184 results on '"de Silva, Ranil"'
Search Results
152. Cardiovascular Drugs and the Management of Heart Disease.
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de SILVA, RANIL and CAMICI, PAOLO G
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- 1992
153. Prevalence of sub clinical atherosclerosis among UK South Asians and Europeans
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Jain, Piyush, Kooner, Jaspal, and De Silva, Ranil
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610 - Abstract
Background: South Asians demonstrate high coronary heart disease mortality, largely unexplained by conventional risk factors and unidentified by risk stratification tools. Developments in technology allow us to visualize coronary atherosclerosis non-invasively, thus providing the potential to identify presence of coronary atherosclerosis before it manifests clinically. Coronary artery calcification is closely correlated with total plaque burden and provides an assessment of coronary plaque burden. Myocardial perfusion scintigraphy provides an estimate of myocardial blood flow and thus, severity of coronary artery disease. Increased coronary artery calcification and silent myocardial ischemia predict future risk of coronary heart disease mortality, independent of conventional factors. Inflammation is a key factor in initiation and progression of atherosclerosis. High sensitivity C-reactive protein (CRP) is an important marker of active inflammation and is considered an independent predictor of future cardiovascular events. Thus, markers of subclinical atherosclerosis and inflammation could provide us with a tool for early identification of South Asians at risk of coronary events, unidentified by traditional means. However, majority of the data for such markers is from North American and European populations, with no data evaluating the role of coronary artery calcification, myocardial perfusion scintigraphy and CRP in assessing the coronary heart disease risk in South Asians. Methods and Results: I carried out assessments including coronary artery calcium, myocardial perfusion imaging and assessment of high sensitivity C-reactive protein for a cohort of asymptomatic South Asians and Europeans men and women, aged 35 to 75 years, who were part of the London Life Sciences Population (LOLIPOP) study. I found that: 1) Coronary artery calcification scores were closely associated with age, male gender, cigarette smoking, hypertension, systolic blood pressure, diabetes and total cholesterol. 2) There were no differences in either coronary artery calcification prevalence or mean levels of coronary artery calcification between South Asians and Europeans, after adjustment for the measured cardiovascular risk factors. 3) Presence of diabetes and increasing coronary artery calcification were independent predictors for silent myocardial ischemia. 4) South Asian ethnicity did not influence the prevalence or the extent of silent myocardial ischemia, after adjustment for conventional risk factors. 5) C-reactive protein levels did not correlate with measures of plaque burden. 5) South Asian ethnicity was an independent predictor of inflammation as seen by levels of high sensitivity C-reactive protein. This effect was independent of, and remained significant after adjusting for conventional cardiovascular risk factors and novel factors linked to inflammation such as diabetes and indices of abdominal obesity. Conclusions: While traditional risk factor correlate well with markers of atherosclerosis, the higher coronary heart disease risk and mortality observed in South Asians is not identified by markers of atherosclerotic burden such as coronary artery calcification and myocardial perfusion scintigraphy. South Asians have elevated levels of inflammation as seen by high sensitivity C-reactive protein levels. C-reactive protein levels are not correlated with coronary artery calcium or myocardial ischemia measured by myocardial perfusion scintigraphy. These findings suggest a role of factors such as systemic and plaque inflammation, unrelated to and unmeasured by plaque burden assessment in the higher coronary heart disease mortality observed among South Asians. The study therefore suggests a role of potential risk stratification tools reflecting the multisystem nature of CHD. These could be a combination of clinical risk factors contributing towards CHD, imaging of atherosclerotic plaque and assessment of plaque or systemic inflammation.
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- 2015
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154. Apoferritin and Dps as drug delivery vehicles: Some selected examples in oncology.
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Kuruppu, Anchala I., Turyanska, Lyudmila, Bradshaw, Tracey D., Manickam, Sivakumar, Galhena, Bandula Prasanna, Paranagama, Priyani, and De Silva, Ranil
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DRUG carriers , *FERRITIN , *DNA-binding proteins , *TARGETED drug delivery , *ONCOLOGY , *NANOMEDICINE - Abstract
The ideal nanoparticle should be able to encapsulate either pharmaceutical agents or imaging probes so that it could treat or image clinical tumours by targeting the cancer site efficiently. Further, it would be an added advantage if it demonstrates: small size, built in targeting, biocompatibility and biodegradability. Ferritin, which is an endogenous self-assembling protein, stores iron and plays a role in iron homeostasis. When iron atoms are removed apoferritin (AFt) is formed which consists of a hollow shell where it can be used to load guest molecules. Due to its unique architecture, AFt has been investigated as a versatile carrier for tumour theranostic applications. DNA-binding protein from starved cells (Dps), which also belongs to the ferritin family, is a protein found only in prokaryotes. It is used to store iron and protect chromosomes from oxidative damage; because of its architecture, Dps could also be used as a delivery vehicle. Both these nano particles are promising in the field of oncology, especially due to their stability, solubility and biocompatibility features. Further their exterior surface can be modified for better tumour-targeting ability. More studies, are warranted to determine the immunogenicity, biodistribution, and clearance from the body. This review discusses a few selected examples of the remarkable in vitro and in vivo studies that have been carried out in the recent past with the use of AFt and Dps in targeting and delivery of various pharmaceutical agents, natural products and imaging probes in the field of oncology. • Nanomedicine has received a lot of attention in the field of cancer, where drug targeting is a major issue. • Protein apoferritin nanoparticle offer benefits as drug delivery vehicles due to their biocompatibility and targeting. • Apoferritin encapsulated drugs are rapidly sequestration by cancer cells and are well tolerated in vivo. • DNA-binding protein from starved cells which is structurally similar to apoferritin, can be used as a nano delivery agent. [ABSTRACT FROM AUTHOR]
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- 2022
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155. Consensus Standards for Acquisition, Measurement, and Reporting of Intravascular Optical Coherence Tomography Studies: A Report From the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation
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Tearney, Guillermo J., Regar, Evelyn, Akasaka, Takashi, Adriaenssens, Tom, Barlis, Peter, Bezerra, Hiram G., Bouma, Brett, Bruining, Nico, Cho, Jin-man, Chowdhary, Saqib, Costa, Marco A., de Silva, Ranil, Dijkstra, Jouke, Di Mario, Carlo, Dudeck, Darius, Falk, Erlin, Feldman, Marc D., Fitzgerald, Peter, Garcia, Hector, and Gonzalo, Nieves
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MEDICAL communication , *OPTICAL coherence tomography , *INTRAVASCULAR ultrasonography , *SCIENTIFIC community , *STANDARDIZATION , *ACQUISITION of data , *PEER review committees - Abstract
