Objective: To determine the incidence of sudden cardiac death (SCD) according to left ventricular ejection fraction (LVEF) in post myocardial infarction (MI) survivors in the primary percutaneous coronary intervention (PCI) era.

Design: A multicenter observational prospective registered cohort study.

Setting: Reduced LVEF is currently the best available predictor of SCD in MI survivors. Early revascularization, such as primary PCI, reduces mortality in acute MI patients.

Patients: 4,122 consecutive patients (mean age 66+12 years, 73.7% male) with acute MI, who were discharged alive.

Main outcome measures: The primary end point was SCD, and a secondary end point was death from any cause.

Results: Patients were categorized into 3 groups: LVEF>40% (n=3416), LVEF≤40% and >30% (n=507) and LVEF≤30% (n=199). Among all patients, 77.8% received PCI and 3.7% received coronary artery bypass graft surgery. During an average follow-up of 4.1 years, SCD was 1.2% and mortality was 13.1% . Patients with LVEF≤30% and LVEF≤40% and >30% were at increased risk for SCD (HR 5.99, 95% CI: 2.73-13.14, P<0.001, HR 3.37, 95% CI: 1.74-6.50, P<0.001, respectively), and mortality (HR 3.85, 95% CI: 2.96-5.00, P<0.001, HR 1.66, 95% CI: 1.66-2.57, P<0.001, respectively), compared to patients with LVEF>40%. Kaplan-Meier estimates of SCD in our patients with LVEF≤30% were 2.9%, 5.1% and 5.1% at 1, 3 and 5 years, respectively.

Conclusions: There is a low incidence of SCD in post MI survivors in the primary PCI era although LVEF is a predictor of increased risk for SCD.

Background: We compared the degree of systemic inflammation and its relationship to the angiographic outcomes after drug-eluting stent (DES) implantations.

Methods: We implanted a single DES in 79 stable angina patients (50 men; 60.4±9.5 years of age; sirolimus-eluting stent (SES), n=38; paclitaxel-eluting stent (PES), n=41). The hs-CRP and IL-6 levels were determined before and at 24, 72 hours, and 4 weeks after the PCI. An angiography and IVUS were performed.

Results: The hs-CRP and IL-6 levels at baseline did not differ between the two groups. The hs-CRP increased significantly from baseline at 24 hr and 72 hr after the PCI in both groups and there was a significant increase in the IL-6 level at 24 hr after the PCI in both groups. However, there was no significant difference between the two groups in any of the hs-CRP or IL-6 measurements. At follow up, the late lumen loss was significantly higher in the PES group than in the SES group (0.57±0.56 mm vs. 0.28±0.58 mm, respectively, p=0.020). The neointimal hyperplasia (NIH) volume in the PES group was significantly higher than that in the SES group (23.1±22.7 vs. 3.8±7.1 mm³, respectively, p=0.000). The percent luminal volume reduction was higher in the PES group than in the SES group (18.9 vs. 3.9 %, p=0.002). The absolute values or change in the inflammatory markers did not correlate with the NIH or stent volume reduction.

Conclusions: Our study showed that the benefits obtained from the SESs, which reduce neointimal proliferation, are not likely mediated by the attenuation of the systemic inflammatory markers, hs-CRP or IL-6.

NICE Guidance on the use of drug-eluting stents (DES) was published in July 2008 . The guidance replaces sections 1.2 1.4 of NICE technology appraisal guidance number 71 which was published in 2003 . This part-review indicates under what circumstances drug-eluting stents are recommended as a cost effective use of NHS resources in England and Wales. 1. Drug-eluting stents are recommended for use in percutaneous coronary intervention for the treatment of coronary artery disease, within their instructions for use, only if: • the target artery to be treated has less than a 3 mm calibre or the lesion is longer than 15 mm, and • the price difference between drug-eluting stents and bare-metal stents is no more than £300.

There have been major changes in the delivery of services to patients with coronary disease over the last two decades. These include primary percutaneous coronary intervention (PCI) for patients with ST elevation myocardial infarction (STEMI) and an early invasive strategy for those with non-STEMI acute coronary syndromes (ACS). In these settings patients undergo angiography with a view to immediate angioplasty (so-called "follow-on" or "ad-hoc" angioplasty) or early coronary artery bypass grafting (CABG). Chest pain clinics identify patients who need early angiography and these and other elective patients are frequently listed for a potential follow-on procedure. These changes have made revascularisation units more efficient, with greater patient throughput and reduced hospital bed-days. In the UK, they have played a major part in significantly reducing waiting times for procedures.

The idea that low-dose aspirin could be recommended for vascular protection on the grounds of age alone, irrespective of the levels of other vascular risk factors, seems to have been first suggested by the Editor of Archives of Internal Medicine, who, in 1991 wrote: ‘In my opinion, aspirin therapy is indicated in US men aged 50 years or older and in women after the menopause’.¹ Later, a group of British organisations organisations recommended cardioprotection by daily aspirin for subjects aged over 50 years ‘whose hypertension, if present, is controlled’.² The US Preventive Services Task Force stated that ‘men older than 40 years [and] postmenopausal women... may wish to consider aspirin therapy’.³ Most recently, a report from Wales,⁴ based on the individual risk factor data for subjects in a large population cohort, together with data for a cohort of women, gave evidence suggesting that aspirin prophylaxis is reasonable from about 42 years of age on average for men, and for 80% of men from about age 49 years, while in women the average age when aspirin prophylaxis becomes reasonable was judged to be about 53 years. A report, published as a companion paper to this last, vigorously opposed the idea of aspirin prophylaxis on the grounds of age alone.⁵

Objective: We sought to quantify left atrial longitudinal function by tissue Doppler (TDI) and two-dimensional (2D) strain in patients with hypertrophic cardiomyopathy (HCM).

Design: Case-control study.

Setting: Tertiary University hospital.

Patients: Forty three consecutive patients with familial HCM, aged 49±18 years, along with 21 patients with non-HCM left ventricular hypertrophy (LVH, 52±12 years) and 27 healthy volunteers (42±13 years).

Interventions: Subjects were studied by both TDI and 2D left atrial strain during all three atrial phases (reservoir, conduit, contractile), as well as by left ventricular systolic strain; total atrial deformation (TAD) was defined as the sum of maximum positive and maximum negative strain during a cardiac cycle.

Main outcome measures: Left atrial longitudinal function.

Results: Both TDI and 2D atrial strain and TAD were significantly reduced in HCM, compared to the other two groups in all atrial phases (p<0.001 in most cases); left ventricular systolic strain was also significantly reduced in HCM (p<0.001). Adding 2D contractile atrial strain to a model of conventional echo measurements (left atrial diameter and volume index, interventricular septal thickness and E/A ratio and E/e¢ ratios) increased its prognostic value in differentiating HCM from non-HCM LVH (p of the change <0.001), while addition of TDI atrial strain or left ventricular strain did not. A cutoff for 2D contractile strain of -10.82% discriminated HCM from non-HCM LVH with a sensitivity of 82% and a specificity of 81%. Intra- and inter-observer variabilities for atrial strain in HCM were 16% and 17.5% for TDI and 8% and 9.5% for 2D, respectively. Processing time per case in HCM was 12.5±2.6 min for TDI versus 3.8±1.2 min for 2D strain (p<0.001).

Conclusion: Left atrial longitudinal function is reduced in HCM compared to non-HCM LVH and healthy controls. In addition, 2D atrial strain has an additive value in differentiating HCM from non-HCM LVH and it is more reproducible and less time consuming compared to TDI strain.

