NIHR Cardiovascular Biomedical Research Unit

London, United Kingdom

NIHR Cardiovascular Biomedical Research Unit

London, United Kingdom
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O'Neill D.,University College London | Nicholas O.,University College London | Gale C.P.,University of Leeds | Gale C.P.,York Teaching Hospital | And 7 more authors.
Circulation: Cardiovascular Quality and Outcomes | Year: 2017

Background - The relationship between procedural volume and prognosis after percutaneous coronary intervention (PCI) remains uncertain, with some studies finding in favor of an inverse association and some against. This UK study provides a contemporary reassessment in one of the few countries in the world with a nationally representative PCI registry. Methods and Results - A nationwide cohort study was performed using the national British Cardiovascular Intervention Society registry. All adult patients undergoing PCI in 93 English and Welsh NHS hospitals between 2007 and 2013 were analyzed using hierarchical modeling with adjustment for patient risk. Of 427 467 procedures (22.0% primary PCI) in 93 hospitals, 30-day mortality was 1.9% (4.8% primary PCI). 87.1% of centers undertook between 200 and 2000 procedures annually. Case mix varied with center volume. In centers with 200 to 399 PCI cases per year, a smaller proportion were PCI for ST-segment-elevation myocardial infarction (8.4%) than in centers with 1500 to 1999 PCI cases per year (24.2%), but proportionally more were for ST-segment-elevation myocardial infarction with cardiogenic shock (8.4% versus 4.3%). For the overall PCI cohort, after risk adjustment, there was no significant evidence of worse, or better, outcomes in lower volume centers from our own study, or in combination with results from other studies. For primary PCI, there was also no evidence for increased or decreased mortality in lower volume centers. Conclusions - After adjustment for differences in case mix and clinical presentation, this study supports the conclusion of no trend for increased mortality in lower volume centers for PCI in the UK healthcare system. © 2017 American Heart Association, Inc.

Jordan K.P.,Keele University | Timmis A.,NIHR Cardiovascular Biomedical Research Unit | Croft P.,Keele University | Van Der Windt D.A.,Keele University | And 5 more authors.
BMJ (Online) | Year: 2017

Objective To ascertain long term cardiovascular outcomes in patients whose chest pain remained undiagnosed six months after first presentation. Design Cohort study. Setting UK electronic health record database (CALIBER) linking primary care, secondary care, coronary registry, and death registry information. Participants 172 180 adults aged ≥18 from 223 general practices presenting with a first episode of recorded chest pain, classified from medical records as diagnosed (noncoronary condition or angina) or undiagnosed (cause unattributed) at first consultation between 2002 and 2009 and with no previous record of cardiovascular disease. Main outcom e measures Fatal or non-fatal cardiovascular events over 5.5 years'f follow-up. Adjustments were made for age, sex, deprivation, body mass index, smoking status, year of index presentation, and previous records of diabetes or hypertension or previous prescriptions for lipid lowering drugs. Results At the index presentation, 72.4% of patients (124 688) did not have a cause attributed for their chest pain; 118 687 (95.2%) of these did not receive any type of cardiovascular diagnosis over the next six months. Only a minority of patients in all three groups (non-coronary 2.0% (769 of 39 232); unattributed 11.7% (14 582 of 124 688); angina 31.5% (2606 of 8260)) had a recorded cardiac diagnostic investigation in the first six months after presentation. The long term incidence of cardiovascular events was higher in those whose chest pain remained unattributed after six months (5126 of 109 628; 4.7%) compared with patients with an initial diagnosis of non-coronary pain (1073 of 36 097; 3.0%) (adjusted hazard ratios for 0.5-1 year after presentation: 1.95, 95% confidence interval 1.66 to 2.31; for 1-3 years: 1.35, 1.23 to 1.48); for 3-5.5 years: 1.21, 1.08 to 1.37). Owing to the larger number of patients in the unattributed group, there were more excess myocardial infarctions in the long term in this group (214 more than expected based on the rate in the non-coronary group) than in the angina group (132 more than expected). Patients who had cardiac diagnostic investigations in the first six months had a higher long term risk of cardiovascular events, regardless of the initial chest pain label. Incidence of unattributed chest pain and angina decreased between 2002 (124 per 10 000 person years and 13 per 10 000 person years, respectively) and 2009 (107 per 10 000 person years and 5 per 10 000 person years, respectively), but the incidence of chest pain attributed to a non-coronary cause remained stable (37-40 per 10 000 person years). Risk of cardiovascular events did not change over time. Conclusions Most patients with first onset chest pain do not have a diagnosis recorded at presentation or in the subsequent six months, including those who undergo cardiac investigations. These patients have an increased risk of cardiovascular events for at least five years. Efforts to better assess and reduce the cardiovascular risk of such patients are warranted.

