Inflammatory risk and cardiovascular events in patients without obstructive coronary artery disease: the ORFAN multicentre, longitudinal cohort study.

BACKGROUND: Coronary computed tomography angiography (CCTA) is the first line investigation for chest pain, and it is used to guide revascularisation. However, the widespread adoption of CCTA has revealed a large group of individuals without obstructive coronary artery disease (CAD), with unclear prognosis and management. Measurement of coronary inflammation from CCTA using the perivascular fat attenuation index (FAI) Score could enable cardiovascular risk prediction and guide the management of individuals without obstructive CAD. The Oxford Risk Factors And Non-invasive imaging (ORFAN) study aimed to evaluate the risk profile and event rates among patients undergoing CCTA as part of routine clinical care in the UK National Health Service (NHS); to test the hypothesis that coronary arterial inflammation drives cardiac mortality or major adverse cardiac events (MACE) in patients with or without CAD; and to externally validate the performance of the previously trained artificial intelligence (AI)-Risk prognostic algorithm and the related AI-Risk classification system in a UK population. METHODS: This multicentre, longitudinal cohort study included 40 091 consecutive patients undergoing clinically indicated CCTA in eight UK hospitals, who were followed up for MACE (ie, myocardial infarction, new onset heart failure, or cardiac death) for a median of 2·7 years (IQR 1·4-5·3). The prognostic value of FAI Score in the presence and absence of obstructive CAD was evaluated in 3393 consecutive patients from the two hospitals with the longest follow-up (7·7 years [6·4-9·1]). An AI-enhanced cardiac risk prediction algorithm, which integrates FAI Score, coronary plaque metrics, and clinical risk factors, was then evaluated in this population. FINDINGS: In the 2·7 year median follow-up period, patients without obstructive CAD (32 533 [81·1%] of 40 091) accounted for 2857 (66·3%) of the 4307 total MACE and 1118 (63·7%) of the 1754 total cardiac deaths in the whole of Cohort A. Increased FAI Score in all the three coronary arteries had an additive impact on the risk for cardiac mortality (hazard ratio [HR] 29·8 [95% CI 13·9-63·9], p<0·001) or MACE (12·6 [8·5-18·6], p<0·001) comparing three vessels with an FAI Score in the top versus bottom quartile for each artery. FAI Score in any coronary artery predicted cardiac mortality and MACE independently from cardiovascular risk factors and the presence or extent of CAD. The AI-Risk classification was positively associated with cardiac mortality (6·75 [5·17-8·82], p<0·001, for very high risk vs low or medium risk) and MACE (4·68 [3·93-5·57], p<0·001 for very high risk vs low or medium risk). Finally, the AI-Risk model was well calibrated against true events. INTERPRETATION: The FAI Score captures inflammatory risk beyond the current clinical risk stratification and CCTA interpretation, particularly among patients without obstructive CAD. The AI-Risk integrates this information in a prognostic algorithm, which could be used as an alternative to traditional risk factor-based risk calculators. FUNDING: British Heart Foundation, NHS-AI award, Innovate UK, National Institute for Health and Care Research, and the Oxford Biomedical Research Centre.

The Use and Efficacy of FFR-CT: Real-World Multicenter Audit of Clinical Data With Cost Analysis.

BACKGROUND: Fractional flow reserve-computed tomography (FFR-CT) is endorsed by UK and U.S. chest pain guidelines, but its clinical effectiveness and cost benefit in real-world practice are unknown. OBJECTIVES: The purpose of this study was to audit the use of FFR-CT in clinical practice against England's National Institute for Health and Care Excellence guidance and assess its diagnostic accuracy and cost. METHODS: A multicenter audit was undertaken covering the 3 years when FFR-CT was centrally funded in England. For coronary computed tomographic angiograms (CCTAs) submitted for FFR-CT analysis, centers provided data on symptoms, CCTA and FFR-CT findings, and subsequent management. Audit standards included using FFR-CT only in patients with stable chest pain and equivocal stenosis (50%-69%). Diagnostic accuracy was evaluated against invasive FFR, when performed. Follow-up for nonfatal myocardial infarction and all-cause mortality was undertaken. The cost of an FFR-CT strategy was compared to alternative stress imaging pathways using cost analysis modeling. RESULTS: A total of 2,298 CCTAs from 12 centers underwent FFR-CT analysis. Stable chest pain was the main symptom in 77%, and 40% had equivocal stenosis. Positive and negative predictive values of FFR-CT were 49% and 76%, respectively. A total of 46 events (2%) occurred over a mean follow-up period of 17 months; FFR-CT (cutoff: 0.80) was not predictive. The FFR-CT strategy costs £2,102 per patient compared with an average of £1,411 for stress imaging. CONCLUSIONS: In clinical practice, the National Institute for Health and Care Excellence criteria for using FFR-CT were met in three-fourths of patients for symptoms and 40% for stenosis. FFR-CT had a low positive predictive value, making its use potentially more expensive than conventional stress imaging strategies.