Patients with type 2 diabetes experience high rates of co-morbid conditions such as hypertension and dyslipidemia that further compound their already increased risk of developing ischemic heart disease (IHD). IHD and hypertension, in turn, represent conditions that are major precursors of congestive heart failure (CHF), adding to the cardiovascular disease (CVD) burden in this patient population. This is reflected in the reported estimate of IHD prevalence in diabetics (approximating 22%)1and the reported 10-year incidence of CHF among elderly patients with newly diagnosed type 2 diabetes (exceeding 50%).2 The American Heart Association and the American Diabetes Association have also noted in a joint scientific statement paper that CVD contributes to more than three-quarters of all death in diabetic patients.3

Carotid ultrasound is a well-established research tool that can identify the presence of atherosclerosis and quantify the degree of arterial injury in a broad range of populations. A specific application of carotid ultrasound, measurement of intima-media thickness (IMT), precisely quantifies the combined thicknesses of intimal and medial layers of the arterial wall. Carotid IMT values are strongly associated with abnormal levels of risk factors for atherosclerotic vascular disease and prevalent vascular disease, and independently predict future cardiovascular disease events.[1] In well-trained hands, the accuracy and reproducibility of carotid IMT are unsurpassed among non-invasive tests of arterial injury. The strong evidence base associating increased cardiovascular disease risk with increasing carotid IMT has led to this test being recommended, in selected adults, as a clinical tool to assist with CVD risk prediction.

The British Cardiovascular Society (BCS) receives many guidelines and appraisals on various cardiovascular conditions and treatments. BCS is a stakeholder in guidelines and appraisals produced by organisations such as the National Institute for Clinical Excellence, and others. As such, BCS is frequently involved in the writing, reviewing, criticising and modifying of guidelines and appraisals. After publication, BCS formally reviews national and international guidelines and appraisals. As a constituent member, the BCS is required to endorse guidelines produced by the European Society of Cardiology. All of this work is professionally undertaken by BCS members without reward; this work is co-ordinated by the Clinical Standards Division of the BCS. The BCS feels that there is a role for publication of formal reviews of new guidelines and appraisals published by national and international organisations. These reviews are intended to set the place of new guidelines and appraisals in the context of the current management of the relevant cardiovascular condition, and to compare the new guidance with previously published guidelines and appraisals. These reviews are also intended to compare the place of new guidelines and appraisals in the context of national and international differences in the current management of the relevant cardiovascular condition, with specific relevance to cardiovascular practice in the United Kingdom. The BCS and Heart plan to publish these reviews in Heart. The first review below by Hall and Barth relates to the recently published Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. We hope that this will be the first of a regular series of reviews of national and international guidelines and appraisals.

The introduction of new healthcare technologies requires an appropriate discourse between clinicians who identify problems to be overcome and industrial partners that provide potential solutions. New products go through a tight regulatory process before they can be widely used. Although this process is somewhat different for medical devices compared with drugs, the principles are the same: demonstration of proof of principle and safety, and identification of patients most likely to benefit. However, their use nowadays depends as much on a demonstration of cost-effectiveness as on clinical effectiveness. Cost-effectiveness analysis requires quantification of both clinical effect and overall costs of different treatments.

The concept of intravascular stent implantation was first described by Dotter et al in 1969 in an animal model.¹ However, balloon expendable intravascular stenting was not carried out until 2 decades later after improvements in stent design and technology. Clinical trials were first performed in the late 80s in adults with coronary artery obstructions.² Soon, Dr Mullins and other paediatric interventionalists adopted the Palmaz stent designed by Dr Julio Palmaz for iliac, biliary, renal and intrahepatic porta-caval shunt. They used it in virtually all vascular obstructions associated with congenital heart diseases.³ In 1992, stenting was first applied in right ventricular outflow tract (RVOT) conduit obstruction resistant to balloon angioplasty.⁴ More extensive clinical experience demonstrated that stenting effectively prolongs RVOT conduit lifespan.⁵ Recent advances in balloon-expendable stent technology provided through valved stents a novel therapy for both RVOT conduit obstruction and regurgitation.⁶

Background: In patients with coronary artery disease (CAD), a well grown collateral circulation has been shown to be important. The aim of this prospective study using peripheral blood monocytes was to identify marker genes for an extensively grown coronary collateral circulation.

Methods: Collateral flow index (CFI) was obtained invasively by angioplasty pressure sensor guidewire in 160 individuals (110 patients with CAD, and 50 individuals without CAD). RNA was extracted from monocytes followed by microarray-based gene-expression analysis. 76 selected genes were analysed by real-time polymerase chain reaction (PCR). ROC analysis based on differential gene expression was then performed to separate individuals with poor (CFI<0.21) and well developed collaterals (CFI³0.21) Thereafter, the influence of the chemokine MCP-1 on the expression of six selected genes was tested by PCR.

Results: The expression of 203 genes significantly correlated with CFI (p=0.000002-0.00267) in patients with CAD and 56 genes in individuals without CAD (p=00079-0.0430). Biological pathway analysis revealed 76 of those genes belonging to 4 different pathways: angiogenesis, integrin-, platelet derived growth factor-, and transforming growth factor b-signalling. Three genes in each subgroup differentiated with high specificity among individuals with low and high CFI (³0.21). Two out of these genes showed pronounced differential expression between the two groups after cell stimulation with MCP-1.

Conclusions: Genetic factors play a role in the formation and the pre-formation of the coronary collateral circulation. Gene expression analysis in peripheral blood monocytes can be used for non-invasive differentiation between individuals with poorly and with well grown collaterals. MCP-1 can influence the arteriogenic potential of monocytes.

Objective: We sought to assess vascular remodelling and neointima formation after implantation of bioabsorbable magnesium alloy stents (AMS).

Design: Randomized experimental study Interventions AMS (n=11), sirolimus-eluting stents (CypherÒ; n=11) and bare-metal stents (BMS; n=9) were randomly implanted in 31 porcine coronary arteries (n=11 pigs).

Main outcome measures: Neointima formation was measured by histomorphometry at 90 days. Vascular remodelling defined as change in external elastic membrane area from index intervention to follow-up was assessed by serial intravascular ultrasound (IVUS).

Results: By histomorphometry, lumen [median (quartiles); AMS: 1.75 mm2 (1.07-3.26), Cypher 2.52 mm2 (2.22-5.01), BMS 4.55 mm2 (3.2-7.44); p=0.013] and external elastic membrane area [AMS: 5.56 mm2 (4.09-6.95), Cypher 7.95 mm2 (6.45-10.92), BMS 9.08 mm2 (7.85-11.63); p=0.014] were smallest after AMS implantation. By IVUS, external elastic membrane area at follow-up was smallest [AMS: 7.5±2.8 mm2, Cypher 9.1±2.7 mm2, BMS 9.9±3.1 mm2; p=0.33] and change in external elastic membrane area from index intervention to follow-up [remodelling; AMS: -1.0±3.1 mm2, Cypher 1.0±0.8 mm2, BMS 0.9±1.2 mm2; p=0.30] was greatest in the AMS group. In a dichotomized IVUS assessment of vascular remodelling, 6 AMS stents were remodelled (negative remodelling: n=5; positive remodelling: n=1) at 90 days follow-up (AMS versus Cypher+BMS: p=0.001). Neointima formation was smallest in the AMS group (p<0.05 for both histomorphometry and IVUS).

Conclusion: Coronary implantation of absorbable magnesium stents, as compared to two non-absorbable stents, was associated with the smallest lumen area at 3-month follow-up due to negative vascular remodelling.

Objective: To determine an appropriate age threshold to prescribe aspirin among men and women without diabetes for primary cardiovascular disease (CVD) prevention.

Design: Cross-sectional study.

Setting: 304 general practices in England and Wales contributing to The Health Improvement Network (THIN) electronic patient files.