Timmis A.,NIHR Cardiovascular Biomedical Research Unit | Roobottom C.A.,Derriford Hospital
Heart | Year: 2017

In the 2016 update of the stable chest pain guideline, the National Institute for Health and Care Excellence (NICE) has made radical changes to the diagnostic paradigm that it-like other international guidelines-had previously placed at the centre of its recommendations. No longer are quantitative assessments of the disease probability considered necessary to determine the need for diagnostic testing and the choice of test. Instead, the recommendation is for no diagnostic testing if chest pain is judged to be 'non-anginal' and CT coronary angiography (CTCA) in patients with 'typical' or 'atypical' chest pain with additional perfusion imaging only if there is uncertainty about the functional significance of coronary lesions. The new emphasis on anatomical-A s opposed to functional-testing is driven in large part by cost-effectiveness analysis and despite inevitable resource implications NICE calculates that annual savings for the population of England will be significant. In making CTCA the default diagnostic testing strategy in its updated chest pain guideline, NICE has responded emphatically to calls from trialists for CTCA to have a greater role in the diagnostic pathway of patients with suspected angina. © 2017 Article author(s).

Gunn J.,University of Sheffield | Siotia A.,Northern General Hospital | Malkin C.J.,Northern General Hospital | Iqbal J.,University of Sheffield | And 2 more authors.
Catheterization and Cardiovascular Interventions | Year: 2012

Objectives: We studied the acute safety and feasibility of a pericardium-covered stent (PCS) in the obliteration of massive coronary thrombus. Background: Thrombus is frequently encountered in the setting of acute myocardial infarction, and conventional pharmacological and aspiration approaches are not always successful in dispersing or removing it, especially when it is very substantial. Methods: We treated nine patients (10 lesions) in the setting of an acute coronary syndrome characterized by the presence of substantial (TIMI grade 3-4) thrombus in a large caliber native coronary artery, persisting after conventional treatment, with percutaneous implantation of an equine PCS graft. Nine of 10 lesions were in large right coronary arteries. Results: Deployment was successful in nine of 10 lesions. In all nine cases, the filling defect was immediately eliminated and there was restoration or maintenance of TIMI grade 3 blood flow. There was one in-hospital stent thrombosis in a 56-year-old male, who had only received aspirin due to a coexistent stroke. This patient underwent successful repeat percutaneous intervention but died later of complications of the stroke. There were no 30-day events, and medium-term follow-up continues. Conclusions: A PCS graft is a potentially useful device to treat massive thrombus burden in the setting of acute coronary syndrome. A larger study is warranted. Copyright © 2011 Wiley Periodicals, Inc.

Gulati R.,Mayo Medical School | Raphael C.E.,NIHR Cardiovascular Biomedical Research Unit | Negoita M.,Medtronic Inc. | Pocock S.J.,London School of Hygiene and Tropical Medicine | Gersh B.J.,Mayo Medical School
Nature Reviews Cardiology | Year: 2016

Renal denervation has a chequered history. Dramatic reductions in blood pressure after denervation of the renal arteries were observed in early trials, but later trials in which denervation was tested against a sham procedure produced neutral results. Although a sound pathophysiological basis exists for interruption of the renal sympathetic nervous system as a treatment for hypertension, trial data to date are insufficient to support renal denervation as an established clinical therapy. In this Perspectives article, we summarize the currently available trial data, device development, and trials in progress, and provide recommendations for future trial design. © 2016 Macmillan Publishers Limited.

