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
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88 results found

Rajkumar CA, Wereski R, Parsonage W, Cullen L, Khamis R, Foley M, Harrell FE, Shun-Shin MJ, Mills NL, Al-Lamee RKet al., 2022, Association Between High-Sensitivity Cardiac Troponin, Myocardial Ischemia, and Revascularization in Stable Coronary Artery Disease., J Am Coll Cardiol, Vol: 79, Pages: 2185-2187

Journal article

Hartley A, Khamis R, 2022, Voice Biomarkers: The Most Modern and Least Invasive Tool for Coronary Assessment?, MAYO CLINIC PROCEEDINGS, Vol: 97, Pages: 816-818, ISSN: 0025-6196

Journal article

Kaura A, Hartley A, Panoulas V, Glampson B, Shah ASV, Davies J, Mulla A, Woods K, Omigie J, Shah AD, Thursz MR, Elliott P, Hemmingway H, Williams B, Asselbergs FW, O'Sullivan M, Lord GM, Trickey A, Sterne JA, Haskard DO, Melikian N, Francis DP, Koenig W, Shah AM, Kharbanda R, Perera D, Patel RS, Channon KM, Mayet J, Khamis Ret al., 2022, Mortality risk prediction of high-sensitivity C-reactive protein in suspected acute coronary syndrome: a cohort study, PLoS Medicine, Vol: 19, ISSN: 1549-1277

BACKGROUND: There is limited evidence on the use of high-sensitivity C-reactive protein (hsCRP) as a biomarker for selecting patients for advanced cardiovascular (CV) therapies in the modern era. The prognostic value of mildly elevated hsCRP beyond troponin in a large real-world cohort of unselected patients presenting with suspected acute coronary syndrome (ACS) is unknown. We evaluated whether a mildly elevated hsCRP (up to 15 mg/L) was associated with mortality risk, beyond troponin level, in patients with suspected ACS. METHODS AND FINDINGS: We conducted a retrospective cohort study based on the National Institute for Health Research Health Informatics Collaborative data of 257,948 patients with suspected ACS who had a troponin measured at 5 cardiac centres in the United Kingdom between 2010 and 2017. Patients were divided into 4 hsCRP groups (<2, 2 to 4.9, 5 to 9.9, and 10 to 15 mg/L). The main outcome measure was mortality within 3 years of index presentation. The association between hsCRP levels and all-cause mortality was assessed using multivariable Cox regression analysis adjusted for age, sex, haemoglobin, white cell count (WCC), platelet count, creatinine, and troponin. Following the exclusion criteria, there were 102,337 patients included in the analysis (hsCRP <2 mg/L (n = 38,390), 2 to 4.9 mg/L (n = 27,397), 5 to 9.9 mg/L (n = 26,957), and 10 to 15 mg/L (n = 9,593)). On multivariable Cox regression analysis, there was a positive and graded relationship between hsCRP level and mortality at baseline, which remained at 3 years (hazard ratio (HR) (95% CI) of 1.32 (1.18 to 1.48) for those with hsCRP 2.0 to 4.9 mg/L and 1.40 (1.26 to 1.57) and 2.00 (1.75 to 2.28) for those with hsCRP 5 to 9.9 mg/L and 10 to 15 mg/L, respectively. This relationship was independent of troponin in all suspected ACS patients and was further verified in those who were confirmed to have an ACS diagnosis by clinical coding. The main limitation of our study is that we did not

Journal article

Khamis R, Hartley A, Caga-Anan M, Pandey S, Marceddu C, Kojima C, Chang S-H, Boyle JJ, Johnson JL, Björkbacka H, Guo L, Finn AV, Virmani R, Nilsson J, Haskard Det al., 2022, A monoclonal autoantibody against a cryptic epitope on tissue-adherent low-density lipoprotein for molecular imaging in atherosclerosis, JACC: Cardiovascular Imaging, ISSN: 1876-7591