Participants: Individuals aged between 30 to 75 years without diabetes, not prescribed any lipid lowering therapy with no previous history of cardiovascular disease. Individuals would have been registered by their practices for the whole of the preceding 12 months to be included in the analysis.

Outcomes measures: Relation between age and CHD risk, and the age threshold at which individuals without diabetes develop an estimated 10-year coronary heart disease risk of 10% or more.

Results: The age transition from <10% to >10%, 10-year CHD risk for men and women without diabetes occurred at ages of 47.8 for men and 57.3 for women respectively.

Conclusions: Aspirin should routinely be considered to all men and women without diabetes above the ages of 48 and 57 years respectively for primary CVD prevention. For individuals below these age thresholds or for those above the age of 75 years, decision to initiate aspirin should be based on patient’s individual cardiovascular risk profiles. These proposed age thresholds aims to take into account patient’s gender, their bleeding risk and the cardio-protective benefits of low-dose aspirin therapy.

Objective: Areas of intramyocardial late enhancement (LE) at delayed enhanced magnetic resonance imaging (DE-MRI) and reduction of myocardial phosphocreatine (PCr)/ATP-ratio at phosphorous MR spectroscopy (³¹P-MRS), are both reported in hypertrophic cardiomyopathy (HCM) and indicate areas of increased interstitial myocardial space with fibrosis and impairment of myocardial energy metabolism, respectively. We sought to ascertain whether in HCM patients the abnormal features of left ventricular (LV) interstitial space revealed by DE-MRI correlated with impaired LV energy metabolism shown at ³¹P-MRS.

Design and patients: 19 patients with HCM proved by histological analysis of multiple endomyocardial biopsies and with normal coronary arteries, underwent cardiac Magnetic Resonance imaging including DE-MRI and ³¹P-MRS. DE-MRI for detection and quantification of Late Enahncement (LE) and ³¹P-MRS to assess the myocardial PCr/ATP-ratio were performed by means of a 1.5T magnet. 19 healthy subjects matched for gender and age were studied by ³¹P-MRS, as control group.

Results: LE areas in the LV wall were found in 17 out of 19 patients with an extension ranging from 0.8 to 19.5% of the LV-mass (mean value: 7.6 ± 5.6%). The PCr/ATP-ratio was lower in HCM patients when compared to control subjects (2.18 ± 0.41 vs 2.41 ± 0.30; P<0.05). LE% and PCr/ATP-ratio were inversely related (R=-0.57; P<0.05) and LE% was the stronger predictor of PCr/ATP-ratio by multivariate analysis.

Conclusions: This study demonstrated that the known alteration of PCr/ATP-ratio observed in HCM patients is correlated with the presence of fibrotic areas in the myocardium of left ventricle.

In this issue of Heart, Del Rosso A., Ungar A., Maggi R. et al. report the results of a prospective validation study of a clinical assessment tool for adults attending the emergency department with a history of transient loss of consciousness. The scoring system, which ‘cannot be used as a substitute for clinical judgment of the experts’ is geared towards identifying those patients who have a cardiac cause and intends to serve as an aid for junior doctors providing front line care in busy emergency departments. The proposed screening tool has a high sensitivity and relatively high specificity.

Objective: To undertake a systematic review and meta-analysis of randomised placebo-controlled trials of oxygen therapy in myocardial infarction (MI).

Design: A systematic search of Medline, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, EMBASE and CINHAL was undertaken using the key words "oxygen" and "myocardial infarction" to identify randomised placebo-controlled trials of oxygen therapy in MI.

Main outcome measures: The primary clinical outcome was mortality; secondary outcomes were infarct size, occurrence of ventricular arrhythmias and opiate use.

Results: Two of 51 potentially relevant studies met the criteria. The one study with substantive clinical outcome data reported that high flow oxygen was associated with a non-significant increased risk of death (risk ratio 2.9, 95% CI 0.8 to 10.3, P=0.08), and a greater serum aspartate aminotransferase level (difference 19.2 IU/ml, 95% CI 0 to 38.4, P=0.05) in uncomplicated MI. Neither of the identified studies had adequate statistical power to detect clinically important differences in other clinical outcome measures.

Conclusion: There is little evidence by which to determine the efficacy and safety of high flow oxygen therapy in MI. The evidence that does exist suggests that the routine use of high flow oxygen in uncomplicated MI may result in a greater infarct size and possibly increase the risk of mortality.

Objective: To investigate the usefulness of N-terminal pro-brain natriuretic peptide (NT-proBNP) as a predictive marker for angiographically significant coronary artery disease (CAD) and CAD severity compared with other newer biochemical risk markers and classical risk factors in patients with clinically suspected CAD.

Design: Cross-sectional evaluation of NT-proBNP in a large consecutive series of patients without a history of myocardial infarction referred for elective coronary angiography (CAG) between March 2004 and January 2005. The value of NT-proBNP for predicting CAD was assessed and compared with high sensitivity C-reactive protein (hs-CRP), gamma-glutamyltransferase (GGT), and traditional risk factors.

Setting: Tertiary care center, Department of Cardiology, Innsbruck Medical University, Austria.

Patients: 561 men and 287 women aged between 20-86 years. (median 65 years).

Interventions: None.

Main outcome measures: Association of NT-proBNP with the severity of CAD, left ventricular dysfunction and comparison of predictive values of NT-proBNP, hs-CRP, GGT, and traditional CAD risk factors.

Results: Of all tested newer biochemical risk markers NT-proBNP performed best. In a multinomial logistic regression model NT-proBNP but not hs-CRP or GGT was significantly associated with 3-vessel CAD adjusted for age, sex, ventricular, renal function and classical risk factors (odds ratio=1.667; 95% CI 1.003-2.772; p=0.049). However, NT-proBNP had no additive predictive value to traditional cardiovascular risk factors for the prediction of angiographically significant CAD in a binary logistic regression model.

Conclusions: The predictive value of NT-proBNP for CAD severity is better than of hs-CRP or GGT. However, NT-proBNP is also of limited value compared with traditional risk factors for predicting significant CAD.

Background: Although higher blood pressures are generally recognised to be an adverse prognostic marker in risk assessment of cardiology patients, its relationship to risk in chronic heart failure (CHF) may be different. We set out to examine systematically the published literature on the relationship between blood pressure and mortality in CHF.

Methods: We used Medline and EMBASE to identify studies that gave a hazard or relative risk ratio for systolic blood pressure in a stable chronic heart failure population. Included studies were analysed to obtain a unified hazard ratio and quantify the degree of confidence.

Results: 10 studies met the inclusion criteria, giving a total population of 8088, with 29222 person-years of follow up. All studies showed that a higher systolic blood pressure was a favourable prognostic marker in chronic heart failure, in contrast to the general population where it is an indicator of poorer prognosis. The decrease in mortality rates associated with a 10 mmHg higher SBP was 13% (95% CI 10%-15%) in the heart failure population. This was not related to aetiology, ACE inhibitor or â blocker use.

Conclusion: Systolic blood pressure is an easily-measured, continuous variable that has a remarkably consistent relationship with mortality within the chronic heart failure population. We should not neglect the potential of this simple variable in outpatient assessment of patients with chronic heart failure. One possible application of this information is in the optimization of cardiac resynchronization devices.

The NICE guideline, ‘Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease’ (1) is a significant advance over earlier more fragmented approaches to cardiovascular risk. The guideline provides strategies for identification of patients at risk, lipid modification in primary and secondary prevention and unifies treatment approaches to coronary heart disease, stroke and peripheral vascular disease. This guideline does not give recommendations for patients with underlying disorders that increase cardiovascular disease risk, but NICE guidance on diabetes which includes lipid modification has also just been published (2) and NICE guidance on familial hypercholesterolaemia is due shortly.

