Publications
98 results found
Hartley A, Pradeep M, Shah HA, et al., 2020, THE EFFECT OF MAJOR VASCULAR SURGERY ON OXIDIZED LDL, ITS ANTIBODIES, COMPLEMENT AND COMPLEXES, Publisher: ELSEVIER IRELAND LTD, Pages: E56-E57, ISSN: 0021-9150
Seligman H, Sen S, Nijjer S, et al., 2020, Management of Acute Coronary Syndromes During the Coronavirus Disease 2019 Pandemic: Deviations from Guidelines and Pragmatic Considerations for Patients and Healthcare Workers, Interventional Cardiology Review, Vol: 15, Pages: e16-e16, ISSN: 1756-1477
Coronavirus disease 2019 (COVID-19) is forcing cardiology departments to rapidly adapt existing clinical guidelines to a new reality and this is especially the case for acute coronary syndrome pathways. In this focused review, the authors discuss how COVID-19 is affecting acute cardiology care and propose pragmatic guideline modifications for the diagnosis and management of acute coronary syndrome patients, particularly around the appropriateness of invasive strategies as well as length of hospital stay. The authors also discuss the use of personal protective equipment for healthcare workers in cardiology. Based on shared global experiences and growing peer-reviewed literature, it is possible to put in place modified acute coronary syndrome treatment pathways to offer safe pragmatic decisions to patients and staff.
Rajkumar C, Shun-Shin M, Seligman H, et al., 2020, Placebo-Controlled Efficacy of Percutaneous Coronary Intervention for Focal and Diffuse Patterns of Stable Coronary Artery Disease: A Secondary Analysis From ORBITA, 32nd Annual Transcatheter Cardiovascular Therapeutics Symposium (TCT CONNECT), Publisher: ELSEVIER SCIENCE INC, Pages: B165-B165, ISSN: 0735-1097
Little C, Jabbour R, Kotecha T, et al., 2020, Primary PCI for STEMI During the COVID-19 Pandemic in London: A Systematic Analysis of Pathway Activation and Outcomes, 32nd Annual Transcatheter Cardiovascular Therapeutics Symposium (TCT CONNECT), Publisher: ELSEVIER SCIENCE INC, Pages: B96-B96, ISSN: 0735-1097
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Abdelrahman KM, Chen MY, Dey AK, et al., 2020, Coronary Computed Tomography Angiography From Clinical Uses to Emerging Technologies <i>JACC</i> State-of-the-Art Review, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 76, Pages: 1226-1243, ISSN: 0735-1097
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Tomaniak M, Katagiri Y, Modolo R, et al., 2020, Vulnerable plaques and patients: state-of-the-art, European Heart Journal, Vol: 41, Pages: 2997-3004, ISSN: 0195-668X
Despite advanced understanding of the biology of atherosclerosis, coronary heart disease remains the leading cause of death worldwide. Progress has been challenging as half of the individuals who suffer sudden cardiac death do not experience premonitory symptoms. Furthermore, it is well-recognized that also a plaque that does not cause a haemodynamically significant stenosis can trigger a sudden cardiac event, yet the majority of ruptured or eroded plaques remain clinically silent. In the past 30 years since the term 'vulnerable plaque' was introduced, there have been major advances in the understanding of plaque pathogenesis and pathophysiology, shifting from pursuing features of 'vulnerability' of a specific lesion to the more comprehensive goal of identifying patient 'cardiovascular vulnerability'. It has been also recognized that aside a thin-capped, lipid-rich plaque associated with plaque rupture, acute coronary syndromes (ACS) are also caused by plaque erosion underlying between 25% and 60% of ACS nowadays, by calcified nodule or by functional coronary alterations. While there have been advances in preventive strategies and in pharmacotherapy, with improved agents to reduce cholesterol, thrombosis, and inflammation, events continue to occur in