Carlisle T.,Imperial College London | Carlisle T.,National Health Research Institute | Carthy E.R.,Imperial College London | Carthy E.R.,National Health Research Institute | And 10 more authors.
European Respiratory Journal | Year: 2014

The prevalence of obstructive sleep apnoea (OSA) increases with age, yet the risk factors for OSA in older people remain poorly understood. This study aimed to define the age-related changes in upper airway morphology in carefully matched groups of healthy older (>60 years, n=11) and younger (<40 years, n=14) males, using direct (magnetic resonance imaging (MRI)) and indirect (acoustic reflection) imaging. The median (interquartile range) combined retropalatal and retroglossal pharyngeal length was greater in older than in younger males (older 8.8 (7.8-9.0) cm, younger 7.8 (7.0-8.3) cm; p=0.03), as was the soft palate cross-sectional area (older 43.1 (36.0-48.8) cm2, younger 35.3 (30.5-40.5) cm2; p=0.03), parapharyngeal fat pad diameter (older 1.7 (1.4-2.2) cm, younger 1.2 (1.0-1.8) cm; p=0.03) and cross-sectional area of the fat pads (older 13.8 (9.1-17.1) cm2; younger 7.4 (5.9-13.0) cm2; p=0.02) as measured by MRI. Using acoustic reflection, pharyngeal calibre (older 4.8 (3.8-6.6) cm2, younger 3.4 (2.8-4.6) cm2; p=0.03), pharyngeal volume (older 35.1 (30.9-55.4) cm3, younger 27.2 (22.7-44.2) cm3; p=0.04) and glottis area (older 2.7 (2.1-3.9) cm2, younger 1.3 (1.1-1.9) cm 2; p=0.003) were also larger in older participants compared with younger participants. There was no difference in craniofacial measures between groups, including volumetric data and hyoid bone position. The larger pharyngeal calibre observed in older males may be compensating for an age-related enlargement in pharyngeal soft tissue that predisposes to OSA. Copyright ©ERS 2014.

Ellam T.J.,Northern General Hospital | Ellam T.J.,NIHR Cardiovascular Biomedical Research Unit
Nephron - Clinical Practice | Year: 2011

Current guidelines illogically recommend that a different approach is taken to the correction for creatinine generation rate when estimating glomerular filtration rate (GFR) and when interpreting urine albumin:creatinine ratio (ACR). Age, gender and race are routinely used to adjust for predicted muscle mass in GFR estimation, even though estimated GFR is expressed per unit body surface area. Conversely, ACR is at most adjusted with the use of gender-specific classification thresholds. This difference is surprising since the proportional effect of muscle mass on serum and urine creatinine is identical. Failure to adjust for creatinine generation rate compromises ACR, potentially adversely affecting management decisions and mislabelling individuals as having/not having CKD. A greater ACR is also a marker of low muscle mass, which has confounding prognostic effects. Determination of the optimal method to adjust ACR for estimated muscle mass should improve its performance. Routine reporting of the resulting 'estimated albumin excretion rate', as for routine eGFR reporting, would remove the need for gender-specific thresholds. Copyright © 2011 S. Karger AG, Basel.

House M.J.,University of Western Australia | Fleming A.J.,University of Western Australia | De Jonge M.D.,Australian Synchrotron | Paterson D.,Australian Synchrotron | And 6 more authors.
Journal of Cardiovascular Magnetic Resonance | Year: 2014

Background: MRI assessment of cardiac iron is particularly important for assessing transfusion-dependent anaemia patients. However, comparing the iron distribution from histology or bulk samples to MRI is not ideal. Non-destructive, high-resolution imaging of post-mortem samples offers the ability to examine iron distributions across large samples at resolutions closer to those used in MRI. The aim of this ex vivo case study was to compare synchrotron X-ray fluorescence microscopy (XFM) elemental iron maps with magnetic resonance transverse relaxation rate maps of cardiac tissue samples from an iron-loaded patient.Methods. Two 5 mm thick slices of formalin fixed cardiac tissue from a Diamond Blackfan anaemia patient were imaged in a 1.5 T MR scanner. R2and R2∗transverse relaxation rate maps were generated for both slices using RF pulse recalled spin echo and gradient echo acquisition sequences. The tissue samples were then imaged at the Australian Synchrotron on the X-ray Fluorescence Microscopy beamline using a focussed incident X-ray beam of 18.74 keV and the Maia 384 detector. The event data were analyzed to produce elemental iron maps (uncalibrated) at 25 to 60 microns image resolution.Results: The R2and R2∗maps and profiles for both samples showed very similar macro-scale spatial patterns compared to the XFM iron distribution. Iron appeared to preferentially load into the lateral epicardium wall and there was a strong gradient of decreasing iron, R2and R2∗from the epicardium to the endocardium in the lateral wall of the left ventricle and to a lesser extent in the septum. On co-registered images XFM iron was more strongly correlated to R2∗(r = 0.86) than R2(r = 0.79). There was a strong linear relationship between R2∗and R2(r = 0.87).Conclusions: The close qualitative and quantitative agreement between the synchrotron XFM iron maps and MR relaxometry maps indicates that iron is a significant determinant of R2and R2∗in these ex vivo samples. The R2and R2∗maps of human heart tissue give information on the spatial distribution of tissue iron deposits. © 2014 House et al.; licensee BioMed Central Ltd.

