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1.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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2.
  • Backes, Claudia, et al. (författare)
  • Production and processing of graphene and related materials
  • 2020
  • Ingår i: 2D Materials. - : IOP Publishing. - 2053-1583. ; 7:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present an overview of the main techniques for production and processing of graphene and related materials (GRMs), as well as the key characterization procedures. We adopt a 'hands-on' approach, providing practical details and procedures as derived from literature as well as from the authors' experience, in order to enable the reader to reproduce the results. Section I is devoted to 'bottom up' approaches, whereby individual constituents are pieced together into more complex structures. We consider graphene nanoribbons (GNRs) produced either by solution processing or by on-surface synthesis in ultra high vacuum (UHV), as well carbon nanomembranes (CNM). Production of a variety of GNRs with tailored band gaps and edge shapes is now possible. CNMs can be tuned in terms of porosity, crystallinity and electronic behaviour. Section II covers 'top down' techniques. These rely on breaking down of a layered precursor, in the graphene case usually natural crystals like graphite or artificially synthesized materials, such as highly oriented pyrolythic graphite, monolayers or few layers (FL) flakes. The main focus of this section is on various exfoliation techniques in a liquid media, either intercalation or liquid phase exfoliation (LPE). The choice of precursor, exfoliation method, medium as well as the control of parameters such as time or temperature are crucial. A definite choice of parameters and conditions yields a particular material with specific properties that makes it more suitable for a targeted application. We cover protocols for the graphitic precursors to graphene oxide (GO). This is an important material for a range of applications in biomedicine, energy storage, nanocomposites, etc. Hummers' and modified Hummers' methods are used to make GO that subsequently can be reduced to obtain reduced graphene oxide (RGO) with a variety of strategies. GO flakes are also employed to prepare three-dimensional (3d) low density structures, such as sponges, foams, hydro- or aerogels. The assembly of flakes into 3d structures can provide improved mechanical properties. Aerogels with a highly open structure, with interconnected hierarchical pores, can enhance the accessibility to the whole surface area, as relevant for a number of applications, such as energy storage. The main recipes to yield graphite intercalation compounds (GICs) are also discussed. GICs are suitable precursors for covalent functionalization of graphene, but can also be used for the synthesis of uncharged graphene in solution. Degradation of the molecules intercalated in GICs can be triggered by high temperature treatment or microwave irradiation, creating a gas pressure surge in graphite and exfoliation. Electrochemical exfoliation by applying a voltage in an electrolyte to a graphite electrode can be tuned by varying precursors, electrolytes and potential. Graphite electrodes can be either negatively or positively intercalated to obtain GICs that are subsequently exfoliated. We also discuss the materials that can be amenable to exfoliation, by employing a theoretical data-mining approach. The exfoliation of LMs usually results in a heterogeneous dispersion of flakes with different lateral size and thickness. This is a critical bottleneck for applications, and hinders the full exploitation of GRMs produced by solution processing. The establishment of procedures to control the morphological properties of exfoliated GRMs, which also need to be industrially scalable, is one of the key needs. Section III deals with the processing of flakes. (Ultra)centrifugation techniques have thus far been the most investigated to sort GRMs following ultrasonication, shear mixing, ball milling, microfluidization, and wet-jet milling. It allows sorting by size and thickness. Inks formulated from GRM dispersions can be printed using a number of processes, from inkjet to screen printing. Each technique has specific rheological requirements, as well as geometrical constraints. The solvent choice is critical, not only for the GRM stability, but also in terms of optimizing printing on different substrates, such as glass, Si, plastic, paper, etc, all with different surface energies. Chemical modifications of such substrates is also a key step. Sections IV-VII are devoted to the growth of GRMs on various substrates and their processing after growth to place them on the surface of choice for specific applications. The substrate for graphene growth is a key determinant of the nature and quality of the resultant film. The lattice mismatch between graphene and substrate influences the resulting crystallinity. Growth on insulators, such as SiO2, typically results in films with small crystallites, whereas growth on the close-packed surfaces of metals yields highly crystalline films. Section IV outlines the growth of graphene on SiC substrates. This satisfies the requirements for electronic applications, with well-defined graphene-substrate interface, low trapped impurities and no need for transfer. It also allows graphene structures and devices to be measured directly on the growth substrate. The flatness of the substrate results in graphene with minimal strain and ripples on large areas, allowing spectroscopies and surface science to be performed. We also discuss the surface engineering by intercalation of the resulting graphene, its integration with Si-wafers and the production of nanostructures with the desired shape, with no need for patterning. Section V deals with chemical vapour deposition (CVD) onto various transition metals and on insulators. Growth on Ni results in graphitized polycrystalline films. While the thickness of these films can be optimized by controlling the deposition parameters, such as the type of hydrocarbon precursor and temperature, it is difficult to attain single layer graphene (SLG) across large areas, owing to the simultaneous nucleation/growth and solution/precipitation mechanisms. The differing characteristics of polycrystalline Ni films facilitate the growth of graphitic layers at different rates, resulting in regions with differing numbers of graphitic layers. High-quality films can be grown on Cu. Cu is available in a variety of shapes and forms, such as foils, bulks, foams, thin films on other materials and powders, making it attractive for industrial production of large area graphene films. The push to use CVD graphene in applications has also triggered a research line for the direct growth on insulators. The quality of the resulting films is lower than possible to date on metals, but enough, in terms of transmittance and resistivity, for many applications as described in section V. Transfer technologies are the focus of section VI. CVD synthesis of graphene on metals and bottom up molecular approaches require SLG to be transferred to the final target substrates. To have technological impact, the advances in production of high-quality large-area CVD graphene must be commensurate with those on transfer and placement on the final substrates. This is a prerequisite for most applications, such as touch panels, anticorrosion coatings, transparent electrodes and gas sensors etc. New strategies have improved the transferred graphene quality, making CVD graphene a feasible option for CMOS foundries. Methods based on complete etching of the metal substrate in suitable etchants, typically iron chloride, ammonium persulfate, or hydrogen chloride although reliable, are