Objectives We aimed to generate and characterize IgG monoclonal autoantibodies in atherosclerosis for targeting of novel molecular determinants.Background Antibody-based constructs for molecular imaging and therapeutic delivery provide promising opportunities for the diagnosis and treatment of atherosclerosis.Methods We created hybridomas from an unimmunized LDL receptor-deficient (Ldlr-/-) mouse and selected an IgG2b isotype autoantibody, LO9, for further characterization.Results LO9 reacted well with native LDL bound to immobilized matrix components, and less well to oxidized LDL. LO9 binding to immobilized native LDL was not neutralized by fluid-phase native LDL, indicating an adhesion-dependent epitope. We localized the epitope to a 20 amino-acid peptide sequence (P5) in the globular amino-terminus of apolipoprotein B. LO9 reacted with antigen in mouse atherosclerosis and in both human stable and ruptured coronary atherosclerosis. Furthermore, in vivo near-infrared fluorescence molecular tomographic imaging and ex vivo confocal microscopy showed that intravenously injected LO9 localized beneath endothelium of the aortic arch in Ldlr-/- mice, in the vicinity of macrophages.Conclusions We believe LO9 is the first example of an IgG autoantibody that reacts with a native LDL epitope revealed by adherence to tissue matrix. Antibodies against adherent native LDL have potential as molecular targeting agents for imaging of and therapeutic delivery to atherosclerosis.

Journal article

Hartley A, Pradeep M, Van den Berg V, Khan AHA, Shah HA, Allaf M, Chow A, Caga-Anan M, Shalhoub J, Koenig W, Fisher M, Haskard D, Khamis Ret al., 2022, Depletion of homeostatic antibodies against malondialdehyde-modified low-density lipoprotein correlates with adverse events in major vascular surgery, Antioxidants, Vol: 11, ISSN: 2076-3921

We aimed to investigate if major vascular surgery induces LDL oxidation, and whether circulating antibodies against malondialdehyde-modified LDL (MDA-LDL) alter dynamically in this setting. We also questioned relationships between these biomarkers and post-operative cardiovascular events. Major surgery can induce an oxidative stress response. However, the role of the humoral immune system in clearance of oxidized LDL following such an insult is unknown. Plasma samples were obtained from a prospective cohort of 131 patients undergoing major non-cardiac vascular surgery, with samples obtained preoperatively and at 24- and 72 h postoperatively. Enzyme-linked immunoassays were developed to assess MDA-LDL-related antibodies and complexes. Adverse events were myocardial infarction (primary outcome), and a composite of unstable angina, stroke and all-cause mortality (secondary outcome). MDA-LDL significantly increased at 24 h post-operatively (p < 0.0001). Conversely, levels of IgG and IgM anti-MDA-LDL, as well as IgG/IgM-MDA-LDL complexes and total IgG/IgM, were significantly lower at 24 h (each p < 0.0001). A smaller decrease in IgG anti-MDA-LDL related to combined clinical adverse events in a post hoc analysis, withstanding adjustment for age, sex, and total IgG (OR 0.13, 95% CI [0.03–0.5], p < 0.001; p value for trend <0.001). Major vascular surgery resulted in an increase in plasma MDA-LDL, in parallel with a decrease in antibody/complex levels, likely due to antibody binding and subsequent removal from the circulation. Our study provides novel insight into the role of the immune system during the oxidative stress of major surgery, and suggests a homeostatic clearance role for IgG antibodies, with greater reduction relating to downstream adverse events.

