Imperial College London

Dr. Ramzi Y Khamis MB ChB PhD FESC FRCP

Faculty of MedicineNational Heart & Lung Institute

Clinical Senior Lecturer in Cardiology
 
 
 
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Contact

 

+44 (0)20 7594 6842r.khamis

 
 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

76 results found

Hartley A, Shalhoub J, Khamis R, 2021, Trends in Mortality from Aortic Stenosis in Europe: 2000-2017, Frontiers in Cardiovascular Medicine, ISSN: 2297-055X

Journal article

Hajhosseiny R, Munoz C, Cruz G, Khamis R, Kim WY, Prieto C, Botnar RMet al., 2021, Coronary magnetic resonance angiography in chronic coronary syndromes, Front Cardiovasc Med, Vol: 8, ISSN: 2297-055X

Cardiovascular disease is the leading cause of mortality worldwide, with atherosclerotic coronary artery disease (CAD) accounting for the majority of cases. X-ray coronary angiography and computed tomography coronary angiography (CCTA) are the imaging modalities of choice for the assessment of CAD. However, the use of ionising radiation and iodinated contrast agents remain drawbacks. There is therefore a clinical need for an alternative modality for the early identification and longitudinal monitoring of CAD without these associated drawbacks. Coronary magnetic resonance angiography (CMRA) could be a potential alternative for the detection and monitoring of coronary arterial stenosis, without exposing patients to ionising radiation or iodinated contrast agents. Further advantages include its versatility, excellent soft tissue characterisation and suitability for repeat imaging. Despite the early promise of CMRA, widespread clinical utilisation remains limited due to long and unpredictable scan times, onerous scan planning, lower spatial resolution, as well as motion related image quality degradation. The past decade has brought about a resurgence in CMRA technology, with significant leaps in image acceleration, respiratory and cardiac motion estimation and advanced motion corrected or motion-resolved image reconstruction. With the advent of artificial intelligence, great advances are also seen in deep learning-based motion estimation, undersampled and super-resolution reconstruction promising further improvements of CMRA. This has enabled high spatial resolution (1 mm isotropic), 3D whole heart CMRA in a clinically feasible and reliable acquisition time of under 10 min. Furthermore, latest super-resolution image reconstruction approaches which are currently under evaluation promise acquisitions as short as 1 min. In this review, we will explore the recent technological advances that are designed to bring CMRA closer to clinical reality.

Journal article

Hartley A, Khamis R, 2021, A novel immunoassay for malondialdehyde-conjugated low-density lipoprotein measures dynamic changes in the blood of patients undergoing coronary artery bypass graft surgery, Antioxidants, ISSN: 2076-3921

Oxidized low-density lipoproteins play an important role in tissue pathology. In this study, we report a sensitive novel enzyme-linked immunosorbent assay for the detection of malondial-dehyde-modified low-density lipoprotein (MDA-LDL), a key component of oxidized LDL. The assay is capable of measuring a variable presence of MDA-LDL within human plasma and serum. We demonstrate the robust nature of the assay on samples stored for over 20 months, as well as high inter-operator reproducibility (r=0.74, p <0.0001). The assay was capable of detecting dynamic changes in patient blood samples after coronary artery bypass graft surgery, indicating synthesis or release of MDA-LDL with the oxidative stress of surgery, followed by homeostatic clearance. This robust, sensitive and specific assay for circulating MDA-LDL will serve as a valuable trans-lational tool for the improved detection of oxidative forms of LDL in response to a range of physiological or pathological stimuli, with potential clinical applicability.

Journal article

Rajkumar C, Shun-Shin M, Seligman H, Ahmad Y, Warisawa T, Cook C, Howard J, Ganesananthan S, Amarin L, Khan C, Ahmed A, Nowbar A, Foley M, Assomull R, Keenan N, Sehmi J, Keeble T, davies J, Tang K, Gerber R, Cole G, O'Kane P, Sharp A, Khamis R, Kanaganayagam G, Petraco R, Ruparelia N, Malik I, Nijjer S, Sen S, Francis D, Al-Lamee Ret al., 2021, Placebo-controlled efficacy of percutaneous coronary intervention for focal and diffuse patterns of stable coronary artery disease, Circulation: Cardiovascular Interventions, Vol: 14, Pages: 809-818, ISSN: 1941-7640