Intense, sustained physical activity results, over time, in physiological conditioning. In aiming to optimise cardiovascular performance, the heart undergoes quite dramatic changes. Some of these physiological changes, in particular those relating to myocardial hypertrophy, may mimic pathological states, which are well known to pose cardiovascular risk.

Guidelines for the prevention of cardiovascular disease (CVD) are greatly time-dependent due to the rapid increase of knowledge in this important research area. However, at each point in time the knowledge base behind all guidelines on CVD prevention e.g. blood lipid modification is common, international, and easily available to all clinical scientists and opinion leaders engaged in the formulation of those guidelines. Nevertheless they differ markedly between continents, countries and regions. There are several reasons for this: not only factual differences in risk factor distribution between different populations but also local customs and traditions and individual influences from scientists and clinicians involved in the authorship of the guidelines. Recently a new guideline for Lipid Modification by the National Institute for Health and Clinical Excellence in UK was issued (NICE-LMG) (Give actual reference here!). Close in time the Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine European societies and by invited experts) issued their guidelines [1]. The Joint European and NICE Lipid Modification guideline thus are issued with essentially the same knowledge base. It is of interest to see how these two documents agree and differ. Patterns in the "guideline culture" are that local guidelines adopt from more general ones, e.g. national guidelines adopt from European guidelines. Also, the closer the authors are to the health care provider, the more restrictive they seem to be in recommending more comprehensive (and more expensive) diagnosis, treatment and follow-up. One fact that could modify more local guidance from general is of course also professional specialty of the members of the development group. In the NICE-LMG there is a preponderance of general practitioners and that has its impact on the present document.

Objective To compare baseline cardiovascular risk management between people recruited from two different healthcare systems, to a research trial of an intervention to optimize secondary prevention.

Design Cross-sectional study.

Setting General practices, randomly selected: 16 in Northern Ireland (NI) (UK NHS, infrastructure, pay-for-performance); 32 in Republic of Ireland (RoI) (mixed healthcare economy, less infrastructure, no pay-for-performance).

Patients 903 (mean age 67.5 years; 69.9% male); randomly selected, known coronary heart disease.

Main outcome measures Blood pressure, cholesterol, medications; validated questionnaires for diet (DINE), exercise (Godin), quality of life (SF12); healthcare usage.

Results More RoI than NI participants had systolic BP>140 mmHg (37% v 28%, p=0.01) and cholesterol >5mmol/l (24% v 17%, p=0.02): RoI mean systolic BP was higher (139 v 132 mm Hg). More RoI participants reported a high fibre intake (35% v 23%), higher levels of physical activity (62% v 44%), and better physical and mental health (SF12); they had more GP (5.6 v 4.4) and fewer nurse visits (1.6 v 2.1) in the previous year. Fewer in RoI (55% v 70%) were prescribed B blockers. Both groups ACE inhibitor (41%; 48%) prescribing was similar; high proportions were prescribed statins (84%; 85%) and aspirin (83%; 77%).

Conclusions Blood pressure and cholesterol are better controlled among patients in a primary healthcare system with a strong infrastructure supporting computerization and rewarding measured performance but this is not associated with healthier lifestyle or better quality of life. Further exploration of differences in professionals and patients engagement in secondary prevention in different healthcare systems is needed.

Kawasaki disease (KD) is an acute self-limiting systemic vasculitis of unknown aetiology. It is the most common cause of acquired heart disease in young children. The intense inflammatory process has a predilection for the coronary arteries, resulting in the development of aneurysmal lesions, arterial thrombotic occlusion or potentially sudden death.

There is no specific diagnostic test; however treatment with immunoglobulin and aspirin is effective at reducing cardiac complications from 25% to 4.7% in the UK.

Inflammation of the myocardium, endocardium or pericardium can occur early in the disease and endothelial dysfunction along with abnormalities of myocardial blood flow may require ongoing medication, interventional catheterisation or even cardiac surgery.

There are several new pharmacological therapies which may have important roles to play in managing KD in children and adolescents. This review includes discussion of the history of the disease, the diagnostic challenges, epidemiology, aetiology, pathology, immunopathogenesis, therapy, genetic influences, and the long-term cardiovascular sequelae.

Since their publication in 2000, the Newcastle Protocols1 on head-up tilt testing in the diagnosis of vasovagal syncope and related disorders have provided a succinct and practical guide for those setting up and managing syncope services incorporating the investigation and management of neurally mediated disorders. In the intervening seven years our protocols have changed in line with published evidence on new methodologies and management strategies and our own clinical experience (with more than 1000 new and 3000 review patients seen per year at our specialist syncope facility), so the time is ripe for a fresh approach. Much of this information is available in a number of important papers on syncope management2-4 and pacing indications;5,6 while comprehensive, these guidelines are also lengthy and inclusive of competing methodologies. They are therefore less accessible for those needing a more prescriptive and pragmatic view. The Newcastle Protocols 2008 presented below provide such a view. Since these protocols reflect current clinical practice, an exhaustive review of the evidence base for the various methodologies presented will not be attempted – the reader should consult the more detailed papers referenced if this is required.2-6 Similarly some prior knowledge of the subject matter is assumed, in particular the differentiation between syncope and non-syncopal loss of consciousness as well as the diagnostic process leading to head-up tilt table testing.2,3 The protocols are designed for adults with syncope (defined as transient loss of consciousness with loss of postural tone and spontaneous and complete recovery), with no upper limit on age.

Background: Several prospective studies have evaluated the association between body mass index (BMI) and cardiovascular mortality among patients with type 2 diabetes, however, the results are controversial.

Objective: To investigate the association of different BMI distributions with total and cardiovascular mortality among diabetic patients.

Methods: A total of 30534 Ukrainian males and 58909 females with type 2 diabetes from the nationwide population-based diabetes register were included in this study.

Results: During the mean follow-up of 2.7 years, 7804 deaths were recorded, of which 3320 were due to cardiovascular disease. After adjustment for age, smoking and alcohol drinking, the hazard ratios across the five BMI categories (<23, 23-24.9, 25-29.9 [reference group], 30-34.9 and >=35 kg/m²) among diabetic men were 1.57 (95% CI 1.42-1.74), 1.16 (1.05-1.28), 1.0, 1.01 (0.91-1.12) and 1.24 (1.02-1.50) for total mortality, and 1.67 (95% CI 1.42-1.95), 1.30 (1.12-1.51), 1.0, 1.13 (0.96-1.34) and 1.54 (1.16-2.05) for cardiovascular mortality, respectively. The respective hazard ratios among diabetic women were 1.34 (95% CI 1.22-1.47), 1.00 (0.91-1.10), 1.0, 1.04 (0.97-1.12) and 1.27 (1.14-1.41) for total mortality, and 1.36 (95% CI 1.18-1.57), 1.06 (0.92-1.21), 1.0, 1.12 (1.01-1.25) and 1.35 (1.15-1.59) for cardiovascular mortality. Additional adjustment for systolic blood pressure, total cholesterol, history of cardiovascular disease, diabetes treatments and duration of diabetes affected the results only slightly.

Conclusions: The present study indicated a U-shaped association between BMI and total and cardiovascular mortality among diabetic men and women.

Objective: Laboratory tests including optical platelet aggregometry (OPA), Platelet Function Analyser (PFA-100TM), and thromboxane B2 (TXB2) metabolite levels have been used to define aspirin resistance. This study characterized the prevalence of aspirin resistance in patients with ischaemic heart disease (IHD) and investigated the concordance and repeatability of these tests.

Design, Setting and Patients: Consecutive outpatients with stable IHD were enrolled. They were commenced on 150mg aspirin daily (Day 0) and had platelet function assessment (OPA and PFA-100TM) and quantitative analysis of serum/urine TXB2 at Day ³7 and then at a second visit approximately two weeks later.