Objectives: The purpose of this document is to make the output of the International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT) Standardization and Validation available to medical and scientific communities, through a peer-reviewed publication, in the interest of improving the diagnosis and treatment of patients with atherosclerosis, including coronary artery disease. Background: Intravascular optical coherence tomography (IVOCT) is a catheter-based modality that acquires images at a resolution of ∼10 μm, enabling visualization of blood vessel wall microstructure in vivo at an unprecedented level of detail. IVOCT devices are now commercially available worldwide, there is an active user base, and the interest in using this technology is growing. Incorporation of IVOCT in research and daily clinical practice can be facilitated by the development of uniform terminology and consensus-based standards on use of the technology, interpretation of the images, and reporting of IVOCT results. Methods: The IWG-IVOCT, comprising more than 260 academic and industry members from Asia, Europe, and the United States, formed in 2008 and convened on the topic of IVOCT standardization through a series of 9 national and international meetings. Results: Knowledge and recommendations from this group on key areas within the IVOCT field were assembled to generate this consensus document, authored by the Writing Committee, composed of academicians who have participated in meetings and/or writing of the text. Conclusions: This document may be broadly used as a standard reference regarding the current state of the IVOCT imaging modality, intended for researchers and clinicians who use IVOCT and analyze IVOCT data. [ABSTRACT FROM AUTHOR]
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- 2012
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156. Optical coherence tomography characteristics of in-stent restenosis are different between first and second generation drug eluting stents☆
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Nikolaos V. Konstantinidis, Carlo Di Mario, Kadriye Orta Kilickesmez, Nicolas Foin, Rodrigo Estévez-Loureiro, Juan Carlos Rama-Merchan, Carlos Moreno Vinues, Gianni Dall'Ara, Alistair C. Lindsay, Carlo Zivelonghi, Ranil de Silva, Alessio Mattesini, Matteo Ghione, Gioel Gabrio Secco, Michele Pighi, Kilickesmez, Kadriye, Dall'Ara, Gianni, Rama-Merchan, Juan Carlo, Ghione, Matteo, Mattesini, Alessio, Vinues, Carlos Moreno, Konstantinidis, Nikolao, Pighi, Michele, Estevez-Loureiro, Rodrigo, Zivelonghi, Carlo, Lindsay, Alistair C., Secco, Gioel G., Foin, Nicola, De Silva, Ranil, and Di Mario, Carlo
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In-stent restenosis ,medicine.medical_specialty ,medicine.medical_treatment ,Neoatherosclerosis ,chemistry.chemical_compound ,Optical coherence tomography ,Restenosis ,medicine ,Neoatherosclerosi ,cardiovascular diseases ,Drug eluting stent ,medicine.diagnostic_test ,business.industry ,Stent ,equipment and supplies ,medicine.disease ,Paclitaxel ,chemistry ,Homogeneous ,Drug-eluting stent ,Time course ,Original Article ,Radiology ,In stent restenosis ,business ,Cardiology and Cardiovascular Medicine ,In-stent restenosi - Abstract
Aims: Characterization of neointimal tissue is essential to understand the pathophysiology of in-stent restenosis (ISR) after drug eluting stent (DES) implantation. Using optical coherence tomography (OCT), we compared the morphologic characteristics of ISR between first and second generation DES. Methods and Results: OCT was performed in 66 DES-ISR, defined as >. 50% angiographic diameter stenosis within the stented segment. Patients with ISR of first generation sirolimus-eluting stents (SES), paclitaxel eluting stents (PES) and second generation zotarolimus-eluting stents (ZES), everolimus-eluting stents (EES) and biolimus-eluting stents (BES) were enrolled. Quantitative and qualitative ISR tissue analysis was performed at 1-mm intervals along the entire stent, and categorised as homogeneous, heterogeneous and neo-atherosclerosis. The presence of microvessels and peri-strut low intensity area (PSLIA) was determined in all ISR. Neoatherosclerosis was identified by lipid, calcium and thin-cap fibro-atheroma (TCFA) like lesions. We compared the two DES generations at both early (. 1. year) follow-ups.In second generation DES a heterogeneous pattern was prevalent both before and after 1. year (57.1% and 58.6% respectively). Neo-atherosclerosis was more common in the early period in first generation DES (19.4% vs 11.7%, p.
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- 2014
157. Inducing Persistent Flow Disturbances Accelerates Atherogenesis and Promotes Thin Cap Fibroatheroma Development in D374Y-PCSK9 Hypercholesterolemic Minipigs
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Niels Peter Andersen, Anouk L. Post, Jacob F. Bentzon, Martin M. Bjørklund, Ranil de Silva, Alessio Mattesini, Carlo Di Mario, Anna K. Grøndal, Rob Krams, Ryan M. Pedrigi, Vikram V. Mehta, Nilesh Pareek, Niels Ramsing Holm, Hans Erik Bøtker, Gianni Dall'Ara, Nicolas Foin, Christian Bo Poulsen, Erling Falk, Enrico Petretto, Justin E. Davies, Winston Banya, Ismail Dogu Kilic, Other Research, Biomedical Engineering and Physics, Graduate School, Poulsen, Christian Bo, Mehta, Vikram V., Holm, Niels Ramsing, Pareek, Nilesh, Post, Anouk L., Kilic, Ismail Dogu, Banya, Winston A.S., Dall'Ara, Gianni, Mattesini, Alessio, Bjørklund, Martin M., Andersen, Niels P., Grøndal, Anna K., Petretto, Enrico, Foin, Nicola, Davies, Justin E., Di Mario, Carlo, Bentzon, Jacob Fog, Bøtker, Hans Erik, Falk, Erling, Krams, Rob, De Silva, Ranil, Royal Brompton & Harefield NHS Foundation Trust, and British Heart Foundation
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Cardiac & Cardiovascular Systems ,Time Factors ,Swine ,medicine.medical_treatment ,Hemodynamics ,PROGRESSION ,hemodynamics ,Coronary Angiography ,Animals, Genetically Modified ,biophysics ,Intravascular ultrasound ,Stent ,1102 Cardiorespiratory Medicine and Haematology ,Tomography ,IN-VIVO ,Coronary Vessel ,Atherosclerotic ,Plaque ,medicine.diagnostic_test ,Optical coherence ,atherogenesis ,REGIONS ,Coronary Vessels ,Plaque, Atherosclerotic ,Shear stre ,SCAFFOLD IMPLANTATION ,medicine.anatomical_structure ,Atherosclerosi ,Cardiology ,Swine, Miniature ,Stents ,Proprotein Convertases ,Shear Strength ,Cardiology and Cardiovascular Medicine ,Life Sciences & Biomedicine ,Tomography, Optical Coherence ,medicine.medical_specialty ,thin cap fibroatheroma ,Time Factor ,CORONARY ATHEROSCLEROTIC PLAQUE ,Hypercholesterolemia ,shear stress ,1117 Public Health and Health Services ,Coronary circulation ,Internal medicine ,Coronary Circulation ,Physiology (medical) ,INTRAVASCULAR ULTRASOUND ,Shear stress ,medicine ,Animals ,Endothelium ,Hemodynamic ,optical coherence tomography ,Science & Technology ,business.industry ,Animal ,1103 Clinical Sciences ,NATURAL-HISTORY ,Blood flow ,Atherosclerosis ,medicine.disease ,ENDOTHELIAL SHEAR-STRESS ,Proprotein Convertase ,Surgery ,Stenosis ,Disease Models, Animal ,Thin-cap fibroatheroma ,Peripheral Vascular Disease ,Cardiovascular System & Hematology ,Biophysic ,Regional Blood Flow ,Cardiovascular System & Cardiology ,PATTERNS ,UPDATE ,Stress, Mechanical ,business - Abstract
Background— Although disturbed flow is thought to play a central role in the development of advanced coronary atherosclerotic plaques, no causal relationship has been established. We evaluated whether inducing disturbed flow would cause the development of advanced coronary plaques, including thin cap fibroatheroma. Methods and Results— D374Y -PCSK9 hypercholesterolemic minipigs (n=5) were instrumented with an intracoronary shear-modifying stent (SMS). Frequency-domain optical coherence tomography was obtained at baseline, immediately poststent, 19 weeks, and 34 weeks, and used to compute shear stress metrics of disturbed flow. At 34 weeks, plaque type was assessed within serially collected histological sections and coregistered to the distribution of each shear metric. The SMS caused a flow-limiting stenosis, and blood flow exiting the SMS caused regions of increased shear stress on the outer curvature and large regions of low and multidirectional shear stress on the inner curvature of the vessel. As a result, plaque burden was ≈3-fold higher downstream of the SMS than both upstream of the SMS and in the control artery ( P P P P Conclusions— These data support a causal role for lowered and multidirectional shear stress in the initiation of advanced coronary atherosclerotic plaques. Persistently lowered shear stress appears to be the principal flow disturbance needed for the formation of thin cap fibroatheroma.