Background Physiological assessment with pressure wire pullback can characterize coronary artery disease (CAD) with a focal or diffuse pattern. However, the clinical relevance of this distinction is unknown. We use data from ORBITA to test if the pattern of CAD predicts the placebo-controlled efficacy of percutaneous coronary intervention (PCI) on stress echocardiography ischemia and symptom endpoints.Methods164 patients in ORBITA underwent blinded instantaneous wave-free ratio (iFR) pullback assessment prior to randomization. Focal disease was defined as 0.03 iFR unit drop within 15mm, rather than over a longer distance. Analyses were performed using regression modelling. ResultsIn the PCI arm (n=85), 48 were focal and 37 were diffuse. In the placebo arm (n=79), 35 were focal and 44 were diffuse. Focal stenoses were associated with significantly lower fractional flow reserve (FFR) and iFR values than diffusely diseased vessels (focal mean FFR and iFR 0.600.15 and 0.650.24, diffuse 0.780.10 and 0.880.08 respectively, p<0.0001). With adjustment for this difference, PCI for focal stenoses resulted in significantly greater reduction in stress echo ischemia than PCI for diffuse disease (p<0.05). The effect of PCI on between-arm pre-randomization-adjusted exercise time was 9.32 seconds (95% CI, -17.1 to 35.7s; p=0.487). When stratified for pattern of disease, there was no detectable difference between focal and diffuse CAD (Pinteraction=0.700). PCI improved Seattle Angina Questionnaire angina frequency score and freedom from angina more than placebo (p=0.034; p=0.0035). However, there was no evidence of interaction between the physiological pattern of CAD and these effects (Pinteraction=0.436; Pinteraction=0.908).ConclusionPCI achieved significantly greater reduction of stress echocardiography ischemia in focal compared to diffuse CAD. However, for symptom endpoints, no such difference was observed.

Journal article

Albaghdadi MS, Ikegami R, Kassab MB, Gardecki JA, Kunio M, Chowdhury MM, Khamis R, Libby P, Tearney GJ, Jaffer FAet al., 2021, Near-Infrared Autofluorescence in Atherosclerosis Associates With Ceroid and Is Generated by Oxidized Lipid-Induced Oxidative Stress, ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, Vol: 41, Pages: E385-E398, ISSN: 1079-5642

Journal article

Mikhail G, Khawaja SA, Mohan P, Jabbour R, Bampouri T, Bowsher G, Hassan AMM, Huq F, Baghdasaryan L, Wang B, Sethi A, Sen S, Petraco R, Ruparelia N, Nijjer S, Malik IS, Foale R, Bellamy M, Kooner J, Rana BS, Cole G, Sutaria N, Kanaganayagam G, Nihoyannopoulos P, Fox K, Plymen CM, Pabari P, Howard L, Davies R, Hajoi G, Lo Giudice F, Kanagaratnam P, Anderson J, Chukwuemeka A, Khamis R, Varnava A, Baker CSR, Francis D, Asaria P, Al-Lamee Ret al., 2021, COVID-19 and its impact on the cardiovascular system, Open Heart, Vol: 8, Pages: 1-9, ISSN: 2053-3624

Objectives: The clinical impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has varied across countries with varying cardiovascular manifestations. We review the cardiac presentations, in-hospital outcomes and development of cardiovascular complications in the initial cohort of SARS-CoV-2 positive patients at Imperial College Healthcare NHS Trust, United Kingdom.Methods: We retrospectively analysed 498 COVID-19 positive adult admissions to our institute from 7th March to 7th April 2020. Patient data was collected for baseline demographics, co-morbidities and in-hospital outcomes, especially relating to cardiovascular intervention.Results:Mean age was 67.4±16.1 years and 62.2%(n=310) were male. 64.1%(n=319) of our cohort had underlying cardiovascular disease (CVD) with 53.4%(n=266) having hypertension. 43.2%(n=215) developed acute myocardial injury. Mortality was significantly increased in those patients with myocardial injury (47.4% vs 18.4%,p<0.001). Only 4 COVID-19 patients had invasive coronary angiography,2 underwent percutaneous coronary intervention and 1 required a permanent pacemaker implantation. 7.0%(n=35) of patients had an inpatient echocardiogram. Acute myocardial injury (OR 2.39,1.31-4.40,p=0.005) and history of hypertension (OR 1.88 ,1.01-3.55,p=0.049) approximately doubled the odds of in-hospital mortality in patients admitted with COVID-19 after other variables had been controlled for.Conclusion:Hypertension, pre-existing CVD and acute myocardial injury were associated with increased in-hospital mortality in our cohort of COVID-19 patients. However, only a low number of patients required invasive cardiac intervention.