patients receiving optimal medical treatment. Although at present the positive predictive value of imaging precursors of the culprit plaques remains too low for clinical relevance, improving coronary plaque imaging may be instrumental in guiding pharmacotherapy intensity and could facilitate optimal allocation of novel, more aggressive, and costly treatment strategies. Recent technical and diagnostic advances justify continuation of interdisciplinary research efforts to improve cardiovascular prognosis by both systemic and 'local' diagnostics and therapies. The present state-of-the-art document aims to present and critically appraise the latest evidence, developments, and future perspectives in detection, prevent
van den Berg VJ, Vroegindewey MM, Kardys I, et al., 2019, Anti-oxidized LDL antibodies and coronary artery disease: a systematic review, Antioxidants (Basel), Vol: 8, ISSN: 2076-3921
Antibodies to oxidized LDL (oxLDL) may be associated with improved outcomes in cardiovascular disease. However, analysis is restricted by heterogenous study design and endpoints. Our objective was to conduct a comprehensive systematic review assessing anti-oxLDL antibodies in relation to coronary artery disease (CAD). Through a systematic literature search, we identified all studies assessing the relationship of either, IgG or IgM ox-LDL/ copper-oxLDL/ malondialdehyde-LDL, with coronary atherosclerosis or cardiovascular events in populations with, and without, established CAD. Systematic review best practices were adhered to and study quality was assessed. An initial electronic database search identified 2059 records, which was subsequently followed by abstract and full-text review. Finally, we included 18 studies with over 1811 patients with CAD. The studies varied according to populations studied, conventional cardiovascular risk factors and interventional modalities used to assess CAD. IgM anti-oxLDL antibodies were found to indicate protection from more severe CAD and possibly cardiovascular events, whilst the relationship with IgG is more complex and difficult to elucidate, with studies reporting divergent results. In this systematic review, there is evidence that suggests a relationship between anti-oxLDL antibodies and CAD, especially for the IgM subclass. However, further studies, with well-characterized prospective cohorts, will be important to clarify these associations.
Kaura A, Hartley A, Panoulas V, et al., 2019, HsCRP predicts mortality beyond troponin in 102,337 patients with suspected acute coronary syndrome (CRP-RISK study), Congress of the European-Society-of-Cardiology (ESC) / World Congress of Cardiology, Publisher: OXFORD UNIV PRESS, Pages: 1302-1302, ISSN: 0195-668X
Kaura A, Hartley A, Panoulas V, et al., 2019, THE ROLE OF HIGH-SENSITIVITY C-REACTIVE PROTEIN IN PREDICTING MORTALITY BEYOND TROPONIN IN OVER 100,000 PATIENTS WITH SUSPECTED ACUTE CORONARY SYNDROME (NIHR HEALTH INFORMATICS COLLABORATIVE CRP-RISK STUDY), Annual Conference of the British-Cardiovascular-Society (BCS) - Digital Health Revolution, Publisher: BMJ PUBLISHING GROUP, Pages: A120-A121, ISSN: 1355-6037
Kaura A, Hartley A, Panoulas V, et al., 2019, HSCRP PREDICTS MORTALITY BEYOND TROPONIN IN 102,337 PATIENTS WITH SUSPECTED ACUTE CORONARY SYNDROME IN THE UK NATIONAL INSTITUTE FOR HEALTH RESEARCH CRP-RISK STUDY, 68th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), Publisher: ELSEVIER SCIENCE INC, Pages: 10-10, ISSN: 0735-1097
Hartley A, Haskard D, Khamis R, 2019, Oxidized LDL and anti-oxidized LDL antibodies in atherosclerosis – Novel insights and future directions in diagnosis and therapy, Trends in Cardiovascular Medicine, Vol: 29, Pages: 22-26, ISSN: 1050-1738
