Adam Timmis

99mTc : technetium-99m 201TI : thallium 201 ABCB1 : ATP-binding cassette sub-family B member 1 ABI : ankle-brachial index ACC : American College of Cardiology ACCF : American College of Cardiology Foundation ACCOMPLISH : Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension ACE : angiotensin converting enzyme ACIP : Asymptomatic Cardiac Ischaemia Pilot ACS : acute coronary syndrome ADA : American Diabetes Association ADP : adenosine diphosphate AHA : American Heart Association ARB : angiotensin II receptor antagonist ART : Arterial Revascularization Trial ASCOT : Anglo-Scandinavian Cardiac Outcomes Trial ASSERT : Asymptomatic atrial fibrillation and Stroke Evaluation in pacemaker patients and the atrial fibrillation Reduction atrial pacing Trial AV : atrioventricular BARI 2D : Bypass Angioplasty Revascularization Investigation 2 Diabetes BEAUTIFUL : Morbidity-Mortality Evaluation of the If Inhibitor Ivabradine in Patients With Coronary Artery Disease and Left Ventricular Dysfunction BIMA : bilateral internal mammary artery BMI : body mass index BMS : bare metal stent BNP : B-type natriuretic peptide BP : blood pressure b.p.m. : beats per minute CABG : coronary artery bypass graft CAD : coronary artery disease CAPRIE : Clopidogrel vs. Aspirin in Patients at Risk of Ischaemic Events CASS : Coronary Artery Surgery Study CCB : calcium channel blocker CCS : Canadian Cardiovascular Society CFR : coronary flow reserve CHARISMA : Clopidogrel for High Atherothrombotic Risk and Ischaemic Stabilization, Management and Avoidance CI : confidence interval CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease Epidemiology Collaboration CMR : cardiac magnetic resonance CORONARY : The CABG Off or On Pump Revascularization Study COURAGE : Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation COX-1 : cyclooxygenase-1 COX-2 : cyclooxygenase-2 CPG : Committee for Practice Guidelines CT : computed tomography CTA : computed tomography angiography CV : cardiovascular CVD : cardiovascular disease CXR : chest X-ray CYP2C19*2 : cytochrome P450 2C19 CYP3A : cytochrome P3A CYP3A4 : cytochrome P450 3A4 CYP450 : cytochrome P450 DANAMI : Danish trial in Acute Myocardial Infarction DAPT : dual antiplatelet therapy DBP : diastolic blood pressure DECOPI : Desobstruction Coronaire en Post-Infarctus DES : drug-eluting stents DHP : dihydropyridine DSE : dobutamine stress echocardiography EACTS : European Association for Cardiothoracic Surgery EECP : enhanced external counterpulsation EMA : European Medicines Agency EASD : European Association for the Study of Diabetes ECG : electrocardiogram Echo : echocardiogram ED : erectile dysfunction EF : ejection fraction ESC : European Society of Cardiology EXCEL : Evaluation of XIENCE PRIME or XIENCE V vs. Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization FAME : Fractional Flow Reserve vs. Angiography for Multivessel Evaluation FDA : Food & Drug Administration (USA) FFR : fractional flow reserve FREEDOM : Design of the Future Revascularization Evaluation in patients with Diabetes mellitus: Optimal management of Multivessel disease GFR : glomerular filtration rate HbA1c : glycated haemoglobin HDL : high density lipoprotein HDL-C : high density lipoprotein cholesterol HR : hazard ratio HRT : hormone replacement therapy hs-CRP : high-sensitivity C-reactive protein HU : Hounsfield units ICA : invasive coronary angiography IMA : internal mammary artery IONA : Impact Of Nicorandil in Angina ISCHEMIA : International Study of Comparative Health Effectiveness with Medical and Invasive Approaches IVUS : intravascular ultrasound JSAP : Japanese Stable Angina Pectoris KATP : ATP-sensitive potassium channels LAD : left anterior descending LBBB : left bundle branch block LIMA : Left internal mammary artery LDL : low density lipoprotein LDL-C : low density lipoprotein cholesterol LM : left main LMS : left main stem LV : left ventricular LVEF : left ventricular ejection fraction LVH : left ventricular hypertrophy MACE : major adverse cardiac events MASS : Medical, Angioplasty, or Surgery Study MDRD : Modification of Diet in Renal Disease MERLIN : Metabolic Efficiency with Ranolazine for Less Ischaemia in Non-ST-Elevation Acute Coronary Syndromes MERLIN-TIMI 36 : Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes: Thrombolysis In Myocardial Infarction MET : metabolic equivalents MI : myocardial infarction MICRO-HOPE : Microalbuminuria, cardiovascular and renal sub-study of the Heart Outcomes Prevention Evaluation study MPI : myocardial perfusion imaging MRI : magnetic resonance imaging NO : nitric oxide NSAIDs : non-steroidal anti-inflammatory drugs NSTE-ACS : non-ST-elevation acute coronary syndrome NYHA : New York Heart Association OAT : Occluded Artery Trial OCT : optical coherence tomography OMT : optimal medical therapy PAR-1 : protease activated receptor type 1 PCI : percutaneous coronary intervention PDE5 : phosphodiesterase type 5 PES : paclitaxel-eluting stents PET : positron emission tomography PRECOMBAT : Premier of Randomized Comparison of Bypass Surgery vs. Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease PTP : pre-test probability PUFA : polyunsaturated fatty acid PVD : peripheral vascular disease QoL : quality of life RBBB : right bundle branch block REACH : Reduction of Atherothrombosis for Continued Health RITA-2 : Second Randomized Intervention Treatment of Angina ROOBY : Veterans Affairs Randomized On/Off Bypass SAPT : single antiplatelet therapy SBP : systolic blood pressure SCAD : stable coronary artery disease SCORE : Systematic Coronary Risk Evaluation SCS : spinal cord stimulation SES : sirolimus-eluting stents SIMA : single internal mammary artery SPECT : single photon emission computed tomography STICH : Surgical Treatment for Ischaemic Heart Failure SWISSI II : Swiss Interventional Study on Silent Ischaemia Type II SYNTAX : SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery TC : total cholesterol TENS : transcutaneous electrical neural stimulation TERISA : Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina TIME : Trial of Invasive vs. Medical therapy TIMI : Thrombolysis In Myocardial Infarction TMR : transmyocardial laser revascularization TOAT : The Open Artery Trial WOEST : What is the Optimal antiplatElet and anticoagulant therapy in patients with oral anticoagulation and coronary StenTing Guidelines summarize and evaluate all evidence available, at the time of the writing process, on a particular issue with the aim of assisting physicians in selecting the best management strategies for an individual patient with a given condition, taking into account the impact on outcome, as well …

The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared. In this study, we aimed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease.We used linked electronic health records from 1997 to 2010 in the CALIBER (CArdiovascular research using LInked Bespoke studies and Electronic health Records) programme to assemble a cohort of 1·25 million patients, 30 years of age or older and initially free from cardiovascular disease, a fifth of whom received blood pressure-lowering treatments. We studied the heterogeneity in the age-specific associations of clinically measured blood pressure with 12 acute and chronic cardiovascular diseases, and estimated the lifetime risks (up to 95 years of age) and cardiovascular disease-free life-years lost adjusted for other risk factors at index ages 30, 60, and 80 years. This study is registered at ClinicalTrials.gov, number NCT01164371.During 5·2 years median follow-up, we recorded 83,098 initial cardiovascular disease presentations. In each age group, the lowest risk for cardiovascular disease was in people with systolic blood pressure of 90-114 mm Hg and diastolic blood pressure of 60-74 mm Hg, with no evidence of a J-shaped increased risk at lower blood pressures. The effect of high blood pressure varied by cardiovascular disease endpoint, from strongly positive to no effect. Associations with high systolic blood pressure were strongest for intracerebral haemorrhage (hazard ratio 1·44 [95% CI 1·32-1·58]), subarachnoid haemorrhage (1·43 [1·25-1·63]), and stable angina (1·41 [1·36-1·46]), and weakest for abdominal aortic aneurysm (1·08 [1·00-1·17]). Compared with diastolic blood pressure, raised systolic blood pressure had a greater effect on angina, myocardial infarction, and peripheral arterial disease, whereas raised diastolic blood pressure had a greater effect on abdominal aortic aneurysm than did raised systolic pressure. Pulse pressure associations were inverse for abdominal aortic aneurysm (HR per 10 mm Hg 0·91 [95% CI 0·86-0·98]) and strongest for peripheral arterial disease (1·23 [1·20-1·27]). People with hypertension (blood pressure ≥140/90 mm Hg or those receiving blood pressure-lowering drugs) had a lifetime risk of overall cardiovascular disease at 30 years of age of 63·3% (95% CI 62·9-63·8) compared with 46·1% (45·5-46·8) for those with normal blood pressure, and developed cardiovascular disease 5·0 years earlier (95% CI 4·8-5·2). Stable and unstable angina accounted for most (43%) of the cardiovascular disease-free years of life lost associated with hypertension from index age 30 years, whereas heart failure and stable angina accounted for the largest proportion (19% each) of years of life lost from index age 80 years.The widely held assumptions that blood pressure has strong associations with the occurrence of all cardiovascular diseases across a wide age range, and that diastolic and systolic associations are concordant, are not supported by the findings of this high-resolution study. Despite modern treatments, the lifetime burden of hypertension is substantial. These findings emphasise the need for new blood pressure-lowering strategies, and will help to inform the design of randomised trials to assess them.Medical Research Council, National Institute for Health Research, and Wellcome Trust.

The contemporary associations of type 2 diabetes with a wide range of incident cardiovascular diseases have not been compared. We aimed to study associations between type 2 diabetes and 12 initial manifestations of cardiovascular disease.We used linked primary care, hospital admission, disease registry, and death certificate records from the CALIBER programme, which links data for people in England recorded in four electronic health data sources. We included people who were (or turned) 30 years or older between Jan 1, 1998, to March 25, 2010, who were free from cardiovascular disease at baseline. The primary endpoint was the first record of one of 12 cardiovascular presentations in any of the data sources. We compared cumulative incidence curves for the initial presentation of cardiovascular disease and used Cox models to estimate cause-specific hazard ratios (HRs). This study is registered at ClinicalTrials.gov (NCT01804439).Our cohort consisted of 1 921 260 individuals, of whom 1 887 062 (98·2%) did not have diabetes and 34 198 (1·8%) had type 2 diabetes. We observed 113 638 first presentations of cardiovascular disease during a median follow-up of 5·5 years (IQR 2·1-10·1). Of people with type 2 diabetes, 6137 (17·9%) had a first cardiovascular presentation, the most common of which were peripheral arterial disease (reported in 992 [16·2%] of 6137 patients) and heart failure (866 [14·1%] of 6137 patients). Type 2 diabetes was positively associated with peripheral arterial disease (adjusted HR 2·98 [95% CI 2·76-3·22]), ischaemic stroke (1·72 [1·52-1·95]), stable angina (1·62 [1·49-1·77]), heart failure (1·56 [1·45-1·69]), and non-fatal myocardial infarction (1·54 [1·42-1·67]), but was inversely associated with abdominal aortic aneurysm (0·46 [0·35-0·59]) and subarachnoid haemorrhage (0·48 [0·26-0.89]), and not associated with arrhythmia or sudden cardiac death (0·95 [0·76-1·19]).Heart failure and peripheral arterial disease are the most common initial manifestations of cardiovascular disease in type 2 diabetes. The differences between relative risks of different cardiovascular diseases in patients with type 2 diabetes have implications for clinical risk assessment and trial design.Wellcome Trust, National Institute for Health Research, and Medical Research Council.

Abstract Aims The 2019 report from the European Society of Cardiology (ESC) Atlas provides a contemporary analysis of cardiovascular disease (CVD) statistics across 56 member countries, with particular emphasis on international inequalities in disease burden and healthcare delivery together with estimates of progress towards meeting 2025 World Health Organization (WHO) non-communicable disease targets. Methods and results In this report, contemporary CVD statistics are presented for member countries of the ESC. The statistics are drawn from the ESC Atlas which is a repository of CVD data from a variety of sources including the WHO, the Institute for Health Metrics and Evaluation, and the World Bank. The Atlas also includes novel ESC sponsored data on human and capital infrastructure and cardiovascular healthcare delivery obtained by annual survey of the national societies of ESC member countries. Across ESC member countries, the prevalence of obesity (body mass index ≥30 kg/m2) and diabetes has increased two- to three-fold during the last 30 years making the WHO 2025 target to halt rises in these risk factors unlikely to be achieved. More encouraging have been variable declines in hypertension, smoking, and alcohol consumption but on current trends only the reduction in smoking from 28% to 21% during the last 20 years appears sufficient for the WHO target to be achieved. The median age-standardized prevalence of major risk factors was higher in middle-income compared with high-income ESC member countries for hypertension {23.8% [interquartile range (IQR) 22.5–23.1%] vs. 15.7% (IQR 14.5–21.1%)}, diabetes [7.7% (IQR 7.1–10.1%) vs. 5.6% (IQR 4.8–7.0%)], and among males smoking [43.8% (IQR 37.4–48.0%) vs. 26.0% (IQR 20.9–31.7%)] although among females smoking was less common in middle-income countries [8.7% (IQR 3.0–10.8) vs. 16.7% (IQR 13.9–19.7%)]. There were associated inequalities in disease burden with disability-adjusted life years per 100 000 people due to CVD over three times as high in middle-income [7160 (IQR 5655–8115)] compared with high-income [2235 (IQR 1896–3602)] countries. Cardiovascular disease mortality was also higher in middle-income countries where it accounted for a greater proportion of potential years of life lost compared with high-income countries in both females (43% vs. 28%) and males (39% vs. 28%). Despite the inequalities in disease burden across ESC member countries, survey data from the National Cardiac Societies of the ESC showed that middle-income member countries remain severely under-resourced compared with high-income countries in terms of cardiological person-power and technological infrastructure. Under-resourcing in middle-income countries is associated with a severe procedural deficit compared with high-income countries in terms of coronary intervention, device implantation and cardiac surgical procedures. Conclusion A seemingly inexorable rise in the prevalence of obesity and diabetes currently provides the greatest challenge to achieving further reductions in CVD burden across ESC member countries. Additional challenges are provided by inequalities in disease burden that now require intensification of policy initiatives in order to reduce population risk and prioritize cardiovascular healthcare delivery, particularly in the middle-income countries of the ESC where need is greatest.

The European Society of Cardiology (ESC) Atlas has been compiled by the European Heart Agency to document cardiovascular disease (CVD) statistics of the 56 ESC member countries. A major aim of this 2017 data presentation has been to compare high-income and middle-income ESC member countries to identify inequalities in disease burden, outcomes, and service provision. The Atlas utilizes a variety of data sources, including the World Health Organization, the Institute for Health Metrics and Evaluation, and the World Bank to document risk factors, prevalence, and mortality of cardiovascular disease and national economic indicators. It also includes novel ESC-sponsored survey data of health infrastructure and cardiovascular service provision provided by the national societies of the ESC member countries. Data presentation is descriptive with no attempt to attach statistical significance to differences observed in stratified analyses. Important differences were identified between the high-income and middle-income member countries of the ESC with regard to CVD risk factors, disease incidence, and mortality. For both women and men, the age-standardized prevalence of hypertension was lower in high-income countries (18% and 27%) compared with middle-income countries (24% and 30%). Smoking prevalence in men (not women) was also lower (26% vs. 41%) and together these inequalities are likely to have contributed to the higher CVD mortality in middle-income countries. Declines in CVD mortality have seen cancer becoming a more common cause of death in a number of high-income member countries, but in middle-income countries declines in CVD mortality have been less consistent where CVD remains the leading cause of death. Inequalities in CVD mortality are emphasized by the smaller contribution they make to potential years of life lost in high-income countries compared with middle-income countries both for women (13% vs. 23%) and men (20% vs. 27%). The downward mortality trends for CVD may, however, be threatened by the emerging obesity epidemic that is seeing rates of diabetes increasing across all the ESC member countries. Survey data from the National Cardiac Societies showed that rates of cardiac catheterization and coronary artery bypass surgery, as well as the number of specialist centres required to deliver them, were greatest in the high-income member countries of the ESC. The Atlas confirmed that these ESC member countries, where the facilities for the contemporary treatment of coronary disease were best developed, were often those in which declines in coronary mortality have been most pronounced. Economic resources were not the only driver for delivery of equitable cardiovascular health care, as some middle-income ESC member countries reported rates for interventional procedures and device implantations that matched or exceeded the rates in wealthier member countries. In documenting national CVD statistics, the Atlas provides valuable insights into the inequalities in risk factors, health care delivery, and outcomes of CVD across the ESC member countries. The availability of these data will underpin the ESC’s ambitious mission ‘to reduce the burden of cardiovascular disease’ not only in its member countries but also in nation states around the world.

Understanding and improving the prognosis of a disease or health condition is a priority in clinical research and practice. In this article, the authors introduce a framework of four interrelated themes in prognosis research, describe the importance of the first of these themes (understanding future outcomes in relation to current diagnostic and treatment practices), and introduce recommendations for the field of prognosis research

Abstract Aims This report from the European Society of Cardiology (ESC) Atlas Project updates and expands upon the widely cited 2019 report in presenting cardiovascular disease (CVD) statistics for the 57 ESC member countries. Methods and results Statistics pertaining to 2019, or the latest available year, are presented. Data sources include the World Health Organization, the Institute for Health Metrics and Evaluation, the World Bank, and novel ESC sponsored data on human and capital infrastructure and cardiovascular healthcare delivery. New material in this report includes sociodemographic and environmental determinants of CVD, rheumatic heart disease, out-of-hospital cardiac arrest, left-sided valvular heart disease, the advocacy potential of these CVD statistics, and progress towards World Health Organization (WHO) 2025 targets for non-communicable diseases. Salient observations in this report: (i) Females born in ESC member countries in 2018 are expected to live 80.8 years and males 74.8 years. Life expectancy is longer in high income (81.6 years) compared with middle-income (74.2 years) countries. (ii) In 2018, high-income countries spent, on average, four times more on healthcare than middle-income countries. (iii) The median PM2.5 concentrations in 2019 were over twice as high in middle-income ESC member countries compared with high-income countries and exceeded the EU air quality standard in 14 countries, all middle-income. (iv) In 2016, more than one in five adults across the ESC member countries were obese with similar prevalence in high and low-income countries. The prevalence of obesity has more than doubled over the past 35 years. (v) The burden of CVD falls hardest on middle-income ESC member countries where estimated incidence rates are ∼30% higher compared with high-income countries. This is reflected in disability-adjusted life years due to CVD which are nearly four times as high in middle-income compared with high-income countries. (vi) The incidence of calcific aortic valve disease has increased seven-fold during the last 30 years, with age-standardized rates four times as high in high-income compared with middle-income countries. (vii) Although the total number of CVD deaths across all countries far exceeds the number of cancer deaths for both sexes, there are 15 ESC member countries in which cancer accounts for more deaths than CVD in males and five-member countries in which cancer accounts for more deaths than CVD in females. (viii) The under-resourced status of middle-income countries is associated with a severe procedural deficit compared with high-income countries in terms of coronary intervention, ablation procedures, device implantation, and cardiac surgical procedures. Conclusion Risk factors and unhealthy behaviours are potentially reversible, and this provides a huge opportunity to address the health inequalities across ESC member countries that are highlighted in this report. It seems clear, however, that efforts to seize this opportunity are falling short and present evidence suggests that most of the WHO NCD targets for 2025 are unlikely to be met across ESC member countries.