time- and resource-consuming, with damage to graphene and production of metal and etchant residues. Electrochemical delamination in a low-concentration aqueous solution is an alternative. In this case metallic substrates can be reused. Dry transfer is less detrimental for the SLG quality, enabling a deterministic transfer. There is a large range of layered materials (LMs) beyond graphite. Only few of them have been already exfoliated and fully characterized. Section VII deals with the growth of some of these materials. Amongst them, h-BN, transition metal tri- and di-chalcogenides are of paramount importance. The growth of h-BN is at present considered essential for the development of graphene in (opto) electronic applications, as h-BN is ideal as capping layer or substrate. The interesting optical and electronic properties of TMDs also require the development of scalable methods for their production. Large scale growth using chemical/physical vapour deposition or thermal assisted conversion has been thus far limited to a small set, such as h-BN or some TMDs. Heterostructures could also be directly grown. Section VIII discusses advances in GRM functionalization. A broad range of organic molecules can be anchored to the sp(2) basal plane by reductive functionalization. Negatively charged graphene can be prepared in liquid phase (e.g. via intercalation chemistry or electrochemically) and can react with electrophiles. This can be achieved both in dispersion or on substrate. The functional groups of GO can be further derivatized. Graphene can also be noncovalently functionalized, in particular with polycyclic aromatic hydrocarbons that assemble on the sp(2) carbon network by pi-pi stacking. In the liquid phase, this can enhance the colloidal stability of SLG/FLG. Approaches to achieve noncovalent on-substrate functionalization are also discussed, which can chemically dope graphene. Research efforts to derivatize CNMs are also summarized, as well as novel routes to selectively address defect sites. In dispersion, edges are the most dominant defects and can be covalently modified. This enhances colloidal stability without modifying the graphene basal plane. Basal plane point defects can also be modified, passivated and healed in ultra-high vacuum. The decoration of graphene with metal nanoparticles (NPs) has also received considerable attention, as it allows to exploit synergistic effects between NPs and graphene. Decoration can be either achieved chemically or in the gas phase. All LMs,
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3.
  • Hudson, Lawrence N, et al. (författare)
  • The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
  • 2017
  • Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
  • Tidskriftsartikel (refereegranskat)abstract
    • The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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4.
  • Palmerini, Tullio, et al. (författare)
  • Risk-Benefit of 1-Year DAPT After DES Implantation in Patients Stratified by Bleeding and Ischemic Risk.
  • 2021
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 1558-3597 .- 0735-1097. ; 78:20, s. 1968-1986
  • Tidskriftsartikel (refereegranskat)abstract
    • Although a 1-year duration of dual antiplatelet therapy (DAPT) is used in many patients after drug-eluting stent (DES) implantation, the evidence supporting this duration is uncertain.The authors investigated the risk-benefit profile of 1-year vs≤6-month DAPT after DES using 2 novel scores to risk stratify bleeding and ischemic events.Ischemic and bleeding risk scores were generated from ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents), a multicenter, international, "all-comers" registry that enrolled 8,665 patients treated with DES. The risk-benefit profile of 1-year vs≤6-month DAPT was then investigated across risk strata from an individual patient data pooled dataset of 7 randomized trials that enrolled 15,083 patients treated with DES.In the derivation cohort, the ischemic score and the bleeding score had c-indexes of 0.76 and 0.66, respectively, and both were well calibrated. In the pooled dataset, no significant difference was apparent in any ischemic endpoint between 1-year and≤6-month DAPT, regardless of the risk strata. In the overall dataset, there was no significant difference in the risk of clinically relevant bleeding between 1-year and≤6-month DAPT; however, among 2,508 patients at increased risk of bleeding, 1-year compared with≤6-month DAPT was associated with greater bleeding (HR: 2.80; 95%CI: 1.12-7.13) without a reduced risk of ischemic events in any risk strata, including those with acute coronary syndromes. These results were consistent in a network meta-analysis.In the present large-scale study, compared with≤6-month DAPT, a 1-year duration of DAPT was not associated with reduced adverse ischemic events in any risk strata (including acute coronary syndromes) but was associated with greater bleeding in patients at increased risk of bleeding.
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5.
  • Algaba, Juan-Carlos, et al. (författare)
  • Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign
  • 2021
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1
  • Forskningsöversikt (refereegranskat)abstract
    • In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M o˙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded.
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6.
  • Bourantas, Christos V., et al. (författare)
  • Prognostic Implications of Severe Coronary Calcification in Patients Undergoing Coronary Artery Bypass Surgery : An Analysis of the SYNTAX Study
  • 2015
  • Ingår i: Catheterization and cardiovascular interventions. - : Wiley. - 1522-1946 .- 1522-726X. ; 85:2, s. 199-206
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesTo investigate the prognostic implications of the presence of severe lesion calcification in patients undergoing coronary artery bypass graft (CABG) operation. BackgroundThere is robust evidence that lesion calcification is a predictor of worse prognosis in patients undergoing percutaneous coronary intervention; however, there is limited data about the prognostic implication of lesion calcium in patients treated with CABG. MethodsWe retrospectively analyzed data from 1,545 patients who underwent CABG and were recruited in the SYNTAX study and CABG registry. Two experts reviewed the angiographic data and classified patients in two groups: those with severely calcified coronary arteries and those without severe lesion calcification. Clinical outcomes at 5-year follow-up were collected and compared in the two groups. ResultsOne out of three patients exhibited severe lesion calcification (n=588). Patients with calcified coronaries had an increased mortality at 5-year follow-up (17.1% vs. 9.9%, P<0.001) and a higher event rate of death-myocardial infarction (MI) compared with those without (19.4% vs. 13.2%, P=0.003), but there was no statistical significant difference between the two groups for major adverse cardiovascular events (MACE, 26.8% vs. 21.8%, P=0.057). In multivariate Cox regression analysis severe lesion calcification was an independent predictor of an increased all-cause mortality (hazard ratio: 1.39, 95% confidence interval: 1.02-1.89; P=0.037) but it was not an independent predictor of the combined end-points death-MI or MACE. ConclusionsSevere lesion calcification is associated with an increased mortality in patients undergoing CABG, but it is not an independent predictor of death-MI or MACE. This paradox can be attributed to the fact that CABG allows perfusion of the healthy coronaries bypassing the diseased arteries and thus it minimizes the risk of coronary events due to progressive atherosclerosis. (c) 2014 Wiley Periodicals, Inc.