Main outcome measures: We assessed the prevalence of aspirin resistance by each method, concordance between methods of measuring response to aspirin, and association between time points to assess the predictability of response over time.

Results: One hundred seventy two patients (62.7 ± SD 8.7 years, 83.1% male) were recruited. At visits one and two, respectively, 1.7% and 4.7% were aspirin resistant by OPA, whereas 22.1% and 20.3% were aspirin resistant by PFA-100TM. There were poor associations between PFA-100TM and OPA, and between TXB2 metabolites and platelet function tests. OPA and PFA-100TM results were poorly associated between visits ( = 0.16 and = 0.42, respectively) as were TXB2 metabolites, suggesting that aspirin resistance is not predictable over time.

Conclusions: The prevalence of aspirin resistance is dependent on the method of testing. Response varies on a temporal basis, indicating that testing on a single occasion is inadequate to diagnose resistance or guide therapy in a clinical setting.

Background - Retinopathy lesions are fairly common findings in clinic settings and may predict risk of coronary heart disease (CHD).

Objective - To examine whether retinopathy independently predicts risk of coronary heart disease (CHD)-related mortality in persons with and without diabetes.

Methods - In an Australian population-based cohort of persons with (n=199) and without (n=2768) diabetes (Blue Mountains Eye Study, total n=2967), we assessed the presence and severity of retinopathy from retinal photographs. 12-year cumulative CHD deaths were ascertained from Australian National Death Index records.

Results - Over 12 years, 353 participants (11.9%) had incident CHD-related deaths. Retinopathy was present in 57/199 (28.6%) participants with, and in 268/2768 (9.7%) without diabetes. The presence of retinopathy increased the CHD mortality rate per person-years by an equivalent amount (0.005) as the presence of diabetes itself (12-year CHD mortality rate per person-years of 0.010 in persons with neither diabetes nor retinopathy, 0.015 with diabetes alone, 0.016 with retinopathy alone). After adjusting for cardiovascular risk factors, retinopathy remained an independent predictor of CHD death both in persons with diabetes (Hazard Ratio [HR] 2.21, 95% confidence interval [CI] 1.20-4.05) and in those without diabetes (HR 1.33, CI 1.02-1.83). Moderate retinopathy was associated with adjusted HR 6.68 (CI 2.24-20.0) in persons with diabetes, and adjusted HR 2.29 (CI 1.10-4.76), in persons without diabetes.

Conclusions - A finding of retinopathy in persons with or without diabetes may signal increased CHD risk. The increased CHD mortality associated with retinopathy in persons without diabetes was equivalent to the presence of diabetes itself.

Mortality rates from coronary heart disease (CHD), and from acute myocardial infarction (AMI) in particular, have been declining steadily since the 1970s[1, 2]. Data from the MONICA study suggests that two thirds of this decline can be attributed to changes in the incidence of first CHD events[1]. Since the end of the MONICA study, CHD incidence has been monitored through national registries based on continuous updating of routinely collected data from hospital records[3]. These data, however, are not without limitations. In this edition of heart, Cheuk Chan et al.[4] show that data from total hospital admissions can be misleading. Previous reports based on the same data showed a marked increase in hospital admissions for AMI, signalling a new epidemic of CHD[5]. In a thorough re-analysis, Cheuk Chan et al. demonstrate that this is solely due to an increase in AMI readmissions and changes in diagnostic practices, rather than an increase in the incidence of first AMI[4]. In fact, as in several other Western populations[1, 2], incidence of first AMI has been declining steadily in New Zealand since 1993.

Patients with acute coronary syndrome (ACS) often have raised blood glucose concentrations when admitted to hospital; a marker for poorer prognosis. Interventions to rapidly normalise blood glucose inconsistently are applied and with uncertain utility. Here we review the association of hyperglycaemia with outcome, present evidence that this hyperglycaemia reflects more than a pre-existing diabetic state and discuss mechanisms by which glucose may adversely affect the course of acute myocardial infarction (AMI). Finally, we seek evidence that intensive insulin treatment improves outcome.

Aim: The purpose of study was to test whether quantitative stress echocardiography using contrast-based myocardial blood flow (MBF, ml/min/g) measurements can detect coronary artery disease in humans.

Methods: 48 patients eligible for pharmacologic stress testing by myocardial contrast echocardiography (MCE) and willing to undergo subsequent coronary angiography were prospectively enrolled in the study. Baseline and adenosine-induced (140microgr/kg/min) hyperemic MBF was analyzed according to a 3-coronary-artery-territory model. Vascular territories were categorized into three groups with increasing stenosis severity defined as percent diameter reduction by quantitative coronary angiography.

Results: Myocardial blood flow reserve (MBFR), i.e. the ratio of hyperemic to baseline MBF, was obtained in 128 (89%) territories. Mean±SD baseline MBF was 1.073±0.395ml/min/g and did not differ between territories supplied by coronary arteries with mild (<50% stenosis), moderate (50%-74% stenosis) or severe (>75% stenosis) disease. Mean±SD hyperemic MBF and MBFR were 2.509±1.078ml/min/g and 2.54±1.03, respectively, and decreased linearly (r²=0.21 and r²=0.39) with stenosis severity. ROC analysis revealed that a territorial MBFR<1.94 detected >50% stenosis with 89% sensitivity and 92% specificity.

Conclusion: Quantitative stress testing based on myocardial blood flow measurements derived from contrast echocardiography is a new method for the non-invasive and reliable assessment of coronary artery disease in humans.

Background In elite athletes left ventricular morphologic changes are predicted to alter passive pressure/volume characteristics by reducing myocardial stiffness and increasing compliance.

Aim We investigated the utility of a new Doppler tissue index based on the pressure volume relation ((E/Ea)/LVEDD), which provides a measure of myocardial stiffness, and assessed its usefulness in detecting cardiac adaptation in elite rowers.

Methods Thirty-six international rowers (mean age 27±7 years,) who had trained intensively for 15-20 hours per week for more than 5 years and a control group of 30 sedentary but otherwise normal subjects (mean age 26±8 years,) were consented and enrolled into the study. The groups were similar in age and gender. Left ventricular (LV) septal and posterior wall thickness, mass, chamber size, transmitral Doppler peak early (E) and late (A) diastolic filling velocities and isovolumic relaxation times were measured. Early diastolic myocardial velocities (Ea) were averaged from 4 sites at the mitral annulus; Diastolic stiffness was assessed with the use of three indices E, Ea, and the left ventricular end diastolic diameter in diastole (LVEDD). The ratio, [(E/Ea)/LVEDD], represents a pressure/volume relationship and provides a novel index of diastolic stiffness. Rowers were further divided into 2 groups based on the presence or absence of left ventricular hypertrophy (LVH), ≤ 12mm and > 12mm.

Results There was no significant difference in Ea (4 site average) between the two groups, but there was a difference in the stiffness index, with rowers having significantly more compliant ventricles (p=0.0003). When compared with controls and adjusted for body surface area (BSA) and heart rate this difference remained statistically significant (p= 0.016). When the rowers were divided into 2 groups based on the presence or absence of LVH there was no difference in the stiffness index (p = 0.68)

Conclusions The key distinguishing feature of intense training is a reduction of myocardial stiffness despite the development of left ventricular hypertrophy.

At the end of 2007, Science recognized human genetic variation as the "breakthrough of the year" (1). Beginning in April last year and extending through the current year, on nearly a weekly basis, major advances have been made to unravel common DNA sequence variants that are incontrovertibly associated with common diseases. The number of diseases that have been reported on is now greater than 50, and many cardiovascular conditions are included in this avalanche of discoveries. There probably has been more progress in understanding the genomics of disease in the past year than for several previous decades in aggregate.

