Publications by authors named "Neal G Uren"

24 Publications

  • Page 1 of 1

Initial experience of a large, self-expanding, and fully recapturable transcatheter aortic valve: The UK & Ireland Implanters' registry.

Catheter Cardiovasc Interv 2019 03 5;93(4):751-757. Epub 2018 Nov 5.

Cardiology Clinical Academic Group, St. George's, University of London and St. George's University Hospitals NHS Foundation Trust, London, United Kingdom.

Objectives: The UK & Ireland Implanters' registry is a multicenter registry which reports on real-world experience with novel transcatheter heart valves.

Background: The 34 mm Evolut R transcatheter aortic valve is a self-expanding and fully recapturable transcatheter aortic valve, designed to treat patients with a large aortic annulus.

Methods: Between January 2017 and April 2018, clinical, procedural and 30-day outcome data were prospectively collected from all patients receiving the 34 mm Evolut R valve across 17 participating centers in the United Kingdom and Ireland. The primary efficacy outcome was the Valve Academic Research Consortium-2(VARC-2)-defined endpoint of device success. The primary safety outcome was the VARC-2-defined composite endpoint of early safety at 30 days.

Results: A total of 217 patients underwent attempted implant. Mean age was 79.5 ± 8.8 years and Society of Thoracic Surgeons Predicted Risk of Mortality Score 5.2% ± 3.4%. Iliofemoral access was used in 91.2% of patients. Device success was 79.7%. Mean gradient was 7.0 ± 4.6 mmHg and effective orifice area 2.0 ± 0.6 cm . Paravalvular regurgitation was more than mild in 7.2%. A new permanent pacemaker was implanted in 15.7%. Early safety was demonstrated in 91.2%. At 30 days, all-cause mortality was 3.2%, stroke 3.7%, and major vascular complication 2.3%.

Conclusions: Real-world experience of the 34 mm Evolut R transcatheter aortic valve demonstrated acceptable procedural success, safety, valve function, and incidence of new permanent pacemaker implantation.
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http://dx.doi.org/10.1002/ccd.27934DOI Listing
March 2019

The relationship between the basal coronary translesional pressure ratio and fractional flow reserve.

Catheter Cardiovasc Interv 2017 Nov 2;90(5):745-753. Epub 2017 Aug 2.

Edinburgh Heart Centre, Royal Infirmary of Edinburgh, United Kingdom.

Aim: Fractional flow reserve (FFR) allows for physiological definition of coronary lesion severity but requires induction of maximal coronary circulation hyperemia with administration of adenosine leading to coronary resistive vessel vasodilatation. However, the hyperemic response to adenosine, and therefore the calculation of FFR, may be affected by dysfunction of the coronary microvasculature. The aim was to define the relationship between basal P /P and FFR and identify lesion-independent predictors of the change in P /P with hyperemia.

Methods And Results: One hundred and sixty-six consecutive patients undergoing FFR measurement were prospectively enrolled (mean age 62.6 ± 10.3 years, 27% females). Basal P /P , FFR, and delta P /P (difference between basal P /P and FFR) were recorded. Independent predictors of delta P /P included angiographic lesion severity, lesion length, gender, body mass index, and total cholesterol:HDL cholesterol ratio. The best basal P /P cutoff value to predict lesion physiological significance was 0.87 (positive predictive value of 100% for an FFR value ≤0.80) and the best cutoff for nonsignificance was 0.93 (negative predictive value of 98% for an FFR value >0.80).

Conclusion: The delta P /P may be affected by patient gender, body mass index, and cholesterol profile. A basal P /P value of ≥0.93 is highly predictive of an FFR >0.80. Conversely, a basal P /P value of ≤0.87 is highly predictive of an FFR ≤0.80. © 2017 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ccd.27027DOI Listing
November 2017

Optical coherence tomography versus intravascular ultrasound to evaluate stent implantation in patients with calcific coronary artery disease.

Open Heart 2015;2(1):e000225. Epub 2015 Dec 22.

Royal Infirmary of Edinburgh , Edinburgh , UK.

Aims: Stent underexpansion and malapposition are associated with adverse outcomes following percutaneous coronary intervention, but detection and treatment can be challenging in the presence of extensive coronary artery calcification. Frequency domain optical coherence tomography (FD-OCT) is a novel intravascular imaging technique with greater spatial resolution than intravascular ultrasound (IVUS) but its role in the presence of extensive coronary calcification remains unclear. We sought to determine the utility of FD-OCT compared to IVUS imaging to guide percutaneous coronary intervention in patients with severe calcific coronary artery disease.

Methods: 18 matched IVUS and FD-OCT examinations were evaluated following coronary stent implantation in 12 patients (10 male; mean age 70±7 years) undergoing rotational atherectomy for symptomatic calcific coronary artery disease.

Results: In-stent luminal areas were smaller (minimum in-stent area 6.77±2.18 vs 7.19±2.62 mm(2), p<0.05), while reference lumen dimensions were similar with FD-OCT compared with IVUS. Stent malapposition was detected in all patients by FD-OCT and in 10 patients by IVUS. The extent of stent malapposition detected was greater (20% vs 6%, p<0.001) with FD-OCT compared to IVUS. Postdilation increased the in-stent luminal area (minimum in-stent area: 8.15±1.90 vs 7.30±1.62 mm(2), p<0.05) and reduced the extent of stent malapposition (19% vs 34%, p<0.005) when assessed by FD-OCT, but not IVUS.