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7.
  • Bucchiarone, A., et al. (författare)
  • POLYGLOT for Gamified Education : Mixing Modelling and Programming Exercises
  • 2021
  • Ingår i: Companion Proceedings - 24th International Conference on Model-Driven Engineering Languages and Systems, MODELS-C 2021. - : IEEE. - 9781665424844 ; , s. 606-610
  • Konferensbidrag (refereegranskat)abstract
    • Gamification refers to the employment of gaming mechanisms for non-gaming purposes. Its aim is promoting the engagement of target users in pursuing certain goals, e.g. completing education paths. In this paper we present POLYGLOT, a gamified notebook-like programming environment. The gamification extension was built to target programming languages education, and in this work we illustrate how the approach is adaptable to text-based modelling languages. In particular, we demonstrate the use of gamification tailored to SysML v2 modelling.Each exercise is defined as a sequence of steps framed into notebook cells. On each cell submission, the POLYGLOT extension for.NET interactive runs several analyzers to gain insights of the student code before invoking the gamification engine, which checks if the gathered data fits the teacher-defined expectations. Interestingly, since cell contents are language independent and exercise evaluations are delegated to the gamification engine, this solution enables the creation of heterogeneous narratives, that is gamification scenarios mixing languages in the proposed exercises. 
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8.
  • Costa, Francesco, et al. (författare)
  • Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score : a pooled analysis of individual-patient datasets from clinical trials
  • 2017
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 389:10073, s. 1025-1034
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y(12) inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose.Methods: A total of 14 963 patients treated with DAPT after coronary stenting-largely consisting of aspirin and clopidogrel and without indication to oral anticoagulation-were pooled at a single-patient level from eight multicentre randomised clinical trials with independent adjudication of events. Using Cox proportional hazards regression, we identified predictors of out-of-hospital Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding stratified by trial, and developed a numerical bleeding risk score. The predictive performance of the novel score was assessed in the derivation cohort and validated in patients treated with percutaneous coronary intervention from the PLATelet inhibition and patient Outcomes (PLATO) trial (n=8595) and BernPCI registry (n=6172). The novel score was assessed within patients randomised to different DAPT durations (n=10 081) to identify the effect on bleeding and ischaemia of a long (12-24 months) or short (3-6 months) treatment in relation to baseline bleeding risk.Findings: The PRECISE-DAPT score (age, creatinine clearance, haemoglobin, white-blood-cell count, and previous spontaneous bleeding) showed a c-index for out-of-hospital TIMI major or minor bleeding of 0.73 (95% CI 0.61-0.85) in the derivation cohort, and 0.70 (0.65-0.74) in the PLATO trial validation cohort and 0.66 (0.61-0.71) in the BernPCI registry validation cohort. A longer DAPT duration significantly increased bleeding in patients at high risk (score >= 25), but not in those with lower risk profiles (p(interaction)=0.007), and exerted a significant ischaemic benefit only in this latter group.Interpretation: The PRECISE-DAPT score is a simple five-item risk score, which provides a standardised tool for the prediction of out-of-hospital bleeding during DAPT. In the context of a comprehensive clinical evaluation process, this tool can support clinical decision making for treatment duration.
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9.
  • Costa, Francesco, et al. (författare)
  • Dual Antiplatelet Therapy Duration Based on Ischemic and Bleeding Risks After Coronary Stenting
  • 2019
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 73:7, s. 741-754
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUNDComplex percutaneous coronary intervention (PCI) is associated with higher ischemic risk, which can be mitigated by long-term dual antiplatelet therapy (DAPT). However, concomitant high bleeding risk (HBR) may be present, making it unclear whether short-or long-term DAPT should be prioritized.OBJECTIVESThis study investigated the effects of ischemic (by PCI complexity) and bleeding (by PRECISE-DAPT [PREdicting bleeding Complications in patients undergoing stent Implantation and SubsequEnt Dual AntiPlatelet Therapy] score) risks on clinical outcomes and on the impact of DAPT duration after coronary stenting.METHODSComplex PCI was defined as $ 3 stents implanted and/or $ 3 lesions treated, bifurcation stenting and/or stent length > 60 mm, and/or chronic total occlusion revascularization. Ischemic and bleeding outcomes in high ($ 25) or nonhigh (< 25) PRECISE-DAPT strata were evaluated based on randomly allocated duration of DAPT.RESULTSAmong 14,963 patients from 8 randomized trials, 3,118 underwent complex PCI and experienced a higher rate of ischemic, but not bleeding, events. Long-term DAPT in non-HBR patients reduced ischemic events in both complex (absolute risk difference:-3.86%; 95% confidence interval:-7.71 to thorn0.06) and noncomplex PCI strata (absolute risk difference:-1.14%; 95% confidence interval:-2.26 to-0.02), but not among HBR patients, regardless of complex PCI features. The bleeding risk according to the Thrombolysis In Myocardial Infarction scale was increased by long-term DAPT only in HBR patients, regardless of PCI complexity.CONCLUSIONS Patients who underwent complex PCI had a higher risk of ischemic events, but benefitted from long-term DAPT only if HBR features were not present. These data suggested that when concordant, bleeding, more than ischemic risk, should inform decision-making on the duration of DAPT.
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10.
