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1.  Optical coherence tomography versus intravascular ultrasound to evaluate stent implantation in patients with calcific coronary artery disease 
Open Heart  2015;2(1):e000225.
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.
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.
In-stent luminal areas were smaller (minimum in-stent area 6.77±2.18 vs 7.19±2.62 mm2, 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 mm2, p<0.05) and reduced the extent of stent malapposition (19% vs 34%, p<0.005) when assessed by FD-OCT, but not IVUS.
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
PMCID: PMC4692048  PMID: 26719807
2.  Systemic Atherosclerotic Inflammation Following Acute Myocardial Infarction: Myocardial Infarction Begets Myocardial Infarction 
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.
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: Unique identifier: NCT01749254.
PMCID: PMC4599491  PMID: 26316523
18F-fluorodeoxyglucose positron emission and computed tomography; atherosclerosis; inflammation; vulnerable plaque
3.  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.
Observer variability can influence the assessment of CT coronary angiography (CTCA) and the subsequent diagnosis of angina pectoris due to coronary heart disease.
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.
Patients had a mean body mass index of 29 (28, 30) kg/m2, 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.
Multicentre multidetector CTCA has excellent agreement in patients under investigation for suspected angina due to coronary heart disease.
Trial registration number
PMCID: PMC4442169  PMID: 26019881
4.  A low-dose comprehensive cardiac CT protocol assessing anatomy, function, perfusion, and viability 
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.
PMCID: PMC3605584  PMID: 23333187
Myocardial perfusion; Computed tomography coronary angiography; Coronary heart disease; Radiation dose
5.  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 
Newby, David E | Williams, Michelle C | Flapan, Andrew D | Forbes, John F | Hargreaves, Allister D | Leslie, Stephen J | Lewis, Steff C | McKillop, Graham | McLean, Scott | Reid, John H | Sprat, James C | Uren, Neal G | van Beek, Edwin J | Boon, Nicholas A | Clark, Liz | Craig, Peter | Flather, Marcus D | McCormack, Chiara | Roditi, Giles | Timmis, Adam D | Krishan, Ashma | Donaldson, Gillian | Fotheringham, Marlene | Hall, Fiona J | Neary, Paul | Cram, Louisa | Perkins, Sarah | Taylor, Fiona | Eteiba, Hany | Rae, Alan P | Robb, Kate | Barrie, Dawn | Bissett, Kim | Dawson, Adelle | Dundas, Scot | Fogarty, Yvonne | Ramkumar, Prasad Guntur | Houston, Graeme J | Letham, Deborah | O’Neill, Linda | Pringle, Stuart D | Ritchie, Valerie | Sudarshan, Thiru | Weir-McCall, Jonathan | Cormack, Alistair | Findlay, Iain N | Hood, Stuart | Murphy, Clare | Peat, Eileen | Allen, Barbara | Baird, Andrew | Bertram, Danielle | Brian, David | Cowan, Amy | Cruden, Nicholas L | Dweck, Marc R | Flint, Laura | Fyfe, Samantha | Keanie, Collette | MacGillivray, Tom J | Maclachlan, David S | MacLeod, Margaret | Mirsadraee, Saeed | Morrison, Avril | Mills, Nicholas L | Minns, Fiona C | Phillips, Alyson | Queripel, Laura J | Weir, Nicholas W | Bett, Fiona | Divers, Frances | Fairley, Katie | Jacob, Ashok J | Keegan, Edith | White, Tricia | Gemmill, John | Henry, Margo | McGowan, James | Dinnel, Lorraine | Francis, C Mark | Sandeman, Dennis | Yerramasu, Ajay | Berry, Colin | Boylan, Heather | Brown, Ammani | Duffy, Karen | Frood, Alison | Johnstone, Janet | Lanaghan, Kirsten | MacDuff, Ross | MacLeod, Martin | McGlynn, Deborah | McMillan, Nigel | Murdoch, Laura | Noble, Colin | Paterson, Victoria | Steedman, Tracey | Tzemos, Nikolaos
Trials  2012;13:184.
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.
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.
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 Identifier: NCT01149590
PMCID: PMC3667058  PMID: 23036114
Computed tomography; Coronary heart disease; Rapid access chest pain clinic
6.  Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol 
Contrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease.
We designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance.
Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of acetylcysteine on renal function and identify an appropriate route for future dose response studies and in time randomized controlled trials.
Trial registration
Clinical NCT00558142; EudraCT: 2006-003509-18.
PMCID: PMC3293780  PMID: 22305183
Contrast-induced nephropathy; acetylcysteine; prevention; kidney; contrast media
7.  The effect of intensive lipid lowering on coronary atheroma and clinical outcome 
Heart  2006;93(2):149-151.
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.
PMCID: PMC1861387  PMID: 17035507
atherosclerosis; cholesterol; hydroxymethylglutaryl‐CoA reductase inhibitors; inflammation
8.  Non-invasive assessment of coronary artery bypass graft patency using 16-slice computed tomography angiography 
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.
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.
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.
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.
PMCID: PMC1894797  PMID: 17550615
9.  Myopericarditis in Churg-Strauss Syndrome 
Texas Heart Institute Journal  1991;18(2):127-131.
Churg-Strauss syndrome is a disseminated vasculitis with multisystem involvement, characterized by necrotizing arteritis, eosinophilic infiltration, and extravascular granuloma formation. In as many as 60% of all cases, the heart may be affected. We describe a 30-year-old man in whom pericarditis was followed by the development of a large pericardial effusion, with evidence of impaired right and left ventricular function. The patient had a 5-year history of asthma. Early therapy with high-dose prednisolone and azathioprine led to resolution of the pericardial effusion and prevented a further reduction in biventricular function. (Texas Heart Institute Journal 1991;18:127-31)
PMCID: PMC324980  PMID: 15227496
Churg-Strauss syndrome; echocardiography; eosinophilia; eosinophilic granuloma; myocarditis; pericarditis; vasculitis

Results 1-9 (9)