van den Berg VJ, Haskard DO, Fedorowski A, et al., 2018, IgM anti-malondialdehyde low density lipoprotein antibody levels indicate coronary heart disease and necrotic core characteristics in the Nordic Diltiazem (NORDIL) study and the Integrated Imaging and Biomarker Study 3 (IBIS-3)., EBioMedicine, Vol: 36, Pages: 63-72, ISSN: 2352-3964
BACKGROUND: Certain immunoglobulins (Ig) are proposed to have protective functions in atherosclerosis. OBJECTIVES: We tested whether serum levels of IgG and IgM autoantibodies against malondialdehyde low density lipoprotein (MDA-LDL) are associated with clinical coronary heart disease (CHD) and unfavorable plaque characteristics. METHODS: NORDIL was a prospective study investigating adverse cardiovascular outcomes in hypertensive patients. IBIS-3 analyzed lesions in a non-culprit coronary artery with <50% stenosis using radiofrequency intravascular ultrasound (RF-IVUS) and near-infrared spectroscopy (NIRS). Imaging was repeated after a median of 386 days on rosuvastatin. Associations of antibodies with incident CHD and imaging parameters were assessed in the two sub-studies respectively. FINDINGS: From 10,881 NORDIL patients, 87 had serum sampled at baseline and developed CHD over 4.5 years, matched to 227 controls. Higher titers of IgM anti-MDA-LDL had a protective effect on adverse outcomes, with odds ratio 0.29 (0.11, 0.76; p = 0.012; p = 0.016 for trend). Therefore, the effect was explored at the lesional level in IBIS-3. 143 patients had blood samples and RF-IVUS measurements available, and NIRS was performed in 90 of these. At baseline, IgM anti-MDA-LDL levels had a strong independent inverse relationship with lesional necrotic core volume (p = 0.027) and percentage of plaque occupied by necrotic core (p = 0.011), as well as lipid core burden index (p = 0.024) in the worst 4 mm segment. INTERPRETATION: Our study supports the hypothesis that lower circulating levels of IgM anti-MDA-LDL are associated with clinical CHD development, and for the first time relates these findings to atherosclerotic plaque characteristics that are linked to vulnerability.
Khan TZ, Haskard D, Caga-Anan M, et al., 2018, OXIDISED LDL AND ANTI-OXIDISED LDL ANTIBODIES ARE REDUCED BY LIPOPROTEIN APHERESIS IN A RANDOMISED CONTROLLED TRIAL ON PATIENTS WITH REFRACTORY ANGINA AND ELEVATED LIPOPROTEIN(A), 86th Congress of the European-Atherosclerosis-Society (EAS), Publisher: ELSEVIER IRELAND LTD, Pages: E31-E32, ISSN: 0021-9150
Al-Lamee R, Thompson D, Dehbi H-M, et al., 2018, Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial, Lancet, Vol: 391, Pages: 31-40, ISSN: 0140-6736
BACKGROUND: Symptomatic relief is the primary goal of percutaneous coronary intervention (PCI) in stable angina and is commonly observed clinically. However, there is no evidence from blinded, placebo-controlled randomised trials to show its efficacy. METHODS: ORBITA is a blinded, multicentre randomised trial of PCI versus a placebo procedure for angina relief that was done at five study sites in the UK. We enrolled patients with severe (≥70%) single-vessel stenoses. After enrolment, patients received 6 weeks of medication optimisation. Patients then had pre-randomisation assessments with cardiopulmonary exercise testing, symptom questionnaires, and dobutamine stress echocardiography. Patients were randomised 1:1 to undergo PCI or a placebo procedure by use of an automated online randomisation tool. After 6 weeks of follow-up, the assessments done before randomisation were repeated at the final assessment. The primary endpoint was difference in exercise time increment between groups. All analyses were based on the intention-to-treat principle and the study population contained all participants who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02062593. FINDINGS: ORBITA enrolled 230 patients with ischaemic symptoms. After the medication optimisation phase and between Jan 6, 2014, and Aug 11, 2017, 200 patients underwent randomisation, with 105 patients assigned PCI and 95 assigned the placebo procedure. Lesions had mean area stenosis of 84·4% (SD 10·2), fractional flow reserve of 0·69 (0·16), and instantaneous wave-free ratio of 0·76 (0·22). There was no significant difference in the primary endpoint of exercise time increment between groups (PCI minus placebo 16·6 s, 95% CI -8·9 to 42·0, p=0·200). There were no deaths. Serious adverse events included four pressure-wire related complications in the placebo group, which required PCI, and five major bleeding