  • D'Ascenzo, Fabrizio, et al. (författare)
  • Incidence and predictors of coronary stent thrombosis : Evidence from an international collaborative meta-analysis including 30 studies, 221,066 patients, and 4276 thromboses
  • 2013
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 167:2, s. 575-584
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Stent thrombosis remains among the most feared complications of percutaneous coronary intervention (PCI) with stenting. However, data on its incidence and predictors are sparse and conflicting. We thus aimed to perform a collaborative systematic review on incidence and predictors of stent thrombosis.METHODS: PubMed was systematically searched for eligible studies from the drug-eluting stent (DES) era (1/2002-12/2010). Studies were selected if including ≥2000 patients undergoing stenting or reporting on ≥25 thromboses. Study features, patient characteristics, and incidence of stent thrombosis were abstracted and pooled, when appropriate, with random-effect methods (point estimate [95% confidence intervals]), and consistency of predictors was formally appraised.RESULTS:A total of 30 studies were identified (221,066 patients, 4276 thromboses), with DES used in 87%. After a median of 22months, definite, probable, or possible stent thrombosis had occurred in 2.4% (2.0%; 2.9%), with acute in 0.4% (0.2%; 0.6%), subacute in 1.1% (1.0%; 1.3%), late in 0.5% (0.4%; 0.6%), and very late in 0.6% (0.4%; 0.8%). Similar figures were computed for studies reporting only on DES. From a total of 47 candidate variables, definite/probable stent thrombosis was more commonly and consistently predicted by early antiplatelet therapy discontinuation, extent of coronary disease, and stent number/length, with acute coronary syndrome at admission, diabetes, smoking status, and bifurcation/ostial disease also proving frequent predictors, but less consistently.CONCLUSIONS:Despite numerous possible risk factors, the most common and consistent predictors of stent thrombosis are early antiplatelet therapy discontinuation, extent of coronary disease, and stent number/length.
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11.
  • Farooq, Vasim, et al. (författare)
  • Anatomical and clinical characteristics to guide decision making between coronary artery bypass surgery and percutaneous coronary intervention for individual patients : development and validation of SYNTAX score II
  • 2013
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 381:9867, s. 639-650
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The anatomical SYNTAX score is advocated in European and US guidelines as an instrument to help clinicians decide the optimum revascularisation method in patients with complex coronary artery disease. The absence of an individualised approach and of clinical variables to guide decision making between coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) are limitations of the SYNTAX score. SYNTAX score II aimed to overcome these limitations. Methods SYNTAX score II was developed by applying a Cox proportional hazards model to results of the randomised all comers SYNTAX trial (n=1800). Baseline features with strong associations to 4-year mortality in either the CABG or the PCI settings (interactions), or in both (predictive accuracy), were added to the anatomical SYNTAX score. Comparisons of 4-year mortality predictions between CABG and PCI were made for each patient. Discriminatory performance was quantified by concordance statistics and internally validated with bootstrap resampling. External validation was done in the multinational all comers DELTA registry (n=2891), a heterogeneous population that included patients with three-vessel disease (26%) or complex coronary artery disease (anatomical SYNTAX score >= 33, 30%) who underwent CABG or PCI. The SYNTAX trial is registered with ClinicalTrials.gov, number NCT00114972. Findings SYNTAX score II contained eight predictors: anatomical SYNTAX score, age, creatinine clearance, left ventricular ejection fraction (LVEF), presence of unprotected left main coronary artery (ULMCA) disease, peripheral vascular disease, female sex, and chronic obstructive pulmonary disease (COPD). SYNTAX score II significantly predicted a difference in 4-year mortality between patients undergoing CABG and those undergoing PCI (p(interaction) 0.0037). To achieve similar 4-year mortality after CABG or PCI, younger patients, women, and patients with reduced LVEF required lower anatomical SYNTAX scores, whereas older patients, patients with ULMCA disease, and those with COPD, required higher anatomical SYNTAX scores. Presence of diabetes was not important for decision making between CABG and PCI (p(interaction) 0.67). SYNTAX score II discriminated well in all patients who underwent CABG or PCI, with concordance indices for internal (SYNTAX trial) validation of 0.725 and for external (DELTA registry) validation of 0.716, which were substantially higher than for the anatomical SYNTAX score alone (concordance indices of 0.567 and 0.612, respectively). A nomogram was constructed that allowed for an accurate individualised prediction of 4-year mortality in patients proposing to undergo CABG or PCI. Interpretation Long-term (4-year) mortality in patients with complex coronary artery disease can be well predicted by a combination of anatomical and clinical factors in SYNTAX score II. SYNTAX score II can better guide decision making between CABG and PCI than the original anatomical SYNTAX score.
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12.
  • Farooq, Vasim, et al. (författare)
  • Incidence and multivariable correlates of long-term mortality in patients treated with surgical or percutaneous revascularization in the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) trial.
  • 2012
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 33:24, s. 3105-3113
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims The aim of this investigation was to determine the incidence and multivariable correlates of long-term (4-year) mortality in patients treated with surgical or percutaneous revascularization in the synergy between percutaneous coronary intervention (PCI) with TAXUS Express and Cardiac Surgery (SYNTAX) trial. Methods and results A total of 1800 patients were randomized to undergo coronary artery bypass graft (CABG) surgery (n = 897) or PCI (n = 903). Prospectively collected baseline and peri- and post-procedural data were used to determine independent correlates of 4-year all-cause death in the CABG and the PCI arms (Cox proportional hazards model). Four-year mortality rates in the CABG and the PCI arms were 9.0% [74 deaths (12 in-hospital)] and 11.8% [104 deaths (16 in-hospital)], respectively (log-rank P-value = 0.063). Censored data comprised 78 patients (8.7%) in the CABG arm, and 24 patients (2.7%) in the PCI arm (log-rank P-value < 0.001). Within the CABG arm, the strongest independent correlates of 4-year mortality were lack of discharge aspirin [hazard ratio (HR) 3.56; 95% CI: 2.04, 6.21; P < 0.001], peripheral vascular disease (PVD) (HR: 2.65; 95% CI: 1.49, 4.72; P = 0.001), chronic obstructive pulmonary disease, age, and serum creatinine. Within the PCI arm, the strongest independent correlate of 4-year mortality was lack of post-procedural anti-platelet therapy (HR: 152.16; 95% CI: 53.57, 432.22; P < 0.001), with 10 reported early (within 45 days) in-hospital deaths secondary to multifactorial causes precluding administration of anti-platelet therapy. Other independent correlates of mortality in the PCI arm included amiodarone therapy on discharge, pre-procedural poor left ventricular ejection fraction, a 'history of gastrointestinal bleeding or peptic ulcer disease', PVD (HR: 2.13; 95% CI: 1.26, 3.60; P = 0.005), age, female gender (HR: 1.60; 95% CI: 1.01, 2.56; P = 0.048), and the SYNTAX score (Per increase in 10 points: HR: 1.25; 95% CI: 1.06, 1.47; P = 0.007). Conclusion Independent correlates of 4-year mortality in the SYNTAX trial were multifactorial. Lack of discharge aspirin and lack of post-procedural anti-platelet therapy were the strongest independent correlates of mortality in the CABG and the PCI arms, respectively. Peripheral vascular disease is a common independent correlate of 4-year mortality and may be a marker of the severity of baseline coronary disease and risk of future native coronary disease (and extra-cardiac disease) progression.