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- 2015
158. ABSORB biodegradable stents versus second-generation metal stents: A comparison study of 100 complex lesions treated under OCT guidance
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Mattesini, A., Secco, G. G., Dall'Ara, G., Ghione, M., Rama Merchan, J. C., Lupi, A., Viceconte, GIUSEPPE NICOLA, Lindsay, A. C., De Silva, R., Foin, N., Naganuma, T., Valente, S., Colombo, A., Di Mario, C., Mattesini, Alessio, Secco, Gioel G., Dall'Ara, Gianni, Ghione, Matteo, Rama-Merchan, Juan C., Lupi, Alessandro, Viceconte, Nicola, Lindsay, Alistair C., De Silva, Ranil, Foin, Nicola, Naganuma, Toru, Valente, Serafina, Colombo, Antonio, and Di Mario, Carlo
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Male ,Time Factors ,Time Factor ,Polymers ,Polyesters ,Polyester ,Predictive Value of Test ,Coronary Artery Disease ,Coronary Angiography ,Prosthesis Design ,Predictive Value of Tests ,Absorbable Implant ,Absorbable Implants ,London ,Drug-Eluting Stent ,Stent ,Humans ,Prospective Studies ,Lactic Acid ,Angioplasty, Balloon, Coronary ,Polymer ,Coronary Vessel ,Aged ,optical coherence tomography ,Metal ,Drug-Eluting Stents ,Middle Aged ,Coronary Vessels ,Prosthesis Failure ,Prospective Studie ,Treatment Outcome ,Italy ,Metals ,Case-Control Studies ,Stents ,bioresorbable vascular scaffold ,Female ,Case-Control Studie ,Cardiology and Cardiovascular Medicine ,Tomography, Optical Coherence ,Human - Abstract
Objectives The aim of this study was to compare the acute performance of the PLLA ABSORB bioresorbable vascular scaffold (BVS) (Abbott Vascular, Santa Clara, California) with second-generation metal drug-eluting stents (DES) in complex coronary artery lesions. Background Thick polymer-based BVS have different mechanical properties than thin second-generation DES. Data on the acute performance of BVS are limited to simple coronary lesions treated in trials with strict inclusion criteria. Methods Fifty complex coronary lesions (all type American College of Cardiology/American Heart Association B2-C) treated with a BVS undergoing a final optical coherence tomography (OCT) examination were compared with an equal number of matched lesions treated with second-generation DES. The following stent performance indexes were assessed with OCT: mean and minimal area, residual area stenosis (RAS), incomplete strut apposition (ISA), tissue prolapse, eccentricity index, symmetry index, strut fracture, and edge dissection. Results One hundred lesions from 73 patients were analyzed. A higher balloon diameter/reference vessel diameter ratio was used for predilation in the BVS group (p < 0.01). Most of the BVS and DES were post-dilated with short noncompliant (NC) balloons of similar diameter. OCT showed in the BVS group a higher tissue prolapse area (p = 0.08) and greater incidence of ISA at the proximal edge (p = 0.04) with no difference in the overall ISA. The RAS was 20.2% in the BVS group and 21.7% in the DES group (p = 0.32). There was no difference in the eccentricity index. The minimal and mean lumen areas were similar in the 2 groups. Two cases of strut fractures occurred after the BVS, whereas none was observed in the DES. Conclusions Based on OCT, the BVS showed similar post-procedure area stenosis, minimal lumen area, and eccentricity index as second-generation DES. The different approach for lesion preparation and routine use of OCT guidance during BVS expansion may have contributed to these results. © 2014 by the American College of Cardiology Foundation.
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- 2014
159. Characterization of dynamic changes in cardiac microstructure after reperfused ST-elevation myocardial infarction by biphasic diffusion tensor cardiovascular magnetic resonance.
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Rajakulasingam R, Ferreira PF, Scott AD, Khalique Z, Azzu A, Molto M, Conway M, Falaschetti E, Cheng K, Hammersley DJ, Cantor EJ, Tindale A, Beattie CJ, Banerjee A, Wage R, Soundarajan RK, Dalby M, Nielles-Vallespin S, Pennell DJ, and de Silva R
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Background and Aims: Microstructural disturbances underlie dysfunctional contraction and adverse left ventricular (LV) remodelling after ST-elevation myocardial infarction (STEMI). Biphasic diffusion tensor cardiovascular magnetic resonance (DT-CMR) quantifies dynamic reorientation of sheetlets (E2A) from diastole to systole during myocardial thickening, and markers of tissue integrity [mean diffusivity (MD) and fractional anisotropy (FA)]. This study investigated whether microstructural alterations identified by biphasic DT-CMR: (i) enable contrast-free detection of acute myocardial infarction (MI); (ii) associate with severity of myocardial injury and contractile dysfunction; and (iii) predict adverse LV remodelling., Methods: Biphasic DT-CMR was acquired 4 days (n = 70) and 4 months (n = 66) after reperfused STEMI and in healthy volunteers (HVOLs) (n = 22). Adverse LV remodelling was defined as an increase in LV end-diastolic volume ≥ 20% at 4 months. MD and FA maps were compared with late gadolinium enhancement images., Results: Widespread microstructural disturbances were detected post-STEMI. In the acute MI zone, diastolic E2A was raised and systolic E2A reduced, resulting in reduced E2A mobility (all P < .001 vs. adjacent and remote zones and HVOLs). Acute global E2A mobility was the only independent predictor of adverse LV remodelling (odds ratio .77; 95% confidence interval .63-.94; P = .010). MD and FA maps had excellent sensitivity and specificity (all > 90%) and interobserver agreement for detecting MI presence and location., Conclusions: Biphasic DT-CMR identifies microstructural alterations in both diastole and systole after STEMI, enabling detection of MI presence and location as well as predicting adverse LV remodelling. DT-CMR has potential to provide a single contrast-free modality for MI detection and prognostication of patients after acute STEMI., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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160. Coronary Sinus Reducer Therapy for Refractory Angina and its Role in Modern Interventional Practice: A Contemporary Review.
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Cheng K, Hill JM, and de Silva R
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Coronary sinus reducer (CSR) implantation is an emerging treatment option for patients with refractory angina. This condition represents a major global cardiovascular healthcare challenge, with patients experiencing chronic anginal symptoms that significantly impair their quality of life and for whom few effective treatments exist. The clinical burden of refractory angina is only set to grow because of improved survival from coronary artery disease, increased life expectancy and the presence of residual angina after percutaneous or surgical coronary revascularisation. Therefore, new, effective, evidence-based therapies are urgently needed. In this review, we highlight the unmet clinical needs of patients with refractory angina, discuss the development of the CSR device and review the preclinical and clinical evidence base underlying CSR implantation. In addition, we discuss the current role of CSR implantation in contemporary interventional practice, highlighting knowledge gaps and discussing areas of on-going research., Competing Interests: Disclosure: KC is supported by a British Heart Foundation Clinical Research and Training Fellowship (FS/CRTF/22/24369). JMH reports speaker honoraria and institutional grants from Abbott, Abiomed, Boston Scientific and Shockwave Medical and equity from Shockwave. RDS has received speaker and proctoring fees from Neovasc, institutional research support from Shockwave Medical and is supported by a British Heart Foundation Clinical Study Grant (CS/F/20/35120)., (Copyright © The Author(s), 2024. Published by Radcliffe Group Ltd.)