<b>Objective</b> To determine the completeness and diagnostic validity of myocardial infarction recording across four national health record sources in primary care, hospital care, a disease registry, and mortality register. <b>Design</b> Cohort study. <b>Participants</b> 21 482 patients with acute myocardial infarction in England between January 2003 and March 2009, identified in four prospectively collected, linked electronic health record sources: Clinical Practice Research Datalink (primary care data), Hospital Episode Statistics (hospital admissions), the disease registry MINAP (Myocardial Ischaemia National Audit Project), and the Office for National Statistics mortality register (cause specific mortality data). <b>Setting</b> One country (England) with one health system (the National Health Service). <b>Main outcome measures</b> Recording of acute myocardial infarction, incidence, all cause mortality within one year of acute myocardial infarction, and diagnostic validity of acute myocardial infarction compared with electrocardiographic and troponin findings in the disease registry (gold standard). <b>Results</b> Risk factors and non-cardiovascular coexisting conditions were similar across patients identified in primary care, hospital admission, and registry sources. Immediate all cause mortality was highest among patients with acute myocardial infarction recorded in primary care, which (unlike hospital admission and disease registry sources) included patients who did not reach hospital, but at one year mortality rates in cohorts from each source were similar. 5561 (31.0%) patients with non-fatal acute myocardial infarction were recorded in all three sources and 11 482 (63.9%) in at least two sources. The crude incidence of acute myocardial infarction was underestimated by 25-50% using one source compared with using all three sources. Compared with acute myocardial infarction defined in the disease registry, the positive predictive value of acute myocardial infarction recorded in primary care was 92.2% (95% confidence interval 91.6% to 92.8%) and in hospital admissions was 91.5% (90.8% to 92.1%). <b>Conclusion</b> Each data source missed a substantial proportion (25-50%) of myocardial infarction events. Failure to use linked electronic health records from primary care, hospital care, disease registry, and death certificates may lead to biased estimates of the incidence and outcome of myocardial infarction. <b>Trial registration </b>NCT01569139 clinicaltrials.gov.

In a prospective, multicenter, randomized controlled trial, 4,146 patients were randomized to receive standard care or standard care plus coronary computed tomography angiography (CCTA).The purpose of this study was to explore the consequences of CCTA-assisted diagnosis on invasive coronary angiography, preventive treatments, and clinical outcomes.In post hoc analyses, we assessed changes in invasive coronary angiography, preventive treatments, and clinical outcomes using national electronic health records.Despite similar overall rates (409 vs. 401; p = 0.451), invasive angiography was less likely to demonstrate normal coronary arteries (20 vs. 56; hazard ratios [HRs]: 0.39 [95% confidence interval (CI): 0.23 to 0.68]; p < 0.001) but more likely to show obstructive coronary artery disease (283 vs. 230; HR: 1.29 [95% CI: 1.08 to 1.55]; p = 0.005) in those allocated to CCTA. More preventive therapies (283 vs. 74; HR: 4.03 [95% CI: 3.12 to 5.20]; p < 0.001) were initiated after CCTA, with each drug commencing at a median of 48 to 52 days after clinic attendance. From the median time for preventive therapy initiation (50 days), fatal and nonfatal myocardial infarction was halved in patients allocated to CCTA compared with those assigned to standard care (17 vs. 34; HR: 0.50 [95% CI: 0.28 to 0.88]; p = 0.020). Cumulative 6-month costs were slightly higher with CCTA: difference $462 (95% CI: $303 to $621).In patients with suspected angina due to coronary heart disease, CCTA leads to more appropriate use of invasive angiography and alterations in preventive therapies that were associated with a halving of fatal and non-fatal myocardial infarction. (Scottish COmputed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590).

International research for acute myocardial infarction lacks comparisons of whole health systems. We assessed time trends for care and outcomes in Sweden and the UK.We used data from national registries on consecutive patients registered between 2004 and 2010 in all hospitals providing care for acute coronary syndrome in Sweden and the UK. The primary outcome was all-cause mortality 30 days after admission. We compared effectiveness of treatment by indirect casemix standardisation. This study is registered with ClinicalTrials.gov, number NCT01359033.We assessed data for 119,786 patients in Sweden and 391,077 in the UK. 30-day mortality was 7·6% (95% CI 7·4-7·7) in Sweden and 10·5% (10·4-10·6) in the UK. Mortality was higher in the UK in clinically relevant subgroups defined by troponin concentration, ST-segment elevation, age, sex, heart rate, systolic blood pressure, diabetes mellitus status, and smoking status. In Sweden, compared with the UK, there was earlier and more extensive uptake of primary percutaneous coronary intervention (59% vs 22%) and more frequent use of β blockers at discharge (89% vs 78%). After casemix standardisation the 30-day mortality ratio for UK versus Sweden was 1·37 (95% CI 1·30-1·45), which corresponds to 11,263 (95% CI 9620-12,827) excess deaths, but did decline over time (from 1·47, 95% CI 1·38-1·58 in 2004 to 1·20, 1·12-1·29 in 2010; p=0·01).We found clinically important differences between countries in acute myocardial infarction care and outcomes. International comparisons research might help to improve health systems and prevent deaths.Seventh Framework Programme for Research, National Institute for Health Research, Wellcome Trust (UK), Swedish Association of Local Authorities and Regions, Swedish Heart-Lung Foundation.

Efficacy and safety of current means to prevent cerebrovascular thrombosis in patients at high risk of stroke are suboptimal. In theory, anchoring fibrinolytic plasminogen activators to the luminal surface of the cerebral endothelium might arrest formation of occlusive clots in this setting. We tested this approach using the recombinant construct antiplatelet-endothelial cell adhesion molecule (PECAM) single-chain variable fragment (scFv)-urokinase-type plasminogen activator (uPA), fusing low-molecular-weight single-chain urokinase-type plasminogen activator with a scFv of an antibody directed to the stably expressed endothelial surface determinant PECAM-1, implicated in inflammation and thrombosis. Studies in mice showed that scFv-uPA, but not unconjugated uPA 1) accumulates in the brain after intravascular injection, 2) lyses clots lodged in the cerebral arterial vasculature without hemorrhagic complications, 3) provides rapid and stable cerebral reperfusion, and 4) alleviates post-thrombotic brain edema. Effective and safe thromboprophylaxis in the cerebral arterial circulation by anti-PECAM scFv-uPA represents a prototype of a new paradigm to prevent recurrent cerebrovascular thrombosis.

Abstract Aims The aim of this study was to derive and validate the SCORE2-Older Persons (SCORE2-OP) risk model to estimate 5- and 10-year risk of cardiovascular disease (CVD) in individuals aged over 70 years in four geographical risk regions. Methods and results Sex-specific competing risk-adjusted models for estimating CVD risk (CVD mortality, myocardial infarction, or stroke) were derived in individuals aged over 65 without pre-existing atherosclerotic CVD from the Cohort of Norway (28 503 individuals, 10 089 CVD events). Models included age, smoking status, diabetes, systolic blood pressure, and total- and high-density lipoprotein cholesterol. Four geographical risk regions were defined based on country-specific CVD mortality rates. Models were recalibrated to each region using region-specific estimated CVD incidence rates and risk factor distributions. For external validation, we analysed data from 6 additional study populations {338 615 individuals, 33 219 CVD validation cohorts, C-indices ranged between 0.63 [95% confidence interval (CI) 0.61–0.65] and 0.67 (0.64–0.69)}. Regional calibration of expected-vs.-observed risks was satisfactory. For given risk factor profiles, there was substantial variation across the four risk regions in the estimated 10-year CVD event risk. Conclusions The competing risk-adjusted SCORE2-OP model was derived, recalibrated, and externally validated to estimate 5- and 10-year CVD risk in older adults (aged 70 years or older) in four geographical risk regions. These models can be used for communicating the risk of CVD and potential benefit from risk factor treatment and may facilitate shared decision-making between clinicians and patients in CVD risk management in older persons.

The goal of cardiovascular disease (CVD) research using linked bespoke studies and electronic health records (CALIBER) is to provide evidence to inform health care and public health policy for CVDs across different stages of translation, from discovery, through evaluation in trials to implementation, where linkages to electronic health records provide new scientific opportunities. The initial approach of the CALIBER programme is characterized as follows: (i) Linkages of multiple electronic heath record sources: examples include linkages between the longitudinal primary care data from the Clinical Practice Research Datalink, the national registry of acute coronary syndromes (Myocardial Ischaemia National Audit Project), hospitalization and procedure data from Hospital Episode Statistics and cause-specific mortality and social deprivation data from the Office of National Statistics. Current cohort analyses involve a million people in initially healthy populations and disease registries with ∼10(5) patients. (ii) Linkages of bespoke investigator-led cohort studies (e.g. UK Biobank) to registry data (e.g. Myocardial Ischaemia National Audit Project), providing new means of ascertaining, validating and phenotyping disease. (iii) A common data model in which routine electronic health record data are made research ready, and sharable, by defining and curating with meta-data >300 variables (categorical, continuous, event) on risk factors, CVDs and non-cardiovascular comorbidities. (iv) Transparency: all CALIBER studies have an analytic protocol registered in the public domain, and data are available (safe haven model) for use subject to approvals. For more information, e-mail s.denaxas@ucl.ac.uk.

Diagnosis is the traditional basis for decision-making in clinical practice. Evidence is often lacking about future benefits and harms of these decisions for patients diagnosed with and without disease. We propose that a model of clinical practice focused on patient prognosis and predicting the likelihood of future outcomes may be more useful. Disease diagnosis can provide crucial information for clinical decisions that influence outcome in serious acute illness. However, the central role of diagnosis in clinical practice is challenged by evidence that it does not always benefit patients and that factors other than disease are important in determining patient outcome. The concept of disease as a dichotomous ‘yes’ or ‘no’ is challenged by the frequent use of diagnostic indicators with continuous distributions, such as blood sugar, which are better understood as contributing information about the probability of a patient’s future outcome. Moreover, many illnesses, such as chronic fatigue, cannot usefully be labelled from a disease-diagnosis perspective. In such cases, a prognostic model provides an alternative framework for clinical practice that extends beyond disease and diagnosis and incorporates a wide range of information to predict future patient outcomes and to guide decisions to improve them. Such information embraces non-disease factors and genetic and other biomarkers which influence outcome. Patient prognosis can provide the framework for modern clinical practice to integrate information from the expanding biological, social, and clinical database for more effective and efficient care.

For acute myocardial infarction (AMI) without heart failure (HF), it is unclear if β-blockers are associated with reduced mortality.The goal of this study was to determine the association between β-blocker use and mortality in patients with AMI without HF or left ventricular systolic dysfunction (LVSD).This cohort study used national English and Welsh registry data from the Myocardial Ischaemia National Audit Project. A total of 179,810 survivors of hospitalization with AMI without HF or LVSD, between January 1, 2007, and June 30, 2013 (final follow-up: December 31, 2013), were assessed. Survival-time inverse probability weighting propensity scores and instrumental variable analyses were used to investigate the association between the use of β-blockers and 1-year mortality.Of 91,895 patients with ST-segment elevation myocardial infarction and 87,915 patients with non-ST-segment elevation myocardial infarction, 88,542 (96.4%) and 81,933 (93.2%) received β-blockers, respectively. For the entire cohort, with >163,772 person-years of observation, there were 9,373 deaths (5.2%). Unadjusted 1-year mortality was lower for patients who received β-blockers compared with those who did not (4.9% vs. 11.2%; p < 0.001). However, after weighting and adjustment, there was no significant difference in mortality between those with and without β-blocker use (average treatment effect [ATE] coefficient: 0.07; 95% confidence interval [CI]: -0.60 to 0.75; p = 0.827). Findings were similar for ST-segment elevation myocardial infarction (ATE coefficient: 0.30; 95% CI: -0.98 to 1.58; p = 0.637) and non-ST-segment elevation myocardial infarction (ATE coefficient: -0.07; 95% CI: -0.68 to 0.54; p = 0.819).Among survivors of hospitalization with AMI who did not have HF or LVSD as recorded in the hospital, the use of β-blockers was not associated with a lower risk of death at any time point up to 1 year. (β-Blocker Use and Mortality in Hospital Survivors of Acute Myocardial Infarction Without Heart Failure; NCT02786654).

Given the recent declines in heart attack and stroke incidence, it is unclear how women and men differ in first lifetime presentations of cardiovascular diseases (CVDs). We compared the incidence of 12 cardiac, cerebrovascular, and peripheral vascular diseases in women and men at different ages.We studied 1 937 360 people, aged ≥ 30 years and free from diagnosed CVD at baseline (51% women), using linked electronic health records covering primary care, hospital admissions, acute coronary syndrome registry, and mortality (Cardiovascular Research Using LInked Bespoke Studies and Electronic Records [CALIBER] research platform). During 6 years median follow-up between 1997 and 2010, 114 859 people experienced an incident cardiovascular diagnosis, the majority (66%) of which were neither myocardial infarction nor ischemic stroke. Associations of male sex with initial diagnoses of CVD, however, varied from strong (age-adjusted hazard ratios, 3.6-5.0) for abdominal aortic aneurysm, myocardial infarction, and unheralded coronary death (particularly >60 years), through modest (hazard ratio, 1.5-2.0) for stable angina, ischemic stroke, peripheral arterial disease, heart failure, and cardiac arrest, to weak (hazard ratio <1.5) for transient ischemic attack, intracerebral hemorrhage, and unstable angina, and inverse (0.69) for subarachnoid hemorrhage (all P<0.001).The majority of initial presentations of CVD are neither myocardial infarction nor ischemic stroke, yet most primary prevention studies focus on these presentations. Sex has differing associations with different CVDs, with implications for risk prediction and management strategies.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01164371.

Aims The Heart Failure Association (HFA) of the European Society of Cardiology (ESC) developed the HFA Atlas to provide a contemporary description of heart failure (HF) epidemiology, resources, reimbursement of guideline‐directed medical therapy (GDMT) and activities of the National Heart Failure Societies (NHFS) in ESC member countries. Methods and results The HFA Atlas survey was conducted in 2018–2019 in 42 ESC countries. The quality and completeness of source data varied across countries. The median incidence of HF was 3.20 [interquartile range (IQR) 2.66–4.17] cases per 1000 person‐years, ranging from ≤2 in Italy and Denmark to &gt;6 in Germany. The median HF prevalence was 17.20 (IQR 14.30–21) cases per 1000 people, ranging from ≤12 in Greece and Spain to &gt;30 in Lithuania and Germany. The median number of HF hospitalizations was 2671 (IQR 1771–4317) per million people annually, ranging from &lt;1000 in Latvia and North Macedonia to &gt;6000 in Romania, Germany and Norway. The median length of hospital stay for an admission with HF was 8.50 (IQR 7.38–10) days. Diagnostic and management resources for HF varied, with high‐income ESC member countries having substantially more resources compared with middle‐income countries. The median number of hospitals with dedicated HF centres was 1.16 (IQR 0.51–2.97) per million people, ranging from &lt;0.10 in Russian Federation and Ukraine to &gt;7 in Norway and Italy. Nearly all countries reported full or partial reimbursement of standard GDMT, except ivabradine and sacubitril/valsartan. Almost all countries reported having NHFS or working groups and nearly half had HF patient organizations. Conclusions The first report from the HFA Atlas has shown considerable heterogeneity in HF disease burden, the resources available for its management and data quality across ESC member countries. The findings emphasize the need for a systematic approach to the capture of HF statistics so that inequalities and improvements in care may be quantified and addressed.

Abstract Aims To develop and validate a recalibrated prediction model (SCORE2-Diabetes) to estimate the 10-year risk of cardiovascular disease (CVD) in individuals with type 2 diabetes in Europe. Methods and results SCORE2-Diabetes was developed by extending SCORE2 algorithms using individual-participant data from four large-scale datasets comprising 229 460 participants (43 706 CVD events) with type 2 diabetes and without previous CVD. Sex-specific competing risk-adjusted models were used including conventional risk factors (i.e. age, smoking, systolic blood pressure, total, and HDL-cholesterol), as well as diabetes-related variables (i.e. age at diabetes diagnosis, glycated haemoglobin [HbA1c] and creatinine-based estimated glomerular filtration rate [eGFR]). Models were recalibrated to CVD incidence in four European risk regions. External validation included 217 036 further individuals (38 602 CVD events), and showed good discrimination, and improvement over SCORE2 (C-index change from 0.009 to 0.031). Regional calibration was satisfactory. SCORE2-Diabetes risk predictions varied several-fold, depending on individuals’ levels of diabetes-related factors. For example, in the moderate-risk region, the estimated 10-year CVD risk was 11% for a 60-year-old man, non-smoker, with type 2 diabetes, average conventional risk factors, HbA1c of 50 mmol/mol, eGFR of 90 mL/min/1.73 m2, and age at diabetes diagnosis of 60 years. By contrast, the estimated risk was 17% in a similar man, with HbA1c of 70 mmol/mol, eGFR of 60 mL/min/1.73 m2, and age at diabetes diagnosis of 50 years. For a woman with the same characteristics, the risk was 8% and 13%, respectively. Conclusion SCORE2-Diabetes, a new algorithm developed, calibrated, and validated to predict 10-year risk of CVD in individuals with type 2 diabetes, enhances identification of individuals at higher risk of developing CVD across Europe.

To evaluate the effect of opt-in compared with opt-out recruitment strategies on response rate and selection bias.Double blind randomised controlled trial.Two general practices in England.510 patients with angina.Patients were randomly allocated to an opt-in (asked to actively signal willingness to participate in research) or opt-out (contacted repeatedly unless they signalled unwillingness to participate) approach for recruitment to an observational prognostic study of patients with angina.Recruitment rate and clinical characteristics of patients.The recruitment rate, defined by clinic attendance, was 38% (96/252) in the opt-in arm and 50% (128/258) in the opt-out arm (P = 0.014). Once an appointment had been made, non-attendance at the clinic was similar (20% opt-in arm v 17% opt-out arm; P = 0.86). Patients in the opt-in arm had fewer risk factors (44% v 60%; P = 0.053), less treatment for angina (69% v 82%; P = 0.010), and less functional impairment (9% v 20%; P = 0.023) than patients in the opt-out arm.The opt-in approach to participant recruitment, increasingly required by ethics committees, resulted in lower response rates and a biased sample. We propose that the opt-out approach should be the default recruitment strategy for studies with low risk to participants.