Conclusions: Acute stent malapposition occurs frequently in patients with calcific coronary disease undergoing rotational atherectomy and stent implantation. In the presence of extensive coronary artery calcification, FD-OCT affords enhanced stent visualisation and detection of malapposition, facilitating improved postdilation stent apposition and minimal luminal areas.

Trial Registration Number: NCT02065102.
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http://dx.doi.org/10.1136/openhrt-2014-000225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4692048PMC
December 2015

Systemic Atherosclerotic Inflammation Following Acute Myocardial Infarction: Myocardial Infarction Begets Myocardial Infarction.

J Am Heart Assoc 2015 Aug 27;4(9):e001956. Epub 2015 Aug 27.

Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (N.V.J., I.T., A.V.S., K.C., A.T.V., S.R.A., A.S., T.Y.H., A.J.M., S.P.L., W.A.J., N.G.U., N.L.M., K.A.F., M.R.D., D.E.N.) Clinical Research Imaging Centre, University of Edinburgh, United Kingdom (N.V.J., I.T., A.V.S., K.C., A.T.V., S.R.A., W.A.J., N.G.U., N.L.M., A.M.F., E.R.B., K.A.F., M.R.D., D.E.N.) Edinburgh Heart Centre, Royal Infirmary of Edinburgh, United Kingdom (N.V.J., I.T., A.V.S., K.C., A.T.V., S.R.A., W.A.J., N.G.U., N.L.M., K.A.F., M.R.D., D.E.N.).

Background: Preclinical data suggest that an acute inflammatory response following myocardial infarction (MI) accelerates systemic atherosclerosis. Using combined positron emission and computed tomography, we investigated whether this phenomenon occurs in humans.

Methods And Results: Overall, 40 patients with MI and 40 with stable angina underwent thoracic 18F-fluorodeoxyglucose combined positron emission and computed tomography scan. Radiotracer uptake was measured in aortic atheroma and nonvascular tissue (paraspinal muscle). In 1003 patients enrolled in the Global Registry of Acute Coronary Events, we assessed whether infarct size predicted early (≤30 days) and late (>30 days) recurrent coronary events. Compared with patients with stable angina, patients with MI had higher aortic 18F-fluorodeoxyglucose uptake (tissue-to-background ratio 2.15±0.30 versus 1.84±0.18, P<0.0001) and plasma C-reactive protein concentrations (6.50 [2.00 to 12.75] versus 2.00 [0.50 to 4.00] mg/dL, P=0.0005) despite having similar aortic (P=0.12) and less coronary (P=0.006) atherosclerotic burden and similar paraspinal muscular 18F-fluorodeoxyglucose uptake (P=0.52). Patients with ST-segment elevation MI had larger infarcts (peak plasma troponin 32 300 [10 200 to >50 000] versus 3800 [1000 to 9200] ng/L, P<0.0001) and greater aortic 18F-fluorodeoxyglucose uptake (2.24±0.32 versus 2.02±0.21, P=0.03) than those with non-ST-segment elevation MI. Peak plasma troponin concentrations correlated with aortic 18F-fluorodeoxyglucose uptake (r=0.43, P=0.01) and, on multivariate analysis, independently predicted early (tertile 3 versus tertile 1: relative risk 4.40 [95% CI 1.90 to 10.19], P=0.001), but not late, recurrent MI.

Conclusions: The presence and extent of MI is associated with increased aortic atherosclerotic inflammation and early recurrent MI. This finding supports the hypothesis that acute MI exacerbates systemic atherosclerotic inflammation and remote plaque destabilization: MI begets MI.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01749254.
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http://dx.doi.org/10.1161/JAHA.115.001956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599491PMC
August 2015

Observer variability in the assessment of CT coronary angiography and coronary artery calcium score: substudy of the Scottish COmputed Tomography of the HEART (SCOT-HEART) trial.

Open Heart 2015;2(1):e000234. Epub 2015 May 19.

Clinical Research Imaging Centre, University of Edinburgh , Edinburgh , UK.

Introduction: Observer variability can influence the assessment of CT coronary angiography (CTCA) and the subsequent diagnosis of angina pectoris due to coronary heart disease.

Methods: We assessed 210 CTCAs from the Scottish COmputed Tomography of the HEART (SCOT-HEART) trial for intraobserver and interobserver variability. Calcium score, coronary angiography and image quality were evaluated. Coronary artery disease was defined as none (<10%), mild (10-49%), moderate (50-70%) and severe (>70%) luminal stenosis and classified as no (<10%), non-obstructive (10-70%) or obstructive (>70%) coronary artery disease. Post-CTCA diagnosis of angina pectoris due to coronary heart disease was classified as yes, probable, unlikely or no.

Results: Patients had a mean body mass index of 29 (28, 30) kg/m(2), heart rate of 58 (57, 60)/min and 62% were men. Intraobserver and interobserver agreements for the presence or absence of coronary artery disease were excellent (95% agreement, κ 0.884 (0.817 to 0.951) and good (91%, 0.791 (0.703 to 0.879)). Intraobserver and interobserver agreement for the presence or absence of angina pectoris due to coronary heart disease were excellent (93%, 0.842 (0.918 to 0.755) and good (86%, 0.701 (0.799 to 0.603)), respectively. Observer variability of calcium score was excellent for calcium scores below 1000. More segments were categorised as uninterpretable with 64-multidetector compared to 320-multidetector CTCA (10.1% vs 2.6%, p<0.001) but there was no difference in observer variability.

Conclusions: Multicentre multidetector CTCA has excellent agreement in patients under investigation for suspected angina due to coronary heart disease.