Opportunities and challenges of implementing computed tomography fractional flow reserve into clinical practice.

CT-derived fractional flow reserve (CT-FFR) uses computational fluid dynamics to derive non-invasive FFR to determine the haemodynamic significance of coronary artery lesions. Studies have demonstrated good diagnostic accuracy of CT-FFR and reassuring short-term clinical outcome data.As a prerequisite, high-quality CT coronary angiography (CTCA) images are required with good heart rate control and pre-treatment with glyceryl trinitrate, which would otherwise render CTCA as unsuitable for CT-FFR. CT-FFR can determine the functional significance of CAD lesions, and there are supportive data for its use in clinical decision-making. However, the downstream impact on myocardial ischaemic burden or viability cannot be obtained.Several challenges remain with implementation of CT-FFR, including interpretation, training, availability, resource utilisation and funding. Further research is required to determine which cases should be considered for clinical CT-FFR analysis, with additional practical guidance on how to implement this emerging technique in clinical practice. Furthermore, long-term prognostic data are required before widespread clinical implementation of CT-FFR can be recommended.While there are several potential opportunities for CT-FFR, at present there remain important systemic and technical limitations and challenges that need to be overcome prior to routine integration of CT-FFR into clinical practice.

Outcome Measures in UCLP: The Modified 5-Year-Olds'-Index-Development and Reliability.

OBJECTIVE: Can we reliably discriminate severity within the existing categories of the 5-Year-Olds' Index? DESIGN: Retrospective method comparison and development study. SETTING: School of Oral and Dental Science, University of Bristol. METHODS: Dental study models of 5-year-olds with unilateral cleft lip and palate (UCLP) were collected from the archives of 2 national cleft surveys (n = 351). One hundred randomly selected models were ranked to construct the modified 5-Year-Olds' Index and also scored using a visual analogue scale (VAS). Reliability testing was performed on 51 study models. Visual analogue scale scores were used to aid statistical analysis and investigate the reliability of a VAS for outcome measurement. The modified 5-Year-Olds' Index was then applied to 198 study models of 5-year-olds with UCLP. RESULTS: The modified 5-Year-Olds' Index showed excellent intra and interexaminer agreement (intraclass correlation > 0.94) and good discrimination of severity. When applied to the Cleft Care UK participants (n = 198), the modified 5-Year-Olds' Index showed good discrimination of severity within the better categories (groups 1-3) of the 5-Year-Olds' Index. Visual analogue Scale scores resulted in unacceptable variation between measurements. CONCLUSIONS: The new modified 5-Year-Olds' Index is a reliable method of assessing outcomes at 5 years of age and showed improved discriminatory power between the "better" outcome categories than the original 5-Year-Olds' Index. A VAS was found to be unsuitable for assessing outcome at 5 years of age for children with UCLP.

A cross-sectional survey of cardiovascular health and lifestyle habits of hospital staff in the UK: Do we look after ourselves?

Background A high prevalence of stress-related disorders is well known among healthcare professionals. We set out to assess the prevalence of cardiovascular risk factors and compliance with national dietary and physical activity recommendations in NHS staff in the UK with comparison between clinical and non-clinical staff, and national surveys. Design A multi-centre cross-sectional study. Methods A web-based questionnaire was developed to include anonymised data on demographics, job role, cardiovascular risk factors and diseases, dietary habits, physical activity and barriers towards healthy lifestyle. This was distributed to staff in four NHS hospitals via emails. Results A total of 1158 staff completed the survey (response rate 13%) with equal distribution between the clinical and non-clinical groups. Most staff were aged 26-60 years and 79% were women. Half of the staff were either overweight or obese (51%) with no difference between the groups ( P = 0.176), but there was a lower prevalence of cardiovascular risk factors compared to the general population. The survey revealed a low compliance (17%) with the recommended intake of five-a-day portions of fruit and vegetables, and that of moderate or vigorous physical activity (56%), with no difference between the clinical and non-clinical staff ( P = 0.6). However, more clinical staff were exceeding the alcohol recommendations ( P = 0.02). Lack of fitness facilities and managerial support, coupled with long working hours, were the main reported barriers to a healthy lifestyle. Conclusions In this survey of UK NHS staff, half were found to be overweight or obese with a lower prevalence of cardiovascular risk factors compared to the general population. There was a low compliance with the five-a-day fruit and vegetables recommendation and physical activity guidelines, with no difference between the clinical and non-clinical staff.