The anti-anginal efficacy and safety of ranolazine in diabetic and non-diabetic patients included in the Combination Assessment of Ranolazine In Stable Angina (CARISA) trial (JAMA 2004;291:309) were studied. Glycaemic control was also assessed in CARISA and its long-term open-label extension study.Patients with chronic angina enrolled in CARISA (189 with diabetes, 634 without diabetes) on background atenolol, diltiazem, or amlodipine therapy were randomized to placebo, ranolazine 750 or 1000 mg twice daily for 12 weeks, during which exercise tolerance, angina frequency, nitroglycerin usage, glucose, HbA(1c), and lipids were measured. Patients completing the randomized study could enroll in an ongoing open-label extension study and were evaluated every 3 months. Ranolazine produced similar improvements in exercise parameters, nitroglycerin use, and angina frequency in diabetic and non-diabetic patients. Adverse events were similar between groups. Fasting glucose and lipids remained unaltered in diabetic patients after 12 weeks of therapy. In a post hoc analysis, ranolazine 750 and 1000 mg reduced HbA(1c) vs. placebo by 0.48+/-0.18% (P=0.008) and 0.70+/-0.18% (P=0.0002), respectively; the HbA(1c) levels appeared to remain unchanged over time during long-term therapy.Anti-anginal efficacy and safety of ranolazine for angina were similar between diabetic and non-diabetic patients. Ranolazine significantly improved glycaemic control in diabetic patients.

The relation between both time and frequency domain analyses of RR variability and mortality was examined in a series of 226 consecutive patients with acute myocardial infarction admitted to 3 district hospitals in London. All patients underwent 24-hour Holter monitoring early after infarction (mean 83 hours, range 48 to 180), and time and frequency domain analyses of RR variability were performed using commercially available software. During an 8-month follow-up period (range 3 to 12 months), there were 19 cardiac deaths (8.4%). Time domain analysis confirmed reduced RR variability (SDRR, SDANN, SD) among nonsurvivors compared with survivors. However, there was no difference between the groups when the percentage of absolute differences between successive RR intervals >50 ms (pNN50) and the root-mean-square of successive differences (RMSSD)—vagal measures of RR variability—were analyzed. Frequency domain analysis demonstrated a significant difference between those who died and the survivors when the low-frequency component—modulated by both vagal and sympathetic mechanisms—was analyzed; however, this was less marked when the high-frequency component—modulated by vagal activity—was analyzed. None of these measures of RR variability was related to infarct site or left ventricular ejection fraction. In conclusion, the data confirm the association between low RR variability and mortality after acute myocardial infarction. However, the mechanism does not appear to relate exclusively to decreased parasympathetic tone. The data suggest that the increased risk of early mortality associated with reduced RR variability reflects an imbalance in sympathovagal function that is unrelated to left ventricular function.

To record prognosis and determinants of outcome in patients with acute myocardial infarction since thrombolysis was introduced.Observational study.London district general hospital.608 consecutive patients admitted to the coronary care unit with acute myocardial infarction between 1 January 1988 and 31 December 1991.All cause mortality, non-fatal ischaemic events (myocardial infarction, unstable angina), and revascularisation.Of the 608 patients, 89 (14.6%) died in hospital. 507 [corrected] patients were followed up after discharge from hospital. Mortality (95% confidence interval) at 30 days, one year, and three years was 16.0% (13.4% to 19.2%), 21.7% (18.6% to 25.2%), and 29.4% (25.3% to 33.9%) respectively. Event free survival (survival without a non-fatal ischaemic event) was 80.4% (77.0% to 83.4%) at 30 days, 66.8% (62.8% to 70.5%) at one year, and 56.1% (51.3% to 60.6%) at three years. Survival in patients treated with thrombolysis was considerably higher than in those not given thrombolysis (three year survival: 76.7% v 54.3%), although the incidence of non-fatal ischaemic events was the same in the two groups. Multivariate determinants of six month survival were left ventricular failure, treatment with thrombolysis and aspirin, smoking history, bundle branch block, and age. For patients who survived six months, age was the only factor related to long term survival.Although patients treated by thrombolysis had a relatively good prognosis, long term mortality and the incidence of non-fatal recurrent ischaemic events remained high. Effective strategies for the identification and treatment of high risk patients need to be reassessed.

Background. An association between infections and vascular events has been observed, but the specific effect of influenza and influenza-like illnesses on triggering acute myocardial infarction (AMI) is unclear.

Systematic evaluations of the quality of research on a single prognostic biomarker are rare. We sought to evaluate the quality of prognostic research evidence for the association of C-reactive protein (CRP) with fatal and nonfatal events among patients with stable coronary disease.We searched MEDLINE (1966 to 2009) and EMBASE (1980 to 2009) and selected prospective studies of patients with stable coronary disease, reporting a relative risk for the association of CRP with death and nonfatal cardiovascular events. We included 83 studies, reporting 61,684 patients and 6,485 outcome events. No study reported a prespecified statistical analysis protocol; only two studies reported the time elapsed (in months or years) between initial presentation of symptomatic coronary disease and inclusion in the study. Studies reported a median of seven items (of 17) from the REMARK reporting guidelines, with no evidence of change over time. The pooled relative risk for the top versus bottom third of CRP distribution was 1.97 (95% confidence interval [CI] 1.78-2.17), with substantial heterogeneity (I(2) = 79.5). Only 13 studies adjusted for conventional risk factors (age, sex, smoking, obesity, diabetes, and low-density lipoprotein [LDL] cholesterol) and these had a relative risk of 1.65 (95% CI 1.39-1.96), I(2) = 33.7. Studies reported ten different ways of comparing CRP values, with weaker relative risks for those based on continuous measures. Adjusting for publication bias (for which there was strong evidence, Egger's p<0.001) using a validated method reduced the relative risk to 1.19 (95% CI 1.13-1.25). Only two studies reported a measure of discrimination (c-statistic). In 20 studies the detection rate for subsequent events could be calculated and was 31% for a 10% false positive rate, and the calculated pooled c-statistic was 0.61 (0.57-0.66).Multiple types of reporting bias, and publication bias, make the magnitude of any independent association between CRP and prognosis among patients with stable coronary disease sufficiently uncertain that no clinical practice recommendations can be made. Publication of prespecified statistical analytic protocols and prospective registration of studies, among other measures, might help improve the quality of prognostic biomarker research.

Objective: To determine whether rapid access chest pain clinics are clinically effective by comparison of coronary event rates in patients diagnosed with angina with rates in patients diagnosed with non-cardiac chest pain and the general population.Design: Multicentre cohort study of consecutive patients with chest pain attending the rapid access chest pain clinics (RACPCs) of six hospitals in England.Participants: 8762 patients diagnosed with either non-cardiac chest pain (n = 6396) or incident angina without prior myocardial infarction (n = 2366) at first cardiological assessment, followed up for a median of 2.57 (interquartile range 1.96-4.15)years.Main outcome measures: Primary end point-death due to coronary heart disease (International Classification of Diseases (ICD)10 I20-I25) or acute coronary syndrome (non-fatal myocardial infarction (ICD10 I21-I23), hospital admission with unstable angina (I24.0,I24.8, I24.9)).Secondary end points-allcause mortality (ICD I20), cardiovascular death (ICD10 I00-I99), or non-fatal myocardial infarction or nonfatal stroke (I60-I69).Results: The cumulative probability of the primary end point in patients diagnosed with angina was 16.52% (95% confidence interval (CI) 14.88% to 18.32%) after 3 years compared with 2.73% (95% CI 2.29% to 3.25%) in patients with non-cardiac chest pain.Coronary standardised mortality ratios for men and women with angina aged ,65 years were 3.52 (95% CI 1.98 to 5.07) and 4.39 (95% CI 1.14 to 7.64).Of the 599 patients who had the primary end point, 194 (32.4%) had been diagnosed with non-cardiac chest pain.These patients were younger, less likely to have typical symptoms, more likely to be south Asian and more likely to have a normal resting electrocardiogram than patients with angina who had the primary end point.Conclusion: RACPCs are successful in identifying patients with incident angina who are at high coronary risk, but there is a need to reduce misdiagnosis and improve outcomes in patients diagnosed with non-cardiac chest pain who accounted for nearly one third of cardiac events during follow-up.

Background Recent experimental evidence suggests that socioeconomic characteristics of neighbourhoods influence cardiovascular health, but observational studies which examine deprivation across a wide range of cardiovascular diseases (CVDs) are lacking. Methods Record-linkage cohort study of 1.93 million people to examine the association between small-area socioeconomic deprivation and 12 CVDs. Health records covered primary care, hospital admissions, a myocardial infarction registry and cause-specific mortality in England (CALIBER). Patients were aged ≥30 years and were initially free of CVD. Cox proportional hazard models stratified by general practice were used. Findings During a median follow-up of 5.5 years 114,859 people had one of 12 initial CVD presentations. In women the hazards of all CVDs except abdominal aortic aneurysm increased linearly with higher small-area socioeconomic deprivation (adjusted HR for most vs. least deprived ranged from 1.05, 95%CI 0.83–1.32 for abdominal aortic aneurysm to 1.55, 95%CI 1.42–1.70 for heart failure; I2 = 81.9%, τ2 = 0.01). In men heterogeneity was higher (HR ranged from 0.89, 95%CI 0.75–1.06 for cardiac arrest to 1.85, 95%CI 1.67–2.04 for peripheral arterial disease; I2 = 96.0%, τ2 = 0.06) and no association was observed with stable angina, sudden cardiac death, subarachnoid haemorrhage, transient ischaemic attack and abdominal aortic aneurysm. Lifetime risk difference between least and most deprived quintiles was most marked for peripheral arterial disease in women (4.3% least deprived, 5.8% most deprived) and men (4.6% least deprived, 7.8% in most deprived); but it was small or negligible for sudden cardiac death, transient ischaemic attack, abdominal aortic aneurysm and ischaemic and intracerebral haemorrhage, in both women and men. Conclusions Associations of small-area socioeconomic deprivation with 12 types of CVDs were heterogeneous, and in men absent for several diseases. Findings suggest that policies to reduce deprivation may impact more strongly on heart failure and peripheral arterial disease, and might be more effective in women.

The population with stable coronary artery disease (SCAD) is growing but validated models to guide their clinical management are lacking. We developed and validated prognostic models for all-cause mortality and non-fatal myocardial infarction (MI) or coronary death in SCAD.Models were developed in a linked electronic health records cohort of 102 023 SCAD patients from the CALIBER programme, with mean follow-up of 4.4 (SD 2.8) years during which 20 817 deaths and 8856 coronary outcomes were observed. The Kaplan-Meier 5-year risk was 20.6% (95% CI, 20.3, 20.9) for mortality and 9.7% (95% CI, 9.4, 9.9) for non-fatal MI or coronary death. The predictors in the models were age, sex, CAD diagnosis, deprivation, smoking, hypertension, diabetes, lipids, heart failure, peripheral arterial disease, atrial fibrillation, stroke, chronic kidney disease, chronic pulmonary disease, liver disease, cancer, depression, anxiety, heart rate, creatinine, white cell count, and haemoglobin. The models had good calibration and discrimination in internal (external) validation with C-index 0.811 (0.735) for all-cause mortality and 0.778 (0.718) for non-fatal MI or coronary death. Using these models to identify patients at high risk (defined by guidelines as 3% annual mortality) and support a management decision associated with hazard ratio 0.8 could save an additional 13-16 life years or 15-18 coronary event-free years per 1000 patients screened, compared with models with just age, sex, and deprivation.These validated prognostic models could be used in clinical practice to support risk stratification as recommended in clinical guidelines.

The contemporary associations of type 2 diabetes with a wide range of incident cardiovascular diseases have not been compared. Previous studies have focussed on myocardial infarction and stroke, and these conditions are the usual outcomes chosen in clinical trials in type 2 diabetes, but other diseases such as heart failure and angina are also major causes of morbidity in diabetes. We aimed to study associations between type 2 diabetes and 12 initial manifestations of cardiovascular disease.We used linked electronic health records from 1997 to 2010 in the CALIBER (cardiovascular research using linked bespoke studies and electronic health records) programme to investigate the absolute and relative risks associated with type 2 diabetes in a cohort of 1·92 million patients in England. We included patients aged 30 years and older who were free from cardiovascular disease at baseline. This study is registered with ClinicalTrials.gov, number NCT01804439.We observed 113 638 first presentations of cardiovascular disease during a median follow-up of 5·5 years (IQR 2·1-10·1). 34 198 people had type 2 diabetes: 6137 experienced a first cardiovascular presentation, of which the most common were peripheral arterial disease (16·2%, n=992) and heart failure (14·1%, n=866). Type 2 diabetes was strongly positively associated with peripheral arterial disease (adjusted cause-specific hazard ratio 2·98, 95% CI 2·76-3·22), ischaemic stroke (1·72, 1·52-1·95), stable angina (1·62, 1·49-1·77), heart failure (1·56, 1·45-1·69), and non-fatal myocardial infarction (1·54 1·42-1·67), but inversely associated with abdominal aortic aneurysm (0·46, 0·35-0·59) and subarachnoid haemorrhage (0·48, 0·26-0·89).This study suggests that associations of type 2 diabetes vary with different incident cardiovascular diseases. These findings have implications for clinical risk assessment and choice of primary endpoint in trials on type 2 diabetes.Wellcome Trust, National Institute for Health Research, UK Medical Research Council.

Evaluation of quality of care is an integral part of modern healthcare, and has become an indispensable tool for health authorities, the public, the press and patients. However, measuring quality of care is difficult, because it is a multifactorial and multidimensional concept that cannot be estimated solely on the basis of patients’ clinical outcomes. Thus, measuring the process of care through quality indicators (QIs) has become a widely used practice in this context. Other professional societies have published QIs for the evaluation of quality of care in the context of acute myocardial infarction (AMI), but no such indicators exist in Europe. In this context, the European Society of Cardiology (ESC) Acute Cardiovascular Care Association (ACCA) has reflected on the measurement of quality of care in the context of AMI (ST segment elevation myocardial infarction (STEMI) and non-ST segment elevation myocardial infarction (NSTEMI)) and created a set of QIs, with a view to developing programmes to improve quality of care for the management of AMI across Europe. We present here the list of QIs defined by the ACCA, with explanations of the methodology used, scientific justification and reasons for the choice for each measure.

It is not known how smoking affects the initial presentation of a wide range of chronic and acute cardiovascular diseases (CVDs), nor the extent to which associations are heterogeneous. We estimated the lifetime cumulative incidence of 12 CVD presentations, and examined associations with smoking and smoking cessation.Cohort study of 1.93 million people aged ≥30years, with no history of CVD, in 1997-2010. Individuals were drawn from linked electronic health records in England, covering primary care, hospitalizations, myocardial infarction (MI) registry and cause-specific mortality (the CALIBER programme).During 11.6 million person-years of follow-up, 114859 people had an initial non-fatal or fatal CVD presentation. By age 90 years, current vs never smokers' lifetime risks varied from 0.4% vs 0.2% for subarachnoid haemorrhage (SAH), to 8.9% vs 2.6% for peripheral arterial disease (PAD). Current smoking showed no association with cardiac arrest or sudden cardiac death [hazard ratio (HR)=1.04, 95% confidence interval (CI) 0.91-1.19).The strength of association differed markedly according to disease type: stable angina (HR=1.08, 95% CI 1.01-1.15),transient ischaemic attack (HR=1.41, 95% CI 1.28-1.55), unstable angina (HR=1.54, 95% CI 1.38-1.72), intracerebral haemorrhage (HR=1.61, 95% CI 1.37-1.89), heart failure (HR=1.62, 95% CI 1.47-1.79), ischaemic stroke (HR=1.90, 95% CI 1.72-2.10), MI (HR=2.32, 95% CI 2.20-2.45), SAH (HR= 2.70, 95% CI 2.27-3.21), PAD (HR=5.16, 95% CI 4.80-5.54) and abdominal aortic aneurysm (AAA) (HR=5.18, 95% CI 4.61-5.82). Population-attributable fractions were lower for women than men for unheralded coronary death, ischaemic stroke, PAD and AAA. Ten years after quitting smoking, the risks of PAD, AAA (in men) and unheralded coronary death remained increased (HR=1.36, 1.47 and 2.74, respectively).The heterogeneous associations of smoking with different CVD presentations suggests different underlying mechanisms and have important implications for research, clinical screening and risk prediction.

Within the SCOT-HEART (Scottish COmputed Tomography of the HEART Trial) trial of patients with stable chest pain, the use of coronary computed tomography angiography (CTA) reduced the rate of death from coronary heart disease or nonfatal myocardial infarction (primary endpoint).This study sought to assess the consistency and mechanisms of the 5-year reduction in this endpoint.In this open-label trial, 4,146 participants were randomized to standard care alone or standard care plus coronary CTA. This study explored the primary endpoint by symptoms, diagnosis, coronary revascularizations, and preventative therapies.Event reductions were consistent across symptom and risk categories (p = NS for interactions). In patients who were not diagnosed with angina due to coronary heart disease, coronary CTA was associated with a lower primary endpoint incidence rate (0.23; 95% confidence interval [CI]: 0.13 to 0.35 vs. 0.59; 95% CI: 0.42 to 0.80 per 100 patient-years; p < 0.001). In those who had undergone coronary CTA, rates of coronary revascularization were higher in the first year (hazard ratio [HR]: 1.21; 95% CI: 1.01 to 1.46; p = 0.042) but lower beyond 1 year (HR: 0.59; 95% CI: 0.38 to 0.90; p = 0.015). Patients assigned to coronary CTA had higher rates of preventative therapies throughout follow-up (p < 0.001 for all), with rates highest in those with CT-defined coronary artery disease. Modeling studies demonstrated the plausibility of the observed effect size.The beneficial effect of coronary CTA on outcomes is consistent across subgroups with plausible underlying mechanisms. Coronary CTA improves coronary heart disease outcomes by enabling better targeting of preventative treatments to those with coronary artery disease. (Scottish COmputed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590).

