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The Getting It Right First Time (GIRFT) process is designed to improve the care of patients in the NHS in England through in-depth review of services, benchmarking and presenting a data-driven evidence base to support change. It started as a pilot project targeting unwarranted variation in elective orthopaedic surgery. It rapidly became apparent that the approach of clinically-led deep dives to review the activity in individual orthopaedic units was effective in improving standards of care but also resulted in substantial cost savings that could be reinvested in the clinical service. GIRFT has now expanded to encompass 40 clinical specialties and is funded by NHS England. We describe the ethos of networks and give examples of GIRFT specialty programmes that have made networks a key component of their recommendations.

Cet article examine les sources de l’accumulation de liquidites par les societes non financieres en France. Nous explorons notamment des explications par les couts, en proposant une mesure du cout de detention de liquidites specifique a l’entreprise, qui depend a la fois des couts de financement a court terme des entreprises et de la part des actifs financiers liquides qui generent des interets. L’analyse suggere qu’au moins un quart de la hausse de la tresorerie a l’actif des entreprises entre 2011 et 2016 decoule d’une tendance a la baisse du cout de detention de ces liquidites. En integrant l’impact supplementaire des evolutions macroeconomiques, l’explication par les couts rend compte de pres de 40 % de la hausse de la tresorerie. On identifie egalement que les entreprises conservent des liquidites afin de pouvoir exploiter de futures opportunites d’investissement, quelles que soient les conditions financieres lorsqu’elles se presenteront. Nos resultats suggerent que l’accumulation de liquidites par les entreprises dans le but de se premunir contre le risque de manquer des opportunites d’investissement en periode de ralentissement est un stabilisateur economique.

More than 300 000 procedures are performed in cardiac catheter laboratories in the UK each year. The variety and complexity of percutaneous cardiovascular procedures have both increased substantially since the early days of invasive cardiology, when it was largely focused on elective coronary angiography and single chamber (right ventricular) permanent pacemaker implantation. Modern-day invasive cardiology encompasses primary percutaneous coronary intervention, cardiac resynchronisation therapy, complex arrhythmia ablation and structural heart interventions. These procedures all carry the risk of cardiac arrest.We have developed evidence-based guidelines for the management of cardiac arrest in adult patients in the catheter laboratory. The guidelines include recommendations which were developed by collaboration between nine professional and patient societies that are involved in promoting high-quality care for patients with cardiovascular conditions. We present a set of protocols which use the skills of the whole catheter laboratory team and which are aimed at achieving the best possible outcomes for patients who suffer a cardiac arrest in this setting. We identified six roles and developed a treatment algorithm which should be adopted during cardiac arrest in the catheter laboratory. We recommend that all catheter laboratory staff undergo regular training for these emergency situations which they will inevitably face.

Adjustment costs impair the optimal allocation of production factor across firms. In this paper, we use the cost associated with corporate relocation to explore the effect of the adjustment costs of the premises size on factor demand. We rely on the tax on realized capital gains on real estate asset, which entails varying real estate adjustment costs across firms, to empirically study the effect of these frictions on firms' behaviour. We develop a general equilibrium model, with heterogeneous firms, that sheds light on the implication of the level of the fixed costs associated with the adjustment of real estate on the change in firms' labor demand following productivity shocks. This model predicts that employment growth of firms facing positive productivity shocks shrinks with the level of the frictions. Confronting these results using French firm-level data over the period 1994-2013, we find that higher adjustment costs constrain relocation and reduce job creation of the most dynamic firms. The highlighted frictions have noticeable macroeconomic effects.