Low gradient aortic stenosis (LGAS) represents about 5% to 10% of all cases of severe AS and is the most challenging subgroup of patients with AS in terms of management. The term LGAS is usually applied to patients with a mean gradient < 30 mmHg (or 40 mmHg), an aortic valve area (AVA) < 1 cm2, and an ejection fraction (EF) < 35% (or 40%. Low EF in LGAS may be caused by severe low-flow AS with inadequate compensatory LV hypertrophy, called afterload mismatch, but also by another myocardial disease (such as extensive fibrosis, associated cardiomyopathy or myocardial infarction(MI), in which case, AS is not the primary problem. The essential problem for clinicians is to distinguish true severe low-flow AS, responsible for low EF, from pseudo-severe AS comprising mild-to-moderate AS associated with another cause of left ventricular dysfunction (LVD).Very low gradient may be observed in true severe low-flow AS, while the decreased AVA observed in pseudo-severe AS reflects poor opening of the aortic valve directly related to low transvalvular flow. For the clinician, the 2 main questions in LGAS are: -how severe is the AS? – which patients can benefit from surgery?

Consider this scenario. A 65 year old patient hospitalized with a troponin positive acute coronary syndrome (ACS) is initially managed with intensive antithrombotic therapy. Angiography is performed via the femoral artery, demonstrating a tight thrombus containing lesion in the left anterior descending artery that involves the first diagonal branch. Percutaneous coronary intervention (PCI) is performed, with a stent implanted into the left anterior descending artery, utilising a kissing balloon procedure to achieve an excellent final result. After this successful and uneventful procedure, the patient is transferred back to the cardiology ward. The following day the patient is noted to have a low blood pressure and complains of groin discomfort. Inspection reveals an extensive haematoma at the femoral puncture site. A large and expanding haematoma is demonstrated by ultrasound examination with an associated fall in hemoglobin to 7.2 g/dL. An immediate transfusion of 3 units of blood is administered and vascular surgical repair is required. Is this a rare, inconvenient, benign and unavoidable component of contemporary ACS management? The MORTAL study, published in this edition of HEART (1), complements an extensive and rapidly evolving literature that can help to answer these questions.

Objective: To assess whether 64-slice computed tomography (CT) angiography might replace some coronary angiography (CA) for diagnosis and assessment of coronary artery disease (CAD).

Methods: We searched electronic databases, conference proceedings and scanned reference lists of included studies. Eligible studies compared 64-slice CT with a reference standard of CA in adults with suspected/known CAD, reporting sensitivity and specificity or true and false positives and negatives. Data were pooled using the hierarchical summary receiver operating characteristic model.

Results: Forty studies were included; 28 provided sufficient data for inclusion in the meta-analyses, all using a cutoff of ¡Y 50% stenosis to define significant CAD. In patient-based detection (n=1286) 64-slice CT pooled sensitivity was 99% (95% credible interval (CrI) 97 to 99%), specificity 89% (95% CrI 83 to 94%), median positive predictive value (PPV) across studies 93% (range 64 to 100%) and negative predictive value (NPV) 100% (range 86 to 100%). In segment-based detection (n=14199) 64-slice CT pooled sensitivity was 90% (95% CrI 85 to 94%), specificity 97% (95% CrI 95 to 98%), median positive predictive value (PPV) across studies 76% (range 44 to 93%) and negative predictive value (NPV) 99% (range 95 to 100%).

Conclusions: 64-slice CT is highly sensitive for patient-based detection of CAD and has high NPV. An ability to rule out significant CAD means that it may have a role in the assessment of chest pain, particularly when the diagnosis remains uncertain despite clinical evaluation and simple non-invasive testing.

Aim: To compare prognosis for patients with a diagnosis of angina alone to patients post acute myocardial infarction (AMI) and / or revascularisation and/or angina.

Design: Community-based retrospective cohort study.

Setting: A random selection of 37 Irish general practices.

Participants: 1,609 adults with ischaemic heart disease (IHD) identified in 2000/1.

Intervention: Medical records searches and postal questionnaires in 2000/1 and 2005/6.

Outcome measures: Primary: all-cause and IHD-related mortality. Secondary: acute myocardial infarction (AMI), cardiac artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA); physical and mental health status, process of care measurements and behavioural risk factor outcomes.

Results: Compared with patients with previous AMI and / or revascularisation and / or angina, patients with angina alone had similar risks of all-cause and IHD-related death: hazard ratios of 0.73 (95% CI 0.55 – 0.98) and 0.65 (95% CI 0.44 - 0.98) respectively were not significant at the p=0.01 level. No statistically significant differences were identified in risks of subsequent AMI, CABG or PTCA, or other outcomes.

Conclusions: Prognosis for patients with angina alone was similar to those with previous AMI and/ or revascularization and /or angina. The clinical importance of angina should not be underestimated in primary care. Further descriptive research is needed amongst representative community cohorts of people with angina.

Background: Acute rheumatic fever (ARF) is a multi-organ disease triggered by infection with Lancefield Group-A Streptococci (GAS). Despite the effectiveness of antibiotic treatment of streptococcal pharyngitis in reducing the incidence of ARF, developing countries continue to experience a high burden of the disease and its chronic sequel, rheumatic heart disease (RHD).

Aim: To summarise all population-based studies of the incidence of ARF worldwide.

Method: A systematic review of all published prospective population-based studies of the incidence of first episode of ARF was conducted. The outcome measures were overall mean incidence rate of first attack of ARF per year (calculated over the entire study period for each study), and annum specific incidence rate (for studies documenting cases for each year of study).

Results: A search of MEDLINE, EMBASE, and other health-related databases identified 10 eligible studies conducted in 10 countries on all inhabited continents, except Africa. The overall mean incidence rate of first attack of ARF ranged from 5 to 51/100,000 population (mean 19/100,000; 95% confidence interval (CI) 9-30/100,000). A low incidence rate of "T10/100,000 per year was found in America and Western Europe. By contrast, a higher incidence (>10/100,000) was documented in Eastern Europe, Middle East, Asia, and Australasia. Yearly incidence rates were highest in the Middle East. Studies with longitudinal data displayed a falling incidence over time.

Conclusion: Despite an apparent fall in incidence over time, ARF incidence rates remain relatively high in Eastern Europe, the Middle East, and Australasia. Studies of ARF incidence are required in Africa, a continent that bears a high burden of RHD, and yet has no reliable information on ARF incidence rates.

In contrast to the challenges that frustrate the complete genetic delineation of complex common diseases (e.g. type 2 diabetes mellitus or coronary disease),[1–3] there has been extensive success in the delineation of highly penetrant loci in rarer disorders that conform to Mendelian inheritance.[4] Linkage studies in multi-case, multi-generation families have identified >1,300 of such causal genes. Hypertrophic cardiomyopathy (HCM) represents the first, and hence perhaps best-known, example of an inherited cardiac disorder to be understood in this way and its study has epitomized the application of genetics to cardiovascular disease.[5, 6]

Fifty years ago, the first modern reports of what we now recognise as HCM were authored by a surgeon, Sir Russell Brock, and a pathologist, Donald Teare. These classical papers stimulated an intense and sometimes controversial field of study, focussed in large part on the characterisation of left ventricular outflow tract obstruction. Detailed invasive haemodynamic investigations highlighted the extraordinary dynamic nature of this new form of outflow obstruction, and numerous surgical therapies were proposed and abandoned. The introduction of echocardiography allowed investigators to determine the mechanism for obstruction–an adverse interaction between a hypertrophied septum and abnormal movement of the mitral valve toward the septum–but also showed that obstruction was not a universal feature of the disease. The focus of this article is to review the historical controversies surrounding left ventricular outflow tract obstruction in hypertrophic cardiomyopathy, and to discuss the modern approach to its assessment and treatment.