Felkin L.E.,Imperial College London | Narita T.,Queen Mary, University of London | Germack R.,Imperial College London | Shintani Y.,Queen Mary, University of London | And 12 more authors.
Circulation | Year: 2011

Background-: Calcineurin is a calcium-regulated phosphatase that plays a major role in cardiac hypertrophy. We previously described that alternative splicing of the calcineurin Aβ (CnAβ) gene generates the CnAβ1 isoform, with a unique C-terminal region that is different from the autoinhibitory domain present in all other CnA isoforms. In skeletal muscle, CnAβ1 is necessary for myoblast proliferation and stimulates regeneration, reducing fibrosis and accelerating the resolution of inflammation. Its role in the heart is currently unknown. Methods and Results-: We generated transgenic mice overexpressing CnAβ1 in postnatal cardiomyocytes under the control of the α-myosin heavy chain promoter. In contrast to previous studies using an artificially truncated calcineurin, CnAβ1 overexpression did not induce cardiac hypertrophy. Moreover, transgenic mice showed improved cardiac function and reduced scar formation after myocardial infarction, with reduced neutrophil and macrophage infiltration and decreased expression of proinflammatory cytokines. Immunoprecipitation and Western blot analysis showed interaction of CnAβ1 with the mTOR complex 2 and activation of the Akt/SGK cardioprotective pathway in a PI3K-independent manner. In addition, gene expression profiling revealed that CnAβ1 activated the transcription factor ATF4 downstream of the Akt/mTOR pathway to promote the amino acid biosynthesis program, to reduce protein catabolism, and to induce the antifibrotic and antiinflammatory factor growth differentiation factor 15, which protects the heart through Akt activation. Conclusions-: Calcineurin Aβ1 shows a unique mode of action that improves cardiac function after myocardial infarction, activating different cardioprotective pathways without inducing maladaptive hypertrophy. These features make CnAβ1 an attractive candidate for the development of future therapeutic approaches. © 2011 American Heart Association, Inc.

PubMed | St Georges Hospital and NIHR Cardiovascular Biomedical Research Unit
Type: Journal Article | Journal: Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance | Year: 2016

T2* magnetic resonance of tissue iron concentration has improved the outcome of transfusion dependant anaemia patients. Clinical evaluation is performed at 1.5T but scanners operating at 3T are increasing in numbers. There is a paucity of data on the relative merits of iron quantification at 3T vs 1.5T.A total of 104 transfusion dependent anaemia patients and 20 normal volunteers were prospectively recruited to undergo cardiac and liver T2* assessment at both 1.5T and 3T. Intra-observer, inter-observer and inter-study reproducibility analysis were performed on 20 randomly selected patients for cardiac and liver T2*.Association between heart and liver T2* at 1.5T and 3T was non-linear with good fit (R (2)=0.954, p<0.001 for heart white-blood (WB) imaging; R (2)=0.931, p<0.001 for heart black-blood (BB) imaging; R (2)=0.993, p<0.001 for liver imaging). R2* approximately doubled between 1.5T and 3T with linear fits for both heart and liver (94, 94 and 105% respectively). Coefficients of variation for intra- and inter-observer reproducibility, as well as inter-study reproducibility trended to be less good at 3T (3.5 to 6.5%) than at 1.5T (1.4 to 5.7%) for both heart and liver T2*. Artefact scores for the heart were significantly worse with the 3T BB sequence (median 4, IQR 2-5) compared with the 1.5T BB sequence (4 [3-5], p=0.007).Heart and liver T2* and R2* at 3T show close association with 1.5T values, but there were more artefacts at 3T and trends to lower reproducibility causing difficulty in quantifying low T2* values with high tissue iron. Therefore T2* imaging at 1.5T remains the gold standard for clinical practice. However, in centres where only 3T is available, equivalent values at 1.5T may be approximated by halving the 3T tissue R2* with subsequent conversion to T2*.

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