BackgroundDisturbances of copper (Cu) homeostasis can lead to hypertrophic cardiac phenotypes (eg, Wilson’s disease). We previously identified abnormal Cu homeostasis in patients with hypertrophic cardiomyopathy (HCM) and, therefore, hypothesised that Cu2+–selective chelation with trientine dihydrochloride may slow or reverse disease progression in HCM. The aim of this study was, therefore to explore the clinical efficacy, safety and tolerability of trientine in HCM.MethodsIn this medicines and healthcare products regulatory agency (MHRA) registered open-label pilot study, we treated 20 HCM patients with trientine for 6 months. Patients underwent a comprehensive assessment schedule including separate cardiac magnetic resonance imaging (CMR) and CMR 31P-spectroscopy at baseline and end of therapy. Predefined end points included changes in left ventricular mass (LVM), markers of LV fibrosis, markers of LV performance and myocardial energetics. Ten matched patients with HCM were studied as controls.ResultsTrientine treatment was safe and tolerated. Trientine caused a substantial increase in urinary copper excretion (0.42±0.2 vs 2.02±1.0, p=0.001) without affecting serum copper concentrations. Treatment was associated with significant improvements in total atrial strain and global longitudinal LV strain using both Echo and CMR. LVM decreased significantly in the treatment arm compared with the control group (−4.2 g v 1.8 g, p=0.03). A strong trend towards an absolute decrease in LVM was observed in the treatment group (p=0.06). These changes were associated with a significant change in total myocardial volume driven by a significant reduction in extracellular matrix (ECM) volume (43.83±18.42 mL vs 41.49±16.89 mL, p=0.04) as opposed to pure cellular mass reduction and occurred against a background of significant ECM volume increase in the control group (44.59±16.50 mL vs 47.48±19.30 mL, p=0.02). A non-significant 10% increase in myocardial phosphocreatine/adenosine triphosphate (PCr/ATP) ratio with trientine therapy (1.27±0.44 vs 1.4±0.39) was noted.ConclusionsCu2+–selective chelation with trientine in a controlled environment is safe and a potential future therapeutic target. A phase 2b trial is now underway.

The Getting It Right First Time (GIRFT) process is designed to improve the care of patients in the National Health Service (NHS) in England through in-depth review of services, benchmarking and presenting a data-driven evidence base to support change. Although it started as a pilot project targeting unwarranted variation in elective orthopaedic surgery, it rapidly became apparent that the approach of clinically led deep dives to review the activity in individual orthopaedic units was effective in improving standards of care and resulted in substantial cost savings that could be reinvested in the clinical service. GIRFT has now expanded to encompass 40 clinical specialties and is funded nationally by the NHS in England. The purpose of this article is to describe its application and benefit to cardiology.

ObjectiveTo estimate the population prevalence and treatable burden of severe aortic stenosis (AS) in the UK.MethodsWe adapted a contemporary model of the population profile of symptomatic and asymptomatic severe AS in Europe and North America to estimate the number of people aged ≥55 years in the UK who might benefit from surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI).ResultsWith a point prevalence of 1.48%, we estimate that 291 448 men and women aged ≥55 years in the UK had severe AS in 2019. Of these, 68.3% (199 059, 95% CI 1 77 201 to 221 355 people) would have been symptomatic and, therefore, more readily treated according to their surgical risk profile; the remaining 31.7% of cases (92 389, 95% CI 70 093 to 144 247) being asymptomatic. Based on historical patterns of intervention, 58.4% (116 251, 95% CI 106 895 to 1 25 606) of the 199 059 symptomatic cases would qualify for SAVR, with 7208 (95% CI 7091 to 7234) being assessed as being in a high, preoperative surgical risk category. Among the remaining 41.6% (82 809, 95% CI 73 453 to 92 164) of cases potentially unsuitable for SAVR, an estimated 61.7% (51 093, 95% CI 34 780 to 67 655) might be suitable for TAVI. We estimate that 172 859 out of 291 448 prevalent cases of severe AS (59.3%) will subsequently die within 5 years without proactive management.ConclusionsThese data suggest a high burden of severe AS in the UK requiring surgical or transcatheter intervention that challenges the ongoing capacity of the National Health Service to meet the needs of those affected.