<b>Objective</b> To assess the between hospital variation in use of guideline recommended treatments and clinical outcomes for acute myocardial infarction in Sweden and the United Kingdom. <b>Design</b> Population based longitudinal cohort study using nationwide clinical registries. <b>Setting and participants</b> Nationwide registry data comprising all hospitals providing acute myocardial infarction care in Sweden (SWEDEHEART/RIKS-HIA, n=87; 119 786 patients) and the UK (NICOR/MINAP, n=242; 391 077 patients), 2004-10. <b>Main outcome measures</b> Between hospital variation in 30 day mortality of patients admitted with acute myocardial infarction. <b>Results</b> Case mix standardised 30 day mortality from acute myocardial infarction was lower in Swedish hospitals (8.4%) than in UK hospitals (9.7%), with less variation between hospitals (interquartile range 2.6% <i>v</i> 3.5%). In both countries, hospital level variation and 30 day mortality were inversely associated with provision of guideline recommended care. Compared with the highest quarter, hospitals in the lowest quarter for use of primary percutaneous coronary intervention had higher volume weighted 30 day mortality for ST elevation myocardial infarction (10.7% <i>v</i> 6.6% in Sweden; 12.7% <i>v</i> 5.8% in the UK). The adjusted odds ratio comparing the highest with the lowest quarters for hospitals’ use of primary percutaneous coronary intervention was 0.70 (95% confidence interval 0.62 to 0.79) in Sweden and 0.68 (0.60 to 0.76) in the UK. Differences in risk between hospital quarters of treatment for non-ST elevation myocardial infarction and secondary prevention drugs for all discharged acute myocardial infarction patients were smaller than for reperfusion treatment in both countries. <b>Conclusion</b> Between hospital variation in 30 day mortality for acute myocardial infarction was greater in the UK than in Sweden. This was associated with, and may be partly accounted for by, the higher practice variation in acute myocardial infarction guideline recommended treatment in the UK hospitals. High quality healthcare across all hospitals, especially in the UK, with better use of guideline recommended treatment, may not only reduce unacceptable practice variation but also deliver improved clinical outcomes for patients with acute myocardial infarction. <b>Clinical trials registration</b> Clinical trials NCT01359033.

To investigate sex differences in acute myocardial infarction (AMI) guideline-indicated care as defined by the European Society of Cardiology (ESC) Acute Cardiovascular Care Association (ACCA) quality indicators.Nationwide cohort study comprising 691 290 AMI hospitalisations in England and Wales (n=233 hospitals) from the Myocardial Ischaemia National Audit Project between 1 January 2003 and 30 June 2013.There were 34.5% (n=238 489) women (median age 76.7 (IQR 66.3-84.0) years; 33.9% (n=80 884) ST-elevation myocardial infarction (STEMI)) and 65.5% (n=452 801) men (median age 67.1 (IQR 56.9-77.2) years; 42.5% (n=192 229) STEMI). Women less frequently received 13 of the 16 quality indicators compared with men, including timely reperfusion therapy for STEMI (76.8% vs 78.9%; p<0.001), timely coronary angiography for non-STEMI (24.2% vs 36.7%; p<0.001), dual antiplatelet therapy (75.4% vs 78.7%) and secondary prevention therapies (87.2% vs 89.6% for statins, 82.5% vs 85.6% for ACE inhibitor/angiotensin receptor blockers and 62.6% vs 67.6% for beta-blockers; all p<0.001). Median 30-day Global Registry of Acute Coronary Events risk score adjusted mortality was higher for women than men (median: 5.2% (IQR 1.8%-13.1%) vs 2.3% (IQR 0.8%-7.1%), p<0.001). An estimated 8243 (95% CI 8111 to 8375) deaths among women could have been prevented over the study period if their quality indicator attainment had been equal to that attained by men.According to the ESC ACCA AMI quality indicators, women in England and Wales less frequently received guideline-indicated care and had significantly higher mortality than men. Greater attention to the delivery of recommended AMI treatments for women has the potential to reduce the sex-AMI mortality gap.

AimsTo assess the international validity of using hospital record data to compare long-term outcomes in heart attack survivors.

The optimal treatment option for in-stent restenosis is currently unclear.Systematic review and meta-analysis of the effect of drug-eluting balloons (DEB) to treat in-stent restenosis.Trials were identified through a literature search from 2005 through 7 November 2012.Randomised clinical trials comparing DEB with a control treatment (plain balloon angioplasty or drug-eluting stents).Main endpoints of interest were major adverse cardiac events (MACE), target lesion revascularisation (TLR), binary in-segment restenosis, stent thrombosis (ST), myocardial infarction (MI) and mortality. A random-effects model was used to calculate the pooled relative risks (RR) with 95% CIs.Five studies and a total of 801 patients were included in this analysis. Follow-up duration ranged from 12 to 60months. Most endpoints were significantly reduced for DEB compared with the control groups. For MACE, the relative risk RR was 0.46 (0.31 to 0.70), p<0.001, for TLR it was 0.34 (0.16 to 0.73); p=0.006, for angiographic in-segment restenosis it was 0.28 (0.14 to 0.58); p<0.001. There was a lower mortality for DEB (RR 0.48 (0.24 to 0.95); p=0.034). The incidence of MI was numerically lower, but the differences were not statistically significant (RR 0.68 (0.32 to 1.48); p=0.337). There was no difference in the risk of ST (RR 1.12 (0.23 to 5.50), p=0.891).In-stent restenosis is the bane of coronary angioplasty, and drug-eluting balloon angioplasty is a promising treatment option in this situation. It reduces the risk for MACE compared with plain balloon angioplasty or implantation of a Taxus Liberte drug-eluting stent.

National electronic health records (EHR) are increasingly used for research but identifying disease cases is challenging due to differences in information captured between sources (e.g. primary and secondary care). Our objective was to provide a transparent, reproducible model for integrating these data using atrial fibrillation (AF), a chronic condition diagnosed and managed in multiple ways in different healthcare settings, as a case study.Potentially relevant codes for AF screening, diagnosis, and management were identified in four coding systems: Read (primary care diagnoses and procedures), British National Formulary (BNF; primary care prescriptions), ICD-10 (secondary care diagnoses) and OPCS-4 (secondary care procedures). From these we developed a phenotype algorithm via expert review and analysis of linked EHR data from 1998 to 2010 for a cohort of 2.14 million UK patients aged ≥ 30 years. The cohort was also used to evaluate the phenotype by examining associations between incident AF and known risk factors.The phenotype algorithm incorporated 286 codes: 201 Read, 63 BNF, 18 ICD-10, and four OPCS-4. Incident AF diagnoses were recorded for 72,793 patients, but only 39.6% (N = 28,795) were recorded in primary care and secondary care. An additional 7,468 potential cases were inferred from data on treatment and pre-existing conditions. The proportion of cases identified from each source differed by diagnosis age; inferred diagnoses contributed a greater proportion of younger cases (≤ 60 years), while older patients (≥ 80 years) were mainly diagnosed in SC. Associations of risk factors (hypertension, myocardial infarction, heart failure) with incident AF defined using different EHR sources were comparable in magnitude to those from traditional consented cohorts.A single EHR source is not sufficient to identify all patients, nor will it provide a representative sample. Combining multiple data sources and integrating information on treatment and comorbid conditions can substantially improve case identification.

There is limited knowledge of the scale and impact of multimorbidity for patients who have had an acute myocardial infarction (AMI). Therefore, this study aimed to determine the extent to which multimorbidity is associated with long-term survival following AMI.This national observational study included 693,388 patients (median age 70.7 years, 452,896 [65.5%] male) from the Myocardial Ischaemia National Audit Project (England and Wales) who were admitted with AMI between 1 January 2003 and 30 June 2013. There were 412,809 (59.5%) patients with multimorbidity at the time of admission with AMI, i.e., having at least 1 of the following long-term health conditions: diabetes, chronic obstructive pulmonary disease or asthma, heart failure, renal failure, cerebrovascular disease, peripheral vascular disease, or hypertension. Those with heart failure, renal failure, or cerebrovascular disease had the worst outcomes (39.5 [95% CI 39.0-40.0], 38.2 [27.7-26.8], and 26.6 [25.2-26.4] deaths per 100 person-years, respectively). Latent class analysis revealed 3 multimorbidity phenotype clusters: (1) a high multimorbidity class, with concomitant heart failure, peripheral vascular disease, and hypertension, (2) a medium multimorbidity class, with peripheral vascular disease and hypertension, and (3) a low multimorbidity class. Patients in class 1 were less likely to receive pharmacological therapies compared with class 2 and 3 patients (including aspirin, 83.8% versus 87.3% and 87.2%, respectively; β-blockers, 74.0% versus 80.9% and 81.4%; and statins, 80.6% versus 85.9% and 85.2%). Flexible parametric survival modelling indicated that patients in class 1 and class 2 had a 2.4-fold (95% CI 2.3-2.5) and 1.5-fold (95% CI 1.4-1.5) increased risk of death and a loss in life expectancy of 2.89 and 1.52 years, respectively, compared with those in class 3 over the 8.4-year follow-up period. The study was limited to all-cause mortality due to the lack of available cause-specific mortality data. However, we isolated the disease-specific association with mortality by providing the loss in life expectancy following AMI according to multimorbidity phenotype cluster compared with the general age-, sex-, and year-matched population.Multimorbidity among patients with AMI was common, and conferred an accumulative increased risk of death. Three multimorbidity phenotype clusters that were significantly associated with loss in life expectancy were identified and should be a concomitant treatment target to improve cardiovascular outcomes.ClinicalTrials.gov NCT03037255.

To investigate the application of the European Society of Cardiology Acute Cardiovascular Care Association quality indicators (QI) for acute myocardial infarction for the study of hospital performance and 30-day mortality.National cohort study (n = 118,075 patients, n = 211 hospitals, MINAP registry), 2012-13. Overall, 16 of the 20 QIs could be calculated. Eleven QIs had a significant inverse association with GRACE risk adjusted 30-day mortality (all P < 0.005). The association with the greatest magnitude was high attainment of the composite opportunity-based QI (80-100%) vs. zero attainment (odds ratio 0.04, 95% confidence interval 0.04-0.05, P < 0.001), increasing attainment from low (0.42, 0.37- 0.49, P < 0.001) to intermediate (0.15, 0.13-0.16, P < 0.001) was significantly associated with a reduced risk of 30-day mortality. A 1% increase in attainment of this QI was associated with a 3% reduction in 30-day mortality (0.97, 0.97-0.97, P < 0.001). The QI with the widest hospital variation was 'fondaparinux received among NSTEMI' (interquartile range 84.7%) and least variation 'centre organisation' (0.0%), with seven QIs depicting minimal variation (<11%). GRACE risk score adjusted 30-day mortality varied by hospital (median 6.7%, interquartile range 5.4-7.9%).Eleven QIs were significantly inversely associated with 30-day mortality. Increasing patient attainment of the composite quality indicator was the most powerful predictor; a 1% increase in attainment represented a 3% decrease in 30-day standardised mortality. The ESC QIs for acute myocardial infarction are applicable in a large health system and have the potential to improve care and reduce unwarranted variation in death from acute myocardial infarction.

International studies report a decline in mortality following non-ST-elevation myocardial infarction (NSTEMI). Whether this is due to lower baseline risk or increased utilization of guideline-indicated treatments is unknown.To determine whether changes in characteristics of patients with NSTEMI are associated with improvements in outcomes.Data on patients with NSTEMI in 247 hospitals in England and Wales were obtained from the Myocardial Ischaemia National Audit Project between January 1, 2003, and June 30, 2013 (final follow-up, December 31, 2013).Baseline demographics, clinical risk (GRACE risk score), and pharmacological and invasive coronary treatments.Adjusted all-cause 180-day postdischarge mortality time trends estimated using flexible parametric survival modeling.Among 389 057 patients with NSTEMI (median age, 72.7 years [IQR, 61.7-81.2 years]; 63.1% men), there were 113 586 deaths (29.2%). From 2003-2004 to 2012-2013, proportions with intermediate to high GRACE risk decreased (87.2% vs 82.0%); proportions with lowest risk increased (4.2% vs 7.6%; P= .01 for trend). The prevalence of diabetes, hypertension, cerebrovascular disease, chronic obstructive pulmonary disease, chronic renal failure, previous invasive coronary strategy, and current or ex-smoking status increased (all P < .001). Unadjusted all-cause mortality rates at 180 days decreased from 10.8% to 7.6% (unadjusted hazard ratio [HR], 0.968 [95% CI, 0.966-0.971]; difference in absolute mortality rate per 100 patients [AMR/100], -1.81 [95% CI, -1.95 to -1.67]). These findings were not substantially changed when adjusted additively by baseline GRACE risk score (HR, 0.975 [95% CI, 0.972-0.977]; AMR/100, -0.18 [95% CI, -0.21 to -0.16]), sex and socioeconomic status (HR, 0.975 [95% CI, 0.973-0.978]; difference in AMR/100, -0.24 [95% CI, -0.27 to -0.21]), comorbidities (HR, 0.973 [95% CI, 0.970-0.976]; difference in AMR/100, -0.44 [95% CI, -0.49 to -0.39]), and pharmacological therapies (HR, 0.972 [95% CI, 0.964-0.980]; difference in AMR/100, -0.53 [95% CI, -0.70 to -0.36]). However, the direction of association was reversed after further adjustment for use of an invasive coronary strategy (HR, 1.02 [95% CI, 1.01-1.03]; difference in AMR/100, 0.59 [95% CI, 0.33-0.86]), which was associated with a relative decrease in mortality of 46.1% (95% CI, 38.9%-52.0%).Among patients hospitalized with NSTEMI in England and Wales, improvements in all-cause mortality were observed between 2003 and 2013. This was significantly associated with use of an invasive coronary strategy and not entirely related to a decline in baseline clinical risk or increased use of pharmacological therapies.

Current guidelines recommend the use of vitamin K antagonist (VKA) for up to 3-6 months for treatment of left ventricular (LV) thrombus post-acute myocardial infarction (AMI). However, based on evidence supporting non-inferiority of novel oral anticoagulants (NOAC) compared to VKA for other indications such as deep vein thrombosis, pulmonary embolism (PE), and thromboembolic prevention in atrial fibrillation, NOACs are being increasingly used off licence for the treatment of LV thrombus post-AMI. In this study, we investigated the safety and effect of NOACs compared to VKA on LV thrombus resolution in patients presenting with AMI.This was an observational study of 2328 consecutive patients undergoing coronary angiography ± percutaneous coronary intervention (PCI) for AMI between May 2015 and December 2018, at a UK cardiac centre. Patients' details were collected from the hospital electronic database. The primary endpoint was rate of LV thrombus resolution with bleeding rates a secondary outcome. Left ventricular thrombus was diagnosed in 101 (4.3%) patients. Sixty patients (59.4%) were started on VKA and 41 patients (40.6%) on NOAC therapy (rivaroxaban: 58.5%, apixaban: 36.5%, and edoxaban: 5.0%). Both groups were well matched in terms of baseline characteristics including age, previous cardiac history (previous myocardial infarction, PCI, coronary artery bypass grafting), and cardiovascular risk factors (hypertension, diabetes, hypercholesterolaemia). Over the follow-up period (median 2.2 years), overall rates of LV thrombus resolution were 86.1%. There was greater and earlier LV thrombus resolution in the NOAC group compared to patients treated with warfarin (82% vs. 64.4%, P = 0.0018, at 1 year), which persisted after adjusting for baseline variables (odds ratio 1.8, 95% confidence interval 1.2-2.9). Major bleeding events during the follow-up period were lower in the NOAC group, compared with VKA group (0% vs. 6.7%, P = 0.030) with no difference in rates of systemic thromboembolism (5% vs. 2.4%, P = 0.388).These data suggest improved thrombus resolution in post-acute coronary syndrome (ACS) LV thrombosis in patients treated with NOACs compared to VKAs. This improvement in thrombus resolution was accompanied with a better safety profile for NOAC patients vs. VKA-treated patients. Thus, provides data to support a randomized trial to answer this question.

Background Studies have reported significant reduction in acute myocardial infarction–related hospitalizations during the coronavirus disease 2019 (COVID‐19) pandemic. However, whether these trends are associated with increased incidence of out‐of‐hospital cardiac arrest (OHCA) in this population is unknown. Methods and Results Acute myocardial infarction hospitalizations with OHCA during the COVID‐19 period (February 1–May 14, 2020) from the Myocardial Ischaemia National Audit Project and British Cardiovascular Intervention Society data sets were analyzed. Temporal trends were assessed using Poisson models with equivalent pre–COVID‐19 period (February 1–May 14, 2019) as reference. Acute myocardial infarction hospitalizations during COVID‐19 period were reduced by &gt;50% (n=20 310 versus n=9325). OHCA was more prevalent during the COVID‐19 period compared with the pre–COVID‐19 period (5.6% versus 3.6%), with a 56% increase in the incidence of OHCA (incidence rate ratio, 1.56; 95% CI, 1.39–1.74). Patients experiencing OHCA during COVID‐19 period were likely to be older, likely to be women, likely to be of Asian ethnicity, and more likely to present with ST‐segment–elevation myocardial infarction. The overall rates of invasive coronary angiography (58.4% versus 71.6%; P &lt;0.001) were significantly lower among the OHCA group during COVID‐19 period with increased time to reperfusion (mean, 2.1 versus 1.1 hours; P =0.05) in those with ST‐segment–elevation myocardial infarction. The adjusted in‐hospital mortality probability increased from 27.7% in February 2020 to 35.8% in May 2020 in the COVID‐19 group ( P &lt;.001). Conclusions In this national cohort of hospitalized patients with acute myocardial infarction, we observed a significant increase in incidence of OHCA during COVID‐19 period paralleled with reduced access to guideline‐recommended care and increased in‐hospital mortality.

Abstract Aims Quality indicators (QIs) are tools to improve the delivery of evidence-base medicine. In 2017, the European Society of Cardiology (ESC) Association for Acute Cardiovascular Care (ACVC) developed a set of QIs for acute myocardial infarction (AMI), which have been evaluated at national and international levels and across different populations. However, an update of these QIs is needed in light of the accumulated experience and the changes in the supporting evidence. Methods and results The ESC methodology for the QI development was used to update the 2017 ACVC QIs. We identified key domains of AMI care, conducted a literature review, developed a list of candidate QIs, and used a modified Delphi method to select the final set of indicators. The same seven domains of AMI care identified by the 2017 Study Group were retained for this update. For each domain, main and secondary QIs were developed reflecting the essential and complementary aspects of care, respectively. Overall, 26 QIs are proposed in this document, compared to 20 in the 2017 set. New QIs are proposed in this document (e.g. the centre use of high-sensitivity troponin), some were retained or modified (e.g. the in-hospital risk assessment), and others were retired in accordance with the changes in evidence [e.g. the proportion of patients with non-ST segment elevation myocardial infarction (NSTEMI) treated with fondaparinux] and the feasibility assessments (e.g. the proportion of patients with NSTEMI whom risk assessment is performed using the GRACE and CRUSADE risk scores). Conclusion Updated QIs for the management of AMI were developed according to contemporary knowledge and accumulated experience. These QIs may be applied to evaluate and improve the quality of AMI care.