Trial Registration Number: NCT01149590.
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http://dx.doi.org/10.1136/openhrt-2014-000234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4442169PMC
May 2015

Efficacy of a device to narrow the coronary sinus in refractory angina.

N Engl J Med 2015 Feb;372(6):519-27

From Antwerp Cardiovascular Center, Ziekenhuis Netwerk Antwerpen Middelheim, Antwerp (S.V., N.M.), and Ziekenhuis Oost-Limburg Hospital, Genk (M.V.) - both in Belgium; Montreal Heart Institute, Montreal (E.M.J., S.D., J.-F.T.), Ottawa Heart Institute, Ottawa (M.L.), and Neovasc, Richmond, BC (M.S.) - all in Canada; Royal Infirmary of Edinburgh, Edinburgh (M.W.B., N.G.U.), Bradford Royal Infirmary, Bradford (P.S., S.L.), and Kings College Hospital (J.H.) and the National Heart and Lung Institute, Imperial College London, and National Institute for Health Research Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust (R.S.), London - all in the United Kingdom; Kristianstad Central Hospital, Kristianstad, Sweden (T.P.); University Medical Center Utrecht, Utrecht, the Netherlands (P.A.); Rigshospitalet, Copenhagen (T.E.); Cedars-Sinai Medical Center, Los Angeles (T.D.H.); John Ochsner Heart and Vascular Institute, University of Queensland-Ochsner Clinical School, New Orleans (C.J.W.); the Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, and the Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston - both in Massachusetts (E.R.E.); and Tel Aviv Medical Center, Tel Aviv University Medical School, Tel Aviv, Israel (S.B.).

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.).
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http://dx.doi.org/10.1056/NEJMoa1402556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647842PMC
February 2015

Transcatheter aortic valve implantation in the United Kingdom: temporal trends, predictors of outcome, and 6-year follow-up: a report from the UK Transcatheter Aortic Valve Implantation (TAVI) Registry, 2007 to 2012.

Circulation 2015 Mar 30;131(13):1181-90. Epub 2015 Jan 30.

From Queen Elizabeth Hospital, Birmingham, UK (P.F.L.); Royal Brompton and Harefield Hospital, London, UK (N.M., A.D.); James Cook University Hospital, Middlesbrough, UK (M.A.d.B.); Leeds Teaching Hospitals, Leeds, UK (D.J.B.); Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust, London, UK (W.B.); Kings College Hospital, London, UK (P.A.M., O.W.); National Institute for Cardiovascular Outcome Research, London, UK (D.C., D.M.); Sussex Cardiac Centre, Brighton and Sussex University Hospitals, Brighton, UK (D.H.-S., U.T.); St. Thomas's Hospital, London, UK (C.P.Y.); Leicester Cardiovascular Biomedical Research Unit, University Hospital NHS Trust, Leicester, UK (J.K., T.S.); Royal Infirmary of Edinburgh, Edinburgh, UK (N.G.U.); West Midlands Public Health England Centre, Birmingham, UK (J.H.); and University Hospital Southampton, Southampton, UK (H.G.).

Background: We assessed trends in the performance of transcatheter aortic valve implantation in the United Kingdom from the first case in 2007 to the end of 2012. We analyzed changes in case mix, complications, outcomes to 6 years, and predictors of mortality.

Methods And Results: Annual cohorts were examined. Mortality outcomes were analyzed in the 92% of patients from England and Wales for whom independent mortality tracking was available. A total of 3980 transcatheter aortic valve implantation procedures were performed. In successive years, there was an increase in frequency of impaired left ventricular function, but there was no change in Logistic EuroSCORE. Overall 30-day mortality was 6.3%; it was highest in the first cohort (2007-2008), after which there were no further significant changes. One-year survival was 81.7%, falling to 37.3% at 6 years. Discharge by day 5 rose from 16.7% in 2007 and 2008 to 28% in 2012. The only multivariate preprocedural predictor of 30-day mortality was Logistic EuroSCORE ≥40. During long-term follow-up, multivariate predictors of mortality were preprocedural atrial fibrillation, chronic obstructive pulmonary disease, creatinine >200 μmol/L, diabetes mellitus, and coronary artery disease. The strongest independent procedural predictor of long-term mortality was periprocedural stroke (hazard ratio=3.00; P<0.0001). Nonfemoral access and postprocedural aortic regurgitation were also significant predictors of adverse outcome.

Conclusions: We analyzed transcatheter aortic valve implantation in an entire country, with follow-up over 6 years. Although clinical profiles of enrolled patients remained unchanged, longer-term outcomes improved, and patients were discharged earlier. Periprocedural stroke, nonfemoral access, and postprocedural aortic regurgitation are predictors of adverse outcome, along with intrinsic patient risk factors.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.114.013947DOI Listing
March 2015

Image quality with single-heartbeat 320-multidetector computed tomographic coronary angiography.

J Comput Assist Tomogr 2014 May-Jun;38(3):444-50

From the *University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, †Clinical Research Imaging Centre, University of Edinburgh; and ‡Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.

Objective: We aimed to establish the feasibility of single-heartbeat 320-multidetector computed tomographic coronary angiography (CTCA) and assess variables affecting image quality.

Methods: Consecutive patients (n = 249, 38% male) underwent CTCA. Two observers assessed image quality using a 4-point scale (1, excellent; 4, poor).