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- 2024
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161. A 44-year-old man with recurrent ST-segment elevation: a case report of two presentations of Granulomatosis with Polyangiitis.
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Cheng K and de Silva R
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Background: Granulomatosis with Polyangiitis (GPA) is a rare multi-system autoimmune disorder that may present with cardiac manifestations that are often under-recognized. In this report, we discuss a usual case of a patient who presented as a cardiac emergency with recurrent ST elevation and discuss the approach and management., Case Summary: A 44-year-old man presented with two episodes of chest pain associated with ST-segment elevation on 12-lead ECG. Under investigation over the past several weeks for fatigue, nasal congestion, and red eyes, his first presentation was associated with widespread ST-segment elevation and an echogenic myocardium suggestive of myocarditis that was confirmed on cardiac MRI. A week later, the development of chest pain, antero-lateral ST elevation, and regional wall motion abnormalities suggested an acute coronary syndrome and he proceeded to primary percutaneous intervention that treated a lesion in the distal left anterior descending artery secondary to coronary arteritis. Diagnosed with GPA, he was started on immunosuppression and has had a resolution of his cardiac involvement at follow-up., Discussion: This case report describes an unusual case of myocarditis and coronary arteritis presenting acutely in the same patient and emphasizes the importance of considering systemic autoimmune conditions when encountering primarily cardiac presentations. Early recognition and diagnosis of cardiac involvement will improve the long-term outcomes in these patients., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)
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- 2024
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162. The Nairobi Declaration-Reducing the burden of dementia in low- and middle-income countries (LMICs): Declaration of the 2022 Symposium on Dementia and Brain Aging in LMICs.
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Maestre G, Carrillo M, Kalaria R, Acosta D, Adams L, Adoukonou T, Akinwande K, Akinyemi J, Akinyemi R, Akpa O, Alladi S, Allegri R, Arizaga R, Arshad F, Arulogun O, Babalola D, Baiyewu O, Bak T, Bellaj T, Boshe J, Brayne C, Brodie-Mends D, Brown R, Cahn J, Cyrille N, Damasceno A, de Silva R, de Silva R, Djibuti M, Dreyer AJ, Ellajosyula R, Farombi T, Fongang B, Forner S, Friedland R, Garza N, Gbessemehlan A, Georgiou EE, Gouider R, Govia I, Grinberg L, Guerchet M, Gugssa S, Gumikiriza-Onoria JL, Gustafson D, Hogervorst E, Hornberger M, Ibanez A, Ihara M, Ismail O, Issac T, Jönsson L, Kaputu C, Karanja W, Karungi J, Tshala-Katumbay D, Kunkle B, Lee JH, Leroi I, Lewis R, Livingston G, Lopera F, Lwere K, Manes F, Mbakile-Mahlanza L, Mena P, Miller B, Millogo A, Mohamed A, Musyimi C, Mutiso V, Nakasujja N, Ndetei D, Nightingale S, Njamnshi AK, Novotni G, Nyamayaro P, Nyame S, Ogeng'o J, Ogunniyi A, Okada De Oliveira M, Okubadejo N, Orrell M, Orunmuyi A, Owolabi M, Paddick S, A Pericak-Vance M, Pirtosek Z, Potocnik F, Preston B, Raman R, Ranchod K, Rizig M, Rosselli M, Deepa R, Roy U, Salokhiddinov M, Sano M, Sarfo F, Satizabal CL, Sepulveda-Falla D, Seshadri S, Sexton C, Skoog I, St George-Hyslop P, Suemoto C, Tanner J, Thapa P, Toure K, Ucheagwu V, Udeh-Momoh C, Valcour V, Vance J, Varghese M, Vera J, Walker R, Weidner W, Sebastian W, Whitehead Gay P, Zetterberg H, and Zewde Y
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- 2023
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163. Implantation of the coronary sinus reducer for refractory angina due to coronary microvascular dysfunction in the context of apical hypertrophic cardiomyopathy-a case report.
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Cheng K, Keramida G, Baksi AJ, and de Silva R
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Background: Refractory angina leads to a poor quality of life and increased healthcare resource utilization. In this growing population of patients, multiple mechanism(s) of ischaemia may co-exist, including functional disorders of the coronary microcirculation. There are few evidence-based effective therapies resulting in a large unmet clinical need., Case Summary: A 38-year-old woman with refractory angina was referred with daily chest pain despite multiple anti-anginal medications and previous percutaneous coronary intervention. Cardiac magnetic resonance imaging demonstrated apical hypertrophic cardiomyopathy (HCM). Rubidium-82 positron emission tomography (PET) with regadenoson stress confirmed significant myocardial ischaemia in the apex and apical regions (16% of total myocardium) with a global myocardial perfusion reserve (MPR) of 1.23. Coronary angiography confirmed patent stents and no epicardial coronary artery disease. Therefore, the mechanism of ischaemia was thought attributable to coronary microvascular dysfunction (CMD) in the context of HCM. In view of her significant symptoms and large burden of left-sided myocardial ischaemia, a Coronary Sinus Reducer (CSR) was implanted. Repeat PET imaging at 6 months showed a marked reduction in ischaemia (<5% burden), improvement in global MPR (1.58), symptoms, and quality of life., Conclusion: In refractory angina, ischaemia may be due to disorders of both the epicardial and coronary microcirculations. The CSR is a potential therapy for these patients, but its mechanism of action has not been confirmed. This report suggests that CSR implantation may reduce myocardial ischaemia and improve symptoms by acting on the coronary microcirculation. The efficacy of CSR in patients with CMD and its mechanism of action on the coronary microcirculation warrant further investigation., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)
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- 2022
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164. Refractory microvascular angina in hypertrophic cardiomyopathy: a novel therapy?
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Cheng K and de Silva R
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Competing Interests: Conflict of interest: None declared.
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- 2022
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165. 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.
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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, and Serruys PW
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- Aspirin adverse effects, Humans, Leukocyte Count, Platelet Aggregation Inhibitors adverse effects, Ticagrelor adverse effects, Treatment Outcome, Percutaneous Coronary Intervention adverse effects
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Aims: The aim of this study was 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 multi-centre, 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 × 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 at 2 years. Of 14 576 patients included in the present study, 7212 patients (49.5%) were classified as the lower WBC group, who had a significantly lower risk of both ischaemic 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% confidence interval (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 Bleeding Academic Research Consortium type 3 or 5 bleeding between two anti-platelet strategies regardless of the WBC groups., Conclusion: Increased WBC counts, which may reflect degree of inflammation, at the time of index procedure may attenuate the anti-ischaemic benefits of ticagrelor monotherapy observed in patients with lower WBC counts., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)
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- 2022
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166. A multi-disciplinary care pathway improves symptoms, QoL and medication use in refractory angina.