Patients with underlying cardiovascular disease and coronavirus disease 2019 (COVID-19) infection are at increased risk of morbidity and mortality.This study was designed to characterize the presenting profile and outcomes of patients hospitalized with acute coronary syndrome (ACS) and COVID-19 infection.This observational cohort study was conducted using multisource data from all acute NHS hospitals in England. All consecutive patients hospitalized with diagnosis of ACS with or without COVID-19 infection between 1 March and 31 May 2020 were included. The primary outcome was in-hospital and 30-day mortality.A total of 12 958 patients were hospitalized with ACS during the study period, of which 517 (4.0%) were COVID-19-positive and were more likely to present with non-ST-elevation acute myocardial infarction. The COVID-19 ACS group were generally older, Black Asian and Minority ethnicity, more comorbid and had unfavourable presenting clinical characteristics such as elevated cardiac troponin, pulmonary oedema, cardiogenic shock and poor left ventricular systolic function compared with the non-COVID-19 ACS group. They were less likely to receive an invasive coronary angiography (67.7% vs 81.0%), percutaneous coronary intervention (PCI) (30.2% vs 53.9%) and dual antiplatelet medication (76.3% vs 88.0%). After adjusting for all the baseline differences, patients with COVID-19 ACS had higher in-hospital (adjusted odds ratio (aOR): 3.27; 95% confidence interval (CI): 2.41-4.42) and 30-day mortality (aOR: 6.53; 95% CI: 5.1-8.36) compared to patients with the non-COVID-19 ACS.COVID-19 infection was present in 4% of patients hospitalized with an ACS in England and is associated with lower rates of guideline-recommended treatment and significant mortality hazard.

This report from the European Society of Cardiology (ESC) Atlas Project updates and expands upon the widely cited 2019 report in presenting cardiovascular disease (CVD) statistics for the 57 ESC member countries.Statistics pertaining to 2019, or the latest available year, are presented. Data sources include the World Health Organization, the Institute for Health Metrics and Evaluation, the World Bank, and novel ESC sponsored data on human and capital infrastructure and cardiovascular healthcare delivery. New material in this report includes sociodemographic and environmental determinants of CVD, rheumatic heart disease, out-of-hospital cardiac arrest, leftsided valvular heart disease, the advocacy potential of these CVD statistics, and progress towards World Health Organization (WHO) 2025 targets for non-communicable diseases. Salient observations in this report: (i) Females born in ESC member countries in 2018 are expected to live 80.8 years and males 74.8 years. Life expectancy is longer in high income (81.6 years) compared with middle-income (74.2 years) countries. (ii) In 2018, high-income countries spent, on average, four times more on healthcare than middle-income countries. (iii) The median PM2.5 concentrations in 2019 were over twice as high in middle-income ESC member countries compared with high-income countries and exceeded the EU air quality standard in 14 countries, all middle-income. (iv) In 2016, more than one in five adults across the ESC member countries were obese with similar prevalence in high and low-income countries. The prevalence of obesity has more than doubled over the past 35 years. (v) The burden of CVD falls hardest on middle-income ESC member countries where estimated incidence rates are ∼30% higher compared with high-income countries. This is reflected in disability-adjusted life years due to CVD which are nearly four times as high in middle-income compared with high-income countries. (vi) The incidence of calcific aortic valve disease has increased seven-fold during the last 30 years, with age-standardized rates four times as high in high-income compared with middle-income countries. (vii) Although the total number of CVD deaths across all countries far exceeds the number of cancer deaths for both sexes, there are 15 ESC member countries in which cancer accounts for more deaths than CVD in males and five-member countries in which cancer accounts for more deaths than CVD in females. (viii) The under-resourced status of middle-income countries is associated with a severe procedural deficit compared with high-income countries in terms of coronary intervention, ablation procedures, device implantation, and cardiac surgical procedures.Risk factors and unhealthy behaviours are potentially reversible, and this provides a huge opportunity to address the health inequalities across ESC member countries that are highlighted in this report. It seems clear, however, that efforts to seize this opportunity are falling short and present evidence suggests that most of the WHO NCD targets for 2025 are unlikely to be met across ESC member countries.

Cardiovascular disease (CVD) impacts significantly health and social care systems as well as society through premature mortality and disability, with patients requiring care from relatives. Previous pan-European estimates of the economic burden of CVD are now outdated. This study aims to provide novel, up-to-date evidence on the economic burden across the 27 European Union (EU) countries in 2021.Aggregate country-specific resource use data on morbidity, mortality, and health, social and informal care were obtained from international sources, such as the Statistical Office of the European Communities, enhanced by data from the European Society of Cardiology Atlas programme and patient-level data from the Survey of Health, Ageing and Retirement in Europe. Country-specific unit costs were used, with cost estimates reported on a per capita basis, after adjustment for price differentials.CVD is estimated to cost the EU €282 billion annually, with health and long-term care accounting for €155 billion (55%), equalling 11% of EU-health expenditure. Productivity losses accounted for 17% (€48 billion), whereas informal care costs were €79 billion (28%). CVD represented a cost of €630 per person, ranging from €381 in Cyprus to €903 in Germany. Coronary heart disease accounted for 27% (€77 billion) and cerebrovascular diseases for 27% (€76 billion) of CVD costs.This study provides contemporary estimates of the wide-ranging impact of CVD on all aspects of the economy. The data help inform evidence-based policies to reduce the impact of CVD, promoting care access and better health outcomes and economic sustainability.

Objectives. Silent myocardial ischemia is common in patients with diabetes. This study was designed to assess the role of subclinical autonomic impairment in diabetic patients with silent ischemia. Background. Studies have suggested that silent ischemia is more common in diabetic patients with microvascular complications, but this has not been a consistent finding. Methods. Twenty-two diabetic and 30 nondiabetic patients with proved coronary artery disease and a history of angina and ischemia on treadmill stress testing underwent clinical tests of autonomic function and measurement of 24-h heart rate variability. Diabetic patients with a history of microvascular complications were excluded. Results. Although all 52 patients manifested ischemia during treadmill testing, only 36 patients experienced angina (angina group), whereas 16 did not (silent ischemia group). Diabetic and nondiabetic patients were similar in age (59 ± 1 vs. 61 ± 2 years, p = 0.56) and extent of coronary artery disease. However, clinical tests showed reduced parasympathetic function in the diabetic patients (Valsalva ratio 1.38 ± 0.07 vs. 1.60 ± 0.06, p = 0.007). Patients in the silent ischemia group were more often diabetic (33% vs. 63%, p = 0.05) and had prolonged time to ischemia on treadmill testing (200 ± 20 vs. 271 ± 20 s, p = 0.03). In addition, autonomic function was impaired in the silent group (supine/standing heart rate ratio 1.15 ± 0.02 vs. 1.05 ± 0.02, p = 0.002). Subgroup analysis showed that abnormalities of autonomic function were confined to the diabetic patients in the silent group. Conclusions. Despite the absence of overt microvascular complications, diabetic patients with silent exertional ischemia have evidence of significant autonomic impairment compared with findings in symptomatic patients. This difference is not seen in nondiabetic patients and indicates that subclinical neuropathy is an important cause of silent ischemia in patients with diabetes.

Patients with diabetes are prone to silent myocardial infarction and silent exertional ischemia. Although the mechanism is not clear, it may reflect a specific impairment of the sensory innervation of the heart. To test this hypothesis, anginal perceptual threshold was measured in 32 diabetic patients and 36 nondiabetic control patients, all of whom had typical exertional angina. Anginal perceptual threshold was defined as the time from onset of 0.1 mV ST depression to the onset of chest pain during treadmill stress electrocardiography. Although ST depression occurred earlier in the diabetic than in the nondiabetic group (111 +/- 82 versus 216 +/- 162 s, p less than 0.005), the anginal perceptual threshold in the diabetic group was delayed by a mean of 86 s (149 +/- 76 versus 63 +/- 59 s, p less than 0.001), with 95% confidence intervals of 53 to 119 s. Autonomic function tests were abnormal in the diabetic group, and in both groups regression analyses (using a third order polynomial) showed marked prolongations of anginal perceptual threshold as the heart rate responses to the Valsalva maneuver decreased to below the normal range (r = 0.5, p less than 0.001). There was a similar though less pronounced relation between anginal perceptual threshold and the heart rate responses to deep breathing (r = 0.3, p less than 0.02). These data suggest that prolongation of the anginal perceptual threshold may be caused by autonomic neuropathy involving the sensory innervation of the heart. To test sensory function, median nerve conduction studies were performed in 19 patients (10 diabetic and 9 nondiabetic).(ABSTRACT TRUNCATED AT 250 WORDS)

To compare mortality in south Asian (Indian, Pakistani, and Bangladeshi) and white patients in the six months after hospital admission for acute myocardial infarction.Observational study.District general hospital in east London.149 south Asian and 313 white patients aged < 65 years admitted to the coronary care unit with acute myocardial infarction from 1 December 1988 to 31 December 1992.All cause mortality in the first six months after myocardial infarction.The admission rate in the south Asians was estimated to be 2.04 times that in the white patients. Most aspects of treatment were similar in the two groups, except that a higher proportion of the south Asians received thrombolytic drugs (81.2% v 73.8%). After adjustment for age, sex, previous myocardial infarction, and treatment with thrombolysis or aspirin, or both, the south Asians had a poorer survival over the six months from myocardial infarction (hazard ratio 2.02 (95% confidence interval 1.14 to 3.56), P = 0.018), but a substantially higher proportion were diabetic (38% v 11%, P < 0.001), and additional adjustment for diabetes removed much of their excess risk (adjusted hazard ratio 1.26 (0.68 to 2.33), P = 0.47).South Asian patients had a higher risk of admission with myocardial infarction and a higher risk of death over the ensuing six months than the white patients. The higher case fatality among the south Asians, largely attributable to diabetes, may contribute to the increased risk of death from coronary heart disease in south Asians living in Britain.

About 75% of patients with acute myocardial infarction are older than 70 years, but patients in this age group are commonly treated less vigorously than younger patients. This differential treatment may partly reflect clinicians' misconceptions about the outlook of such patients, and the importance of age in clinical decisions. We examined how age does and should affect the management of patients and risk stratification in acute myocardial infarction.In this prospective cohort study, we recruited 1225 consecutive patients admitted with acute myocardial infarction to a district general hospital in east London. The primary endpoint was death. We used tabulation and regression methods to analyse the association between age group and clinical variables.Patients aged 70 years or older took a longer time to arrive in hospital and were less likely to receive thrombolysis or discharge beta-blockers than patients younger than 60 years: odds ratio 0.63 (95% CI 9.45-0.88) for thrombolysis and 0.25 (0.16-0.37) for beta-blockade, adjusted for sex, diabetes, previous acute myocardial infarction, Q wave infarction, and left-ventricular failure. Left-ventricular failure was the strongest independent predictor of death within 1 year of infarction with a hazard ratio of 4.76 (3.53-6.43), adjusted for age, sex, diabetes, and Q wave infarction. Patients aged 70 years or older without left-ventricular failure had significantly better survival at 1 year after acute myocardial infarction than patients under 60 years with left-ventricular failure. 70.8% (62.2-78.2) of the older patients who survived to hospital discharge were still alive 3 years later.Elderly patients with acute myocardial infarction were treated less vigorously than younger patients. The prognosis of acute myocardial infarction, however, was substantially affected by the development of left-ventricular failure and other clinical indices, such that many older patients had a better outlook than younger patients with adverse clinical factors. In planning risk-based management, consideration of age independently of clinical status is inappropriate.

<b>Objectives:</b> To report clinical characteristics, angiographical findings and results of endovascular treatment of patients presenting with dural carotid–cavernous fistulas (DCCFs). <b>Method:</b> Retrospective analysis of 27 consecutive patients with DCCF referred to a specialised interventional neuroradiology department. <b>Results:</b> Orbital and neuro-ophthalmological symptoms were the most common clinical presentation at diagnosis (n = 25). The venous drainage of the fistula involved the ipsilateral superior ophthalmic vein in 24 patients, the contralateral cavernous sinus in 6 and a leptomeningeal vein in 5 patients. Thrombosis of at least one petrosal sinus was found in 23 patients. 7 patients did not receive endovascular treatment: 3 had spontaneous DCCF obliteration, and 4 had only minor clinical symptoms and no leptomeningeal venous drainage on an angiogram. 20 patients received endovascular treatment via either a transvenous (n = 16) or a transarterial approach (n = 4). Complete occlusion of the fistula was obtained in 14 of 16 (87%) patients treated by the transvenous approach and in 1 of 4 (25%) patients treated by the transarterial approach. 16 patients had early clinical improvement after endovascular treatment. One patient had a cerebral haemorrhage after transvenous embolisation of a DCCF with leptomeningeal drainage. On follow-up, all patients treated by the transarterial route remained symptomatic, whereas 10 of 14 (71%) patients cured by the transvenous route were asymptomatic. <b>Conclusions:</b> Transvenous embolisation is a safe and efficient endovascular approach to treat patients with DCCF. However, this technique requires a long learning curve.

To compare rates of revascularisation in south Asian and white patients undergoing coronary angiography in relation to the appropriateness of revascularisation and clinical outcome.Prospective cohort study of patients with two and a half years' follow up; appropriateness of revascularisation rated by nine experts with no knowledge of ethnicity of patient.Tertiary cardiac centre in London with referral from five contiguous health authorities.Consecutive patients (502 south Asian, 2974 white) undergoing coronary angiography in the appropriateness of coronary revascularisation study (ACRE).Coronary revascularisation, non-fatal myocardial infarction, mortality.There was no difference between south Asian and white patients in the proportions deemed appropriate for revascularisation (72% (361) v 68% (2022)) or in the proportions for whom the physician's intended management was revascularisation (39% (196) v 41% (1218)). Among patients appropriate for revascularisation, age adjusted rates of coronary angioplasty (hazard ratio 0.69, 95% confidence interval 0.47 to 1.00, P=0.058) and coronary artery bypass grafting (0.74, 0.58 to 0.91, P=0.007) were lower in south Asian than in white patients. These differences were smaller but still present after adjustment for socioeconomic status and after restriction of analysis to those patients for whom the intended management was revascularisation. There were no differences in mortality and non-fatal myocardial infarction between south Asian and white patients (1.07, 0.78 to 1.47).Among patients deemed appropriate for coronary artery bypass grafting, south Asian patients are less likely than white patients to receive it. This difference is not explained by physician bias.

Heart rate, a major determinant of angina in coronary disease, is also an important predictor of cardiovascular mortality.Lowering heart rate is therefore one of the most important therapeutic approaches in the treatment of stable angina pectoris.To date, b-blockers and some calcium-channel antagonists reduce heart rate, but their use may be limited by adverse reactions or contraindications.Heart rate is determined by spontaneous electrical pacemaker activity in the sinoatrial node controlled by the I f current.Ivabradine is the first specific heart rate-lowering agent that has completed clinical development for stable angina pectoris.It is selective for the I f current, lowering heart rate at concentrations that do not affect other cardiac ionic currents.Specific heart-rate lowering with ivabradine reduces myocardial oxygen demand, simultaneously improving oxygen supply.Ivabradine has no negative inotropic or lusitropic effects, preserving ventricular contractility, and does not change any major electrophysiological parameters unrelated to heart rate.Randomised clinical studies in patients with stable angina show that ivabradine effectively reduces heart rate, improves exercise capacity and reduces the number of angina attacks.It has superior anti-anginal and anti-ischaemic activity to placebo and is non-inferior to atenolol and amlodipine.Ivabradine therefore offers a valuable approach to lowering heart rate exclusively and provides an attractive alternative to conventional treatment for a wide range of patients with confirmed stable angina.

Adherence to evidence-based treatments and its consequences after acute myocardial infarction (MI) are poorly defined. We examined the extent to which clopidogrel treatment initiated in hospital is continued in primary care; the factors predictive of clopidogrel discontinuation and the hazard of death or recurrent MI. We linked the Myocardial Ischaemia National Audit Project registry and the General Practice Research Database to examine adherence to clopidogrel in primary care among patients discharged from hospital after MI (2003–2009). Hospital Episode Statistics and national mortality data were linked, documenting all-cause mortality and non-fatal MI. Of the 7543 linked patients, 4650 were prescribed clopidogrel in primary care within 3 months of discharge. The adjusted odds of still being prescribed clopidogrel at 12 months were similar following non-ST-elevation myocardial infarction (NSTEMI) 53% (95% CI, 51–55) and ST-elevation myocardial infarction (STEMI) 54% (95% CI, 52–56), but contrast with statins: NSTEMI 84% (95% CI, 82–85) and STEMI 89% (95% CI, 87–90). Discontinuation within 12 months was more frequent in older patients [>80 vs. 40–49 years, adjusted hazard ratio (HR) 1.50 (95% CI, 1.15–1.94)] and with bleeding events [HR 1.34 (95% CI, 1.03–1.73)]. 18.15 patients per 100 person-years (95% CI, 16.83–19.58) died or experienced non-fatal MI in the first year following discharge. In patients who discontinued clopidogrel within 12 months, the adjusted HR for death or non-fatal MI was 1.45 (95% CI, 1.22–1.73) compared with untreated patients, and 2.62 (95% CI, 2.17–3.17) compared with patients persisting with clopidogrel treatment. This is the first study to use linked registries to determine persistence of clopidogrel treatment after MI in primary care. It demonstrates that discontinuation is common and associated with adverse outcomes.

<h3>Objective</h3> To investigate temporal changes in survival after acute myocardial infarction (AMI) by early invasive strategy. <h3>Methods</h3> Accelerated failure time and 6-month relative survival analyses stratified by thrombolysis or primary percutaneous coronary intervention (PPCI) for ST elevation myocardial infarction (STEMI) and coronary angiography for non-STEMI (NSTEMI) encompassing 583 466 patients across 247 hospitals in England and Wales over hospital admission periods 2003–2004, 2005–2006, 2007–2008 and 2009–2010. <h3>Results</h3> Survival improved significantly for STEMI patients who received reperfusion therapy (time ratio (TR) 1.47, 95% CI 1.22 to 2.78) and was stable for those who did not (TR 1.02, 95% CI 0.85 to 1.22). While there were significant improvements in survival for NSTEMI patients who underwent coronary angiography (TR 1.39, 95% CI 1.18 to 1.62), there was a significant decline for those who did not (TR 0.70, 95% CI 0.65 to 0.75). Patients without reperfusion therapy or coronary angiography had a greater number of comorbidities, but the use of secondary prevention medications was comparable with patients who received reperfusion therapy or coronary angiography. There was a significant hospital-level survival effect, with higher crude 6-month mortality in hospitals in the lowest coronary angiography and PPCI quartiles (angiography Q1: 16.4% vs Q4: 12.8%; PPCI Q1: 15.8% vs Q4: 12.4%). <h3>Conclusions</h3> Survival rates after AMI have improved. Whereas survival estimates for STEMI patients who did not receive reperfusion therapy were stable, they worsened for NSTEMI patients not receiving coronary angiography.