Results: Mean heart rate was 60 beats per minute (95% confidence interval, 59-62); body mass index, 29 kg/m (28-30); and dose-length product, 283 mGy·cm (266-301). During scanning, 133 (51%) received sublingual glyceryl trinitrate (GTN), 9 (4%) had ectopics, and 12 (5%) had atrial fibrillation. Diagnostic image quality was obtained in 99% with mean image quality of 1.4 (1.3, 1.5). Age, sex, atrial fibrillation, ectopics, diabetes mellitus (12%), and obstructive disease were not related to image quality. A lower heart rate and GTN were associated with improved image quality (P ≤ 0.001).

Conclusions: Optimal image quality in single-heartbeat 320-multidetector CTCA is achievable in 99% of unselected patients. Image quality is improved by lower heart rate and GTN.
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http://dx.doi.org/10.1097/RCT.0000000000000044DOI Listing
June 2014

18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial.

Lancet 2014 Feb 11;383(9918):705-13. Epub 2013 Nov 11.

Centre for Cardiovascular Science, Clinical Research Imaging Centre, and Division of Pathology, University of Edinburgh, Edinburgh, UK.

Background: The use of non-invasive imaging to identify ruptured or high-risk coronary atherosclerotic plaques would represent a major clinical advance for prevention and treatment of coronary artery disease. We used combined PET and CT to identify ruptured and high-risk atherosclerotic plaques using the radioactive tracers (18)F-sodium fluoride ((18)F-NaF) and (18)F-fluorodeoxyglucose ((18)F-FDG).

Methods: In this prospective clinical trial, patients with myocardial infarction (n=40) and stable angina (n=40) underwent (18)F-NaF and (18)F-FDG PET-CT, and invasive coronary angiography. (18)F-NaF uptake was compared with histology in carotid endarterectomy specimens from patients with symptomatic carotid disease, and with intravascular ultrasound in patients with stable angina. The primary endpoint was the comparison of (18)F-fluoride tissue-to-background ratios of culprit and non-culprit coronary plaques of patients with acute myocardial infarction.

Findings: In 37 (93%) patients with myocardial infarction, the highest coronary (18)F-NaF uptake was seen in the culprit plaque (median maximum tissue-to-background ratio: culprit 1·66 [IQR 1·40-2·25] vs highest non-culprit 1·24 [1·06-1·38], p<0·0001). By contrast, coronary (18)F-FDG uptake was commonly obscured by myocardial uptake and where discernible, there were no differences between culprit and non-culprit plaques (1·71 [1·40-2·13] vs 1·58 [1·28-2·01], p=0·34). Marked (18)F-NaF uptake occurred at the site of all carotid plaque ruptures and was associated with histological evidence of active calcification, macrophage infiltration, apoptosis, and necrosis. 18 (45%) patients with stable angina had plaques with focal (18)F-NaF uptake (maximum tissue-to-background ratio 1·90 [IQR 1·61-2·17]) that were associated with more high-risk features on intravascular ultrasound than those without uptake: positive remodelling (remodelling index 1·12 [1·09-1·19] vs 1·01 [0·94-1·06]; p=0·0004), microcalcification (73% vs 21%, p=0·002), and necrotic core (25% [21-29] vs 18% [14-22], p=0·001).

Interpretation: (18)F-NaF PET-CT is the first non-invasive imaging method to identify and localise ruptured and high-risk coronary plaque. Future studies are needed to establish whether this method can improve the management and treatment of patients with coronary artery disease.

Funding: Chief Scientist Office Scotland and British Heart Foundation.
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http://dx.doi.org/10.1016/S0140-6736(13)61754-7DOI Listing
February 2014

Questing for circadian dependence in ST-segment-elevation acute myocardial infarction: a multicentric and multiethnic study.

Circ Res 2013 May;112(10):e110-4

San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy.

Rationale: Four monocentric studies reported that circadian rhythms can affect left ventricular infarct size after ST-segment-elevation acute myocardial infarction (STEMI).

Objective: To further validate the circadian dependence of infarct size after STEMI in a multicentric and multiethnic population.

Methods And Results: We analyzed a prospective cohort of subjects with first STEMI from the First Acute Myocardial Infarction study that enrolled 1099 patients (ischemic time <6 hours) in Italy, Scotland, and China. We confirmed a circadian variation of STEMI incidence with an increased morning incidence (from 6:00 am till noon). We investigated the presence of circadian dependence of infarct size plotting the peak creatine kinase against time onset of ischemia. In addition, we studied the patients from the 3 countries separately, including 624 Italians; all patients were treated with percutaneous coronary intervention. We adopted several levels of analysis with different inclusion criteria consistent with previous studies. In all the analyses, we did not find a clear-cut circadian dependence of infarct size after STEMI.

Conclusions: Although the circadian dependence of infarct size supported by previous studies poses an intriguing hypothesis, we were unable to converge toward their conclusions in a multicentric and multiethnic setting. Parameters that vary as a function of latitude could potentially obscure the circadian variations observed in monocentric studies. We believe that, to assess whether circadian rhythms can affect the infarct size, future study design should not only include larger samples but also aim to untangle the molecular time-dynamic mechanisms underlying such a relation.
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http://dx.doi.org/10.1161/CIRCRESAHA.112.300778DOI Listing
May 2013

A low-dose comprehensive cardiac CT protocol assessing anatomy, function, perfusion, and viability.

J Cardiovasc Comput Tomogr 2013 Jan-Feb;7(1):69-72. Epub 2012 Dec 4.

University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, EH16SU4 UK.