In 1958, Donald Teare, a forensic pathologist in London, reported eight cases of sudden death caused by "asymmetrical hypertrophy or benign tumour" of the heart in the British Heart Journal. In this special issue of Heart, we celebrate the fiftieth anniversary of Teare’s paper and examine its importance in four specially commissioned reviews, written by clinicians whose careers span the half a century since his publication. Discussions on genetics, pathophysiology and treatment are brought up to date in a series of original papers written by contemporary investigators.

The modern description of hypertrophic cardiomyopathy is credited to the London pathologist, Robert Donald Teare who likened the disease to "a tumour of the heart" and published his observations in the British Heart Journal 50 years ago. Teare recognised asymmetrical hypertrophy and myocyte disarray as a familial condition associated with premature and sudden death in young people. He rightly deserves the accolade for bringing a poorly understood, but well recognised phenomenon into the public domain. Thick and heavy hearts had been of interest and investigation to physicians and pathologists for many centuries. This article reviews the early history of hypertrophic cardiomyopathy and reflects on several centuries of progress in our understanding of the condition.

In 1958, the British forensic pathologist, Donald Teare, reported a family in which eight young people had died suddenly from asymmetrical hypertrophy of the left ventricle. Five decades on, the prevention of premature death from ventricular tachyarrhythmia, heart failure and stroke remains a major aim of clinical management in what is now called hypertrophic cardiomyopathy. In this commentary, we review the underlying mechanisms of death and discuss the strengths and weaknesses of current international guidelines for the identification and treatment of high risk patients.

Objective: To examine the impact of heart failure (HF) etiology on long-term outcome after cardiac resynchronization therapy (CRT).

Design: Prospective cohort study.

Setting: University hospital.

Patients: One hundred and nineteen patients (44% with ischemic and 56% non-ischemic etiology) who underwent CRT.

Interventions: Clinical follow up for 39¡À24 months.

Main outcome measures: Cardiovascular mortality, HF and cardiovascular hospitalization were compared by Kaplan-Meier curves between the 2 groups, followed by Cox regression analysis for prognostic predictor(s).

Results: Forty-one (34%) patients died, in whom cardiovascular causes were identified in 32 (27%) patients. The ischemic group had a higher cardiovascular mortality (Log-rank ??2=4.293, p=0.038) and cardiovascular hospitalization (Log-rank ??2=5.123, p=0.024) when compared with the non-ischemic group, though no difference was found in HF hospitalization (Log-rank ??2=0.019, p=0.892). At 3-month, left ventricular reverse remodeling occurred in 52% of the ischemic group and 55% of the non-ischemic group (??2 =0.128, p=0.720). By Cox regression analysis, ischemic etiology and absence of reverse remodeling at 3-month were independent predictors of cardiovascular mortality (HR=2.698, p=0.032; HR=3.541, p=0.030) and cardiovascular hospitalization (HR=1.905, p=0.015; HR=2.361, p=0.004). Furthermore, these 2 factors had an incremental value in predicting cardiovascular mortality when compared with either alone (LV reverse remodeling, Log-rank ??2=10.275 vs. 6.311, p=0.05; Ischemic etiology, Log-rank ??2=10.275 vs. 4.293, p<0.05).

Conclusion: Ischemic etiology of HF is an independent predictor of higher cardiovascular mortality and hospitalization after CRT. This may implicate the progressive nature of coronary heart disease leading to a worse outcome despite similar short-term benefits of CRT.

Objective: To assess the clinical impact of a regional network for the treatment of ST-segment elevation myocardial infarction (STEMI).

Methods: All patients with STEMI (n=1,823) admitted to any of the hospitals of a 1-million inhabitants area during the year 2002 (n=858), i.e. before the network was implemented, and in 2004 (n=965), year of full implementation of the network, were enrolled in this study. The primary evaluation was in-hospital mortality. Secondary outcomes included the incidence of major adverse cardiac and cerebrovascular events (MACCE), defined as death, myocardial infarction, stroke, and coronary revascularisation procedures over 1-year follow-up.

Results: Between 2002 and 2004, there was a major change in reperfusion strategy: primary angioplasty increased from 20.2% to 65.6% (p<.001), fibrinolytic therapy decreased from 38.2% to 10.7% (p<.001), and the rate of patients not undergoing reperfusion was reduced from 41.6% to 23.7% (p<.001). In-hospital mortality decreased from 17.0% to 12.3% (p=.008), and this reduction was sustained at 1-year follow-up (23.9% in 2002 and 18.8% in 2004, p=.009). Similarly, the 1-year incidence of all MACCE was reduced from 39.5% in 2002 to 34.3% in 2004 (p=.01).

Conclusions: Organization of a territorial network for STEMI is associated with increased rates of reperfusion therapy and reduction of in-hospital and 1-year mortality.

Background: A reduced early (E) to late (A) diastolic filling ratio or prolonged deceleration time (DT) of E velocity reflects slowing of left ventricular (LV) relaxation. These findings are believed to indicate significant diastolic dysfunction. However, in patients with a similar grade of diastolic dysfunction at rest, a spectrum of alterations in diastolic function can exist during exercise. This study was sought to evaluate (1) whether exercise could unmask further diastolic abnormalities not evident under rest conditions and (2) whether diastolic functional reserve during exercise is associated with exercise capacity.

Methods: One hundred forty-one subjects (77 male, mean age 57±10) with abnormal LV relaxation, defined as the presence of mitral E/A<0.75 and/or DT>240 ms, underwent supine bicycle exercise with simultaneous respiratory gas analysis and two-dimensional and Doppler echocardiographic study. Mitral inflow and annular velocities were measured at rest and during graded supine bicycle exercise (25 W, 3 minutes increments). LV diastolic function reserve index (DFRI) was calculated as E'xE'base; where E' is the change of E' from baseline to exercise and E'base is early diastolic mitral annular velocity at rest.

Results: The median DFRI at 50W of exercise was 13.5. Patients were classified into two groups: group 1 (n=64), DFRI<13.5; and group 2 (n=77), DRFI>13.5. The ratio of E/E?to stroke volume was used as an index of ventricular elastance (Ed). There were no significant differences in mitral inflow (E, A, E/A, DT) and annular velocities at rest between the two groups. Ed was not significantly different at rest between the groups (0.19±0.07 vs 0.18±0.06 cm/s, p=0.29). However, Ed was significantly higher during exercise in group 1 as compared to group 2 (25 Watts, 0.21±0.09 vs 0.14±0.04, p<0.0001; 50 Watts, 0.22±0.10 vs 0.15±0.04, p<0.0001). The subjects in group 1 had a shorter exercise duration (8.2±2.7 vs 9.4±3.7 minutes, p=0.04) and lower peak oxygen consumption (17.5±4.5 vs 20.2±5.4 ml/kg/min, p=0.005).

Conclusions: Despite similar mitral flow and annular velocities at rest, different responses to exercise were observed in patients with abnormal LV relaxation at rest. Lower LV diastolic functional reserve was associated with higher ventricular elastance during exercise and reduced exercise capacity.

Objective: The purpose of this study was to compare the long-term outcomes of women and men after valve replacement surgery.

Design: Observational study.

Setting: Postoperative aortic valve replacement (AVR) or mitral valve replacement (MVR).

Patients: 3118 patients (1261 women, 1857 men) who underwent AVR or MVR between 1976 and 2006 (2255 AVR, 863 MVR), with mean follow-up of 5.6±4.5 years.

Main outcome measures: The independent effect of gender on the risk of long-term complications (reoperation, stroke, and death) after valve replacement surgery using multivariate actuarial methods.