To measure the association between use of proton pump inhibitors and a range of harmful outcomes in patients using clopidogrel and aspirin.Observational cohort study and self controlled case series.United Kingdom General Practice Research Database with linked data from the Myocardial Ischaemia National Audit Project (MINAP) and the Office for National Statistics (the cardiovascular disease research using linked bespoke studies and electronic records (CALIBER) collaboration)24,471 patients receiving clopidogrel and aspirin.The primary outcome was death or incident myocardial infarction. Secondary outcomes were death, incident myocardial infarction, vascular death, and non-vascular death. Comparisons were made between proton pump inhibitor use and non-use.Of the 24,471 patients prescribed clopidogrel and aspirin, 12,439 (50%) were also prescribed a proton pump inhibitor at some time during the study. Death or incident myocardial infarction occurred in 1419 (11%) patients while they were receiving a proton pump inhibitor compared with 1341 (8%) who were not receiving a proton pump inhibitor. In multivariate analysis, the hazard ratio for the association between proton pump inhibitor use and death or incident myocardial infarction was 1.37 (95% confidence interval 1.27 to 1.48). Comparable results were seen for secondary outcomes and with other 2C19 inhibitors and with non-2C19 inhibitors. With the self controlled case series design to remove the effect of differences between people, there was no association between proton pump inhibitor use and myocardial infarction, with a rate ratio of 0.75 (0.55 to 1.01). Similarly, with the self controlled case series there was no association with myocardial infarction for other 2C19 inhibitors/non-inhibitors.The lack of a specific association and the discrepancy between findings of the analyses between and within people suggests that the interaction between proton pump inhibitors and clopidogrel is clinically unimportant.

The coronary arteries have been regarded as end arteries for decades. However, there are functionally relevant anastomotic vessels, known as collateral arteries, which interconnect epicardial coronary arteries. These vessels provide an alternative source of blood supply to the myocardium in cases of occlusive coronary artery disease. The relevance of these collateral arteries is a matter of ongoing debate, but increasing evidence indicates a relevant protective role in patients with coronary artery disease. The collateral circulation can be assessed by different methods; the gold standard involves intracoronary pressure measurements. While the first clinical trials to therapeutically induce growth of collateral arteries have been unavailing, recent pilot studies using external counterpulsation or growth factors such as granulocyte colony stimulating factor (G-CSF) have shown promising results.

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).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).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.

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

ObjectivesTo compare management of patients with acute non-ST segment elevation myocardial infarction (NSTEMI) in three developed countries with national ongoing registries.BackgroundResults from clinical trials suggest significant variation in care across the world. However, international comparisons in “real world” registries are limited.MethodsWe compared the use of in-hospital procedures and discharge medications for patients admitted with NSTEMI from 2007 to 2010 using the unselective MINAP/NICOR [England and Wales (UK); n = 137,009], the unselective SWEDEHEART/RIKS-HIA (Sweden; n = 45,069), and the selective ACTION Registry-GWTG/NCDR [United States (US); n = 147,438] clinical registries.ResultsPatients enrolled among the three registries were generally similar except those in the US who were younger but had higher rates of smoking, diabetes, hypertension, prior heart failure, and prior MI than in Sweden or in UK. Angiography and percutaneous coronary intervention (PCI) were performed more often in the US (76% and 44%) and Sweden (65% and 42%) relative to the UK (32% and 22%). Discharge betablockers were also prescribed more often in the US (89%) and Sweden (89%) than in the UK (76%). In contrast, discharge statins, angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB), and dual antiplatelet agents (among those not receiving PCI) were higher in the UK (92%, 79%, and 71%) than in the US (85%, 65%, 41%) and Sweden (81%, 69%, and 49%).ConclusionsThe care for patients with NSTEMI differed substantially among the three countries. These differences in care among countries provide an opportunity for future comparative effectiveness research as well as identify opportunities for global quality improvement.

While the association of ethnic group with individual cardiovascular diseases has been studied, little is known about ethnic differences in the initial lifetime presentation of clinical cardiovascular disease in contemporary populations.We studied 1,068,318 people, aged ≥30 years and free from diagnosed CVD at baseline (90.9% White, 3.6% South Asian and 2.9% Black), using English linked electronic health records covering primary care, hospital admissions, acute coronary syndrome registry and mortality registry (CALIBER platform). During 5.7 years median follow-up between 1997-2010, 95,224 people experienced an incident cardiovascular diagnosis. 69.9% (67.2%-72.4%) of initial presentation in South Asian <60 yrs were coronary heart disease presentations compared to 47.8% (47.3%-48.3%) in White and 40.1% (36.3%-43.9%) in Black patients. Compared to White patients, Black patients had significantly lower age-sex adjusted hazard ratios (HRs) for initial lifetime presentation of all the coronary disease diagnoses (stable angina HR 0.80 (95% CI 0.68-0.93); unstable angina- 0.75 (0.59-0.97); myocardial infarction 0.49 (0.40-0.62)) while South Asian patients had significantly higher HRs (stable angina- 1.67 (1.52-1.84); unstable angina 1.82 (1.56-2.13); myocardial infarction- 1.67 (1.49-1.87). We found no ethnic differences in initial presentation with heart failure (Black 0.97 (0.79-1.20); S Asian 1.04(0.87-1.26)). Compared to White patients, Black patients were more likely to present with ischaemic stroke (1.24 (0.97-1.58)) and intracerebral haemorrhage (1.44 (0.97-2.12)). Presentation with peripheral arterial disease was less likely for Black (0.63 (0.50-0.80)) and South Asian patients (0.70 (0.57-0.86)) compared with White patients.While we found the anticipated substantial predominance of coronary heart disease presentations in South Asian and predominance of stroke presentations in Black patients, we found no ethnic differences in presentation with heart failure. We consider the public health and research implications of our findings.NCT02176174, www.clinicaltrials.gov.

To determine whether the effect of South Asian ethnicity differs between studies of incidence and prognosis of coronary disease.Systematic literature review and meta-analysis, and cohort analysis from a national acute coronary syndrome (ACS) registry linked to mortality (National Institute of Cardiovascular Outcomes Research/Myocardial Infarction National Audit Project).International for the review, and England and Wales for the cohort analysis.The numbers of South Asians included in the meta-analysis were 111 555 (incidence) and 14 531 (prognosis) of whom 8251 were from the ACS cohort.Incidence studies: non-fatal myocardial infarction or fatal coronary heart disease; prognostic studies: mortality; HRs for 1-year all-cause death in ACS cohort.South Asians had higher incidence of coronary disease compared with white subjects (HR 1.35 95% CI 1.30 to 1.40) based on meta-analysis of nine studies. Among 10 studies on prognosis, South Asians had better prognosis compared with white subjects (HR 0.78 95% CI 0.74 to 0.82). In the ACS cohort, the impact of diabetes (42.4% of South Asians, 16.9% of white subjects) on 1-year mortality was stronger in South Asians than white subjects (age-adjusted HR 1.83 95% CI 1.59 to 2.11 vs 1.53 95% CI 1.49 to 1.57). However, prognosis was better in South Asians even among diabetics, older people and those living in areas of the highest social deprivation.South Asian ethnicity is associated with higher incidence of coronary disease, but lower mortality once coronary disease is manifest. The dissociation between effects on incidence and prognosis suggests that public health initiatives to reduce inequalities in mortality between South Asian and white populations should focus on primary prevention. This is a CALIBER study with ClinicalTrials.gov Identifier: NCT01163513.

To investigate whether improved survival from non-ST-elevation myocardial infarction (NSTEMI), according to GRACE risk score, was associated with guideline-indicated treatments and diagnostics, and persisted after hospital discharge.National cohort study (n = 389 507 patients, n = 232 hospitals, MINAP registry), 2003-2013. The primary outcome was adjusted all-cause survival estimated using flexible parametric survival modelling with time-varying covariates. Optimal care was defined as the receipt of all eligible treatments and was inversely related to risk status (defined by the GRACE risk score): 25.6% in low, 18.6% in intermediate, and 11.5% in high-risk NSTEMI. At 30 days, the use of optimal care was associated with improved survival among high [adjusted hazard ratio (aHR) -0.66 95% confidence interval (CI) 0.53-0.86, difference in absolute mortality rate (AMR) per 100 patients (AMR/100-0.19 95% CI -0.29 to -0.08)], and intermediate (aHR = 0.74, 95% CI 0.62-0.92; AMR/100 = -0.15, 95% CI -0.23 to -0.08) risk NSTEMI. At the end of follow-up (8.4 years, median 2.3 years), the significant association between the use of all eligible guideline-indicated treatments and improved survival remained only for high-risk NSTEMI (aHR = 0.66, 95% CI 0.50-0.96; AMR/100 = -0.03, 95% CI -0.06 to -0.01). For low-risk NSTEMI, there was no association between the use of optimal care and improved survival at 30 days (aHR = 0.92, 95% CI 0.69-1.38) and at 8.4 years (aHR = 0.71, 95% CI 0.39-3.74).Optimal use of guideline-indicated care for NSTEMI was associated with greater survival gains with increasing GRACE risk, but its use decreased with increasing GRACE risk.

Patients with chronic obstructive pulmonary disease (COPD) have increased mortality following myocardial infarction (MI) compared with patients without COPD. We investigated the extent to which differences in recognition and management after MI could explain the mortality difference.300 161 patients with a first MI between 2003 and 2013 were identified in the UK Myocardial Ischaemia National Audit Project database. Logistic regression was used to compare mortality in hospital and at 180 days postdischarge between patients with and without COPD. Variables relating to inhospital factors (delay in diagnosis, use of reperfusion and time to reperfusion/use of angiography) and use of secondary prevention were sequentially added to models.Mortality was higher for patients with COPD both inhospital (4.6% vs 3.2%) and at 180 days (12.8% vs 7.7%). After adjusting for inhospital factors, the effect of COPD on inhospital mortality after MI was reduced for both ST-elevation myocardial infarctions (STEMIs) and non-STEMIs (STEMIs OR 1.24 (95% CI 1.10 to 1.41) to 1.13 (95% CI 0.99 to 1.29); non-STEMIs OR 1.34 (95% CI 1.24 to 1.45) to 1.16 (95% CI 1.07 to 1.26)). Adjusting for inhospital factors reduced the effect of COPD on mortality after non-STEMI at 180 days (OR 1.56 (95% CI 1.47 to 1.65) to 1.37 (95% CI 1.31 to 1.44)). Adjusting for use of secondary prevention also reduced the effect of COPD on mortality at 180 days for STEMIs and non-STEMIs (STEMIs OR 1.45 (95% CI 1.31 to 1.61) to 1.25 (95% CI 1.11 to 1.41); non-STEMIs OR 1.37 (95% CI 1.31 to 1.44) to 1.26 (95% CI 1.17 to 1.35).Delayed diagnosis, timing and use of reperfusion of a STEMI, use of angiography after a non-STEMI and use of secondary prevention medicines are all potential explanations for the mortality gap after MI in people with COPD.

Abstract Aims As health systems around the world increasingly look to measure and improve the value of care that they provide to patients, being able to measure the outcomes that matter most to patients is vital. To support the shift towards value-based health care in atrial fibrillation (AF), the International Consortium for Health Outcomes Measurement (ICHOM) assembled an international Working Group (WG) of 30 volunteers, including health professionals and patient representatives to develop a standardized minimum set of outcomes for benchmarking care delivery in clinical settings. Methods and results Using an online-modified Delphi process, outcomes important to patients and health professionals were selected and categorized into (i) long-term consequences of disease outcomes, (ii) complications of treatment outcomes, and (iii) patient-reported outcomes. The WG identified demographic and clinical variables for use as case-mix risk adjusters. These included baseline demographics, comorbidities, cognitive function, date of diagnosis, disease duration, medications prescribed and AF procedures, as well as smoking, body mass index (BMI), alcohol intake, and physical activity. Where appropriate, and for ease of implementation, standardization of outcomes and case-mix variables was achieved using ICD codes. The standard set underwent an open review process in which over 80% of patients surveyed agreed with the outcomes captured by the standard set. Conclusion Implementation of these consensus recommendations could help institutions to monitor, compare and improve the quality and delivery of chronic AF care. Their consistent definition and collection, using ICD codes where applicable, could also broaden the implementation of more patient-centric clinical outcomes research in AF.

To examine long-term healthcare utilization and costs of patients with stable coronary artery disease (SCAD). Linked cohort study of 94 966 patients with SCAD in England, 1 January 2001 to 31 March 2010, identified from primary care, secondary care, disease, and death registries. Resource use and costs, and cost predictors by time and 5-year cardiovascular disease (CVD) risk profile were estimated using generalized linear models. Coronary heart disease hospitalizations were 20.5% in the first year and 66% in the year following a non-fatal (myocardial infarction, ischaemic or haemorrhagic stroke) event. Mean healthcare costs were £3133 per patient in the first year and £10 377 in the year following a non-fatal event. First-year predictors of cost included sex (mean cost £549 lower in females), SCAD diagnosis (non-ST-elevation myocardial infarction cost £656 more than stable angina), and co-morbidities (heart failure cost £657 more per patient). Compared with lower risk patients (5-year CVD risk 3.5%), those of higher risk (5-year CVD risk 44.2%) had higher 5-year costs (£23 393 vs. £9335) and lower lifetime costs (£43 020 vs. £116 888). Patients with SCAD incur substantial healthcare utilization and costs, which varies and may be predicted by 5-year CVD risk profile. Higher risk patients have higher initial but lower lifetime costs than lower risk patients as a result of shorter life expectancy. Improved cardiovascular survivorship among an ageing CVD population is likely to require stratified care in anticipation of the burgeoning demand.

Abstract Aims The European Association of Percutaneous Cardiovascular Interventions (EAPCI) Atlas of Interventional Cardiology has been developed to map interventional practice across European Society of Cardiology (ESC) member countries. Here we present the main findings of a 16-country survey in which we examine the national availability of interventional infrastructure, human resource, and procedure volumes. Methods and results Sixteen ESC member countries participated in the EAPCI Atlas survey. Interventional data were collected by the National Cardiac Society of each participating country. An annual median of 5131 [interquartile range (IQR) 4013–5801] diagnostic heart procedures per million people were reported, ranging from &amp;lt;2500 in Egypt and Romania to &amp;gt;7000 in Turkey and Germany. Procedure rates showed significant correlation (r = 0.67, P = 0.013) with gross national income (GNI) per capita. An annual median of 2478 (IQR 1690–2633) percutaneous coronary interventions (PCIs) per million people were reported, ranging from &amp;lt;1000 in Egypt and Romania to &amp;gt;3000 in Switzerland, Poland, and Germany. Procedure rates showed significant correlation with GNI per capita (r = 0.62, P = 0.014). An annual median of 48.2 (IQR 29.1–105.2) transcatheter aortic valve implantation procedures per million people were performed, varying from &amp;lt;25 per million people in Egypt, Romania, Turkey, and Poland to &amp;gt;100 per million people in Denmark, France, Switzerland, and Germany. Procedure rates showed significant correlation with national GNI per capita (r = 0.92, P &amp;lt; 0.001). Conclusion The first report from the EAPCI Atlas has shown considerable international heterogeneity in interventional cardiology procedure volumes. The heterogeneity showed association with national economic resource, a reflection no doubt of the technological costs of developing an interventional cardiology service.

Background International guidelines recommend that for NSTEMI, the timing of invasive strategy (IS) is a function of patient's baseline risk. The extent to which this is delivered across and within healthcare systems is unknown. Methods Data were derived from 137,265 patients admitted with an NSTEMI diagnosis between 2010 and 2015 in England and Wales. Patients were stratified into low, intermediate and high-risk in keeping with international guidelines. Time to IS was categorised into early (24 h), intermediate (25–72 h) and late (>72 h). Multivariable logistic regression models were used to identify independent predictors of guidelines recommended receipt of IS. Results There were 3608 (2.6%) low, 5037 (3.7%) intermediate and 128,621 (93.7%) high-risk patients. Guidelines recommended use of IS was significantly lower in high-risk (16.4%) compared to intermediate (64.7%) and low-risk (62.5%) groups. Both men and women in the low-risk category were almost twice as likely to receive early IS compared to high-risk men (28.9% vs 17%, p < 0.001) and women (26.9% vs 15%, p < 0.001). Women (OR 0.91 95%CI 0.88–0.94), troponin elevation (OR 0.39 95%CI 0.36–0.43) and acute heart failure on admission (OR 0.65 95%CI 0.61–0.70) were strong negative predictors of receiving IS within recommended time in the high-risk group. Conclusion Our study shows that IS for management of NSTEMI is not delivered according to international guidelines recommendations. Specifically, the disconnect between baseline risk and utility of IS increases with increasing risk and women achieve slower access than men to IS.

Objective There are concerns that healthcare and outcomes of black, Asian and minority ethnic (BAME) communities are disproportionately impacted by the COVID-19 pandemic. We investigated admission rates, treatment and mortality of BAME with acute myocardial infarction (AMI) during COVID-19. Methods Using multisource national healthcare records, patients hospitalised with AMI in England during 1 February–27 May 2020 were included in the COVID-19 group, whereas patients admitted during the same period in the previous three consecutive years were included in a pre-COVID-19 group. Multilevel hierarchical regression analyses were used to quantify the changes in-hospital and 7-day mortality in BAME compared with whites. Results Of 73 746 patients, higher proportions of BAME patients (16.7% vs 10.1%) were hospitalised with AMI during the COVID-19 period compared with pre-COVID-19. BAME patients admitted during the COVID-19 period were younger, male and likely to present with ST-elevation acute myocardial infarction. COVID-19 BAME group admitted with non-ST-elevation acute myocardial infarction less frequently received coronary angiography (86.1% vs 90.0%, p&lt;0.001) and had a longer median delay to reperfusion (4.1 hours vs 3.7 hours, p&lt;0.001) compared with whites. BAME had higher in-hospital (OR 1.68, 95% CI 1.27 to 2.28) and 7-day mortality (OR 1.81 95% CI 1.31 to 2.19) during COVID-19 compared with pre-COVID-19 period. Conclusion In this multisource linked cohort study, compared with whites, BAME patients had proportionally higher hospitalisation rates with AMI, less frequently received guidelines indicated care and had higher early mortality during COVID-19 period compared with pre-COVID-19 period. There is a need to develop clinical pathways to achieve equity in the management of these vulnerable populations.