Radiation exposure in cardiac imaging is a major healthcare concern and low-dose cardiac imaging has important implications for patients. We describe the application of a low-dose comprehensive cardiac computed tomography protocol that assesses anatomy, function, perfusion and viability with correlations to invasive coronary angiography and magnetic resonance imaging.
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http://dx.doi.org/10.1016/j.jcct.2012.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605584PMC
August 2013

Role of multidetector computed tomography in the diagnosis and management of patients attending the rapid access chest pain clinic, The Scottish computed tomography of the heart (SCOT-HEART) trial: study protocol for randomized controlled trial.

Trials 2012 Oct 4;13:184. Epub 2012 Oct 4.

University of Edinburgh/BHF Centre for Cardiovascular Science, Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 SU4, UK.

Background: Rapid access chest pain clinics have facilitated the early diagnosis and treatment of patients with coronary heart disease and angina. Despite this important service provision, coronary heart disease continues to be under-diagnosed and many patients are left untreated and at risk. Recent advances in imaging technology have now led to the widespread use of noninvasive computed tomography, which can be used to measure coronary artery calcium scores and perform coronary angiography in one examination. However, this technology has not been robustly evaluated in its application to the clinic.

Methods/design: The SCOT-HEART study is an open parallel group prospective multicentre randomized controlled trial of 4,138 patients attending the rapid access chest pain clinic for evaluation of suspected cardiac chest pain. Following clinical consultation, participants will be approached and randomized 1:1 to receive standard care or standard care plus ≥64-multidetector computed tomography coronary angiography and coronary calcium score. Randomization will be conducted using a web-based system to ensure allocation concealment and will incorporate minimization. The primary endpoint of the study will be the proportion of patients diagnosed with angina pectoris secondary to coronary heart disease at 6 weeks. Secondary endpoints will include the assessment of subsequent symptoms, diagnosis, investigation and treatment. In addition, long-term health outcomes, safety endpoints, such as radiation dose, and health economic endpoints will be assessed. Assuming a clinic rate of 27.0% for the diagnosis of angina pectoris due to coronary heart disease, we will need to recruit 2,069 patients per group to detect an absolute increase of 4.0% in the rate of diagnosis at 80% power and a two-sided P value of 0.05. The SCOT-HEART study is currently recruiting participants and expects to report in 2014.

Discussion: This is the first study to look at the implementation of computed tomography in the patient care pathway that is outcome focused. This study will have major implications for the management of patients with cardiovascular disease.

Trial Registration: ClinicalTrials.gov Identifier: NCT01149590.
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http://dx.doi.org/10.1186/1745-6215-13-184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667058PMC
October 2012

Identification and predictive value of interleukin-6+ interleukin-10+ and interleukin-6- interleukin-10+ cytokine patterns in ST-elevation acute myocardial infarction.

Circ Res 2012 Oct 29;111(10):1336-48. Epub 2012 Aug 29.

Clinical Cardiovascular Biology Centre.

Rationale: At the onset of ST-elevation acute myocardial infarction (STEMI), patients can present with very high circulating interleukin-6 (IL-6(+)) levels or very low-IL-6(-) levels.

Objective: We compared these 2 groups of patients to understand whether it is possible to define specific STEMI phenotypes associated with outcome based on the cytokine response.

Methods And Results: We compared 109 patients with STEMI in the top IL-6 level (median, 15.6 pg/mL; IL-6(+) STEMI) with 96 in the bottom IL-6 level (median, 1.7 pg/mL; IL-6(-) STEMI) and 103 matched controls extracted from the multiethnic First Acute Myocardial Infarction study. We found minimal clinical differences between IL-6(+) STEMI and IL-6(-) STEMI. We assessed the inflammatory profiles of the 2 STEMI groups and the controls by measuring 18 cytokines in blood samples. We exploited clustering analysis algorithms to infer the functional modules of interacting cytokines. IL-6(+) STEMI patients were characterized by the activation of 2 modules of interacting signals comprising IL-10, IL-8, macrophage inflammatory protein-1α, and C-reactive protein, and monocyte chemoattractant protein-1, macrophage inflammatory protein-1β, and monokine induced by interferon-γ. IL-10 was increased both in IL-6(+) STEMI and IL-6(-) STEMI patients compared with controls. IL-6(+)IL-10(+) STEMI patients had an increased risk of systolic dysfunction at discharge and an increased risk of death at 6 months in comparison with IL-6(-)IL-10(+) STEMI patients. We combined IL-10 and monokine induced by interferon-γ (derived from the 2 identified cytokine modules) with IL-6 in a formula yielding a risk index that outperformed any single cytokine in the prediction of systolic dysfunction and death.

Conclusions: We have identified a characteristic circulating inflammatory cytokine pattern in STEMI patients, which is not related to the extent of myocardial damage. The simultaneous elevation of IL-6 and IL-10 levels distinguishes STEMI patients with worse clinical outcomes from other STEMI patients. These observations could have potential implications for risk-oriented patient stratification and immune-modulating therapies.
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http://dx.doi.org/10.1161/CIRCRESAHA.111.262477DOI Listing
October 2012

High-sensitivity C-reactive protein is within normal levels at the very onset of first ST-segment elevation acute myocardial infarction in 41% of cases: a multiethnic case-control study.

J Am Coll Cardiol 2011 Dec;58(25):2654-61

Università Vita-Salute San Raffaele, Istituto Scientifico San Raffaele, Milan, Italy.

Objectives: This study sought to assess the prevalence of normal levels of high sensitivity C-reactive protein (hsCRP) at the very onset of ST-segment elevation myocardial infarction (STEMI).

Background: Levels of hsCRP ≥2 mg/l identify individuals who benefit from lipid lowering and possibly anti-inflammatory agents, but how many patients develop infarction in spite of hsCRP levels <2 mg/l and thus would be ineligible for these treatments?