Hartley A, Haskard D, Khamis R, 2018, Markers of Apoptosis predict cardiovascular outcomes and point to 'response to injury' as a common pathway leading to diabetes and cardiovascular events, EBioMedicine, Vol: 28, Pages: 19-20, ISSN: 2352-3964
Metabolic stress, chronic vascular injury and cellular apoptosis are considered as instrumentally connected in the pathogenesis of atherosclerosis and diabetes (Gistera and Hansson, 2017). The work from Mattisson et al. (Mattisson et al., 2017) sheds light on this potentially important pathway linking cell-mediated death and cardiovascular outcomes. The study spans translational science, from describing an elegant laboratory technique using Fas ligand to induce apoptosis in peripheral blood mononuclear cells and demonstrating release of TNF receptor 1 (TNFR-1), TNF-related apoptosis-inducing ligand receptor 2 (TRAILR-2) and Fas, to studying the cell death receptor plasma levels in a large well-characterized prospective population.
Pandey S, Haskard DO, Khamis R, 2017, Developing a strategy for interventional molecular imaging of oxidized low density lipoprotein in atherosclerosis. An auto-commentary., Molecular Imaging, Vol: 16, ISSN: 1536-0121
The identification of vulnerable coronary artery atherosclerotic plaques offers the prospect of either localized or systematic therapeutic targeting in order to prevent myocardial infarction. Molecular imaging of atherosclerosis adds to morphological imaging by focusing on the immunobiology hidden in and behind the endothelium and therefore may be able to improve the identification of prospective culprit lesions. Our focus has been on identifying arterial accumulation of oxidized low density lipoprotein (oxLDL) by exploiting advances in knowledge of vascular pathobiology. Here, we reflect on our work developing Near Infra-Red Fluorescence (NIRF) imaging of oxLDL using LO1, a monoclonal autoantibody generated in our laboratory. We detail progress to date and discuss our vision on taking the work through the early translational pipeline towards a multi-targeted approach in imaging rupture prone atherosclerotic plaques. Ultimately, molecular imaging of coronary arteries should be able to assess the regional risk that is specific to a lesion, which can then be used in concert with global risk factors to personalize the therapeutic strategy for patients in a way that goes beyond generalized population-based therapies.
Khamis R, Mylotte D, 2017, An old dichotomy in the space(r) age, EUROINTERVENTION, Vol: 13, Pages: 259-261, ISSN: 1774-024X
van den Berg V, Haskard D, Kardys I, et al., 2017, HIGHER IGM ANTI OXIDISED LDL ANTIBODIES POINT TO FAVOURABLE PLAQUE CHARACTERISTICS AS DETERMINED BY RADIO FREQUENCY INTRAVASCULAR ULTRASOUND (RF-IVUS) AND NEAR INFRARED SPECTROSCOPY (NIRS) IN THE INTEGRATED IMAGING AND BIOMARKER STUDY 3 (IBIS-3), Annual Conference of the British-Cardiovascular-Society (BCS), Publisher: BMJ PUBLISHING GROUP, Pages: A112-A113, ISSN: 1355-6037
Khan T, Haskard D, Caga-Anan M, et al., 2017, 94 Oxidised ldl levels correlate with lipoprotein(a) levels and are reduced by lipoprotein apheresis in a randomised study on patients with refractory angina and raised lipoprotein?(a), Annual Conference of the British-Cardiovascular-Society (BCS), Publisher: BMJ Publishing Group, Pages: A69-A69, ISSN: 1355-6037