Journal article

Thompson D, Al-Lamee R, Foley M, Dehbi HM, Thom S, Davies JE, Francis DP, Patel P, Gupta P, ORBITA Investigatorset al., 2021, Achieving optimal adherence to medical therapy by telehealth: Findings from the ORBITA medication adherence sub-study, Pharmacology Research and Perspectives, Vol: 9, Pages: e00710-e00710, ISSN: 2052-1707

INTRODUCTION: The ORBITA trial of percutaneous coronary intervention (PCI) versus a placebo procedure for patients with stable angina was conducted across six sites in the United Kingdom via home monitoring and telephone consultations. Patients underwent detailed assessment of medication adherence which allowed us to measure the efficacy of the implementation of the optimization protocol and interpretation of the main trial endpoints. METHODS: Prescribing data were collected throughout the trial. Self-reported adherence was assessed, and urine samples collected at pre-randomization and at follow-up for direct assessment of adherence using high-performance liquid chromatography with tandem mass spectrometry (HPLC MS/MS). RESULTS: Self-reported adherence was >96% for all drugs in both treatment groups at both stages. The percentage of samples in which drug was detected at pre-randomization and at follow-up in the PCI versus placebo groups respectively was: clopidogrel, 96% versus 90% and 98% versus 94%; atorvastatin, 95% versus 92% and 92% versus 91%; perindopril, 95% versus 97% and 85% versus 100%; bisoprolol, 98% versus 99% and 96% versus 97%; amlodipine, 99% versus 99% and 94% versus 96%; nicorandil, 98% versus 96% and 94% versus 92%; ivabradine, 100% versus 100% and 100% versus 100%; and ranolazine, 100% versus 100% and 100% versus 100%. CONCLUSIONS: Adherence levels were high throughout the study when quantified by self-reporting methods and similarly high proportions of drug were detected by urinary assay. The results indicate successful implementation of the optimization protocol delivered by telephone, an approach that could serve as a model for treatment of chronic conditions, particularly as consultations are increasingly conducted online.

Journal article

Khan TZ, Haskard D, Hartley A, Caga-Annan M, Pennell DJ, Collins P, Barbir M, Khamis Ret al., 2021, 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), Antioxidants, Vol: 10, ISSN: 2076-3921

Aims: An abundance of epidemiological evidence demonstrates that elevated lipoprotein(a) (Lp(a)) represents a significant contributing risk factor towards the development of cardiovascular disease. In particular, raised Lp(a) may play a mechanistic role in patients with refractory angina. Studies have also shown a correlation between oxidised LDL (oxLDL) levels and atherosclerotic burden as well as rates of cardiovascular events. Antibodies against oxLDL (anti-oxLDL) are involved in the removal of oxLDL. Lipoprotein apheresis (LA), which removes lipoproteins using extra-corporeal processes, is an established means of reducing Lp(a), and thereby reduces cardiovascular events. The aim of this study was to investigate the effect of LA on oxLDL and anti-oxLDL levels amongst those with refractory angina in the context of raised Lp(a). Methods: We performed a sub-study within a randomised controlled crossover trial involving 20 patients with refractory angina and raised Lp(a) > 500 mg/L, comparing the effect of three months of blinded weekly LA or sham, followed by crossover to the opposite study arm. We utilized enzyme-linked immunosorbent assays (ELISA) to quantify oxLDL and IgG/ IgM anti-oxLDL antibody levels at baseline and following three months of active LA or sham sessions. Results: Following three months of LA, there was a 30% reduction in oxLDL from 0.37 ± 0.06 to 0.26 ± 0.04 with a mean drop of −0.11 units (U) (95% CI −0.13, −0.09) compared to no significant change with sham therapy (p < 0.0001 between treatment arms). LA also led to a 22% reduction in levels of IgG and IgM anti-oxLDL, again with no significant change demonstrated during sham (p = 0.0036 and p = 0.012, respectively, between treatment arms). Conclusion: Amongst patients with refractory angina in the context of elevated Lp(a), LA significantly lowers levels of oxLDL and anti-oxLDL antibodies, representing potential mechanisms by which LA yields symptomatic and