Methods: We studied 887 patients with unequivocally documented STEMI as the first manifestation of coronary disease and 887 matched control subjects from urban areas of Italy, Scotland, and China. Blood samples were obtained before reperfusion strategies <6 h from symptoms onset in order to limit acute event-related increases.

Results: hsCRP values were similar in samples obtained <2 h, 2 to 4 h, and 4 to 6 h from symptoms onset in all ethnic groups, consistent with the delayed hsCRP elevation after myocardial necrosis and thus indicative of pre-infarction levels. Median hsCRP values were significantly higher in patients than in control subjects: 2.49 (interquartile range [IQR]: 1.18 to 5.55) mg/l versus 1.32 (IQR: 0.58 to 3.10) mg/l (p < 0.0001), which is consistent with previous findings. However, 41% of patients had hsCRP levels <2 mg/l and conversely, 37% of control subjects had values ≥2 mg/l.

Conclusions: The measurement of hsCRP, with a 2 mg/l cutoff, would not have predicted 41% of unequivocally documented STEMIs in 3 ethnic groups without evidence of previous coronary disease, thus indicating both its limitations as an individual prognostic marker and as an indicator of a generalized inflammatory pathogenetic component of STEMI. New specific prognostic and therapeutic approaches should be found for such a large fraction of patients at risk.
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http://dx.doi.org/10.1016/j.jacc.2011.08.055DOI Listing
December 2011

Vasomotor and fibrinolytic responses to kinin receptor agonists in the atherosclerotic human lower limb.

Heart Vessels 2012 Mar 11;27(2):179-85. Epub 2011 Mar 11.

Centre for Cardiovascular Science, University of Edinburgh, Room F2339, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 5SB, UK.

Upregulation of vascular B(1) kinin receptor expression has been reported in human atheroma, but its role remains unclear. We examined vasomotor and fibrinolytic responses to selective B(1) and B(2) kinin receptor agonism in the human femoral circulation and correlated responses with femoral arterial plaque load. Femoral arterial cross-sectional area, blood flow and plaque volume were determined using intravascular ultrasound and Doppler during selective arterial infusion of Lys-des-Arg(9)-bradykinin (B(1) agonist), bradykinin (B(2) agonist) and sodium nitroprusside in eleven patients undergoing diagnostic coronary angiography. Net release of tissue plasminogen activator was determined across the femoral vascular bed. Mean femoral arterial plaque load was 8.1 (±0.9) mm(3)/mm of vessel. Bradykinin and sodium nitroprusside caused dose-dependent increases in femoral blood flow (p < 0.05 and p < 0.005, respectively). Bradykinin caused a dose-dependent increase in net tissue plasminogen activator release (p < 0.05), which was augmented by angiotensin-converting enzyme inhibition (p < 0.05). There were no correlations between plaque load and bradykinin-mediated vasodilation or tissue plasminogen activator release. Lys-des-Arg(9)-bradykinin had no effect on blood flow or tissue plasminogen activator release. The vasomotor and fibrinolytic actions of bradykinin in the femoral circulation are mediated solely by the B(2) kinin receptor, irrespective of the presence of atheroma. In keeping with previous data, bradykinin-mediated tissue plasminogen activator release was augmented in the presence of angiotensin-converting enzyme inhibition consistent with its putative vascular protective effect.
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http://dx.doi.org/10.1007/s00380-011-0124-6DOI Listing
March 2012

Revascularization for renal-artery stenosis.

N Engl J Med 2010 Feb;362(8):763; author reply 763-4

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http://dx.doi.org/10.1056/NEJMpv1002647DOI Listing
February 2010

Non-invasive assessment of coronary artery bypass graft patency using 16-slice computed tomography angiography.

J Cardiothorac Surg 2007 Jun 5;2:27. Epub 2007 Jun 5.

Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.

Background: Invasive coronary angiography is the gold standard means of imaging bypass vessels and carries a small but potentially serious risk of local vascular complications, including myocardial infarction, stroke and death. We evaluated computed tomography as a non-invasive means of assessing graft patency.

Methods: Fifty patients with previous coronary artery bypass surgery who were listed for diagnostic coronary angiography underwent contrast enhanced computed tomography angiography using a 16-slice computed tomography scanner. Images were retrospectively gated to the electrocardiogram and two dimensional axial, multiplanar and three dimensional reconstructions acquired. Sensitivity, specificity, positive and negative predictive value, accuracy and level of agreement for detection of graft patency by multidetector computed tomography.

Results: A total of 116 grafts were suitable for analysis. The specificity of CT for the detection of graft patency was 100%, with a sensitivity of 92.8%, positive predictive value 100%, negative predictive value 85.8% and an accuracy of 94.8%. The kappa value of agreement between the two means of measuring graft patency was 0.9. Mean radiation dose was 9.0 +/- 7.2 mSv for coronary angiography and 18.5 +/- 4 mSv for computed tomography. Pooled analysis of eight studies, incorporating 932 grafts, confirmed a 97% accuracy for the detection of graft patency by multidetector computed tomography.

Conclusion: Computed tomography is an accurate, rapid and non-invasive method of assessing coronary artery bypass graft patency. However, this was achieved at the expense of an increase in radiation dose.
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http://dx.doi.org/10.1186/1749-8090-2-27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1894797PMC
June 2007

The effect of intensive lipid lowering on coronary atheroma and clinical outcome.

Heart 2007 Feb 11;93(2):149-51. Epub 2006 Oct 11.