Prevalence of obstructive coronary artery disease and prognosis in patients with stable symptoms and a zero-coronary calcium score.

AIMS: CT calcium scoring (CTCS) and CT cardiac angiography (CTCA) are widely used in patients with stable chest pain to exclude significant coronary artery disease (CAD). We aimed to resolve uncertainty about the prevalence of obstructive coronary artery disease and long-term outcomes in patients with a zero-calcium score (ZCS). METHODS AND RESULTS: Consecutive patients with stable cardiac symptoms referred for CTCS or CTCS and CTCA from chest pain clinics to a tertiary cardiothoracic centre were prospectively enrolled. In those with a ZCS, the prevalence of obstructive CAD on CTCA was determined. A follow-up for all-cause mortality was obtained from the NHS tracer service. A total of 3914 patients underwent CTCS of whom 2730 (69.7%) also had a CTCA. Half of the patients were men (50.3%) with a mean age of 56.9 years. Among patients who had both procedures, a ZCS was present in 52.2%, with a negative predictive value of 99.5% for excluding ≥70% stenosis on CTCA. During a mean follow-up of 5.2 years, the annual event rate was 0.3% for those with ZCS compared with 1.2% for CS ≥1. The presence of non-calcified atheroma on CTCA in patients with ZCS did not affect the prognostic value (P = 0.98). CONCLUSION: In patients with stable symptoms and a ZCS, obstructive CAD is rare, and prognosis over the long-term is excellent, regardless of whether non-calcified atheroma is identified. A ZCS could reliably be used as a 'gatekeeper' in this patient cohort, obviating the need for further more expensive tests.

Imaging diagnoses and outcome in patients presenting for primary angioplasty but no obstructive coronary artery disease.

OBJECTIVE: A proportion of patients with suspected ST-elevation myocardial infarction (STEMI) presenting for primary percutaneous coronary intervention (PPCI) do not have obstructive coronary disease and other conditions may be responsible for their symptoms and ECG changes. In this study, we set out to determine the prevalence and aetiology of alternative diagnoses in a large PPCI cohort as determined with multimodality imaging and their outcome. METHODS: From 2009 to 2012, 5238 patients with suspected STEMI were referred for consideration of PPCI. Patients who underwent angiography but had no culprit artery for revascularisation and no previous history of coronary artery disease were included in the study. Troponin values, imaging findings and all-cause mortality were obtained from hospital and national databases. RESULTS: A total of 575 (13.0%) patients with a mean age of 58±15 years (69% men) fulfilled the inclusion criteria. A specific diagnosis based on imaging was made in 237 patients (41.2%) including cardiomyopathies (n=104, 18%), myopericarditis (n=48, 8.4%), myocardial infarction/other coronary abnormality (n=27, 4.9%) and severe valve disease (n=23, 4%). Pulmonary embolism and type A aortic dissection were identified in seven (1.2%) and four (0.7%) cases respectively. A total of 40 (7.0%) patients died over a mean follow-up of 42.6 months. CONCLUSIONS: A variety of cardiac and non-cardiac conditions are prevalent in patients presenting with suspected STEMI but culprit-free angiogram, some of which may have adverse outcomes. Further imaging of such patients could thus be useful to help in appropriate management and follow-up.

Cardiac allograft vasculopathy after heart transplantation: electrocardiographically gated cardiac CT angiography for assessment.

PURPOSE: To evaluate the diagnostic accuracy of cardiac computed tomographic (CT) angiography without the use of ß-blockers compared with that of invasive angiography for the detection of cardiac allograft vasculopathy (CAV) in heart transplant recipients. MATERIALS AND METHODS: The study was approved by the research ethics committee and informed consent was obtained. Heart transplant recipients (n = 138) scheduled for routine invasive angiography were prospectively enrolled to undergo CT to evaluate coronary artery calcification and retrospectively gated cardiac CT angiography with a 64-section scanner. The cardiac CT angiographic images were systematically analyzed for image quality. Degree of CAV was assessed by using a 15-coronary segments model. The area under the receiver operating characteristic curve, sensitivity, specificity, and negative and positive predictive values of cardiac CT angiography for detection of CAV with any degree of stenosis and greater than or equal to 50% stenosis were calculated. RESULTS: Coronary artery calcification was absent in 82 patients, five (6%) of whom had CAV with 50% or more stenosis. Interpretable image quality was obtained in 130 (96%) of the 136 patients who completed the study and 1900 (98%) of 1948 segments. At the patient level, cardiac CT angiography had an area under the receiver operating characteristic curve, sensitivity, specificity, and positive and negative predictive values of 0.880 (95% confidence interval: 0.819, 0.941), 98%, 78%, 77%, and 98%, respectively, for diagnosis of CAV with any degree of stenosis, but for CAV with 50% or more stenosis, the corresponding values were 0.942 (95% confidence interval: 0.885, 1.000), 96%, 93%, 72%, and 99%, respectively. None of the 61 patients with normal cardiac CT angiographic results had CAV on the basis of invasive angiographic images. CONCLUSION: The study results show that cardiac CT angiography compares favorably with invasive angiography in detecting CAV in heart transplant recipients and may be a preferable screening technique because of its noninvasive nature. The absence of coronary artery calcification alone is not reliable enough for excluding CAV.