Background Women have excessive mortality rates after acute myocardial infarction compared with men. The extent to which this increased risk can be attributed to differences in treatment is not well-understood. Methods This was an observational follow-up study of 1737 patients admitted with acute myocardial infarction for coronary care between January 1, 1988, and December 31, 1997. Results Compared with men, women took longer to arrive at the hospital (132.5 minutes [range 76 to 291 minutes] vs 120 minutes [range 60 to 240 minutes]; P =.006), were less likely to receive aspirin acutely (87.8% vs 91.3%; P =.03), had longer door-to-needle times (90 minutes [range 60 to 143.5 minutes] vs 78 minutes [range 50 to 131 minutes]; P =.004), and were less likely to be given β-blockers at hospital discharge (31.6% vs 44.9%; P <.0001). Estimated survival (95% confidence interval [CI]) at 30 days was only 78.4% (range 74.4% to 81.9%) for women compared with 88.0% (range 86.1% to 89.7%) for men. Women were older and more often white, but their excess risk (hazard ratio 2.09; 95% CI, 1.59-2.75) persisted after adjustment for age, racial group, and diabetes (hazard ratio 1.52; 95% CI, 1.15-2.01). Additional adjustment for emergency thrombolytic and aspirin therapy caused a further small reduction in the excess risk for women (hazard ratio 1.46; 95% CI, 1.09-1.98), but with adjustment for aspirin and β-blockers prescribed at discharge, the excess risk attributable to being female disappeared as the hazard ratio fell to 0.75 (95% CI, 0.31-1.84). Estimated 30-day survival free of reinfarction and unstable angina was also lower for women than for men (75% [range 71% to 79%] vs 86% [range 84% to 88%]); again, the excess risk for women persisted despite adjustment for age and racial group before disappearing as treatment variables were introduced into the model. The influence of treatment variables on the differential risks for women and men disappeared at 12 months. Conclusions This study has shown that women with acute myocardial infarction arrived later at the hospital, were less likely to be given aspirin therapy acutely, had longer door-to-needle times, and, on discharge from the hospital, were less likely to be prescribed β-blockers for secondary prevention. The data suggest that the failure to treat women as vigorously as men made a significant contribution to their worse outcome. (Am Heart J 2000;140:740-6.)

OBJECTIVES This study was designed to assess the interaction between aspirin and C-reactive protein (CRP) release in unstable angina. BACKGROUND C-reactive protein release in acute coronary syndromes may be a response to myocardial necrosis or may reflect the inflammatory process that drives atherogenesis. Aspirin has the potential to influence CRP release, either by its anti-inflammatory activity or by reducing myocardial necrosis. The clinical significance of this potential interaction has not previously been tested. METHODS We conducted a prospective cohort study of 304 consecutive patients admitted with non-ST-elevation acute coronary syndromes. Serial blood samples were obtained for CRP and troponin I assay. End points were cardiac death and nonfatal myocardial infarction during follow-up for 12 months. RESULTS A total of 174 patients (57%) were taking aspirin before admission. Patients taking aspirin had lower troponin I concentrations throughout the sampling period, only 45 (26.0%) having concentrations >0.1 mg/l compared with 48 (37.8%) patients not taking aspirin (p = 0.03). Maximum CRP concentrations were also lower in patients taking aspirin (8.16 mg/l [3.24 to 24.5]) than in patients not taking aspirin (11.3 mg/l [4.15 to 26.1]), although the difference was not significant. However, there was significant interaction (p = 0.04) between prior aspirin therapy and the predictive value of CRP concentrations for death and myocardial infarction at 12 months. Thus, odds ratios (95% confidence intervals) for events associated with an increase of 1 standard deviation in maximum CRP concentration were 2.64 (1.22–5.72) in patients not pretreated with aspirin compared with 0.98 (0.60–1.62) in patients pretreated with aspirin. CONCLUSIONS The association between CRP and cardiac events in patients with unstable angina is influenced by pretreatment with aspirin. Modification of the acute-phase inflammatory responses to myocardial injury is the major mechanism of this interaction.

In this prospective cohort study we analyzed the impact of admission renal function on the hospital course of 2,503 patients with unstable angina pectoris (UAP) and acute myocardial infarction (AMI). The patients were stratified into quartile groups (Q1 to Q4) defined by baseline corrected creatinine clearance (cCrCl) values of 51.4, 63.8, and 76.8 mg/min/72 kg. The proportions of patients with a discharge diagnosis of AMI increased with declining cCrCl, from 35.5% in Q4 to 46.0% in Q1 (p <0.0001). The frequency of left ventricular (LV) failure (Q4 4.5%, Q1 31.0%, p <0.0001) and cardiac death (Q4 0.5%, Q1 9.5%, p <0.0001) also increased linearly with decreasing cCrCl, with no evidence that the prognostic impact of renal dysfunction was different in AMI or UAP (p for interaction 0.15). Logistic regression analysis confirmed the independent effects of cCrCl on outcome, with odds of LV failure and cardiac death for patients in Q4 being 0.34 (95% confidence intervals 0.16 to 0.72) and 0.14 (95% confidence intervals 0.03 to 0.74), respectively, relative to patients in Q1. No threshold was detected for the adverse effects of renal dysfunction on outcomes; the log odds of LV failure and cardiac death against quartiles of cCrCl both showed significant linear trends (p <0.0001) with each change in quartile, resulting in risk reductions of 55% (odds [SE] 0.45 [0.03]) and 65% (odds [SE]: 0.35 [0.05]), respectively. In conclusion, renal function showed a graded association with LV failure and hospital death that was independent of diagnosis (UAP or AMI) and other baseline variables. There was no detectable threshold of renal dysfunction for these adverse prognostic effects.

Objective : To examine the influence that being female has on the outcome of acute myocardial infarction. Design : Observational follow up study. Setting : London district general hospital. Patients : 216 women and 607 men with acute myocardial infarction admitted to a coronary care unit from 1 January 1988 to 31 December 1992. Main outcome measures : All cause mortality and recurrent ischaemic events in the first six months. Results : Event free survival (95% confidence interval) at six months was 63.3% (56.3% to 69.4%) in women and 76.1% (72.4% to 79.4%) in men, P<0.001. The difference was confined to the first 30 days but thereafter the hazard plots for women and men converged, with reduction of the hazard ratio from 2.36 (1.70 to 3.27) to 0.81 (0.44 to 1.48). Women were older, but their excess risk persisted after adjustment for age, other baseline variables, and indices of severity of infarction (hazard ratio 1.53 (1.09 to 2.15), P=0.015). Women tended to be treated with thrombolysis less commonly than men but the difference was small. Substantially fewer women than men, however, were discharged taking ß blockers (23.3% v 41.4%, P <0.001), and although additional adjustment for discharge treatment did not further reduce the point estimate of the hazard ratio (1.84 (0.89-3.83)), the 95% confidence interval was wide and statistical significance was lost. Conclusions : Women with acute myocardial infarction have a worse prognosis than men but the excess risk is confined to the first 30 days and is only party explained by age and other baseline variables. The tendency for women to receive less vigorous treatment than men must be remedied before gender can be considered to be an independent determinant of risk.

OBJECTIVES: To examine the circadian, seasonal, and weekly rhythms of acute myocardial infarction, and to identify subgroups in whom the rhythms are attenuated or absent to provide further information about the mechanisms of the rhythms and the processes responsible for triggering plaque events. DESIGN AND SETTING: Prospective, observational study in a general hospital. PATIENTS AND METHODS: 1225 consecutive patients admitted to a coronary care unit with acute myocardial infarction were studied. Admission rates were calculated according to the hour of the day (circadian rhythm), day of the week (weekly rhythm), and month of year (seasonal rhythm). The data were analysed for variations within the whole group and within subgroups. RESULTS: A weekly rhythm of acute myocardial infarction could not be demonstrated but there was a trend towards higher admission rates at the beginning of the week. However, the time of onset of symptoms showed significant circadian variation for the group as a whole, peaking in the morning (P = 0.006), against an otherwise fairly constant background rate. Subgroup analysis showed complete absence of the circadian rhythm in patients who were diabetic, South Asian, or taking beta blockers or aspirin on admission. Significant seasonal variation in admission rates was also demonstrated for the group as a whole with a winter peak and a summer trough (P = 0.009). Again, no seasonal rhythm could be demonstrated in patients who were diabetic, South Asian, or taking beta blockers or aspirin on admission. CONCLUSIONS: The absence of circadian and seasonal rhythms of acute myocardial infarction in almost identical subgroups suggests that common mechanisms are involved in driving these rhythms. The autonomic nervous system is a likely candidate because the rhythms were absent in patients taking beta blockers as well as in patients in whom derangement of autonomic function commonly occurs.

INTRAVENOUS leiomyomatosis may be defined as the extension into venous channels of histologically benign smooth-muscle tumors arising either from a uterine myoma or from the walls of a uterine vessel.1 Marshall and Morris2 provided the first English-language report of this condition in 1959; their paper also summarized 16 earlier cases in the European literature. Since 1959, only 28 further cases have appeared in English-language publications.3 4 5 6 7 8 9 10 11 Three reports in the German literature12 13 14 describe autopsy evidence of direct extension of intravenous leiomyomatosis from the pelvic veins into the inferior vena cava and right atrium. We describe a further case of intracardiac spread . . .

Primary percutaneous coronary intervention (PPCI) produces more effective coronary reperfusion and allows immediate risk stratification compared with fibrinolysis. We investigated the safety and feasibility of very early discharge at 2 days following PPCI in selected low-risk cases.This was a prospective observational cohort study of 2779 patients who underwent PPCI between 2004 and 2011. Patients meeting the following criteria were deemed suitable for very early discharge; TIMI III flow, left ventricle (LF) ejection fraction >40%, and rhythmic and haemodynamic stability out to 48 h. Higher-risk patients who did not fulfil these criteria were discharged later according to physician preference. All patients were offered outpatient review by a multidisciplinary team. Endpoints included 30 day readmission rates and major adverse cardiac events (MACE) out to a median of 2.8 years (IQR range: 1.3-4.4 years).1309 (49.3%) PPCI patients met very early discharge criteria, of whom 1117 (85.3%) were actually discharged at 2 days. 620 (23.4%) were discharged at 3 days, and 916 (34.5%) >3 days after admission (median 5, IQR: 4-8) days). Patients discharged at 2 days were younger, and had lower rates of diabetes, renal dysfunction, multivessel coronary artery disease, previous myocardial infarction, and previous coronary artery bypass surgery, compared with patients discharged later. 30-day readmission rates for non-MACE events were 4.8%, 4.9% and 4.6% for patients discharged 2 days, 3 days and >3 days after admission, respectively. MACE rates were lowest in patients discharged at 2 days (9.6%, 95% CI 4.7% to 16.6%) compared with patients discharged at 3 days (12.3% 95% CI 6.0% to 19.2%) and >3 days (28.6% 95% CI 22.9% to 34.7%, p<0.0001) after admission.Our data suggest that discharge of low-risk patients 2 days after successful PPCI is feasible and safe. Over 40% of all patients with ST-elevation myocardial infarction may be suitable for early discharge with important implications for healthcare costs.

Disclosure of potential conflicts of interest (COIs) is used by biomedical journals to guarantee credibility and transparency of the scientific process. Conflict of interest disclosure, however, is not systematically nor consistently dealt with by journals. Recent joint editorial efforts paved the way towards the implementation of uniform vehicles for COI disclosure. This paper provides a comprehensive editorial perspective on classical COI-related issues. New insights into the current COI policies and practices among European Society of Cardiology National Cardiovascular Journals, as derived from a cross-sectional survey using a standardized questionnaire, are discussed.

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.ClinicalTrials.gov Identifier: NCT01149590.

Haemorrhage is a common cause of death in trauma patients. Although transfusions are extensively used in the care of bleeding trauma patients, there is uncertainty about the balance of risks and benefits and how this balance depends on the baseline risk of death. Our objective was to evaluate the association of red blood cell (RBC) transfusion with mortality according to the predicted risk of death.A secondary analysis of the CRASH-2 trial (which originally evaluated the effect of tranexamic acid on mortality in trauma patients) was conducted. The trial included 20,127 trauma patients with significant bleeding from 274 hospitals in 40 countries. We evaluated the association of RBC transfusion with mortality in four strata of predicted risk of death: <6%, 6%-20%, 21%-50%, and >50%. For this analysis the exposure considered was RBC transfusion, and the main outcome was death from all causes at 28 days. A total of 10,227 patients (50.8%) received at least one transfusion. We found strong evidence that the association of transfusion with all-cause mortality varied according to the predicted risk of death (p-value for interaction <0.0001). Transfusion was associated with an increase in all-cause mortality among patients with <6% and 6%-20% predicted risk of death (odds ratio [OR] 5.40, 95% CI 4.08-7.13, p<0.0001, and OR 2.31, 95% CI 1.96-2.73, p<0.0001, respectively), but with a decrease in all-cause mortality in patients with >50% predicted risk of death (OR 0.59, 95% CI 0.47-0.74, p<0.0001). Transfusion was associated with an increase in fatal and non-fatal vascular events (OR 2.58, 95% CI 2.05-3.24, p<0.0001). The risk associated with RBC transfusion was significantly increased for all the predicted risk of death categories, but the relative increase was higher for those with the lowest (<6%) predicted risk of death (p-value for interaction <0.0001). As this was an observational study, the results could have been affected by different types of confounding. In addition, we could not consider haemoglobin in our analysis. In sensitivity analyses, excluding patients who died early; conducting propensity score analysis adjusting by use of platelets, fresh frozen plasma, and cryoprecipitate; and adjusting for country produced results that were similar.The association of transfusion with all-cause mortality appears to vary according to the predicted risk of death. Transfusion may reduce mortality in patients at high risk of death but increase mortality in those at low risk. The effect of transfusion in low-risk patients should be further tested in a randomised trial.www.ClinicalTrials.gov NCT01746953.

The purpose of this study was to compare baseline characteristics and medium-term prognosis in South Asian and Caucasian patients undergoing percutaneous coronary intervention (PCI).It is unclear whether South Asians undergoing PCI have worse outcomes than Caucasians.We performed a retrospective analysis of 279,256 patients undergoing PCI from 2004 to 2011 from the British Cardiovascular Intervention Society national database, of whom 259,318 (92.9%) were Caucasian and 19,938 (7.1%) were South Asian (South Asian includes patients of Pakistani, Indian, Bangladeshi, or Sri Lankan ethnic origin). The main outcome measures were in-hospital major adverse cardiac and cerebrovascular events and all-cause mortality during a median follow-up of 2.8 years (interquartile range: 1.5 to 4.5 years).South Asians were younger (59.69 ± 0.27 years vs. 64.69 ± 0.13 years, p > 0.0001); more burdened by cardiovascular risk factors, particularly diabetes mellitus (42.1 ± 1.2% vs. 15.4 ± 0.4%, p > 0.0001); and more likely to have multivessel coronary disease than Caucasians. In-hospital rates of major adverse cardiac and cerebrovascular events were similar for South Asians and Caucasians (3.5% vs. 2.8%, p = 0.40). Unadjusted Kaplan-Meier estimates of all-cause mortality showed better survival for South Asians compared with Caucasians, after PCI for either acute myocardial infarction or angina. Age-adjusted analysis revealed increased mortality (hazard ratio: 1.24; 95% confidence interval: 1.18 to 1.30), but after adjustment for the substantial variation in baseline risk factors including diabetes, there was no significant difference between South Asians and Caucasians (hazard ratio: 0.99; 95% confidence interval: 0.94 to 1.05).In this large, contemporary cohort of patients treated by PCI, South Asians were younger but had more extensive disease and major risk factors, particularly diabetes. However, after correcting for these differences, in-hospital and medium-term mortality of South Asians was no worse than that of Caucasians. This suggests that in South Asians, the high prevalence of diabetes exerts an adverse influence on mortality, but ethnicity itself is not an independent predictor of outcome.

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Early and accurate diagnosis of acute myocardial infarction is central to successful treatment and improved outcomes. We aimed to investigate the impact of the initial hospital diagnosis on mortality for patients with acute myocardial infarction.Cohort study using data from the Myocardial Ischaemia National Audit Project of patients discharged with a final diagnosis of ST-elevation myocardial infarction (STEMI, n=221,635) and non-STEMI (NSTEMI, n=342,777) between 1 April 2004 and 31 March 2013 in all acute hospitals ( n = 243) in England and Wales. Overall, 168,534 (29.9%) patients had an initial diagnosis which was not the same as their final diagnosis. After multivariable adjustment, for STEMI a change from an initial diagnosis of NSTEMI (time ratio 0.97, 95% confidence interval 0.92-1.01) and chest pain of uncertain cause (0.98, 0.89-1.07) was not associated with a significant reduction in time to death, whereas for other initial diagnoses the time to death was significantly reduced by 21% (0.78, 0.74-0.83). For NSTEMI, after multivariable adjustment, a change from an initial diagnosis of STEMI was associated with a reduction in time to death of 10% (time ratio 0.90, 95% confidence interval 0.83-0.97), but not for chest pain of uncertain cause (0.99, 0.96-1.02). Patients with NSTEMI who had other initial diagnoses had a significant 14% reduction in their time to death (time ratio 0.86, 95% confidence interval 0.84-0.88). STEMI and NSTEMI with other initial diagnoses had low rates of pre-hospital electrocardiograph (24.3% and 21.5%), aspirin on hospitalisation (61.6% and 48.5%), care by a cardiologist (60.0% and 51.5%), invasive coronary procedures (38.8 % and 29.2%), cardiac rehabilitation (68.9% and 62.6%) and guideline indicated medications at time of discharge from hospital. Had the 3.3% of patients with STEMI and 17.9% of NSTEMI who were admitted with other initial diagnoses received an initial diagnosis of STEMI and NSTEMI, then 33 and 218 deaths per year might have been prevented, respectively.Nearly one in three patients with acute myocardial infarction had other diagnoses at first medical contact, who less frequently received guideline indicated care and had significantly higher mortality rates. There is substantial potential, greater for NSTEMI than STEMI, to improve outcomes through earlier and more accurate diagnosis of acute myocardial infarction.

The aim of this study is to develop models to aid the decision to prolong dual antiplatelet therapy (DAPT) that requires balancing an individual patient's potential benefits and harms.Using population-based electronic health records (EHRs) (CALIBER, England, 2000-10), of patients evaluated 1 year after acute myocardial infarction (MI), we developed (n = 12 694 patients) and validated (n = 5613) prognostic models for cardiovascular (cardiovascular death, MI or stroke) events and three different bleeding endpoints. We applied trial effect estimates to determine potential benefits and harms of DAPT and the net clinical benefit of individuals. Prognostic models for cardiovascular events (c-index: 0.75 (95% CI: 0.74, 0.77)) and bleeding (c index 0.72 (95% CI: 0.67, 0.77)) were well calibrated: 3-year risk of cardiovascular events was 16.5% overall (5.2% in the lowest- and 46.7% in the highest-risk individuals), while for major bleeding, it was 1.7% (0.3% in the lowest- and 5.4% in the highest-risk patients). For every 10 000 patients treated per year, we estimated 249 (95% CI: 228, 269) cardiovascular events prevented and 134 (95% CI: 87, 181) major bleeding events caused in the highest-risk patients, and 28 (95% CI: 19, 37) cardiovascular events prevented and 9 (95% CI: 0, 20) major bleeding events caused in the lowest-risk patients. There was a net clinical benefit of prolonged DAPT in 63-99% patients depending on how benefits and harms were weighted.Prognostic models for cardiovascular events and bleeding using population-based EHRs may help to personalise decisions for prolonged DAPT 1-year following acute MI.