The association between raised plasma cholesterol and cardiovascular risk is well established, with consistent evidence associating LDL-cholesterol reduction with a reduction in primary and secondary cardiovascular events. It is believed that intensive lipid lowering may improve clinical outcomes further by acting to stabilise plaque and preventing plaque progression, ultimately reducing plaque vulnerability. However, it remains uncertain whether a continued clinical benefit occurs with intensive lipid lowering or if there is a threshold level below which no further benefit occurs.
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http://dx.doi.org/10.1136/hrt.2006.105676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1861387PMC
February 2007

Rescue angioplasty after failed thrombolytic therapy for acute myocardial infarction.

N Engl J Med 2005 Dec;353(26):2758-68

Department of Cardiology, University Hospitals of Leicester, Leicester, United Kingdom.

Background: The appropriate treatment for patients in whom reperfusion fails to occur after thrombolytic therapy for acute myocardial infarction remains unclear. There are few data comparing emergency percutaneous coronary intervention (rescue PCI) with conservative care in such patients, and none comparing rescue PCI with repeated thrombolysis.

Methods: We conducted a multicenter trial in the United Kingdom involving 427 patients with ST-segment elevation myocardial infarction in whom reperfusion failed to occur (less than 50 percent ST-segment resolution) within 90 minutes after thrombolytic treatment. The patients were randomly assigned to repeated thrombolysis (142 patients), conservative treatment (141 patients), or rescue PCI (144 patients). The primary end point was a composite of death, reinfarction, stroke, or severe heart failure within six months.

Results: The rate of event-free survival among patients treated with rescue PCI was 84.6 percent, as compared with 70.1 percent among those receiving conservative therapy and 68.7 percent among those undergoing repeated thrombolysis (overall P=0.004). The adjusted hazard ratio for the occurrence of the primary end point for repeated thrombolysis versus conservative therapy was 1.09 (95 percent confidence interval, 0.71 to 1.67; P=0.69), as compared with adjusted hazard ratios of 0.43 (95 percent confidence interval, 0.26 to 0.72; P=0.001) for rescue PCI versus repeated thrombolysis and 0.47 (95 percent confidence interval, 0.28 to 0.79; P=0.004) for rescue PCI versus conservative therapy. There were no significant differences in mortality from all causes. Nonfatal bleeding, mostly at the sheath-insertion site, was more common with rescue PCI. At six months, 86.2 percent of the rescue-PCI group were free from revascularization, as compared with 77.6 percent of the conservative-therapy group and 74.4 percent of the repeated-thrombolysis group (overall P=0.05).

Conclusions: Event-free survival after failed thrombolytic therapy was significantly higher with rescue PCI than with repeated thrombolysis or conservative treatment. Rescue PCI should be considered for patients in whom reperfusion fails to occur after thrombolytic therapy.
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http://dx.doi.org/10.1056/NEJMoa050849DOI Listing
December 2005

Intravascular ultrasound: defining plaque regression.

Hosp Med 2005 Jan;66(1):27-31

Department of Cardiology, New Royal Infirmary, Edinburgh EH16 4SA.

Intravascular ultrasound allows accurate assessment of the arterial vessel, including vessel luminal diameter and assessment of vessel disease in terms of plaque morphology, plaque volume and extent of calcification. Recently published trials highlight the role of intravascular ultrasound in monitoring disease progression in a clinical setting.
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http://dx.doi.org/10.12968/hmed.2005.66.1.17532DOI Listing
January 2005

Non-invasive measures of pulse wave velocity correlate with coronary arterial plaque load in humans.

J Hypertens 2004 Feb;22(2):363-8

Department of Cardiology, Western General Hospital, Edinburgh, UK.

Objective: Arterial stiffness is an emerging major risk factor for cardiovascular morbidity and mortality. The aim of the present study was to assess if coronary artery plaque load correlates with non-invasive measures of arterial stiffness.

Design: Prospective investigational study.

Setting: Tertiary university hospital centre.

Patients: Patients undergoing elective diagnostic coronary angiography.

Interventions And Main Outcome Measures: Coronary artery plaque burden was assessed using a 30 MHz intravascular ultrasound catheter during an automated pullback. Proximal coronary artery plaque volume was determined using a validated edge-detection algorithm following three-dimensional computerized reconstruction. Central arterial stiffness was assessed in each patient using applanation tonometry to radial, carotid and femoral pulses, with derivation of aortic pressure augmentation and pulse wave velocity using pulse wave analysis.

Results: In 35 patients (61 +/- 2 years), proximal coronary arterial plaque volume was 5.9 +/- 0.6 mm3/mm of vessel. Plaque volume correlated positively with carotid-radial pulse wave velocity (r = 0.47, P = 0.008) and appeared to correlate with carotid-femoral pulse wave velocity (r = 0.34, P = 0.07). Aortic augmentation (r = 0.24, P = 0.16), augmentation index (r = 0.3, P = 0.08), and pulse pressure (r = 0.22, P = 0.2) did not correlate significantly with proximal coronary artery plaque volume.

Conclusions: Non-invasive measures of carotid-radial pulse wave velocity correlate with the extent of coronary artery plaque volume and may be a useful non-invasive surrogate marker for the extent of coronary atherosclerosis. Our findings are consistent with the suggestion that central aortic stiffness may promote the development of coronary atherosclerosis and ischaemic heart disease.
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http://dx.doi.org/10.1097/00004872-200402000-00021DOI Listing
February 2004

Classification of arterial plaque by spectral analysis in remodelled human atherosclerotic coronary arteries.