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Cheng K and de Silva R
- Abstract
Refractory angina (RA) is a growing clinical problem. Long-term mortality is better than expected and focus has shifted to improving symptoms, quality of life and psychological morbidity. We established a dedicated multi-disciplinary care pathway for patients with RA and assessed its effect on psychological outcomes, quality of life and polypharmacy. We reviewed electronic health records to capture demographics, changes in medication use, and patient-related outcome measures (Seattle Angina Questionnaire [SAQ] and Hospital Anxiety and Depression Scale) before and after enrolment. One hundred and ninety patients were referred to our service. Pre- and post-questionnaire data were available in 83 patients. Anxiety and depression scores significantly improved (p<0.05) as well as quality of life and all subcategories of the SAQ (p<0.0001). Patients were most commonly on three or four anti-anginal drugs. In patients with no demonstrable reversible ischaemia, there was a significant reduction in anti-anginal usage (mean reduction of two drugs) after completion of our pathway (p<0.025). In conclusion, a dedicated multi-disciplinary pathway for RA is associated with improvements in quality of life, mental health and polypharmacy. An ischaemia-driven method to rationalise medication may reduce polypharmacy in patients with RA, particularly in patients with no demonstrable ischaemia., Competing Interests: None declared., (Copyright © 2020 Medinews (Cardiology) Limited.)
- Published
- 2020
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167. Anticancer potential of natural products: a review focusing on Sri Lankan plants.
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Kuruppu A I, Paranagama P, and De Silva R
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- Aquatic Organisms, Combinatorial Chemistry Techniques, Drug Discovery, Humans, Interdisciplinary Communication, Phytotherapy, Species Specificity, Sri Lanka, Antineoplastic Agents pharmacology, Medicine, Traditional methods, Neoplasms therapy, Plant Extracts pharmacology, Plants, Medicinal chemistry
- Abstract
In the pharmaceutical industry, the expected surge in production of new therapeutic entities promised by technological advances, such as high-throughput screening, synthetic libraries and advances in molecular biology and genomics, has not materialized. The unique structural diversity of natural products continues to provide opportunities to discover novel compounds. Secondary metabolites, active components of natural products such as marine organisms, microbial organisms and terrestrial plants, are particularly exciting untapped resources for exploration as medicines. Sri Lanka is home to around 3700 plant species, half of which are considered as medicinal plants. Seventy per cent of the Sri Lankan population relies on this plant-based traditional medicine system for treating various illnesses such as tumors. As such these medicinal plant sources should be used to conquer terminal diseases and for prevention of diseases. Sri Lankan researchers have found several plant species that possess cytotoxic activity. This review summarizes the current information regarding the Sri Lankan plant materials that possess anticancer properties.
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- 2019
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168. New Advances in the Management of Refractory Angina Pectoris.
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Cheng K and de Silva R
- Abstract
Refractory angina is a significant clinical problem and its successful management is often extremely challenging. Defined as chronic angina-type chest pain in the presence of myocardial ischaemia that persists despite optimal medical, interventional and surgical treatment, current therapies are limited and new approaches to treatment are needed. With an ageing population and increased survival from coronary artery disease, clinicians will increasingly encounter this complex condition in routine clinical practice. Novel therapies to target myocardial ischaemia in patients with refractory angina are at the forefront of research and in this review we discuss those in clinical translation and assess the evidence behind their efficacy., Competing Interests: Disclosure: The authors have no conflicts of interest to declare.
- Published
- 2018
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169. Shedding light on inflammation.
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Pareek N, Serruys P, and de Silva R
- Subjects
- Humans, Circadian Rhythm, Inflammation
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- 2017
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170. Management of Refractory Angina Pectoris.
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Cheng K, Sainsbury P, Fisher M, and de Silva R
- Abstract
With improvements in survival from coronary artery disease (CAD) and an ageing population, refractory angina (RA) is becoming an increasingly common clinical problem facing clinicians in routine clinical practice. These patients experience chronic symptoms in the context of CAD, characterised by angina-type pain, which is uncontrolled despite optimal pharmacological, interventional and surgical therapy. Although mortality rates are no worse in this cohort, patients experience a significantly impaired quality of life with disproportionately high utilisation of healthcare services. It has been increasingly recognised that the needs of RA patients are multifactorial and best provided by specialist multi-disciplinary units. In this review, we consider the variety of therapies available to clinicians in the management of RA and discuss the promise of novel treatments., Competing Interests: Disclosure: The authors have no conflicts of interest to declare.
- Published
- 2016
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171. The Role of Ivabradine in the Management of Angina Pectoris.
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Giavarini A and de Silva R
- Subjects
- Angina Pectoris physiopathology, Benzazepines adverse effects, Benzazepines pharmacokinetics, Benzazepines pharmacology, Cardiovascular Agents adverse effects, Cardiovascular Agents pharmacokinetics, Cardiovascular Agents pharmacology, Drug Interactions, Drug Therapy, Combination, Heart Rate drug effects, Humans, Ivabradine, Angina Pectoris drug therapy, Benzazepines therapeutic use, Cardiovascular Agents therapeutic use
- Abstract
Stable angina pectoris affects 2-4 % of the population in Western countries and entails an annual risk of death and nonfatal myocardial infarction of 1-2 % and 3 %, respectively. Heart rate (HR) is linearly related to myocardial oxygen consumption and coronary blood flow, both at rest and during stress. HR reduction is a key target for the prevention of ischemia/angina and is an important mechanism of action of drugs which are recommended as first line therapy for the treatment of angina in clinical guidelines. However, many patients are often unable to tolerate the doses of beta blocker or non-dihydropyridine calcium antagonists required to achieve the desired symptom control. The selective pacemaker current inhibitor ivabradine was developed as a drug for the management of patients with angina pectoris, through its ability to reduce HR specifically. The available data suggest that ivabradine is a well-tolerated and effective anti-anginal agent and it is recommended as a second-line agent for relief of angina in guidelines. However, recent clinical trials of ivabradine have failed to show prognostic benefit and have raised potential concerns about safety. This article will review the available evidence base for the current role of ivabradine in the management of patients with symptomatic angina pectoris in the context of stable coronary artery disease., Competing Interests: Dr. de Silva reports receiving financial support from Servier Laboratories to attend scientific meetings and conduct educational events.
- Published
- 2016
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172. Efficacy of a device to narrow the coronary sinus in refractory angina.
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Verheye S, Jolicœur EM, Behan MW, Pettersson T, Sainsbury P, Hill J, Vrolix M, Agostoni P, Engstrom T, Labinaz M, de Silva R, Schwartz M, Meyten N, Uren NG, Doucet S, Tanguay JF, Lindsay S, Henry TD, White CJ, Edelman ER, and Banai S
- Subjects
- Adult, Aged, Aged, 80 and over, Angina Pectoris classification, Cardiac Catheterization, Coronary Angiography, Equipment Design, Female, Humans, Male, Middle Aged, Patient Acuity, Quality of Life, Surgical Mesh, Angina Pectoris therapy, Cardiac Catheters, Coronary Sinus diagnostic imaging, Myocardial Revascularization instrumentation
- Abstract
Background: Many patients with coronary artery disease who are not candidates for revascularization have refractory angina despite standard medical therapy. The balloon-expandable, stainless steel, hourglass-shaped, coronary-sinus reducing device creates a focal narrowing and increases pressure in the coronary sinus, thus redistributing blood into ischemic myocardium., Methods: We randomly assigned 104 patients with Canadian Cardiovascular Society (CCS) class III or IV angina (on a scale from I to IV, with higher classes indicating greater limitations on physical activity owing to angina) and myocardial ischemia, who were not candidates for revascularization, to implantation of the device (treatment group) or to a sham procedure (control group). The primary end point was the proportion of patients with an improvement of at least two CCS angina classes at 6 months., Results: A total of 35% of the patients in the treatment group (18 of 52 patients), as compared with 15% of those in the control group (8 of 52), had an improvement of at least two CCS angina classes at 6 months (P=0.02). The device was also associated with improvement of at least one CCS angina class in 71% of the patients in the treatment group (37 of 52 patients), as compared with 42% of those in the control group (22 of 52) (P=0.003). Quality of life as assessed with the use of the Seattle Angina Questionnaire was significantly improved in the treatment group, as compared with the control group (improvement on a 100-point scale, 17.6 vs. 7.6 points; P=0.03). There were no significant between-group differences in improvement in exercise time or in the mean change in the wall-motion index as assessed by means of dobutamine echocardiography. At 6 months, 1 patient in the treatment group had had a myocardial infarction; in the control group, 1 patient had died and 3 had had a myocardial infarction., Conclusions: In this small clinical trial, implantation of the coronary-sinus reducing device was associated with significant improvement in symptoms and quality of life in patients with refractory angina who were not candidates for revascularization. (Funded by Neovasc; COSIRA ClinicalTrials.gov number, NCT01205893.).