Journal article

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, Juni P, Hamm C, Steg PG, Windecker S, Onuma Y, Storey RF, Serruys PWet al., 2022, 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, EUROPEAN HEART JOURNAL-CARDIOVASCULAR PHARMACOTHERAPY, Vol: 8, Pages: 39-47, ISSN: 2055-6837

Journal article

Mohan P, Hartley A, Khaldi H, Sethi A, Petraco R, Al-Lamee R, Baker C, Khamis Ret al., 2021, Use of Intravascular Lithotripsy in a Population With a High Prevalence of Renal Disease and Diabetes: Insights From Real-World Data, Publisher: ELSEVIER SCIENCE INC, Pages: B169-B169, ISSN: 0735-1097

Conference paper

Hartley A, Khamis R, Al-Lamee R, Shun-Shin M, Haskard D, Francis Det al., 2021, The placebo-controlled effect of percutaneous coronary intervention on exercise induced changes in anti- malondialdehyde-LDL antibody levels in stable coronary artery disease: a substudy of the ORBITA Trial, Frontiers in Cardiovascular Medicine, Vol: 8, ISSN: 2297-055X

Aim: Malondialdehyde-modified low-density lipoprotein (MDA-LDL) forms a significantcomponent of oxidized LDL. The effects of exercise on levels of MDA-LDL and antiMDA-LDL antibodies are not well understood. Furthermore, it is not known whetherthese can be modified in patients with coronary artery disease by percutaneouscoronary intervention (PCI).Methods: The Objective Randomised Blinded Investigation with optimal medicalTherapy of Angioplasty in stable angina (ORBITA) trial was the first blinded, multicentre randomised trial of PCI versus placebo procedure for angina relief. Serumsamples were available at four time-points: pre-randomisation pre- (P1) and post- (P2)exercise and post-randomisation (six-weeks following the PCI or placebo procedure),pre- (P3) and post- (P4) exercise. ELISAs were performed using laboratory-developedassays for MDA-LDL (adjusted for Apolipoprotein B) and anti-MDA-LDL antibodies.Results: 196 of the 200 patients (age 66.1 [SD 8.99] years, 28% female) with severesingle vessel coronary artery disease suitable for PCI enrolled in the ORBITA trial hadblood available for analysis. With exercise at pre-randomisation (P2 - P1) there wasno significant change in adjusted MDA-LDL (-0.001, 95% CI -0.004 to 0.001; p=0.287);however, IgG and IgM anti-MDA-LDL significantly declined (-0.022, 95% CI -0.029 to-0.014, p<0.0001; -0.016, 95% CI -0.024 to -0.008, p=0.0002, respectively). PCI didnot have a significant impact on either the pre-exercise values (P3 controlling for P1)of MDA-LDL (p=0.102), IgG (p=0.444) or IgM anti-MDA-LDL(p=0.909). Nor did PCIimpact the exercise induced changes in these markers (P4 controlling for P1, P2, andP3) for MDA-LDL (p=0.605), IgG (p=0.725) or IgM anti-MDA-LDL (p=0.171). Prerandomisation ischaemia on stress echo did not impact these interactions.Conclusions: Exercise results in an acute reduction in anti-oxLDL antibodies inpatients with severe single vessel coronary disease, possibly indicating an inductionin homoeostatic

Journal article

Hartley A, Shalhoub J, Khamis R, 2021, Trends in mortality from aortic stenosis in Europe: 2000-2017, Frontiers in Cardiovascular Medicine, Vol: 8, Pages: 1-9, ISSN: 2297-055X

BackgroundTrends in mortality from aortic stenosis across European countries are not wellunderstood, especially given the significant growth in transcatheter aortic valveimplantation (TAVI) in the last 10 years.MethodsAge-standardised death rates were extracted from the World Health OrganisationMortality Database, using the International Classification of Diseases 10th editioncode for non-rheumatic aortic stenosis for those aged >45 years between 2000 and2017. The UK and countries from the European Union with at least 1,000,000inhabitants and at least 50% available datapoints over the study period were included:a total of 23 countries. Trends were described using Joinpoint regression analysis.ResultsNo reductions in mortality were demonstrated across all countries 2000-2017. Largeincreases in mortality were found for Croatia, Poland and Slovakia for both sexes(>300% change). Mortality plateaued in Germany from 2008 in females and 2012 inmales, whilst mortality in the Netherlands declined for both sexes from 2007. Mortalitydifferences between the sexes were observed, with greater mortality for males thanfemales across most countries.ConclusionsMortality from aortic stenosis has increased across Europe from 2000 to 2017. Thereare, however, sizable differences in mortality trends between Eastern and WesternEuropean countries. The need for health resource planning strategies to specificallytarget AS, particularly given the expected increase with aging populations, ishighlighted.

