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.

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 | Anglia, Imperial College London, University College London, Liverpool Heart and Chest 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

Wave intensity analysis (WIA) of the coronary arteries allows description of the predominant mechanisms influencing coronary flow over the cardiac cycle. The data are traditionally derived from pressure and velocity changes measured invasively in the coronary artery. Cardiovascular magnetic resonance (CMR) allows measurement of coronary velocities using phase velocity mapping and derivation of central aortic pressure from aortic distension. We assessed the feasibility of WIA of the coronary arteries using CMR and compared this to invasive data.CMR scans were undertaken in a serial cohort of patients who had undergone invasive WIA. Velocity maps were acquired in the proximal left anterior descending and proximal right coronary artery using a retrospectively-gated breath-hold spiral phase velocity mapping sequence with high temporal resolution (19ms). A breath-hold segmented gradient echo sequence was used to acquire through-plane cross sectional area changes in the proximal ascending aorta which were used as a surrogate of an aortic pressure waveform after calibration with brachial blood pressure measured with a sphygmomanometer. CMR-derived aortic pressures and CMR-measured velocities were used to derive wave intensity. The CMR-derived wave intensities were compared to invasive data in 12 coronary arteries (8 left, 4 right). Waves were presented as absolute values and as a % of total wave intensity. Intra-study reproducibility of invasive and non-invasive WIA was assessed using Bland-Altman analysis and the intraclass correlation coefficient (ICC).The combination of the CMR-derived pressure and velocity data produced the expected pattern of forward and backward compression and expansion waves. The intra-study reproducibility of the CMR derived wave intensities as a % of the total wave intensity (meanstandard deviation of differences) was 0.06.8%, ICC=0.91. Intra-study reproducibility for the corresponding invasive data was 0.04.4%, ICC=0.96. The invasive and CMR studies showed reasonable correlation (r=0.73) with a mean difference of 0.011.5%.This proof of concept study demonstrated that CMR may be used to perform coronary WIA non-invasively with reasonable reproducibility compared to invasive WIA. The technique potentially allows WIA to be performed in a wider range of patients and pathologies than those who can be studied invasively.

PubMed | Santi Antonio e Biagio e Cesare Arrigo Hospital, Cardiovascular Institute and NIHR Cardiovascular Biomedical Research Unit
Type: Comparative Study | Journal: The international journal of cardiovascular imaging | Year: 2016

To assess if enhanced stent visualization (ESV)-guided implantation of overlapping bioresorbable vascular scaffold (BVS) is superior to angiography alone-guided implantation in the reduction of overlap length. WOLFIE is a two-centre prospective open study enrolling 30 patients treated with implantation of at least two overlapping BVS. In the first centre (London), BVS implantation was guided by conventional angiography, while in the second centre (Ferrara), an ESV system was systematically employed. The primary endpoint of the study was overlap length. Secondary endpoints were: stacked struts number, area, thickness, and amount of clusters. In the ESV-guided group, overlap length was significantly lower compared to angiography-guided group [0.9 (0.6-1.8) vs. 2.2 (1.3-3.2) mm, p = 0.02]. Similarly, all secondary endpoints were significantly reduced. ESV-guided implantation of overlapping BVS is safe and effective in minimizing both overlap length and number of stacked struts.

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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