- Published
- 2015
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173. Subintimal TRAnscatheter Withdrawal (STRAW) of hematomas compressing the distal true lumen: a novel technique to facilitate distal reentry during recanalization of chronic total occlusion (CTO).
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Smith EJ, Di Mario C, Spratt JC, Hanratty CG, de Silva R, Lindsay AC, and Grantham JA
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- Aged, Angioplasty, Balloon, Coronary methods, Coronary Artery Bypass adverse effects, Coronary Occlusion diagnosis, Coronary Occlusion etiology, Coronary Occlusion physiopathology, Humans, Male, Postoperative Complications diagnosis, Postoperative Complications physiopathology, Treatment Outcome, Angioplasty, Balloon, Coronary adverse effects, Coronary Occlusion surgery, Decompression, Surgical instrumentation, Decompression, Surgical methods, Hematoma etiology, Hematoma surgery, Hemostasis, Surgical instrumentation, Hemostasis, Surgical methods, Intraoperative Complications surgery, Postoperative Complications surgery
- Abstract
The development of a large hematoma impairing visualization of the distal true lumen is a recognized complication of antegrade recanalization of chronic total occlusions, often forcing the operator to abort the procedure or switch to a retrograde approach. We describe a novel technique utilizing an over-the-wire balloon inflated in the proximal occluded vessel to block inflow and allow aspiration of the blood from the subintimal space. This decompressed the true lumen, restored distal visualization, and allowed successful reentry using a dedicated technology. Utilization of this novel technique may rescue antegrade recanalization attempts complicated by large subintimal hematomas.
- Published
- 2015
174. Bilateral administration of autologous CD133+ cells in ambulatory patients with refractory critical limb ischemia: lessons learned from a pilot randomized, double-blind, placebo-controlled trial.
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Raval AN, Schmuck EG, Tefera G, Leitzke C, Ark CV, Hei D, Centanni JM, de Silva R, Koch J, Chappell RG, and Hematti P
- Subjects
- AC133 Antigen, Aged, Autografts, Double-Blind Method, Extremities pathology, Female, Follow-Up Studies, Humans, Ischemia pathology, Male, Middle Aged, Peripheral Arterial Disease pathology, Recovery of Function, Antigens, CD, Extremities blood supply, Glycoproteins, Ischemia therapy, Peptides, Peripheral Arterial Disease therapy, Stem Cell Transplantation, Stem Cells
- Abstract
Background Aims: CD133+ cells confer angiogenic potential and may be beneficial for the treatment of critical limb ischemia (CLI). However, patient selection, blinding methods and end points for clinical trials are challenging. We hypothesized that bilateral intramuscular administration of cytokine-mobilized CD133+ cells in ambulatory patients with refractory CLI would be feasible and safe., Methods: In this double-blind, randomized sham-controlled trial, subjects received subcutaneous injections of granulocyte colony-stimulating factor (10 μg/kg per day) for 5 days, followed by leukapheresis, and intramuscular administration of 50-400 million sorted CD133+ cells delivered into both legs. Control subjects received normal saline injections, sham leukapheresis and intramuscular injection of placebo buffered solution. Subjects were followed for 1 year. An aliquot of CD133+ cells was collected from each subject to test for genes associated with cell senescence., Results: Seventy subjects were screened, of whom 10 were eligible. Subject enrollment was suspended because of a high rate of mobilization failure in subjects randomly assigned to treatment. Of 10 subjects enrolled (7 randomly assigned to treatment, 3 randomly assigned to control), there were no differences in serious adverse events at 12 months, and blinding was preserved. There were non-significant trends toward improved amputation-free survival, 6-minute walk distance, walking impairment questionnaire and quality of life in subjects randomly assigned to treatment. Successful CD133+ mobilizers expressed fewer senescence-associated genes compared with poor mobilizers., Conclusions: Bilateral administration of autologous CD133+ cells in ambulatory CLI subjects was safe, and blinding was preserved. However, poor mobilization efficiency combined with high CD133+ senescence suggests futility in this approach., (Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
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175. ABSORB biodegradable stents versus second-generation metal stents: a comparison study of 100 complex lesions treated under OCT guidance.
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Mattesini A, Secco GG, Dall'Ara G, Ghione M, Rama-Merchan JC, Lupi A, Viceconte N, Lindsay AC, De Silva R, Foin N, Naganuma T, Valente S, Colombo A, and Di Mario C
- Subjects
- Aged, Angioplasty, Balloon, Coronary adverse effects, Case-Control Studies, Coronary Angiography, Coronary Artery Disease pathology, Coronary Vessels diagnostic imaging, Female, Humans, Italy, Lactic Acid, London, Male, Middle Aged, Polyesters, Polymers, Predictive Value of Tests, Prospective Studies, Prosthesis Design, Prosthesis Failure, Time Factors, Treatment Outcome, Absorbable Implants, Angioplasty, Balloon, Coronary instrumentation, Coronary Artery Disease therapy, Coronary Vessels pathology, Drug-Eluting Stents, Metals, Stents, Tomography, Optical Coherence
- Abstract
Objectives: The aim of this study was to compare the acute performance of the PLLA ABSORB bioresorbable vascular scaffold (BVS) (Abbott Vascular, Santa Clara, California) with second-generation metal drug-eluting stents (DES) in complex coronary artery lesions., Background: Thick polymer-based BVS have different mechanical properties than thin second-generation DES. Data on the acute performance of BVS are limited to simple coronary lesions treated in trials with strict inclusion criteria., Methods: Fifty complex coronary lesions (all type American College of Cardiology/American Heart Association B2-C) treated with a BVS undergoing a final optical coherence tomography (OCT) examination were compared with an equal number of matched lesions treated with second-generation DES. The following stent performance indexes were assessed with OCT: mean and minimal area, residual area stenosis (RAS), incomplete strut apposition (ISA), tissue prolapse, eccentricity index, symmetry index, strut fracture, and edge dissection., Results: One hundred lesions from 73 patients were analyzed. A higher balloon diameter/reference vessel diameter ratio was used for predilation in the BVS group (p < 0.01). Most of the BVS and DES were post-dilated with short noncompliant (NC) balloons of similar diameter. OCT showed in the BVS group a higher tissue prolapse area (p = 0.08) and greater incidence of ISA at the proximal edge (p = 0.04) with no difference in the overall ISA. The RAS was 20.2% in the BVS group and 21.7% in the DES group (p = 0.32). There was no difference in the eccentricity index. The minimal and mean lumen areas were similar in the 2 groups. Two cases of strut fractures occurred after the BVS, whereas none was observed in the DES., Conclusions: Based on OCT, the BVS showed similar post-procedure area stenosis, minimal lumen area, and eccentricity index as second-generation DES. The different approach for lesion preparation and routine use of OCT guidance during BVS expansion may have contributed to these results., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
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176. Optical coherence tomography characteristics of in-stent restenosis are different between first and second generation drug eluting stents.