Journal article

Nurek M, Rayner C, Freyer A, Taylor S, Jaerte L, MacDermott N, Delaney BCet al., 2021, Recommendations for the recognition, diagnosis, and management of long COVID: a Delphi study, British Journal of General Practice, Vol: 71, Pages: E815-E825, ISSN: 0960-1643

Background In the absence of research into therapies and care pathways for long COVID, guidance based on ‘emerging experience’ is needed.Aim To provide a rapid expert guide for GPs and long COVID clinical services.Design and setting A Delphi study was conducted with a panel of primary and secondary care doctors.Method Recommendations were generated relating to the investigation and management of long COVID. These were distributed online to a panel of UK doctors (any specialty) with an interest in, lived experience of, and/or experience treating long COVID. Over two rounds of Delphi testing, panellists indicated their agreement with each recommendation (using a five-point Likert scale) and provided comments. Recommendations eliciting a response of ‘strongly agree’, ‘agree’, or ‘neither agree nor disagree’ from 90% or more of responders were taken as showing consensus.Results Thirty-three clinicians representing 14 specialties reached consensus on 35 recommendations. Chiefly, GPs should consider long COVID in the presence of a wide range of presenting features (not limited to fatigue and breathlessness) and exclude differential diagnoses where appropriate. Detailed history and examination with baseline investigations should be conducted in primary care. Indications for further investigation and specific therapies (for myocarditis, postural tachycardia syndrome, mast cell disorder) include hypoxia/desaturation, chest pain, palpitations, and histamine-related symptoms. Rehabilitation should be individualised, with careful activity pacing (to avoid relapse) and multidisciplinary support.Conclusion Long COVID clinics should operate as part of an integrated care system, with GPs playing a key role in the multidisciplinary team. Holistic care pathways, investigation of specific complications, management of potential symptom clusters, and tailored rehabilitation are needed.

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, Vol: 10, Pages: 1-14, 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

Hartley A, Williams M, Kaura A, Caga-Anan M, Dey D, Dweck M, Haskard D, Newby D, Khamis Ret al., 2021, IGM AND IGG ANTI-OXIDISED LOW-DENSITY LIPOPROTEIN ANTIBODIES PREDICT PROTECTIVE ATHEROSCLEROTIC CHARACTERSTICS ON CARDIAC CT: A SUBSTUDY OF THE SCOTTISH COMPUTED TOMOGRAPHY OF THE HEART (SCOT-HEART) TRIAL, Publisher: BMJ PUBLISHING GROUP, Pages: A162-A162, ISSN: 1355-6037

Conference paper

Marceddu C, Hartley A, Caga-Anan M, Pandey S, Morris Y, Haskard D, Passchier J, Khamis Ret al., 2021, FIRST IN VIVO PRETARGETED PET IMAGING OF ATHEROSCLEROSIS WITH ANTIBODIES AGAINST FORMS OF MODIFIED LIPOPROTEINS, Publisher: BMJ PUBLISHING GROUP, Pages: A126-A128, ISSN: 1355-6037

Conference paper

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, Vol: 36, Pages: 547-558, ISSN: 0267-6591

Journal article

Hartley A, Pradeep M, Shah HA, Allaf M, Chow A, Khan AHA, Caga-Anan M, Fisher M, Haskard D, Khamis Ret 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

Conference paper

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

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

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

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, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 76, Pages: 1226-1243, ISSN: 0735-1097

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

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