Journal article

Naderi H, Robinson S, Swaans MJ, Bual N, Cheung W-S, Reid L, Shun-Shin M, Asaria P, Pabari P, Cole G, Kanaganayagam GS, Sutaria N, Bellamy M, Fox K, Nihoyannopoulos P, Petraco R, Al-Lamee R, Nijjer SS, Sen S, Ruparelia N, Baker C, Mikhail G, Malik I, Khamis R, Varnava A, Francis D, Mayet J, Rana Bet al., 2021, Adapting the role of handheld echocardiography during the COVID-19 pandemic: A practical guide, PERFUSION-UK, ISSN: 0267-6591

Journal article

Seligman H, Sen S, Nijjer S, Al-Lamee R, Clifford P, Sethi A, Hadjiloizou N, Kaprielian R, Ramrakha P, Bellamy M, Khan MA, Kooner J, Foale RA, Mikhail G, Baker CS, Mayet J, Malik I, Khamis R, Francis D, Petraco Ret 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.

Journal article

Rajkumar C, Shun-Shin M, Seligman H, Ahmad Y, Warisawa T, Cook C, Howard J, Amarin L, Nowbar A, Foley M, Assomull R, Keenan N, Sehmi J, Keeble T, Davies J, Tang K, Gerber R, Cole G, O'Kane P, Sharp A, Khamis R, Kanaganayagam G, Petraco R, Ruparelia N, Malik I, Nijjer S, Sen S, Francis D, Al-Lamee Ret 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

Conference paper

Little C, Jabbour R, Kotecha T, Candilio L, Lawson L, Wang B, Manmathan G, Coghlan J, Patel N, Kalra S, Lockie T, Patel D, Smith E, Baker C, Khamis R, Mikhail G, Malik I, Rakhit Ret 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

Conference paper

Ono M, Tomaniak M, Koenig W, Khamis R, de Silva R, Chichareon P, Kawashima H, Hara H, Gao C, Wang R, Huber K, Vrolix M, Jasionowicz P, Wykrzykowska JJ, Piek JJ, Jüni P, Hamm C, Steg PG, Windecker S, Onuma Y, Storey RF, Serruys PW, GLOBAL LEADERS Study Investigatorset al., 2020, Impact of White Blood Cell Count on Clinical Outcomes in Patients Treated with Aspirin-Free Ticagrelor Monotherapy after Percutaneous Coronary Intervention: Insights from the GLOBAL LEADERS Trial., Eur Heart J Cardiovasc Pharmacother

AIMS: To investigate the efficacy and safety of ticagrelor monotherapy in patients undergoing percutaneous coronary intervention (PCI) stratified according to the baseline white blood cell (WBC) count. METHODS AND RESULTS: This is a post-hoc analysis of the GLOBAL LEADERS trial, a multicentre, open-label, randomized all-comer trial in patients undergoing PCI, comparing the experimental strategy (23-month ticagrelor monotherapy following 1-month dual anti-platelet therapy [DAPT]) with the reference strategy (12-month aspirin monotherapy following 12-month DAPT). Patients were stratified into two WBC groups, either < or ≥median WBC count of 7.8 x 109 cells/L (lower or higher WBC group, respectively). The primary endpoint was a composite of all-cause mortality or new Q-wave myocardial infarction (MI) at 2 years.Out of 14,576 patients included in the present study, 7,212 patients (49.5%) were classified as the lower WBC group, who had a significantly lower risk of both ischemic and bleeding outcomes at 2 years. At 2 years, the experimental strategy was associated with a significant lower incidence of the primary endpoint compared with the reference strategy in the lower WBC group (2.8% vs. 4.2%; hazard ratio [HR]: 0.67; 95% CI: 0.52-0.86) but not in the higher WBC group (4.8% vs. 4.7%; HR: 1.01; 95% CI: 0.82-1.25; pinteraction=0.013). There were no significant differences in the risks of BARC type 3 or 5 bleeding between two antiplatelet strategies regardless of the WBC groups. CONCLUSIONS: Increased WBC counts, which may reflect degree of inflammation, at the time of index procedure may attenuate the anti-ischemic benefits of ticagrelor monotherapy observed in patients with lower WBC counts.

