CMV control promoter. For advanced cell engineering strategies our synthetic promoter libraries offer precise control of recombinant transcriptional activity in CHO cells spanning over two orders of magnitude.

A 77-year-old woman with effort angina returned for intervention to her proximal circumflex and second obtuse marginal (OM2) artery. Angiography was undertaken transradially. Mild radial intra-arterial spasm was treated with intra-arterial glyceryl trinitrate, and a hydrophilic-coated guidewire was

Phosphotyrosine-containing proteins are present in the prothoracic glands, muscle, and fat body of Manduca sexta, as determined by immunoprecipitation followed by kinase assay, and by Western blotting. One such protein (Mr 178,000) can also be immunoprecipitated using antibodies directed against the human insulin receptor and insulin receptor substrate. The 178 kD protein appears to be expressed more strongly in prothoracic glands removed just prior to wandering (days 3-4) and prior to pupation (days 7-9), and phosphorylation of the protein is enhanced by an M. sexta brain factor. The results suggest that a tyrosine-kinase-linked molecule similar to the insulin receptor may play a regulatory role in M. sexta. Arch. Insect Biochem. Physiol. 35:99-110, 1997. © 1997 Wiley-Liss, Inc.

We assessed whether interventional complexity in patients presenting with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) predicted long-term outcome. Consecutive patients undergoing PPCI for STEMI underwent SYNTAX scoring, based on angiographic images obtained at coronary intervention. Patients were classified as SYNTAX score (SS) ≤22 (low, L), 23 to 32 [intermediate (IM)], and ≥33 (high, H). The median SS for the cohort was 19 [Interquartile range (IQR), 11.0-25.5] with median tertile scores of L 14 (IQR 9.0-18.5, n = 437), IM 26 (IQR 24.0-28.5, n = 170), and H 36 (IQR 34.5-40.5, n = 67). Two-year freedom from major adverse cardiac events (MACE) was L 88.1%, IM 78.8%, and H 68.7% ( P < .001). Multivariate analysis confirmed that increasing SS tertile was an independent predictor of MACE [IM hazard ratio (HR) 1.61, confidence interval (CI) 1.05-2.47; P = .03, H HR 1.99, CI 1.16-3.41; P = .01]. The SS, when applied to patients undergoing PPCI for STEMI, provides prognostic information.

To assess the utility of left bundle branch block (LBBB) as an activation criterion for primary percutaneous coronary intervention (PPCI).Retrospective observational cohort study.Single UK heart attack centre.Consecutive patients referred for PPCI September 2008-December 2011 (n=2192).Demographic and outcome data were obtained by review of case notes, angiograms and interrogation of local/national databases.Angiographic culprit lesion assessment defined appropriate and inappropriate activations. Patients outcomes were assessed by Major adverse cardiac events (MACE), defined as a composite of mortality and unplanned revascularisation at 1-year.LBBB-activation occurred in 120 patients (5.5%), of whom 21 (17.5%) had acute coronary occlusion angiographically, and were adjudicated appropriately. Compared with appropriate activations for ST segment elevation, appropriate LBBB-activations were older (71.0 ± 9.6 vs 64.2 ± 12.4 years, p=0.01) and more likely to be in cardiogenic shock (19.0% vs 4.3%, p0.01). Extent of disease quantified by the SYNTAX score did not differ (median 21.5, IQR 11.0-27.0 vs 19, 11.0-25.5, p=0.66), but amount of myocardium at-risk was higher in appropriate LBBB-activations (culprit jeopardy score median 4, IQR 2-6 vs 2, 2-4, p=0.02). Final diagnoses for LBBB-activations were acute coronary syndrome (39.2%), non-acute coronary syndrome cardiac chest pain (33.3%) and non-cardiac chest pain (27.5%). In appropriate LBBB-activations 1-year mortality and MACE were higher (23.8% vs 6.6%, p=0.002 and 28.6% vs 10.5%, p=0.007, respectively).Our data suggests that despite its poor specificity for identifying acute coronary occlusion, LBBB should at the present time remain an activation criterion for PPCI and such patients should continue to be transferred to heart attack centres for assessment and treatment.