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13.
  • Farooq, Vasim, et al. (författare)
  • Incidence, correlates, and significance of abnormal cardiac enzyme rises in patients treated with surgical or percutaneous based revascularisation : A substudy from the Synergy between Percutaneous Coronary Interventions with Taxus and Cardiac Surgery (SYNTAX) Trial
  • 2013
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 168:6, s. 5287-5292
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: The aimof the present investigationwas to determine the long-termprognostic association of post-procedural cardiac enzyme elevation within the randomised Synergy between Percutaneous Coronary Intervention (PCI) with TAXUS and Cardiac Surgery (SYNTAX) Trial. Methods: 1800 patients with unprotected left main or de novo three-vessel coronary artery disease were randomised to undergo coronary artery bypass graft (CABG) surgery or PCI. Per protocol patients underwent post-procedural blood sampling with creatine kinase (CK), and the cardiac specific MB iso-enzyme (CK-MB) only if the preceding CK ratiowas = 2x the upper limit of normal (ULN). An independent chemistry laboratory evaluated all collected blood samples. Results: Post-procedural CK sampling was available in 1629 of 1800 patients (90.5%). As per protocol, CK-MB analyses were undertaken in 474 of 491 patients (96.5%) in the CABG arm, and 53 of 61 patients (86.9%) in the PCI arm. Within the CABG arm, despite the limitations of incomplete data, a post-procedural CK-MB ratio <3/>= 3 ULNseparated 4-year mortality into low-and high-risk groups (2.3% vs. 9.5%, p = 0.03). Additionally, in the CABG arm, a post-procedural CK-MB ratio = 3 ULN was associated with an increased frequency of a high SYNTAX Score (= 33) tertile (high [>= 33] SYNTAX Score: 39.5%, intermediate [23-32] SYNTAX Score 31.0%, low [>= 22] SYNTAX Score 29.5%, p = 0.02). Within the PCI arm, a post-procedural CK ratio of >2 or >= 2 ULN separated 4-year mortality into low-and high-risk groups (10.8% vs. 23.3%, p = 0.001). Notably, there was an early (within 6 months) and late (after 2 years) peak in mortality in patients with a post-PCI CK ratio of = 2 ULN. Lack of pre-procedural thienopyridine, carotid artery disease, type 1 diabetes, andpresenceof coronary bifurcationswere independent correlates of a CK ratio = 2 ULNpost-PCI. Conclusion: Cardiac enzyme elevations post-CABG or post-PCI are associatedwith an adverse long-termmortality; the causes of which are multifactorial.
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14.
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15.
  • Farooq, Vasim, et al. (författare)
  • Quantification of Incomplete Revascularization and its Association With Five-Year Mortality in the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) Trial Validation of the Residual SYNTAX Score
  • 2013
  • Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 128:2, s. 141-151
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The residual Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) Score is an objective measure of the degree and complexity of residual stenosis after percutaneous coronary intervention (PCI). Methods and Results In the randomized PCI cohort of the SYNTAX Trial (n=903), the baseline and residual SYNTAX Scores were calculated. Subjects with a residual SYNTAX Score of 0 were defined as having undergone complete revascularization (CR), and a residual SYNTAX Score >0 as incomplete revascularization (ICR). Five-year clinical outcomes were stratified by CR and ICR (tertiles of the residual SYNTAX Score: >0-4, >4-8, and >8). In the PCI cohort, the mean baseline and residual SYNTAX Scores were 28.4 +/- 11.5 and 4.5 +/- 6.9, respectively. The mean SYNTAX Score (representative of the burden of disease removed by PCI) was 23.8 +/- 10.9. The residual SYNTAX Score was distributed as follows: CR, 0 (n=386, 42.7%); ICR, >0 to 4 (n=184, 20.4%), >4 to 8 (n=167, 18.5%), >8 (n=153, 16.9%). A progressively higher residual SYNTAX Score was shown to be a surrogate marker of increasing clinical comorbidity and anatomic complexity. Subjects with CR or residual SYNTAX Scores 8 had comparable 5-year mortality (CR, 8.5%; residual SYNTAX Score >0-4, 8.7%; >4-8, 11.4%; P=0.60). A residual SYNTAX Score >8 was associated with 35.3% all-cause mortality at 5-years (P<0.001). Stratified analyses in the predefined medical treated diabetic and left main subgroups yielded similar results. Conclusions The residual SYNTAX Score was shown to be a powerful indicator of 5-year mortality in the SYNTAX Trial. The residual SYNTAX Score may aid in determining a reasonable level of revascularization.
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16.
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17.