ObjectivesBullying of trainee doctors has been shown to be associated with detrimental outcomes for both doctors and patients. However, there is limited evidence regarding the level of bullying of trainees within medical specialties.MethodsAn annual survey of UK cardiology trainees was conducted through the British Junior Cardiologists’ Association between 2017 and 2020 and asked questions about experiencing and witnessing bullying, and exposure to inappropriate language/behaviour in cardiology departments. Fisher’s exact tests and univariable logistic regression models were used to describe associations between trainee characteristics, and reports of bullying and inappropriate language/behaviour.ResultsOf 1358 trainees, bullying was reported by 152 (11%). Women had 55% higher odds of reporting being bullied (OR: 1.55 95% CI (1.08 to 2.21)). Non-UK medical school graduates were substantially more likely to be bullied (European Economic Area (EEA) OR: 2.22 (1.31 to 3.76), non-EEA/UK OR: 3.16 (2.13 to 4.68)) compared with those graduating from UK-based medical schools. Women were more likely than men to report sexist language (14% vs 4%, pDiscussionBullying and inappropriate language are commonly experienced by cardiology trainees and disproportionately affect women and those who attended non-UK medical schools. Consultants both in cardiology and other specialties are the most commonly reported perpetrators.

Heart and circulatory diseases affect more than seven million people in the UK. Non-invasive cardiac imaging is a critical element of contemporary cardiology practice. Progressive improvements in technology over the last 20 years have increased diagnostic accuracy in all modalities and led to the incorporation of non-invasive imaging into many standard cardiac clinical care pathways. Cardiac imaging tests are requested by a variety of healthcare practitioners and performed in a range of settings from the most advanced hospitals to local health centres. Imaging is used to detect the presence and consequences of cardiovascular disease, as well as to monitor the response to therapies. The previous UK national imaging strategy statement which brought together all of the non-invasive imaging modalities was published in 2010. The purpose of this document is to collate contemporary standards developed by the modality-specific professional organisations which make up the British Cardiovascular Society Imaging Council, bringing together common and essential recommendations. The development process has been inclusive and iterative. Imaging societies (representing both cardiology and radiology) reviewed and agreed on the initial structure. The final document therefore represents a position, which has been generated inclusively, presents rigorous standards, is applicable to clinical practice and deliverable. This document will be of value to a variety of healthcare professionals including imaging departments, the National Health Service or other organisations, regulatory bodies, commissioners and other purchasers of services, and service users, i.e., patients, and their relatives.

The purpose of this document is to update the existing joint British Societies recommendations on multidisciplinary meetings (MDMs) published in 2015 to reflect changes in practice. We aim to provide guidance on the structure and function of MDMs which should be taking place in every cardiac surgical centre. Out of scope are MDMs that do not require the routine presence of a cardiac surgeon such as electrophysiology MDMs and those which are not provided in every centre, such as complex aortic surgery.

Objective: In hypertension, indexes of midwall left ventricular (LV) function may identify patients at higher cardiovascular (CV) risk independent of normal LV ejection fraction (EF). We analyzed the association of baseline and new-onset LV midwall dysfunction with CV outcome in a large population of patients with asymptomatic aortic stenosis (AS). Methods: One thousand four hundred seventy-eight patients with asymptomatic AS and normal EF (≥50%) at baseline in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study were followed for a median of 4.3 years. LV systolic function was assessed by biplane EF and midwall shortening (MWS, low if

One of the biggest controversies in valvular heart diseases is the best treatment strategy in asymptomatic patients with severe, organic mitral valve regurgitation (MR) and preserved left ventricul...

BACKGROUND AND AIMS: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory marker associated with cardiovascular disease. Statins lower both low-density lipoprotein (LDL)-cholesterol and C-reactive protein (CRP), resulting in improved outcomes. However, whether lipid-lowering therapy also lowers suPAR levels is unknown.METHODS: We investigated whether treatment with Simvastatin 40 mg and Ezetimibe 10 mg lowered plasma suPAR levels in 1838 patients with mild-moderate, asymptomatic aortic stenosis, included in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, using a pattern mixture model. A 1-year Cox analysis, adjusted for established cardiovascular risk factors, allocation to study treatment, peak aortic valve velocity and baseline suPAR, was performed to evaluate relationships between change in suPAR with all-cause mortality and the composite endpoint of major cardiovascular events (MCE) composed of ischemic cardiovascular events (ICE) and aortic valve related events (AVE).RESULTS: After 4.3 years of follow-up, suPAR levels had increased by 9.2% (95% confidence interval [CI]: 7.0%-11.5%) in the placebo group, but only by 4.1% (1.9%-6.2%) in the group with lipid-lowering treatment (pCONCLUSIONS: Simvastatin and Ezetimibe treatment impeded the progression of the time-related increase in plasma suPAR levels. Year-1 suPAR was associated with all-cause mortality, MCE, and AVE irrespective of baseline levels (SEAS study: NCT00092677).