Journal article

Abdelrahman KM, Chen MY, Dey AK, Virmani R, Finn AV, Khamis RY, Choi AD, Min JK, Williams MC, Buckler AJ, Taylor CA, Rogers C, Samady H, Antoniades C, Shaw LJ, Budoff MJ, Hoffmann U, Blankstein R, Narula J, Mehta NNet al., 2020, Coronary Computed Tomography Angiography From Clinical Uses to Emerging Technologies: JACC State-of-the-Art Review., J Am Coll Cardiol, Vol: 76, Pages: 1226-1243

Evaluation of coronary artery disease (CAD) using coronary computed tomography angiography (CCTA) has seen a paradigm shift in the last decade. Evidence increasingly supports the clinical utility of CCTA across various stages of CAD, from the detection of early subclinical disease to the assessment of acute chest pain. Additionally, CCTA can be used to noninvasively quantify plaque burden and identify high-risk plaque, aiding in diagnosis, prognosis, and treatment. This is especially important in the evaluation of CAD in immune-driven conditions with increased cardiovascular disease prevalence. Emerging applications of CCTA based on hemodynamic indices and plaque characterization may provide personalized risk assessment, affect disease detection, and further guide therapy. This review provides an update on the evidence, clinical applications, and emerging technologies surrounding CCTA as highlighted at the 2019 National Heart, Lung and Blood Institute CCTA Summit.

Journal article

Tomaniak M, Katagiri Y, Modolo R, Silva RD, Khamis RY, Bourantas CV, Torii R, Wentzel JJ, Gijsen FJH, van Soest G, Stone PH, West NEJ, Maehara A, Lerman A, van der Steen AFW, Lüscher TF, Virmani R, Koenig W, Stone GW, Muller JE, Wijns W, Serruys PW, Onuma Yet 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

Journal article

van den Berg VJ, Vroegindewey MM, Kardys I, Boersma E, Haskard D, Hartley A, Khamis Ret 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.

Journal article

Kaura A, Hartley A, Panoulas V, Glampson B, Davies J, Mulla A, Woods K, Francis DP, Koenig W, Shah AM, Kharbanda R, Perera D, Patel RS, Mayet J, Khamis Ret 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

Conference paper

Kaura A, Hartley A, Panoulas V, Glampson B, Davies J, Mulla A, Woods K, Omigie J, Shah AD, Channon K, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs F, O'Sullivan M, Haskard D, Lord G, Melikian N, Francis D, Koenig W, Perera D, Shah A, Kharbanda R, Patel R, Mayet J, Khamis Ret 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

Conference paper

Kaura A, Hartley A, Panoulas V, Benjamin G, Davies J, Woods K, Mulla A, Shah AD, Channon K, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs FW, Kharbanda R, Lord GM, Melikian N, Patel R, Perera D, Shah A, Francis D, Koenig W, Mayet J, Khamis Ret 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

Conference paper

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

Journal article

van den Berg VJ, Haskard DO, Fedorowski A, Hartley A, Kardys I, Caga-Anan M, Akkerhuis KM, Oemrawsingh RM, van Geuns RJ, de Jaegere P, van Mieghem N, Regar E, Ligthart JMR, Umans VAWM, Serruys PW, Melander O, Boersma E, Khamis RYet 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.

Journal article

Khan TZ, Haskard D, Caga-Anan M, Pennell DJ, Barbir M, Khamis Ret 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

Conference paper

Al-Lamee R, Thompson D, Dehbi H-M, Sen S, Tang K, Davies J, Keeble T, Mielewczik M, Kaprielian R, Malik IS, Nijjer SS, Petraco R, Cook C, Ahmad Y, Howard J, Baker C, Sharp A, Gerber R, Talwar S, Assomull R, Mayet J, Wensel R, Collier D, Shun-Shin M, Thom SA, Davies JE, Francis DP, ORBITA investigatorset 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

Journal article

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.

Journal article

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.

Journal article

Khamis R, Mylotte D, 2017, An old dichotomy in the space(r) age, EUROINTERVENTION, Vol: 13, Pages: 259-261, ISSN: 1774-024X

Journal article

Mann P, Khamis RYJ, Haskard D, Minh T, Kojima C, Ammari T, Caga-Anan M, Nguyen BA, Anderson JR, Evans PC, Johns Met 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

Conference paper

Khan T, Haskard D, Caga-Anan M, Pennell D, Barbir M, Khamis Ret 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

Conference paper

van den Berg V, Haskard D, Kardys I, Anan M, Akkerhuis M, van Geuns R-J, de Jaegere P, van Mieghem N, Regar E, Ligthart J, Umans V, Serruys P, Boersma E, Khamis Ret 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

Conference paper

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

Journal article

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