- Author
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Kilickesmez K, Dall'Ara G, Rama-Merchan JC, Ghione M, Mattesini A, Vinues CM, Konstantinidis N, Pighi M, Estevez-Loureiro R, Zivelonghi C, Lindsay AC, Secco GG, Foin N, De Silva R, and Di Mario C
- Abstract
Aims: Characterization of neointimal tissue is essential to understand the pathophysiology of in-stent restenosis (ISR) after drug eluting stent (DES) implantation. Using optical coherence tomography (OCT), we compared the morphologic characteristics of ISR between first and second generation DES., Methods and Results: OCT was performed in 66 DES-ISR, defined as > 50% angiographic diameter stenosis within the stented segment. Patients with ISR of first generation sirolimus-eluting stents (SES), paclitaxel eluting stents (PES) and second generation zotarolimus-eluting stents (ZES), everolimus-eluting stents (EES) and biolimus-eluting stents (BES) were enrolled. Quantitative and qualitative ISR tissue analysis was performed at 1-mm intervals along the entire stent, and categorised as homogeneous, heterogeneous and neo-atherosclerosis. The presence of microvessels and peri-strut low intensity area (PSLIA) was determined in all ISR. Neoatherosclerosis was identified by lipid, calcium and thin-cap fibro-atheroma (TCFA) like lesions. We compared the two DES generations at both early (< 1 year) and late (> 1 year) follow-ups.In second generation DES a heterogeneous pattern was prevalent both before and after 1 year (57.1% and 58.6% respectively). Neo-atherosclerosis was more common in the early period in first generation DES (19.4% vs 11.7%, p < 0.01), but after one year was more prevalent in second generation DES (7.0% vs 19.3%, p < 0.01). Similar prevalence of TCFAs was observed in both groups in all comparisons., Conclusions: When ISR restenosis occurs in second generation DES, the current data suggest a different time course and different morphological characteristics from first generation. Future prospective studies should evaluate the relationship between ISR morphology, time course and clinical events.
- Published
- 2014
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177. In vivo diffusion tensor MRI of the human heart: reproducibility of breath-hold and navigator-based approaches.
- Author
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Nielles-Vallespin S, Mekkaoui C, Gatehouse P, Reese TG, Keegan J, Ferreira PF, Collins S, Speier P, Feiweier T, de Silva R, Jackowski MP, Pennell DJ, Sosnovik DE, and Firmin D
- Subjects
- Feasibility Studies, Humans, Reproducibility of Results, Sensitivity and Specificity, Biofeedback, Psychology methods, Breath Holding, Cardiac-Gated Imaging Techniques methods, Diffusion Tensor Imaging methods, Image Enhancement methods, Image Interpretation, Computer-Assisted methods, Ventricular Dysfunction, Left pathology
- Abstract
The aim of this study was to implement a quantitative in vivo cardiac diffusion tensor imaging (DTI) technique that was robust, reproducible, and feasible to perform in patients with cardiovascular disease. A stimulated-echo single-shot echo-planar imaging (EPI) sequence with zonal excitation and parallel imaging was implemented, together with a novel modification of the prospective navigator (NAV) technique combined with a biofeedback mechanism. Ten volunteers were scanned on two different days, each time with both multiple breath-hold (MBH) and NAV multislice protocols. Fractional anisotropy (FA), mean diffusivity (MD), and helix angle (HA) fiber maps were created. Comparison of initial and repeat scans showed good reproducibility for both MBH and NAV techniques for FA (P > 0.22), MD (P > 0.15), and HA (P > 0.28). Comparison of MBH and NAV FA (FAMBHday1 = 0.60 ± 0.04, FANAVday1 = 0.60 ± 0.03, P = 0.57) and MD (MDMBHday1 = 0.8 ± 0.2 × 10(-3) mm(2) /s, MDNAVday1 = 0.9 ± 0.2 × 10(-3) mm(2) /s, P = 0.07) values showed no significant differences, while HA values (HAMBHday1Endo = 22 ± 10°, HAMBHday1Mid-Endo = 20 ± 6°, HAMBHday1Mid-Epi = -1 ± 6°, HAMBHday1Epi = -17 ± 6°, HANAVday1Endo = 7 ± 7°, HANAVday1Mid-Endo = 13 ± 8°, HANAVday1Mid-Epi = -2 ± 7°, HANAVday1Epi = -14 ± 6°) were significantly different. The scan duration was 20% longer with the NAV approach. Currently, the MBH approach is the more robust in normal volunteers. While the NAV technique still requires resolution of some bulk motion sensitivity issues, these preliminary experiments show its potential for in vivo clinical cardiac diffusion tensor imaging and for delivering high-resolution in vivo 3D DTI tractography of the heart., (© 2012 Wiley Periodicals, Inc.)
- Published
- 2013
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178. Optical coherence tomography for guidance of distal cell recrossing in bifurcation stenting: choosing the right cell matters.
- Author
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Alegría-Barrero E, Foin N, Chan PH, Syrseloudis D, Lindsay AC, Dimopolous K, Alonso-González R, Viceconte N, De Silva R, and Di Mario C
- Subjects
- Aged, Aged, 80 and over, Coronary Angiography, Female, Humans, Male, Middle Aged, Angioplasty, Balloon, Coronary adverse effects, Stents adverse effects, Tomography, Optical Coherence methods
- Abstract
Aims: The aim of this study was to assess the ability of optical coherence tomography (OCT) to guide recrossing during percutaneous coronary interventions in bifurcations and to reduce strut malapposition., Methods and Results: Fifty-two patients undergoing elective treatment of bifurcation lesions using provisional stenting as default strategy were included in the study. Patients were divided into two groups: OCT-guided stent recrossing (group 1, n=12), and angiography-guided recrossing (group 2, n=40). Malapposition in the various bifurcation segments was compared in the two groups, using propensity score analysis to correct for confounders. In 4/12 patients (33%) of the OCT-guided group after the first attempt to recross the stent towards the SB the wire was found to have crossed in a proximal cell, requiring a second and in one case a third attempt to successfully cross through a distal cell. Patients who were treated using OCT-guided recrossing had a significantly lower number of malapposed stent struts, especially in the quadrants towards the SB ostium (9.5%[7.5-17.4%] vs 42.3%[31.2-54.7%] in the angiography-guided group, p<0.0001)., Conclusions: The rate of strut malapposition was significantly reduced when OCT was used to confirm that wire recrossing was performed in a distal cell of the SB ostium.
- Published
- 2012
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179. Optical coherence tomography: from research to practice.
- Author
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Gutiérrez-Chico JL, Alegría-Barrero E, Teijeiro-Mestre R, Chan PH, Tsujioka H, de Silva R, Viceconte N, Lindsay A, Patterson T, Foin N, Akasaka T, and di Mario C
- Subjects
- Acute Coronary Syndrome diagnosis, Acute Coronary Syndrome pathology, Coronary Artery Disease pathology, Humans, Neointima pathology, Severity of Illness Index, Stents, Ultrasonography, Interventional instrumentation, Biomedical Research instrumentation, Coronary Artery Disease diagnosis, Evidence-Based Medicine instrumentation, Tomography, Optical Coherence instrumentation
- Abstract
Optical coherence tomography (OCT) is a high-resolution imaging technique with great versatility of applications. In cardiology, OCT has remained hitherto as a research tool for characterization of vulnerable plaques and evaluation of neointimal healing after stenting. However, OCT is now successfully applied in different clinical scenarios, and the introduction of frequency domain analysis simplified its application to the point it can be considered a potential alternative to intravascular ultrasound for clinical decision-making in some cases. This article reviews the use of OCT for assessment of lesion severity, characterization of acute coronary syndromes, guidance of intracoronary stenting, and evaluation of long-term results.