  • Farooq, Vasim, et al. (författare)
  • Short-Term and Long-Term Clinical Impact of Stent Thrombosis and Graft Occlusion in the SYNTAX Trial at 5 Years Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery Trial
  • 2013
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 62:25, s. 2360-2369
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives The aim of this study was to report the short-term and long-term clinical impact of stent thrombosis (ST) and graft occlusion (GO) in the final 5-year outcomes of the SYNTAX (SYNergy Between PCI With TAXUS and Cardiac Surgery) trial.Background The clinical effect of newer-generation drug-eluting stents and operative factors in complex coronary artery disease is uncertain.Methods The incidence of 5-year ST and GO, and their association with clinical outcomes, were analyzed in the randomized percutaneous coronary intervention and coronary artery bypass graft cohorts. ST and GO were defined by the SYNTAX protocol definitions (clinical presentation with acute coronary syndrome and angiographic/pathological evidence), the Academic Research Consortium (ARC) definition for ST, and the newly devised "ARC-like" definition of GO (i.e., definite, probable, or possible GO).Results At 5 years, 871 of 903 patients (96.5%) in the percutaneous coronary intervention cohort and 805 of 897 patients (89.7%) in the coronary artery bypass graft cohort completed follow-up. As compared with other vessel locations, protocol ST (72 lesions) occurred more frequently in the left main (14 of 72; 19%) and proximal coronary vasculature (37 of 72; 51%) and protocol GO (41 lesions) with grafts anastomosed to the distal right coronary artery (17 of 41; 42%). The incidence of 5-year ARC definite ST and ARC-like definite GO did not significantly differ (7%[n = 48] vs. 6% [n = 32], log rank p = 0.34); landmark analyses indicated significantly increased ARC definite ST within 30 days (3% [n = 19] vs. 1% [n = 6], log rank p = 0.033) but not >30 days to 5 years (4.2% [n = 29] vs. 4.5% [n = 26], log rank p = 0.78). At presentation, ARC definite ST (n = 48) and ARC-like definite GO (n = 32) were adjudicated to be linked to 4 (8%) and 0 deaths, respectively. At 5 years, ARC definite ST (n = 48) and ARC definite/probable ST (n = 75) were associated with 17 (17 of 48, 35.4%; median days to death: 0 days; interquartile range: 0 to 16 days; maximum: 321 days) and 31 (31 of 75, 41.3%; median: 0 days; interquartile range: 0 to 9 days; maximum: 721 days) cardiac deaths, respectively. At 5 years, ARC-like definite GO (n = 32) and ARC-like definite/probable GO (n = 53) were associated with 0 and 12 (12 of 52, 23.1%; median: 0 days; interquartile range: 0 to 14 days; maximum: 257 days) cardiac deaths, respectively.Conclusions Although the incidence of ST and GO was similar at 5 years, the clinical impact of ST appeared greater, with a negative impact on short-term to long-term mortality.
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18.
  • Farooq, Vasim, et al. (författare)
  • The CABG SYNTAX Score - an angiographic tool to grade the complexity of coronary disease following coronary artery bypass graft surgery : from the SYNTAX Left Main Angiographic (SYNTAX-LE MANS) substudy
  • 2013
  • Ingår i: EuroIntervention. - 1774-024X .- 1969-6213. ; 8:11, s. 1277-1285
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: The SYNTAX Score (SXscore) has established itself as an important prognostic tool in patients undergoing percutaneous coronary intervention (PCI). A limitation of the SXscore is the inability to differentiate outcomes in patients who have undergone prior coronary artery bypass graft (CABG) surgery. The CABG SXscore was devised to address this limitation.METHODS AND RESULTS: In the SYNTAX-LE MANS substudy 115 patients with unprotected left main coronary artery disease (isolated or associated with one, two or three-vessel disease) treated with CABG were prospectively assigned to undergo a 15-month coronary angiogram. An independent core laboratory analysed the baseline SXscore prior to CABG. The 15-month CABG SXscore was calculated by a panel of three interventional cardiologists. The CABG SXscore was calculated by determining the standard SXscore in the "native" coronary vessels ("native SXscore") and deducting points based on the importance of the diseased coronary artery segment (Leaman score) that have a functioning bypass graft anastomosed distally. Points relating to intrinsic coronary disease, such as bifurcation disease or calcification, remain unaltered. The mean 15-month CABG SXscore was significantly lower compared to the mean baseline SXscore (baseline SXscore 31.6, SD 13.1; 15-month CABG SXscore 21.2, SD 11.1; p<0.001). Reproducibility analyses (kappa [k] statistics) indicated a substantial agreement between CABG SXscore measurements (k=0.70; 95% CI [0.50-0.90], p<0.001), with the points deducted to calculate the CABG SXscore the most reproducible measurement (k=0.74; 95% CI [0.53-0.95], p<0.001). Despite the limited power of the study, four-year outcome data (Kaplan-Meier curves) demonstrated a trend towards reduced all-cause death (9.1% vs. 1.8%, p=0.084) and death/CVA/MI (16.4% vs. 7.0%, p=0.126) in the low compared to the high CABG SXscore group.CONCLUSIONS: In this pilot study the calculation of the CABG SXscore appeared feasible, reproducible and may have a long-term prognostic role in patients with complex coronary disease undergoing surgical revascularisation. Validation of this new scoring methodology is required.
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19.
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20.