Background: Significant variations in postoperative levels of parathyroid hormone (PTH), calcium and phosphate exist after renal transplantation, but whether they affect allograft function is unknown. We investigated the association between early post-transplant levels of PTH, calcium and phosphate and graft function. Methods: We performed a single-centre cohort study of renal transplant recipients from Addenbrooke's Hospital, Cambridge, between April 1997 and March 2007, evaluating the association between plasma calcium, phosphate and PTH 1 month after transplantation and change in epidermal growth factor receptor (eGFR) in the first 12 months after transplantation (estimated using the Modification of Diet in Renal Disease Study equation). Differences in eGFR between 26 and 52 weeks after transplantation were computed using mixed effects linear regression models for repeated measures of eGFR, while adjusting for sociodemographic and biochemical variables. Results: Three hundred and forty-three patients were eligible for study. The mean age (standard deviation) at transplant was 43 years (13 years). Between 30 and 90 days after transplantation, the median (25th-75th percentile) eGFR was 33 (26-50) ml/min/1.73 m2, the mean calcium level was 2.4 (0.17) mmol/l and the mean phosphate level was 0.78 (0.23) mmol/l. There was a significant interaction between calcium and phosphate levels (p = 0.006). In patients with low levels of phosphate, higher levels of calcium were associated with declining eGFR over time. However, in patients with a high phosphate level, higher calcium was associated with improved eGFR. Conclusions: Higher serum calcium in patients with low serum phosphate after transplantation is associated with a decline in graft function during the first year after transplantation. Disorders of mineral metabolism after transplant may represent an important therapeutic target to preserve allograft function.

Historical data report fatal myocardial infarction occurring when mildly-stenotic coronary plaques rupture; however, recent data suggest haemodynamically-significant coronary stenoses with fractional flow reserve (FFR) ≤ 0.8 and vessels with high plaque burden and minimum luminal area (MLA)4 mm(2) by intravascular ultrasound (IVUS) may be prognostically important. Therefore, we sought to re-evaluate culprit stenosis severity in patients presenting with ST-segment elevation myocardial infarction (STEMI).Patients undergoing primary percutaneous coronary intervention (PPCI) for STEMI with adjunctive thrombectomy between October 2008 and February 2010 (n = 336/572; 59%) underwent quantitative coronary angiography (QCA) after thrombus aspiration to determine vessel reference area (RA), MLA and percentage area stenosis (AS). To validate findings, QCA and FFR were measured in 50 patients with stable angina and an angiographically-intermediate lesion.STEMI patients had anatomically-severe underlying culprit disease similar to that of the stable cohort (AS: 91.6 ± 9.5% versus 90.1 ± 8.1%; P = 0.11). Additionally, anatomically-severe lesions defined by QCA were more likely to be functionally-significant by FFR and vice-versa (P = 0.02 and 0.002 respectively).These contemporary data suggest that STEMI culprit lesions, defined by luminal stenosis after thrombus aspiration, are angiographically significant, with similar stenosis severity to stable, ischaemia-inducing lesions.

Plaque rupture is the commonest cause of myocardial infarction, occurring particularly in higher-risk lesions such as fibroatheromas. However, prospective virtual-histology intravascular ultrasound (VH-IVUS) studies indicate that

Natural history atherosclerosis studies have identified features of plaque vulnerability using intravascular imaging, but have largely failed to predict future events; whilst physiological indices identify ischemia-inducing lesions, they cannot predict lesion progression. Plaque-specific biomarker

BACKGROUND: Composite end points are common in clinical trials. OBJECTIVE: To describe how composite outcomes are used, constructed, and reported in cardiovascular trials and to evaluate the contribution of individual end points to the composite estimate of effect in those trials. DESIGN: Review of 2-group, parallel-design, randomized cardiovascular trials that used composite end points and were published in 14 clinical journals from 1 January 2000 to 1 January 2007. SETTING: Published randomized trials in cardiovascular medicine and surgery. PARTICIPANTS: Two-group, parallel-design trials published in 14 leading general medical, cardiology, and cardiothoracic surgery journals from 1 January 2000 to 1 January 2007. MEASUREMENTS: The types and numbers of individual events included in the composite outcome and P values and risk estimates for the composite outcome. RESULTS: Of 304 trials published that used composite outcomes, 221 (73%) reported a composite primary outcome and 83 (27%) reported a composite secondary outcome. Composite outcomes comprised a median of 3 (interquartile range, 3 to 4) individual outcomes; death was the most common individual outcome. The total number of individual events and the total number of events represented by the composite outcome differed in 79% of trials. P values for composite outcomes were less than 0.050 more frequently than they were 0.050 or greater. Death as an individual end point made a relatively minimal contribution to estimates of effect summarized by the trials' composite end points, whereas revascularization made a greater contribution. LIMITATION: All-cause and cardiovascular mortality were not distinguished, and the findings might not apply to trials in other fields. CONCLUSION: Composite outcomes in cardiovascular trials are frequent and commonly comprise 3 to 4 individual end points that vary in clinical significance. Discrepancies between the total number of individual events in a trial and those reported for composite outcomes are common. Individual outcomes do not contribute equally to composite measures, so the overall estimate of effect for a composite measure cannot be assumed to apply equally to each of its individual outcomes.