Mann P, Khamis RYJ, Haskard D, et al., 2017, DEVELOPING CAPTURE ASSAYS TO MEASURE CIRCULATING CRP/OXIDISED LOW DENSITY LIPOPROTEIN COMPLEXES IN PATIENTS UNDERGOING CARDIOPULMONARY BYPASS AND EXAMINING USE OF CRP/OXIDISED LOW DENSITY LIPOPROTEIN COMPLEXES AS A BIOMARKER OF ATHEROSCLEROSIS, Annual Conference of the British-Cardiovascular-Society (BCS), Publisher: BMJ PUBLISHING GROUP, Pages: A119-A119, ISSN: 1355-6037
Khamis R, 2017, The translational journey of a new ultra-hydrophilic stent platform: what can we learn?, EUROINTERVENTION, Vol: 12, Pages: 2044-2045, ISSN: 1774-024X
van den Berg VJ, Khamis R, Kardys I, et al., 2016, High Igm Levels Are Inversely Associated With Necrotic Core Assessed by Ivus but Do Not Predict Plaque Progression: Results of the Ibis-3 Study, Scientific Sessions of the American-Heart-Association / Resuscitation Science Symposium, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7322
Hsiao ST, Spencer T, Boldock L, et al., 2016, Endothelial repair in stented arteries is accelerated by inhibition of Rho-associated protein kinase., Cardiovascular Research, Vol: 112, Pages: 689-701, ISSN: 1755-3245
AIMS: Stent deployment causes endothelial cell (EC) denudation, which promotes in-stent restenosis and thrombosis. Thus endothelial regrowth in stented arteries is an important therapeutic goal. Stent struts modify local hemodynamics, however the effects of flow pertubation on EC injury and repair are incompletely understood. By studying the effects of stent struts on flow and EC migration we identified an intervention that promotes endothelial repair in stented arteries. METHODS AND RESULTS: In vitro and in vivo models were developed to monitor endothelialization under flow and the influence of stent struts. A 2D parallel-plate flow chamber with 100 μm ridges arranged perpendicular to the flow was used. Live cell imaging coupled to computational fluid dynamic simulations revealed that EC migrate in the direction of flow upstream from the ridges but subsequently accumulate downstream from ridges at sites of bidirectional flow. The mechanism of EC trapping by bidirectional flow involved reduced migratory polarity associated with altered actin dynamics. Inhibition of Rho-associated protein kinase (ROCK) enhanced endothelialization of ridged surfaces by promoting migratory polarity under bidirectional flow (p<0.01). To more closely mimic the in vivo situation we cultured EC on the inner surface of polydimethylsiloxane tubing containing Coroflex Blue stents (65 μm struts) and monitored migration. ROCK inhibition significantly enhanced EC accumulation downstream from struts under flow (p<0.05). We investigated the effects of ROCK inhibition on re-endothelialization in vivo using a porcine model of EC denudation and stent placement. En face staining and confocal microscopy revealed that inhibition of ROCK using fasudil (30 mg/day via osmotic minipump) significantly increased re-endothelialization of stented carotid arteries (p<0.05). CONCLUSIONS: Stent struts delay endothelial repair by generating localised bidirectional flow which traps migrating EC. ROCK
Khamis RY, 2016, Editorial commentary: Dissecting the gender differences in nonobstructive coronary artery disease: How do we bridge the gap?, Trends in Cardiovascular Medicine, Vol: 27, Pages: 180-181, ISSN: 1873-2615
Kojima C, Ammari T, Caga-Anan M, et al., 2016, Detection of dynamic change in levels of plasma oxidized low density lipoprotein during coronary artery bypass grafting using a natural monoclonal antibody, Congress of the European-Society-of-Cardiology (ESC), Publisher: Oxford University Press (OUP), Pages: 187-188, ISSN: 1522-9645