Ultrasound Med Biol 2004 Feb;30(2):155-9

Department of Cardiology, Lothian University Hospitals NHS Trust, Edinburgh, UK.

We aimed to characterise and to identify the predominant plaque type in vivo using unprocessed radiofrequency (RF) intravascular ultrasound (US) backscatter, in remodelled segments of human atherosclerotic coronary arteries. A total of 16 remodelled segments were identified using a 30-MHz intravascular ultrasound (IVUS) scanner in vivo. Of these, 9 segments were classified as positively remodelled (>1.05 of the total vessel area in comparison with the proximal and distal reference segments) and 7 as negatively remodelled (<0.95 of reference segment area). Spectral parameters (maximum power, mean power, minimum power and power at 30 MHz) were determined and plaque type was defined as mixed fibrous, calcified or lipid-rich. Positively remodelled segments had a larger total vessel area (16.5 +/- 1.1 mm2 vs. 8.7 +/- 0.9 mm2, p<0.01) and plaque area (7.3 +/- 1.1 mm2 vs. 4.4 +/- 0.8 mm2, p=0.05) than negatively remodelled segments. Both positively and negatively remodelled segments had a greater percentage of fibrous plaque (p<0.01) than calcified or lipid-rich plaque. Comparing positively and negatively remodelled segments, there was no significant difference between the proportion of fibrous, calcified or lipid-rich plaque. We have been able to characterise and to identify plaque composition in vivo in human atherosclerotic coronary arteries. Our data suggest that remodelled segments are predominantly composed of fibrous plaque, as identified by RF analysis, although plaque composition is similar, irrespective of the remodelling type.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2003.10.011DOI Listing
February 2004

Influence of differential vascular remodeling on the coronary vasomotor response.

Cardiovasc Res 2003 Aug;59(2):520-6

Department of Cardiology, Royal infirmary, 51 Little France Crescent, Little France, Edinburgh EH16 4SA, UK.

Objectives: Arterial remodeling may increase or decrease the luminal encroachment of atherosclerotic plaques in the coronary circulation. However, the factors determining the nature and consequences of the remodeling process remain poorly characterized. The study aims were to assess whether the pattern of vascular remodeling influences the physical and vasomotor responses of the coronary arteries in vivo in man.

Methods: Coronary vessel area, distensibility and stiffness were determined in positively, negatively and non-remodeled arterial segments using intravascular ultrasound and Doppler flow measurement. Epicardial vasomotor responses were determined following intracoronary boluses of acetylcholine (10(-6) and 10(-4) M), adenosine (24-30 microg) and nitroglycerin (200 microg).

Results: Fifty-six coronary arterial segments were studied in 25 patients. In comparison to non- and positively remodeled segments, negatively remodeled segments had a higher stiffness index (67+/-16 vs. 33+/-5 and 38+/-8, respectively; P<0.02) and appeared to have lower compliance and distensibility (0.66+/-0.17 vs. 1.65+/-0.54 and 0.94+/-0.18/mmHg; P=NS). Non-remodeled segments had a greater change in vessel area with 10(-6) M acetylcholine (4.9+/-0.8%), compared to positively and negatively remodeled segments (0.6+/-1.8% and -4.9+/-1.8%, respectively, P<0.05). A significant degree of preservation of vasodilatation to 10(-6) M acetylcholine was evident in positively remodeled compared with negatively remodeled segments (P<0.05). Nitroglycerin caused greater vasodilatation in non-remodeled segments (7.2+/-3.8%) than either positively or negatively remodeled segments (4.7+/-0.9 and 3.7+/-0.6%, respectively, P<0.05).

Conclusions: Vascular remodeling is an important and major determinant of local epicardial vasomotor responses. Both structural and functional abnormalities are associated with negative remodeling that may contribute to the adverse effects of such lesions.
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http://dx.doi.org/10.1016/s0008-6363(03)00396-1DOI Listing
August 2003

Predictors and outcomes of stent thrombosis: an intravascular ultrasound registry.

Eur Heart J 2002 Jan;23(2):124-32

Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, U.S.A.

Aims: To investigate whether intravascular ultrasound provides additional information regarding the prediction of stent thrombosis, a retrospective multicentre registry was designed to enrol patients with stent thrombosis following stent deployment under ultrasound guidance.

Methods And Results: A total of 53 patients were enrolled (mean age 61+/-9 years) with stable angina (43%), unstable angina (36%), and post-infarct angina (21%) who underwent intracoronary stenting. The majority had balloon angioplasty alone prior to stenting (94%) with 6% also undergoing rotational atherectomy. The indication for stenting was elective (53%), suboptimal result (32%) and bailout (15%). There were 1.6+/-0.8 stents/artery with 87% undergoing high-pressure dilatation (> or =14 atmospheres). The minimum stent area was 7.7+/-2.8 mm(2)with a mean stent expansion of 81.5+/-21.9%. Overall, 94% of cases demonstrated one abnormal ultrasound finding (stent under-expansion, malapposition, inflow/outflow disease, dissection, or thrombus). Angiography demonstrated an abnormality in only 32% of cases (chi-square=30.0, P<0.001). Stent thrombosis occurred at 132+/-125 h after deployment. Myocardial infarction occurred in 67% and there was an overall mortality of 15%.

Conclusion: On comparison with angiography, the vast majority of stents associated with subsequent thrombosis have at least one abnormal feature by intravascular ultrasound at the time of stent deployment.
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http://dx.doi.org/10.1053/euhj.2001.2707DOI Listing
January 2002