  • Farooq, Vasim, et al. (författare)
  • The Negative Impact of Incomplete Angiographic Revascularization on Clinical Outcomes and Its Association With Total Occlusions : The SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) Trial
  • 2013
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 61:3, s. 282-294
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES:The study sought to evaluate the clinical impact of angiographic complete (CR) and incomplete (ICR) revascularization and its association with the presence of total occlusions (TO), after percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery in the "all-comers" SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) trial.BACKGROUND:In patients with complex coronary artery disease undergoing PCI or CABG, the long-term prognostic implications of CR versus ICR is unsettled.METHODS:In this post hoc study, consisting of randomized (n = 1,800) and nested PCI (n = 198) and CABG (n = 649) registries, 4-year clinical outcomes were compared in groups, with and without angiographic CR, in the PCI and CABG arms. Clinical outcomes were analyzed with Kaplan-Meier estimates, log-rank comparisons, and Cox regression analyses. Multivariate predictors of ICR were determined. Similar analyses were undertaken in the TO and non-TO treated groups of both study arms.RESULTS:Angiographic CR was achieved in 52.8% of the PCI arm and 66.9% of the CABG arm. Within the PCI and CABG arms, ICR (compared with CR) seemed to be a surrogate marker of a greater burden of anatomical coronary complexity and clinical comorbidity and was associated with significantly higher frequencies of 4-year mortality, all-cause revascularization, stent thrombosis (PCI arm), and major adverse cardiac and cerebrovascular events. The presence of a TO was the strongest independent predictor of ICR after PCI (hazard ratio: 2.70, 95% confidence interval: 1.98 to 3.67, p < 0.001). Eight hundred and forty patients (PCI: 26.3%, CABG: 36.4%, p < 0.001) were identified to have 1,007 TOs, with 68.1% of TOs located in the proximal-mid coronary vasculature. The findings associating ICR (compared with CR) with higher frequencies of 4-year mortality and major adverse cardiac and cerebrovascular events remained consistent in the TO-treated groups in the PCI and CABG arms.CONCLUSIONS:Within the PCI and CABG arms of the all-comers SYNTAX trial, angiographically determined ICR has a detrimental impact on long-term clinical outcomes, including mortality. This effect remained consistent in patients with and without TOs.
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21.
  • Frigoli, Enrico, et al. (författare)
  • Design and rationale of the Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Standard DAPT Regimen (MASTER DAPT) Study
  • 2019
  • Ingår i: American Heart Journal. - : MOSBY-ELSEVIER. - 0002-8703 .- 1097-6744. ; 209, s. 97-105
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The optimal duration of antiplatelet therapy in high-bleeding risk (HBR) patients with coronary artery disease treated with newer-generation drug-eluting bioresorbable polymer-coated stents remains unclear. Design MASTER DAPT (clinicaltrial.gov NCT03023020) is an investigator-initiated, open-label, multicenter, randomized controlled trial comparing an abbreviated versus a standard duration of antiplatelet therapy after bioresorbable polymer-coated Ultimaster (TANSEI) sirolimus-eluting stent implantation in approximately 4,300 HBR patients recruited from >= 100 interventional cardiology centers globally. After a mandatory 30-day dual-antiplatelet therapy (DAPT) run-in phase, patients are randomized to (a) a single antiplatelet regimen until study completion or up to 5 months in patients with clinically indicated oral anticoagulation (experimental 1-month DAPT group) or (b) continue DAPT for at least 5 months in patients without or 2 in patients with concomitant indication to oral anticoagulation, followed by a single antiplatelet regimen (standard antipkitelet regimen). With a final sample size of 4,300 patients, this study is powered to assess the noninferiority of the abbreviated antiplatelet regimen with respect to the net adverse clinical and major adverse cardiac and cerebral events composite end points and if satisfied for the superiority of abbreviated as compared to standard antiplatelet therapy duration in terms of major or clinically relevant nonmajor bleeding. Study end points will be adjudicated by a blinded Clinical Events Committee. Conclusions The MASTER DAPT study is the first randomized controlled trial aiming at ascertaining the optimal duration of antiplatelet therapy in HBR patients treated with sirolimus-eluting bioresorbable polymer-coated stent implantation.
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22.
  • Hansson, Nicolaj C., et al. (författare)
  • The impact of calcium volume and distribution in aortic root injury related to balloon-expandable transcatheter aortic valve replacement
  • 2015
  • Ingår i: JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY. - : ELSEVIER SCIENCE INC. - 1934-5925. ; 9:5, s. 382-392
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A detailed assessment of calcium within the aortic root may provide important additional information regarding the risk of aortic root injury during transcatheter heart valve replacement (TAVR). Objective: We sought to delineate the effect of calcium volume and distribution on aortic root injury during TAVR. Methods: Thirty-three patients experiencing aortic root injury during TAVR with a balloon-expandable valve were compared with a control group of 153 consecutive TAVR patients without aortic root injury (as assessed by post-TAVR multidetector CT). Using commercial software to analyze contrast-enhanced pre-TAVR CT scans, caltium volume was determined in 3 regions: (1) the overall left ventricular outflow tract (LVOT), extending 10 mm down from the aortic annulus plane; (2) the upper LVOT, extending 2 mm down from the annulus plane; and (3) the aortic valve region. Results: Calcium volumes in the upper LVOT (median, 29 vs 0 mm(3); P less than .0001) and overall LVOT (median, 74 vs 3 mm(3); P = .0001) were higher in patients who experienced aortic root injury compared with the control group. Calcium in the aortic valve region did not differ between groups. Upper LVOT calcium volume was more predictive of aortic root injury than overall LVOT calcium volume (area under receiver operating curve [AUG]; 0.78; 95% confidence interval, 0.69-0.86 vs AUC, 0.71; 95% confidence interval, 0.62-0.82; P = .010). Upper LVOT calcium below the noncoronary cusp was significantly more predictive of aortic root injury compared to calcium underneath the right coronary cusp or the left coronary cusp (AUC, 0.81 vs 0.68 vs 0.64). Prosthesis oversizing greater than20% (likelihood ratio test, P = .028) and redilatation (likelihood ratio test, P = .015) improved prediction of aortic root injury by upper LVOT calcium volume. Conclusion: Calcification of the LVOT, especially in the upper LVOT, located below the noncoronary cusp and extending from the annular region, is predictive of aortic root injury during TAVR with a balloon-expandable valve. (C) 2015 Society of Cardiovascular Computed Tomography. All rights reserved.
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23.