Despite advances in therapeutic strategies, atherosclerotic coronary artery disease (CAD) remains the commonest worldwide cause of morbidity and mortality. DNA damage and repair have been identified as important in atherogenesis. DNA ligase is crucial in single/double stranded DNA break repair by

Background Neointimal strut coverage significantly reduces risk of stent thrombosis, which may allow abbreviated dual anti-platelet therapy if clinically necessary. Optical coherence tomography (OCT) provides unparalleled axial resolution to define strut coverage. We used OCT to assess neointimal strut coverage of Bioresorbable Vascular Scaffolds (BVS) at an earlier timepoint than published studies. Methods OCT imaging was performed at baseline and 1–4 months post-implantation in patients receiving BVS. OCT scaffold strut coverage (strut thickness >160 μm), mean flow/scaffold area (MFA/MSA) and incomplete strut apposition (ISA) were assessed every 1 mm (n = 865 frames) longitudinally throughout the scaffold. Measures were compared at baseline and follow up. Results 20 BVS (median 3.0 × 18 mm) were included in the analysis. 90% of patients were male and mean age was 54.4 ± 9.2 yrs. Median follow up was 70 (range 29–112) days. 16 (80%) stented lesions were classified as AHA B2 or C. At follow-up, only 91/3,280 struts (2.8%) were uncovered. ISA was observed for 60 struts (2.0%) at baseline and 14 struts (0.5%) at follow up (p 2 at baseline to 7.37 mm 2 , at follow up (Δ-5.43%, p 2 ). MSA was not significantly different at follow up (-0.11 mm 2 , Δ-1.27%, p = 0.45). Conclusions BVS exhibited low rates of uncovered struts within four months following implantation. Although MFA had reduced due to neointimal growth, MSA was preserved, implying adequate BVS radial strength despite the complex lesion subset. These data suggest that abbreviated dual-antiplatelet therapy may be possible following BVS implantation if clinically necessary.

Background Autopsy studies demonstrate that the majority of myocardial infarctions are due to rupture of thin-cap fibroatheromata (TCFA). Nevertheless in-vivo prospective studies using virtual-histology intravascular ultrasound (VH-IVUS) show that

A 50-year-old man presented with exertional angina and a positive treadmill test. Coronary angiography demonstrated a significant lesion in the mid-right coronary artery, and he proceeded to percutaneous coronary intervention. Because implantation of a bioresorbable vascular scaffold (BVS) (Abbott

Background Factors affecting prognosis after primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI) include age at presentation, the presence of diabetes mellitus, left ventricular function and/or cardiogenic shock. Although the debate continues over a strategy of complete revascularisation (immediate or staged) vs culprit-only, little is known about the impact of the extent of coronary disease at presentation on prognosis after PPCI. The SYNTAX score, designed to stratify outcomes in multivessel PCI and CABG, has been validated in unselected populations undergoing elective PCI; to date, no studies have assessed its utility in PPCI. Methods Consecutive patients attending a single UK tertiary centre for PPCI between September 2008 and June 2010 (n=695) were included. SYNTAX scoring was performed by a single trained operator blinded to patient details and outcome. Scoring was validated by analysis of 3 separate cohorts by 2 other experienced operators. Patients were split into 3 subgroups as in the SYNTAX trial (score ≤22 (low, L), 22.5–32 (intermediate, IM) and ≥32.5 (high, H)), and patient data and outcome measures obtained by interrogation of local and national databases. Results 671 of 695 patients were included in the analysis with 24 being excluded owing to inability to score (previous CABG, images unavailable). The ability to allocate a SYNTAX tertile was reproducible between observers (r=0.94). Median scores in the 3 groups were: L 14, IM 26, H 36 (Abstract 43 figure 1A). Although there was no correlation between SYNTAX score and patient sex or diabetic status, there was a linear relationship with patient age (r 2 =0.03; p Conclusions The SYNTAX score, when applied to an unselected population of patients undergoing PPCI for STEMI, provides important prognostic information regarding 1-year survival from death and revascularisation. These findings may provide supporting evidence towards routine complete revascularisation of obstructive coronary artery disease after PPCI.