We determined whether high-sensitivity cardiac troponin I can improve the estimation of the pretest probability for obstructive coronary artery disease (CAD) in patients with suspected stable angina.In a prespecified substudy of the SCOT-HEART trial (Scottish Computed Tomography of the Heart), plasma cardiac troponin was measured using a high-sensitivity single-molecule counting assay in 943 adults with suspected stable angina who had undergone coronary computed tomographic angiography. Rates of obstructive CAD were compared with the pretest probability determined by the CAD Consortium risk model with and without cardiac troponin concentrations. External validation was undertaken in an independent study population from Denmark comprising 487 patients with suspected stable angina. Higher cardiac troponin concentrations were associated with obstructive CAD with a 5-fold increase across quintiles (9%-48%; P<0.001) independent of known cardiovascular risk factors (odds ratio, 1.35; 95% confidence interval, 1.25-1.46 per doubling of troponin). Cardiac troponin concentrations improved the discrimination and calibration of the CAD Consortium model for identifying obstructive CAD (C statistic, 0.788-0.800; P=0.004; χ2=16.8 [P=0.032] to 14.3 [P=0.074]). The updated model also improved classification of the American College of Cardiology/American Heart Association pretest probability risk categories (net reclassification improvement, 0.062; 95% confidence interval, 0.035-0.089). The revised model achieved similar improvements in discrimination and calibration when applied in the external validation cohort.High-sensitivity cardiac troponin I concentration is an independent predictor of obstructive CAD in patients with suspected stable angina. Use of this test may improve the selection of patients for further investigation and treatment.URL: https://www.clinicaltrials.gov. Unique identifier: NCT01149590.

BackgroundAdherence to guideline-indicated care for the treatment of non-ST-elevation myocardial infarction (NSTEMI) is associated with improved outcomes. We investigated the extent and consequences of non-adherence to guideline-indicated care across a national health system.

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

To evaluate the diagnostic and prognostic benefits of CT coronary angiography (CTCA) using the 2016 National Institute for Health and Care Excellence (NICE) guidelines for the assessment of suspected stable angina.Post hoc analysis of the Scottish COmputed Tomography of the HEART (SCOT-HEART) trial of 4146 participants with suspected angina randomised to CTCA. Patients were dichotomised into NICE guideline-defined possible angina and non-anginal presentations. Primary (diagnostic) endpoint was diagnostic certainty of angina at 6 weeks and prognostic endpoint comprised fatal and non-fatal myocardial infarction (MI).In 3770 eligible participants, CTCA increased diagnostic certainty more in those with possible angina (relative risk (RR) 2.22 (95% CI 1.91 to 2.60), p<0.001) than those with non-anginal symptoms (RR 1.30 (1.11 to 1.53), p=0.002; pinteraction <0.001). In the possible angina cohort, CTCA did not change rates of invasive angiography (p=0.481) but markedly reduced rates of normal coronary angiography (HR 0.32 (0.19 to 0.52), p<0.001). In the non-anginal cohort, rates of invasive angiography increased (HR 1.82 (1.13 to 2.92), p=0.014) without reducing rates of normal coronary angiography (HR 0.78 (0.30 to 2.05), p=0.622). At 3.2 years of follow-up, fatal or non-fatal MI was reduced in patients with possible angina (3.2% to 1.9%%; HR 0.58 (0.34 to 0.99), p=0.045) but not in those with non-anginal symptoms (HR 0.65 (0.25 to 1.69), p=0.379).NICE-guided patient selection maximises the benefits of CTCA on diagnostic certainty, use of invasive coronary angiography and reductions in fatal and non-fatal myocardial infarction. Patients with non-anginal chest pain derive minimal benefit from CTCA and increase the rates of invasive investigation.ClinicalTrials.gov: NCT01149590;post results.

In patients with suspected angina pectoris, CT coronary angiography (CTCA) clarifies the diagnosis, directs appropriate investigations and therapies, and reduces clinical events. The effect on patient symptoms is currently unknown.In a prospective open-label parallel group multicentre randomised controlled trial, 4146 patients with suspected angina due to coronary heart disease were randomised 1:1 to receive standard care or standard care plus CTCA. Symptoms and quality of life were assessed over 6 months using the Seattle Angina Questionnaire and Short Form 12.Baseline scores indicated mild physical limitation (74±0.4), moderate angina stability (44±0.4), modest angina frequency (68±0.4), excellent treatment satisfaction (92±0.2) and moderate impairment of quality of life (55±0.3). Compared with standard care alone, CTCA was associated with less marked improvements in physical limitation (difference -1.74 (95% CIs, -3.34 to -0.14), p=0.0329), angina frequency (difference -1.55 (-2.85 to -0.25), p=0.0198) and quality of life (difference -3.48 (-4.95 to -2.01), p<0.0001) at 6 months. For patients undergoing CTCA, improvements in symptoms were greatest in those diagnosed with normal coronary arteries or who had their preventative therapy discontinued, and least in those with moderate non-obstructive disease or had a new prescription of preventative therapy (p<0.001 for all).While improving diagnosis, treatment and outcome, CTCA is associated with a small attenuation of the improvements in symptoms and quality of life due to the detection of moderate non-obstructive coronary artery disease.NCT01149590.

Worldwide treatment recommendations for lowering blood pressure continue to be guided predominantly by blood pressure thresholds, despite strong evidence that the benefits of blood pressure reduction are observed in patients across the blood pressure spectrum. In this study, we aimed to investigate the implications of alternative strategies for offering blood pressure treatment, using the UK as an illustrative example.We did a retrospective cohort study in primary care patients aged 30-79 years without cardiovascular disease, using data from the UK's Clinical Practice Research Datalink linked to Hospital Episode Statistics and Office for National Statistics mortality. We assessed and compared four different strategies to determine eligibility for treatment: using 2011 UK National Institute for Health and Care Excellence (NICE) guideline, or proposed 2019 NICE guideline, or blood pressure alone (threshold ≥140/90 mm Hg), or predicted 10-year cardiovascular risk alone (QRISK2 score ≥10%). Patients were followed up until the earliest occurrence of a cardiovascular disease diagnosis, death, or end of follow-up period (March 31, 2016). For each strategy, we estimated the proportion of patients eligible for treatment and number of cardiovascular events that could be prevented with treatment. We then estimated eligibility and number of events that would occur during 10 years in the UK general population.Between Jan 1, 2011, and March 31, 2016, 1 222 670 patients in the cohort were followed up for a median of 4·3 years (IQR 2·5-5·2). 271 963 (22·2%) patients were eligible for treatment under the 2011 NICE guideline, 327 429 (26·8%) under the proposed 2019 NICE guideline, 481 859 (39·4%) on the basis of a blood pressure threshold of 140/90 mm Hg or higher, and 357 840 (29·3%) on the basis of a QRISK2 threshold of 10% or higher. During follow-up, 32 183 patients were diagnosed with cardiovascular disease (overall rate 7·1 per 1000 person-years, 95% CI 7·0-7·2). Cardiovascular event rates in patients eligible for each strategy were 15·2 per 1000 person-years (95% CI 15·0-15·5) under the 2011 NICE guideline, 14·9 (14·7-15·1) under the proposed 2019 NICE guideline, 11·4 (11·3-11·6) with blood pressure threshold alone, and 16·9 (16·7-17·1) with QRISK2 threshold alone. Scaled to the UK population, we estimated that 233 152 events would be avoided under the 2011 NICE guideline (28 patients needed to treat for 10 years to avoid one event), 270 233 under the 2019 NICE guideline (29 patients), 301 523 using a blood pressure threshold (38 patients), and 322 921 using QRISK2 threshold (27 patients).A cardiovascular risk-based strategy (QRISK2 ≥10%) could prevent over a third more cardiovascular disease events than the 2011 NICE guideline and a fifth more than the 2019 NICE guideline, with similar efficiency regarding number treated per event avoided.National Institute for Health Research.

Clinical estimation of the combined effect of several risk factors is unreliable and this resulted in the development of a number of risk estimation systems to guide clinical practice. Here, after defining general principles of risk estimation, the authors describe the evolution of the European Society of Cardiology's (ESC) Systematic COronary Risk Evaluation (SCORE) risk estimation system and some learnings from the data. They move on to describe the establishment of the ESC's Cardiovascular Risk Collaboration and outline its proposed research directions. First among these is the evolution of SCORE 2, which provides updated, calibrated risk estimates for total cardiovascular events for low, moderate, high, and very high-risk regions of Europe. The authors conclude by considering that the future of risk estimation may be to express risk as years of exposure to a cardiovascular risk factor profile rather than risk over a fixed time period, such as 10 years, and how advances in genetics may permit individualized lifetime risk estimation from childhood on.

Cardiovascular disease (CVD) is the leading cause of death across Europe. We estimated lost earnings (productivity losses) associated with premature mortality due to CVD, and separately for its main sub-categories of coronary heart disease and cerebrovascular disease, across 54 country members of the European Society of Cardiology (ESC).We used a standardized approach to estimate working years and earnings lost due to premature death resulting from CVD across the 54 ESC member countries in 2018. Our population-based approach was based on national data on the number of deaths, employment rates, and earnings by age group and sex. We discounted future working years and earnings lost to present values using a 3.5% annual rate. In 2018, there were 4.4 million deaths due to CVD across the 54 countries, with 7.1 million working years lost. This represented productivity losses due to premature death of €62 billion in 2018. Deaths due to coronary heart disease accounted for 47% (€29 billion) of all CVD costs, and cerebrovascular disease accounted for 18% (€11 billion). Approximately 60% (€37 billion) of all productivity losses occurred in the 28 European Union member states, despite accounting for only 42% (1.8 million) of deaths and 21% (1.5 million) of working years lost across the 54 countries.Our study provides a snapshot of the economic consequences posed by premature mortality due to CVD across 54 countries in 2018. The considerable variation across countries highlights the potential gains from policies targeting prevention and care of cardiovascular diseases.

Heart failure has a poor prognosis, yet drugs known to improve outcomes are either not prescribed, or prescribed at sub-therapeutic doses. The National Service Framework (NSF) for coronary heart disease recommended specialist heart failure clinics to address this problem but their efficacy has not been evaluated.To determine the effectiveness of a protocol-driven heart failure clinic staffed by nurse and pharmacist specialists for improving symptoms and optimising treatment with key therapeutic agents, without adversely affecting renal function.Of the 234 patients with at least one follow-up visit, 127 (57%) were receiving none or only one key therapeutic agent when first seen, this was reduced to 25 patients (11%) at most recent follow-up. The improvement in prescription rates was accompanied by significant up-titration of dose, the proportion of patients on "medium" or "high" doses rising from 43 (18%) to 134 (57%) for beta-blockers, and from 129 (55%) to 201 (86%) for ACE-inhibitors/angiotensin receptor blockers. Clinical improvement was reflected in reductions in patients with NYHA functional classes III and IV (93 (40%) to 53 (23%)), and in patients with moderate or severe symptoms. Significant reductions in alcohol consumption and cigarette smoking were recorded. Up-titration of treatment was associated with reductions in heart rate and systolic blood pressure; increases in serum potassium and creatinine concentrations were small.In a heart failure clinic staffed by nurse and pharmacist specialists, it is possible to achieve target doses of key therapeutic agents and improve symptoms without adversely affecting electrolytes or renal function.

Anisoylated plasminogen streptokinase activator complex (APSAC) is a new thrombolytic agent that is of interest because of its ease of administration as an intravenous bolus injection. This report describes the first double-blind, placebo-controlled evaluation of intravenous APSAC for coronary recanalization in acute myocardial infarction. Unequivocal documentation of recanalization was provided by coronary arteriography before and after the drug intervention. Forty patients with acute myocardial infarction underwent coronary arteriography 3.1 ± 1.2 hours after the onset of symptoms. This demonstrated occlusion of the infarct-related coronary artery in 29 patients who were then randomized to treatment with intravenous APSAC, 30 mg (n = 16), and placebo (n = 13) 3.3 ± 1.3 hours after the onset of symptoms. Repeat arteriography 90 minutes later demonstrated recanalization of the infarct-related coronary artery in nine patients who had received APSAC compared with only one patient who had received placebo (56 versus 8%, p < 0.05). The 95% confidence limits for this 48% difference between the groups are 20 to 76%. Arteriography at 3 days showed persistent patency of all recanalized coronary arteries except one (APSAC group) and also showed late recanalization in another four patients, three of whom had received APSAC. In the patients who had a patent infarct-related coronary artery at the initial arteriographic study, patency was maintained throughout the study period regardless of whether the patient was randomized to APSAC (n = 4) or placebo (n = 7). Complications related to APSAC therapy were excessive bruising at the catheterization site in seven patients and minor sensitivity reactions in three. These data confirm the thrombolytic efficacy of APSAC in acute myocardial infarction, and indicate that the drug may be used safely by the intravenous route with a 56% early recanalization rate.

To determine whether coronary angiography for suspected stable angina pectoris is underused in older patients, women, south Asian patients, and those from socioeconomically deprived areas, and, if it is, whether this is associated with higher coronary event rates.Multicentre cohort with five year follow-up.Six ambulatory care clinics in England.1375 consecutive patients in whom coronary angiography was individually rated as appropriate with the Rand consensus method.Receipt of angiography (420 procedures); coronary mortality and acute coronary syndrome events.In a multivariable analysis, angiography was less likely to be performed in patients aged over 64 compared with those aged under 50 (hazard ratio 0.60, 95% confidence interval 0.38 to 0.96), women compared with men (0.42, 0.35 to 0.50), south Asians compared with white people (0.48, 0.34 to 0.67), and patients in the most deprived fifth compared with the other four fifths (0.66, 0.40 to 1.08). Not undergoing angiography when it was deemed appropriate was associated with higher rates of coronary event.At an early stage after presentation with suspected angina, coronary angiography is underused in older people, women, south Asians, and people from deprived areas. Not receiving appropriate angiography was associated with a higher risk of coronary events in all groups. Interventions based on clinical guidance that supports individualised management decisions might improve access and outcomes.

The haemodynamic effects of oral and intravenous salbutamol were investigated in 22 patients with chronic heart failure. Intravenous salbutamol (13 micrograms/min) increased cardiac index by 53 per cent from 1.5 +/- 0.13 1/min per m2 to 2.3 +/- 0.23 1/min per m2 and decreased systemic vascular resistance by 28 per cent from 29.4 +/- 3.9 units to 21.2 +/- 2.5 units. Heart rate rose by 10 per cent from 101 +/- 3.5 beats per minute to 111 +/- 3.2 beats per minute and pulmonary artery end-diastolic pressure fell by 13 per cent from 26.3 +/- 1.8 mmHg to 22.8 +/- 2.1 mmHg. Similar results were obtained after oral salbutamol (8 mg). Cardiac index rose by 40 per cent and systemic vascular resistance fell by 30 per cent. There was a small rise in heart rate and a variable and not significant change in pulmonary artery end-diastolic pressure. Experiments on isolated rabbit papillary muscle showed that salbutamol, at the concentration which exists in patients, had no detectable positive inotropic effect. It is probable that the increase in cardiac output in patients is primarily the result of reduced afterload caused by vasodilatation. Salbutamol is a useful drug in the treatment of chronic heart failure.

The Editors’ Network of the European Society of Cardiology (ESC) defined its mission in the statement published across the national cardiac journals of Europe in 2008.1 The network is now considering ways in which their publications can have a broader influence in the field of postgraduate education. The need for cardiologists to continue to learn throughout their professional life will remain essential. Indeed recognition of the need for postgraduate education was highlighted by Hippocrates long before it was espoused by the medication educationalists and public relations departments. “ Ars longa, vita brevis ” is the Latin translation of Hippocrates’ recognition that for doctors the need to continue learning the art of medicine lasts for all their professional life. In mediaeval times, the foundation of modern day ethical medical practice was laid within the heart of the universities; the long-term future of the medical profession was founded in the concept of doctors as men, and women, of learning and knowledge, rather than the purveyors of non-scientifically based remedies. So how does the modern day editor of a national cardiology journal, crouched over his computer screen, relate to his mediaeval predecessor, the Abbot in charge of the university library selecting the books for scholarly enterprise? The most obvious difference, of course, is that the internet provides modern day authors with …

<b>Objective</b> To determine whether resting and exercise electrocardiograms (ECGs) provide prognostic value that is incremental to that obtained from the clinical history in ambulatory patients with suspected angina attending chest pain clinics. <b>Design</b> Multicentre cohort study. <b>Setting</b> Rapid access chest pain clinics of six hospitals in England. <b>Participants</b> 8176 consecutive patients with suspected angina and no previous diagnosis of coronary artery disease, all of whom had a resting ECG recorded. 4848 patients with a summary exercise ECG result recorded (positive, negative, equivocal for ischaemia) comprised the summary ECG subset of whom 1422 with more detailed exercise ECG data recorded comprised the detailed ECG subset. <b>Main outcome measure</b> Composite of death due to coronary heart disease or non-fatal acute coronary syndrome during median follow-up of 2.46 years. <b>Results</b> Receiver operating characteristics curves for the basic clinical assessment model alone and with the results of resting ECGs were superimposed with little difference in the C statistic. With the exercise ECGs the C statistic in the summary ECG subset increased from 0.70 (95% confidence interval 0.68 to 0.73) to 0.74 (0.71 to 0.76) and in the detailed ECG subset from 0.74 (0.70 to 0.79) to 0.78 (0.74 to 0.82). However, risk stratified cumulative probabilities of the primary end point at one year and six years for all three prognostic indices (clinical assessment only; clinical assessment plus resting ECG; clinical assessment plus resting ECG plus exercise ECG) showed only small differences at all time points and at all levels of risk. <b>Conclusion</b> In ambulatory patients with suspected angina, basic clinical assessment encompasses nearly all the prognostic value of resting ECGs and most of the prognostic value of exercise ECGs. The limited incremental value of these widely applied tests emphasises the need for more effective methods of risk stratification in this group of patients.

Chest pain is very common, and in the United Kingdom about 1% of visits to a general practitioner, 5% of visits to the emergency department, and 25% of emergency hospital admissions are for this symptom.1 Chest pain has many causes, and when the cause could be cardiac in origin, appropriate and timely assessment and diagnostic investigation are needed. This article summarises the most recent recommendations from the National Institute for Health and Clinical Excellence (NICE) on the assessment and diagnosis of recent onset chest pain or discomfort of suspected cardiac origin.2 NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the experience and opinion of the Guideline Development Group (GDG) on what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. Two separate diagnostic pathways are presented. The first is for people with acute chest pain in whom an acute coronary syndrome is suspected. The second is for people with intermittent stable chest pain in whom stable angina is suspected. ### Acute chest pain and suspected acute coronary syndrome #### Initial clinical assessment and referral to hospital