Brida M, Dimopoulos K, Kempny A, et al., 2016, Body mass index in adult congenital heart disease patients: distribution, association with exercise capacity and prognostic implication, Congress of the European-Society-of-Cardiology (ESC), Publisher: Oxford University Press (OUP), Pages: 27-27, ISSN: 1522-9645
Khamis RY, Hughes AD, Caga-Anan M, et al., 2016, High serum immunoglobulin G and M levels predict freedom from adverse cardiovascular events in hypertension: a nested case-control substudy of the Anglo-Scandinavian Cardiac Outcomes Trial, EBioMedicine, Vol: 9, Pages: 372-380, ISSN: 2352-3964
Aims: We aimed to determine whether the levels of total serum IgM and IgG, together with specific antibodies against malondialdehyde-conjugated low-density lipoprotein (MDA-LDL),can improve cardiovascular risk discrimination.Methods and Results: The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) randomized 9098 patients in the UK and Ireland into the Blood Pressure-Lowering Arm. 485 patients that had cardiovascular (CV) events over 5.5 years were age and sex matched with 1367 controls. Higher baseline total serum IgG, and to a lesser extent IgM, were associated with decreased risk of CV events (IgG odds ratio (OR) per one standard deviation (SD) 0.80[95% confidence interval, CI 0.72,0.89], p<0.0001; IgM 0.83[0.75,0.93], p=0.001), and particularly events due to coronary heart disease (CHD) (IgG OR 0.66 (0.57,0.76); p<0.0001, IgM OR 0.81 (0.71,0.93); p=0.002). The association persisted after adjustment for a basic model with variables in the Framingham Risk Score (FRS) as well as following inclusion of C-reactive protein (CRP) and N-terminal pro-B-type natriuretic peptide (NtProBNP). IgG and IgM antibodies against MDA-LDL were also associated with CV events but their significance was lost following adjustment for total serum IgG and IgM respectively. The area under the receiver operator curve for CV events was improved from the basic risk model when adding in total serum IgG, and there was improvement in continuous and categorical net reclassification(17.6% and 7.5% respectively) as well as in the integrated discrimination index.Conclusion: High total serum IgG levels are an independent predictor of freedom from adverse cardiovascular events, particularly those attributed to CHD, in patients with hypertension.
Khamis RY, Haskard DO, Serruys PW, 2016, Translational interventional cardiology: a new editorial priority for EuroIntervention, EuroIntervention, Vol: 12, Pages: 11-13, ISSN: 1969-6213
Khamis RYJ, Ammari T, Mikhail G, 2016, Gender Differences in Coronary Heart Disease, Heart, Vol: 102, Pages: 1142-1149, ISSN: 1468-201X
Learning objectivesCurriculum sections: 2.8 (Acute Coronary Syndromes) and 2.9 (Chronic Ischaemic Heart disease).Learning objectives: outline the differences in the presentation patterns, clinical characteristics, behavioural characteristics and clinical outcomes relating to gender and coronary heart disease (CHD). This will incorporate the following:Knowledge: understand the benefit of cardiovascular interventions in women in comparison with men in both the acute and chronic presentations of CHD. Delineate the data reflecting the need for more research into women and heart disease, coupled with more patient and physician education.Skills: learn the presentation patterns and gender-specific issues related to patients presenting with CHD.Behaviours and attitudes: discuss the preconceived ideas around gender and heart disease, emphasising the need for enhanced assessment of women with heart disease.
Khamis RY, Woollard K, Kojima C, et al., 2016, A NOVEL IGG AUTOANTIBODY, LO9, REACTS SPECIFICALLY WITH ADHERENT LOW DENSITY LIPOPROTEIN (LDL), TARGETS LDL IN ATHEROSCLEROSIS IN VIVO AND STIMULATES MACROPHAGE TNFα RELEASE, Publisher: Elsevier, Pages: 2324-2324, ISSN: 1558-3597
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