access during primary percutaneous coronary intervention for patients receiving glycoprotein inhibitors Control Number: 2917 Submission Type: Abstract Presentation Format: Poster Only New Device/Innovation: No Author(s): Adam J Brown, Nikil K Rajani, Liam M McCormick, Stephen P Hoole, Nick E West Institution(s): University of Cambridge, Cambridge, United Kingdom, Papworth Hospital, Cambridge, United Kingdom Presenter Poster: Dr Adam J Brown, MB BChir View Disclosure University of Cambridge Background: Use of glycoprotein IIb/IIIa inhibitors (GPI) during primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) is known to improve myocardial perfusion and reduce further ischemic events, but is associated with an increase in bleeding risk. Performing PPCI via radial access (rPPCI) is thought to reduce post-procedural bleeding complications and may improve overall survival. We sought to assess whether rPPCI is associated with improved outcomes in patients receiving GPI at our institution. Methods: Consecutive patients undergoing PPCI for STEMI over a four-year period were included. All patients were preloaded with 600mg clopidogrel and 300mg aspirin en-route to PPCI. Interventional strategy and GPI use were left to operator discretion. Patient data and outcome measures were obtained by interrogation of notes and national databases. Bleeding complications were categorized using Bleeding Academic Research Consortium (BARC) definitions. Results: 2,019 patients were included in the analysis (mean age 64.2±12.4yrs, 75.9% male), with 863 receiving GPI. Patients that received GPI were younger (62.7±11.8yrs vs. 64.8±12.6yrs, p< 0.001), more likely to be male (80.5% vs. 73.9%, p< 0.001) but had a higher incidence of cardiogenic shock (5.6% vs. 2.7%, p=0.002). Other baseline demographics were similar. Overall, BARC defined bleeding was more prevalent in those receiving GPI (BARC ≥2 3.0% vs. 0.7%, p< 0.001; BARC ≥3 2.6% vs. 0.2%, p< 0.001). However, patients undergoing rPPCI with GPI had lower bleeding rates when compared with femoral access (0.8% vs. 3.7%, p=0.05). For patients receiving GPI, rPPCI resulted in a significant improvement in 1-year survival (99.2% vs. 93.5%, p=0.01; OR 0.12, 95%CI 0.02-0.87, p=0.04). However, in patients not receiving GPI, no survival benefit for rPPCI was observed (94.4% vs. 93.7%, p=0.70; OR 0.87, 95%CI 0.44-1.71, p=0.69). Conclusions: rPPCI results in lower rates of bleeding and improved survival in patients receiving GPI during PPCI. rPPCI should be considered in patient groups where subsequent use of GPI is likely. CORONARY: STEMI and NSTEMI

Introduction Randomised controlled trials have demonstrated that transradial (TR) percutaneous coronary intervention (PCI) reduces bleeding and improves survival compared with transfemoral access (TF). This benefit may be most marked in the context of primary PCI (pPCI) for ST-elevation myocardial infarction. Due to the learning curve associated with TR PCI, these benefits may not translate immediately into real-world practice.Our study sought to determine the effect on clinical outcomes, as our institution switched from TF to TR access. Methods Consecutive patients presenting for PCI over a four year period (1.1.2008–31.12.2011) were included.The choice of access site and, interventional strategy were left to operator discretion. Haemorrhagic complications were identified and classified according to the Bleeding Academic Research Consortium (BARC) definitions. Results 8166 patients (mean age 64.8 ± 11.5 yrs, 76.2% male) were included. Over the study period, TR access became more prevalent (2008- 2.0%, 2011- 42.7%), and the haemorrhagic complication rate fell (2008- 1.64%, 2011- 0.95%, p = 0.05).TR PCI was associated with lower combined rates of BARC 2, 3 and 5 bleeding compared with TF access (0.30% vs. 1.45%, p As TR access became more prevalent (2009–11), a significant survival benefit was observed at 30 days (TR 99.4% vs. TF 98.5%, p = 0.01) and 1 year (TR 97.7% vs. TF 96.5%, p = 0.03).This benefit was most marked in pPCI (TR 98.0% vs. TF 95.7%, p = 0.06 at 30 days and TR 96.6% vs. TF 92.8%, p = 0.02 at 1 year), and occurred despite comparable levels of cardiogenic shock (TR 0.8% vs. TF 1.2%, p = 0.27) and chronic kidney disease (TR 0.7% vs. TF 1.1%, p = 0.21).Further analysis revealed that TR access was most beneficial in pPCI patients receiving glycoprotein IIb/IIIa inhibitors (1 year survival TR 99.2% vs. TF 93.5%, p = 0.01), with no survival benefit in those not receiving these drugs. Discussion In real-world practice, despite the learning curve, TR access is associated with a reduced rate of access-site related bleeding and a significant survival benefit at 30 days and 1 year. This beneficial effect is most marked in pPCI and specifically when strong antithrombotic agents (e.g. glycoprotein IIb/IIIa inhibitors) are used. Our data supports the hypothesis that reduced bleeding may, in part, be responsible for the survival differences observed between TF and TR access.

A 39-year-old normotensive lady with Ebstein anomaly was admitted with palpitations and chest discomfort. Her ECG demonstrated a narrow complex tachycardia, left axis deviation and T-wave inversion in I, avL and V5-6 (panel A). She received oral β blockers and reverted to sinus rhythm. Subsequent serial ECGs demonstrated a global change of …