- Published
- 2012
- Full Text
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180. Pharmacotherapy: Xanthine oxidase inhibition for relief of angina pectoris.
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de Silva R and Fox KM
- Subjects
- Humans, Allopurinol therapeutic use, Angina Pectoris drug therapy, Enzyme Inhibitors therapeutic use, Xanthine Oxidase antagonists & inhibitors
- Published
- 2010
- Full Text
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181. Simple versus complex approaches to treating coronary bifurcation lesions: direct assessment of stent strut apposition by optical coherence tomography.
- Author
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Tyczynski P, Ferrante G, Moreno-Ambroj C, Kukreja N, Barlis P, Pieri E, De Silva R, Beatt K, and Di Mario C
- Subjects
- Aged, Female, Humans, Male, Middle Aged, Prosthesis Implantation methods, Coronary Artery Disease diagnosis, Coronary Artery Disease surgery, Stents, Tomography, Optical Coherence
- Abstract
Introduction and Objectives: Stenting of coronary bifurcation lesions carries an increased risk of stent deformation and malapposition. Anatomical and pathological observations indicate that the high stent thrombosis rate in bifurcations is due to malapposition of stent struts., Methods: Strut apposition was assessed with optical coherence tomography (OCT) in bifurcation lesions treated either using the simple technique of stent implantation in the main vessel only or a complex technique (i.e. Culotte's). A strut was regarded as malapposed if the gap between its endoluminal surface and the vessel wall was greater than its thickness plus an OCT resolution error margin of 15 microm., Results: Simple and complex (i.e. Culotte's) approaches were used in 17 and 14 patients, respectively. Strut malapposition was significantly more frequent for the half of the bifurcation on same side as the vessel side branch (median, 46.1%; interquartile range [IQR], 35.3-62.5%) than for the half opposite the side branch (9.1%; IQR, 2.2-21.6%), the distal segment (7.5%; IQR, 2.3-20.2%) or the proximal segment (12.6%; IQR, 7.8-23.1%; P< .0001); the gap between strut and vessel wall in malapposed struts was significantly greater in the first segment than the others: 98 microm (IQR, 37-297 microm) vs. 31 microm (IQR, 13-74 microm), 49 microm (IQR, 20-100 microm) and 38 microm (IQR, 17-90 microm), respectively (P< .0001). Using the complex technique had no effect on the prevalence of strut malapposition in the four segments relative to the simple technique (P=.31) but was associated with a smaller gap in the proximal segment (47 microm vs. 60 microm; P=.0008)., Conclusions: In coronary bifurcation lesions, strut malapposition occurred most frequently and was most significant close to the side branch ostium. The use of Culotte's technique did not significantly increase the prevalence of strut malapposition compared with a simple technique.
- Published
- 2010
- Full Text
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182. Intracoronary infusion of autologous mononuclear cells from bone marrow or granulocyte colony-stimulating factor-mobilized apheresis product may not improve remodelling, contractile function, perfusion, or infarct size in a swine model of large myocardial infarction.
- Author
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de Silva R, Raval AN, Hadi M, Gildea KM, Bonifacino AC, Yu ZX, Yau YY, Leitman SF, Bacharach SL, Donahue RE, Read EJ, and Lederman RJ
- Subjects
- Animals, Blood Component Removal methods, Disease Models, Animal, Granulocyte Colony-Stimulating Factor, Magnetic Resonance Imaging, Myocardial Contraction, Myocardial Infarction pathology, Myocardial Infarction physiopathology, Positron-Emission Tomography, Recombinant Proteins, Swine, Swine, Miniature, Treatment Outcome, Hematopoietic Stem Cell Mobilization methods, Hematopoietic Stem Cell Transplantation methods, Myocardial Infarction therapy, Ventricular Remodeling
- Abstract
Aims: In a blinded, placebo-controlled study, we investigated whether intracoronary infusion of autologous mononuclear cells from granulocyte colony-stimulating factor (G-CSF)-mobilized apheresis product or bone marrow (BM) improved sensitive outcome measures in a swine model of large myocardial infarction (MI)., Methods and Results: Four days after left anterior descending (LAD) occlusion and reperfusion, cells from BM or apheresis product of saline- (placebo) or G-CSF-injected animals were infused into the LAD. Large infarcts were created: baseline ejection fraction (EF) by magnetic resonance imaging (MRI) of 35.3 +/- 8.5%, no difference between the placebo, G-CSF, and BM groups (P = 0.16 by ANOVA). At 6 weeks, EF fell to a similar degree in the placebo, G-CSF, and BM groups (-7.9 +/- 6.0, -8.5 +/- 8.8, and -10.9 +/- 7.6%, P = 0.78 by ANOVA). Left ventricular volumes and infarct size by MRI deteriorated similarly in all three groups. Quantitative positron emission tomography (PET) demonstrated significant decline in fluorodeoxyglucose uptake rate in the LAD territory at follow-up, with no histological, angiographic, or PET perfusion evidence of functional neovascularization. Immunofluorescence failed to demonstrate transdifferentiation of infused cells., Conclusion: Intracoronary infusion of mononuclear cells from either BM or G-CSF-mobilized apheresis product may not improve or limit deterioration in systolic function, adverse ventricular remodelling, infarct size, or perfusion in a swine model of large MI.
- Published
- 2008
- Full Text
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183. Early intervention in acute coronary syndrome: is bivalirudin monotherapy an effective antithrombotic strategy?
- Author
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de Silva R and Fox K
- Published
- 2008
- Full Text
- View/download PDF
184. Oxidative stress: apoptosis in neuronal injury.
- Author
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Loh KP, Huang SH, De Silva R, Tan BK, and Zhu YZ
- Subjects
- Alzheimer Disease metabolism, Alzheimer Disease physiopathology, Animals, Brain pathology, Brain physiopathology, Brain Ischemia metabolism, Brain Ischemia physiopathology, Humans, Neurodegenerative Diseases genetics, Neurodegenerative Diseases physiopathology, Neurons pathology, Oxidation-Reduction, Reactive Oxygen Species metabolism, Signal Transduction physiology, Apoptosis physiology, Brain metabolism, Neurodegenerative Diseases metabolism, Neurons metabolism, Oxidative Stress physiology
- Abstract
Apoptosis has been well documented to play a significant role in cell loss during neurodegenerative disorders, such as stroke, Parkinson disease, and Alzheimer's disease. In addition, reactive oxygen species (ROS) has been implicated in the cellular damage during these neurodegenerative disorders. These ROS can react with cellular macromolecular through oxidation and cause the cells undergo necrosis or apoptosis. The control of the redox environment of the cell provides addition regulation in the signal transduction pathways which are redox sensitive. Recently, many researches focus on the relationship between apoptosis and oxidative stress. However, till now, there is no clear and defined mechanisms that how oxidative stress could contribute to the apoptosis. This review hopes to make clear that generation of ROS during brain injury, particularly in ischemic stroke and Alzheimer's Disease, and the fact that oxidative state plays a key role in the regulation and control of the cell survival and cell death through its interaction with cellular macromolecules and signal transduction pathway, and ultimately helps in developing an unique therapy for the treatment of these neurodegenerative disorders.
- Published
- 2006
- Full Text
- View/download PDF
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