Truly stentless autologous pericardial aortic valve replacement: an alternative to standard aortic valve replacement.

OBJECTIVE: The aim of this study was to determine the feasibility and durability of truly stentless aortic valve replacement using autologous pericardium sutured directly onto the aortic wall. METHODS: Eleven patients (mean age, 55.9 years) requiring aortic valve replacement were recruited. A circular piece of pericardium about 8 cm in diameter was harvested and treated in 0.6% glutaraldehyde for 10 minutes. The aortic valve was excised and, with the use of specially designed instruments (CardioMend LLC, Santa Barbara, Calif), the sinotubular junction was sized and the pericardium was tailored to the required size and shape and then sutured directly onto the aortic wall. The reconstructed valve was assessed directly and by echocardiography at the end of the operation; it was assessed by echocardiography and cardiac magnetic resonance imaging at 6 months and yearly. Computed tomographic scan of the aortic valve to assess for valve calcification was performed at last follow-up. RESULTS: Hospital mortality was 0%. Mean follow-up was 6.5 years (range, 5.3-7.5 years). Freedom from structural valve deterioration, thromboembolism, endocarditis and reoperation was 100%, 100%, 72.7%, and 63.6%, respectively. There were 4 reoperations at 4, 13, 15, and 46 months, 3 of them owing to endocarditis and 1 owing to technical failure noted at the time of surgery. The remaining 7 patients are alive and well with a mean New York Heart Association class of 1.3 and normally functioning aortic valves with no calcification. CONCLUSIONS: Truly stentless aortic valve replacement using autologous pericardium sutured directly onto the aortic wall is safe and feasible and has excellent durability up to 7.5 years with no calcification.

Measurement of endothelial function and its clinical utility for cardiovascular risk.

Over the past two decades, the central role of the endothelium in the initiation, progression, and clinical sequelae of atherosclerosis has been increasingly recognized. Assessment of the pathobiology of the endothelium and its ability to act as a potential therapeutic target remains an area of active research interest. Whilst endothelial function has been shown to be a marker for risk of cardiovascular events in high-risk groups, there remains considerable debate about the most appropriate way to assess this. We discuss the different clinical methods to assess endothelial function, focusing on flow-mediated dilatation (FMD) of the brachial artery, highlighting the importance of using a standardized methodology, as well as discussing the clinical limitations of using FMD in individuals.

Sarcoid heart disease.

To this day the aetiology of sarcoidosis continues to elude definition. Partially as a consequence of this, little in the way of new therapies has evolved. The enigma of this condition is that, unusually for a disease with the potential for devastating consequences, many patients show spontaneous resolution and recover. Cardiac involvement can affect individuals of any age, gender or race and has a predilection for the conduction system of the heart. Heart involvement can also cause a dilated cardiomyopathy with consequent progressive heart failure. The most common presentation of this systemic disease is with pulmonary infiltration, but many cases will be asymptomatic and are detected on routine chest radiography revealing lymphadenopathy. Current advances lie in the newer methods of imaging and diagnosing this unusual heart disease. This review describes the pathology and diagnosis of this condition and the newer imaging techniques that have developed for determining cardiac involvement.

Role of computed tomography in risk assessment for coronary heart disease.

Coronary heart disease is the most common cause of death in Western countries, with a rising incidence in developing countries. It is part of the spectrum of cardiovascular diseases that have common end points of myocardial infarction, stroke and death. As these end points often occur suddenly and often in those with no known disease, identification of those people at high risk is important. Besides the known traditional risk factors, direct imaging of the calcified plaque as a marker for atherosclerotic disease has been extensively studied with electron beam computed tomography and now with multislice computed tomography. This review discusses the role of computed tomography in assessment of cardiovascular risk in both people with or without symptoms.