Results: After implantation of an aortic valve bioprosthesis, women had a significantly lower rate of reoperation compared to men (comorbidity-adjusted hazard ratio [HR]: 0.4; 95% confidence intervals [CI]: 0.2, 0.9). In contrast, if an aortic mechanical prosthesis had been implanted, women were more at risk for late stroke compared to men (HR: 1.7; CI: 1.1, 2.7). After adjustment for age and co-morbidities, women had significantly better long-term survival compared to men after bioprosthetic AVR (HR: 0.5; CI: 0.3, 0.6), but there was no survival difference between genders after mechanical AVR. Trends existed towards better survival for women after bioprosthetic MVR (HR: 0.6; CI: 0.4, 1.0) and mechanical MVR (HR: 0.8; CI: 0.5, 1.1).

Conclusion: The long-term outcomes after valve replacement surgery differ between women and men. Although women have more late strokes after valve replacement, they undergo fewer reoperations and have better overall long-term survival compared to men.

The word "Universal" has many applications most notably as an adjective to describe the entire physical universe. One cannot help wondering therefore whether the current redefinition will be robust enough to be applied to other huminoid life forms in this or other galaxies. If it were only robust enough to be applied on planet earth then that in itself would be "a small step for a man but a giant setup for mankind." Taking the first word from the title of the recent Editorial of one the new guideline’s lead authors, the past history, and likely future of this important topic has been / will remain more "evolution" than "big-bang". However, it is very much in the nature and practice of cardiovascular medicine / surgery to "boldly go" and fully explore / tame - this new "Universe". To this end, we would also strongly advocate that professional bodies, research sponsors, healthcare providers / policy-makers / funders – mobilize their forces in full support of this important international agenda.

Symptoms of impaired consciousness (syncope and pre-syncope) occur in 15 – 25% of patients with hypertrophic cardiomyopathy[1]. In young patients a history of recurrent syncope is associated with an increased risk of sudden death[2-5]. Syncope usually occurs without warning or symptoms suggestive of the cause. Detailed investigations identify a probable mechanism in a minority, usually paroxysmal atrial fibrillation or ventricular tachycardia. In the majority however no likely mechanism is found despite repeated 24-hour ambulatory ECG or patient-activated monitoring, exercise testing and invasive electrophysiological studies[1;6]. Empiric treatment with Amiodarone, a pacemaker, or an implantable cardioverter-defibrillator is commonly employed, but is often unsuccessful in relieving the symptoms.

We have previously observed that approximately 30% of patients with HCM have abnormal blood pressure response during maximal upright exercise[8;9]. This was due in the majority of patients to an exaggerated fall in systemic vascular resistance, possibly arising from abnormal activation of stretch-sensitive left ventricular mechanoreceptors[8;10], by a mechanism similar to that described in aortic stenosis[11]. However, in some patients an inadequate cardiac output response to exercise may be responsible[12]. We hypothesised that abnormal vasodepressor-mediated hypotension may also occur during daily life in patients with HCM, and that this may be an important mechanism of syncope when conventional investigations fail to reveal a cause.

Background: Pulmonary hypertension (PH) can occur during exercise and has an adverse effect on functional status, exercise tolerance, and prognosis. However, the role of cardiac function abnormalities on exercise-induced PH in patients with normal left ventricular ejection fraction (LVEF) is unclear.

Objective: The purpose of this study is to analyze exercise-induced PH determinants in patients with normal LVEF.

Methods and Results: Three hundred ninety-six subjects (160 male, mean age 55±13) referred for exercise echocardiography underwent a graded, symptom-limited, supine bicycle exercise with two-dimensional and Doppler echocardiography. Tricuspid regurgitation (TR) velocity was measured at rest and during exercise. Pulmonary artery systolic pressure (PASP) was estimated from TR velocity by adding a right atrial pressure of 10 mmHg. Patients were classified according to exercise induced PH, defined as present if PASP > 50 mmHg at 50 W of exercise. One hundred thirty-five patients (34%) had PASP > 50 mmHg during exercise. Patients with exercise-induced PH were older, more commonly female, and had shorter exercise duration; however, LVEF was significantly higher. The systolic blood pressure at rest and during exercise was significantly higher in patients with exercise-induced PH (rest, 125 ¡3/4 18 vs 132 ¡3/4 18 mmHg, p=0.0003; 25 W, 146 ¡3/4 21 vs 157 ¡3/4 21 mmHg, p<0.0001; 50 W, 157 ¡3/4 24 vs 170 ¡3/4 22 mmHg, p<0.0001; 75W, 168 ¡3/4 23 vs 183 ¡3/4 22 mmHg, p<0.0001).Despite similar resting oxygen saturation, exercise oxygen saturation was significantly lower in subjects with exercise-induced PH than in those without. Numerous echocardiographic variables were significantly different between groups. In multivariate analysis, resting TR velocity (p<0.0001), E/E¡ (p=0.027), age, and gender were the strongest predictors of PASP during exercise.

Conclusion: Exercise-induced PH is common even in subjects with normal LVEF. It is strongly associated with E/E¡ ratio, TR velocity, age, systolic blood pressure during exercise, and gender.

Objective: Impaired endothelial function was demonstrated in HIV-infected persons on protease-inhibitor (PI)-containing antiretroviral therapy, probably due to altered lipid metabolism. Atazanavir is a PI causing less atherogenic lipoprotein changes. We studied whether endothelial function improves after switching from other PI to atazanavir.

Design: Randomized, observer-blind, treatment-controlled trial.

Setting: Three university-based outpatient clinics.

Patients: 39 HIV-infected persons with suppressed viral replication on PI-containing regimens and fasting LDL-cholesterol >3mmol/L.

Intervention: Patients were randomized either to continue the current PI or change to unboosted atazanavir.

Main outcome measures: Endpoints at week 24 were endothelial function assessed by flow-mediated vasodilation (FMD) of the brachial artery, lipid profiles, high sensitive C-reactive protein, malondyaldehyde, total antioxidative capacity and oxidized LDL.

Results: Baseline characteristics and mean FMD values of the two treatment groups were comparable (3.9±1.8% on atazanavir vs. 4.0±1.5% in controls). After 24 weeks’ treatment, FMD decreased to 3.3±1.4% and 3.4±1.7%, respectively (all p=n.s.). Total cholesterol improved in both groups (p=<0.0001 and p=0.01, respectively) but changes were more pronounced on atazanavir (p=0.05, changes between groups). HDL and triglyceride levels improved on atazanavir (p=0.03 and p=0.003, respectively) but not in the control group. Serum inflammatory and oxidative stress parameters did not change; oxidized LDL improved significantly in the atazanavir group.

Conclusions: The switch from another PI to atazanavir among treatment experienced patients did not result in improvement of endothelial function despite significantly improved serum lipids. Not only atherogenic lipid profiles but also direct effects of reverse transcriptase inhibitor plus PI-containing combination on the endothelium may affect vascular function.

ClinicalTrials.gov Identifier: NCT00447070

Paradoxically the heart, which is solely dedicated to supplying blood to the organs, restricts its own blood supply during peak contraction (Figure 1). To overcome this restriction, the heart has numerous mechanisms which delicately balance the blood flow demands of the systemic and coronary circulation.

The past decade of China heralded rapid increase of surgical coronary revascularization and coronary artery bypass grafting (CABG) has now been possible in an increasingly high risk population in China. However, little is known about the current status of CABG surgery in contemporary China. The European System for Cardiac Operative Risk Evaluation (EuroSCORE) was introduced to China for risk-adjustment in 2000 due to the absence of a local risk prediction model. Now it is the most widely used risk prediction algorithm in China. Fuwai Hospital, Beijing, China has developed a national multicentre database of CABG patients, named Chinese CABG Registry Study. We embarked on this study with a view to establish risk stratification and outcome assessment following CABG in Chinese adults as well as to provide a potential clinical research tool for