  • Head, Stuart J., et al. (författare)
  • Coronary artery bypass grafting vs. percutaneous coronary intervention for patients with three-vessel disease : final five-year follow-up of the SYNTAX trial
  • 2014
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 35:40, s. 2821-2830
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Coronary artery bypass grafting (CABG) has been considered the standard of care for patients with three-vessel disease (3VD), but long-term comparative results from randomized trials of CABG vs. percutaneous coronary intervention (PCI) using drug-eluting stents (DES) remain limited. Methods and results Patients with de novo 3VD or left main disease were randomly assigned to PCI with the paclitaxel-eluting first-generation stent or CABG in the SYNTAX trial. This pre-specified analysis presents the 5-year outcomes of patients with 3VD (n = 1095). The rate of major adverse cardiac and cerebrovascular events (MACCE) was significantly higher in patients with PCI compared with CABG (37.5 vs. 24.2%, respectively; P < 0.001). Percutaneous coronary intervention as opposed to CABG resulted in significantly higher rates of the composite of death/stroke/myocardial infarction (MI) (22.0 vs. 14.0%, respectively; P < 0.001), all-cause death (14.6 vs. 9.2%, respectively; P = 0.006), MI (9.2 vs. 4.0%, respectively; P = 0.001), and repeat revascularization (25.4 vs. 12.6%, respectively; P < 0.001); however, stroke was similar between groups at 5 years (3.0 vs. 3.5%, respectively; P = 0.66). Results were dependent on lesion complexity (P for interaction = 0.12); in patients with a low (022) SYNTAX score, PCI vs. CABG resulted in similar rates of MACCE (33.3% vs. 26.8%, respectively; P = 0.21) but significantly more repeat revascularization (25.4% vs. 12.6%, respectively; P = 0.038), while in intermediate (2332) or high (>= 33) SYNTAX score terciles, CABG demonstrated clear superiority in terms of MACCE, death, MI, and repeat revascularization. Differences in MACCE between PCI and CABG were larger in diabetics [hazard ratio (HR) = 2.30] than non-diabetics (HR = 1.51), although the P for interaction failed to reach significance for MACCE (P for interaction = 0.095) or any of the other endpoints. Conclusion Five-year results of patients with 3VD treated with CABG or PCI using the first-generation paclitaxel-eluting DES suggest that CABG should remain the standard of care as it resulted in significantly lower rates of death, MI, and repeat revascularization, while stroke rates were similar. For patients with low SYNTAX scores, PCI is an acceptable revascularization strategy, although at a price of significantly higher rates of repeat revascularization.
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24.
  • Iqbal, Javaid, et al. (författare)
  • Optimal Medical Therapy Improves Clinical Outcomes in Patients Undergoing Revascularization With Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting Insights From the Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) Trial at the 5-Year Follow-Up
  • 2015
  • Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 131:14, s. 1269-1277
  • Tidskriftsartikel (refereegranskat)abstract
    • Background-There is a paucity of data on the use of optimal medical therapy (OMT) in patients with complex coronary artery disease undergoing revascularization with percutaneous coronary intervention or coronary artery bypass grafting (CABG) and its long-term prognostic significance. Methods and Results-The Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial is a multicenter, randomized, clinical trial of patients (n=1800) with complex coronary disease randomized to revascularization with percutaneous coronary intervention or CABG. Detailed drug history was collected for all patients at discharge and at the 1-month, 6-month, 1-year, 3-year, and 5-year follow-ups. OMT was defined as the combination of at least 1 antiplatelet drug, statin, beta-blocker, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. Five-year clinical outcomes were stratified by OMT and non-OMT. OMT was underused in patients treated with coronary revascularization, especially CABG. OMT was an independent predictor of survival. OMT was associated with a significant reduction in mortality (hazard ratio, 0.64; 95% confidence interval, 0.48-0.85; P=0.002) and composite end point of death/myocardial infarction/stroke (hazard ratio, 0.73; 95% confidence interval, 0.58-0.92; P=0.007) at the 5-year follow-up. The treatment effect with OMT (36% relative reduction in mortality over 5 years) was greater than the treatment effect of revascularization strategy (26% relative reduction in mortality with CABG versus percutaneous coronary intervention over 5 years). On stratified analysis, all the components of OMT were important for reducing adverse outcomes regardless of revascularization strategy. Conclusions-The use of OMT remains low in patients with complex coronary disease requiring coronary intervention with percutaneous coronary intervention and even lower in patients treated with CABG. Lack of OMT is associated with adverse clinical outcomes. Targeted strategies to improve OMT use in postrevascularization patients are warranted.
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25.
  • Kageyama, Shigetaka, et al. (författare)
  • Geographic disparity in 10-year mortality after coronary artery revascularization in the SYNTAXES trial
  • 2022
  • Ingår i: International Journal of Cardiology. - : Elsevier. - 0167-5273 .- 1874-1754. ; 368, s. 28-38
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: To investigate geographic disparity in long-term mortality following revascularization in patients with complex coronary artery disease (CAD).Methods and results: The SYNTAXES trial randomized 1800 patients with three-vessel and/or left main CAD to percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) and assessed their survival at 10 years. Patients were stratified according to the region of recruitment: North America (N-A, n = 245), Eastern Europe (E-E, n = 189), Northern Europe (N-E, n = 425), Southern Europe (S-E, n = 263), and Western Europe (W-E, n = 678), which also served as the reference group. Compared to W-E, patients were younger in E-E (62 vs 65 years, p < 0.001), and less frequently male in N-A (65.3% vs 79.6%, p < 0.001). Diabetes (16.0% vs 25.4%, p < 0.001) and peripheral vascular disease (6.8% vs 10.9%, p = 0.025) were less frequent in N-E than W-E. Ejection fraction was highest in W-E (62% vs 56%, p < 0.001). Compared to W-E, the mean anatomic SYNTAX score was higher in S-E (29 vs 31, p = 0.008) and lower in N-A (26, p < 0.001). Crude ten-year mortality was similar in N-A (31.6%), and W-E (30.7%), and significantly lower in E-E (22.5%, p = 0.041), N-E (21.9%, p = 0.003) and S-E (22.0%, p = 0.014). Compared to W-E, adjusted mortality in N-E (HR 0.85, p = 0.019) and S-E (HR 0.72, p = 0.043) remain significantly lower after adjustment for pre-and peri-procedural factors, but no significant interaction (Pinteraction = 0.728) between region and modality of revascularization was seen.Conclusion: In the era of globalization, knowledge, and understanding of geographic disparity are of paramount importance for the correct interpretation of global studies.
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