The paper by Shareen Jaijee and colleagues1 in this edition of Heart puts figures onto what many cardiologists will recognise as an everyday reality of our specialty. It makes unwelcome but not unexpected reading. In the last 15 years, progress with regards to gender representation in UK cardiology practice2 and leadership appears to have stood still or at best run at a pedestrian pace. Female cardiologists are still in a minority, particularly in interventional specialities, in academic cardiology and as leaders and are substantially more likely to have been on the receiving end of inappropriate behaviour from professional colleagues. Disturbingly, a third of female cardiologists reported sexual harassment.1 UK women training in cardiology also report3 experiencing sexism particularly in the latter years of training (15%) when studying in tertiary centres where more interventional cardiology and research training is located and are more likely to change their preferred subspecialty choice away from intervention and electrophysiology.3 Non-cardiology trainee respondents to a survey mentioned witnessing and experiencing bullying and sexism by cardiologists and cardiology trainees as a reason not to choose a career in cardiology, with sexism more often reported by women.4 Negative attitudes and behaviours in UK cardiology therefore affect people at every stage and will likely need multiple actions to stamp out. One positive finding in this paper1 is that the great majority of cardiologists, both male and female, feel positive about their choice of specialty despite the obstacles and negative factors reported. This is …

Background Global iodine-123 metaiodobenzylguanidine (I-MIBG) uptake is predictive of cardiovascular events and mortality in patients with heart failure. Normal variations in global and regional uptake, however, are not well defined and few studies have addressed the functional relevance of I-MIBG uptake and distribution in healthy individuals. Materials and methods We performed I-MIBG scintigraphy and cardiac autonomic function testing using the standardized methodology in 15 healthy individuals (mean age 54.6±5.3 years, male : female 10 : 5) with no evidence of previous myocardial infarction or ischaemic heart disease. Results Early heart to mediastinum ratio (HMR) was 1.67±0.13, late HMR was 1.73±0.16 and washout rate was 19.09±7.63% (4.20-31.30). Regional analysis showed reduced tracer uptake at the apex, base and inferior wall in all individuals. Early and late HMR correlated negatively with RFa (r=-0.603; P=0.05 and r=-0.644; P=0.033) and expiration and inspiration ratio (r=-0.616; P=0.043 and r=-0.676; P=0.022) and positively with LFa/RFa (r=0.711; P=0.014 and r=0.784; P=0.004). Washout rate correlated only with RFa (r=0.642; P=0.033). Conclusion Healthy adults show a heterogeneous pattern of cardiac innervation with reduced regional uptake of I-MIBG. Furthermore, HMR correlates with indices of cardiac sympathetic function, suggesting that it might not only be a useful prognostic marker but may also provide insight into the functional integrity of the cardiac autonomic nervous system.

Mitral regurgitation (MR) is the second most common form of valvular disease requiring surgery. Correct identification of surgical candidates and optimising the timing of surgery are key in management. For primary MR, this relies upon a balance between the peri-operative risks and rates of successful repair in patients undergoing early surgery when asymptomatic with the potential risk of irreversible left ventricular dysfunction if intervention is performed too late. For secondary MR, recognition that this is a highly dynamic condition where MR severity may change is key, although data on outcomes in determining whether concomitant valve intervention is performed with revascularisation has raised questions regarding timing of surgery. There has been substantial interest in the use of stress echocardiography to risk stratify patients in mitral regurgitation. This article reviews the role of stress echocardiography in both primary and secondary mitral regurgitation and discusses how this can help clinicians tackle the challenges of this prevalent condition.

Background Myocardial fibrosis is a key mechanism of left ventricular decompensation in aortic stenosis and can be quantified using cardiovascular magnetic resonance (CMR) measures such as extracellular volume fraction (ECV%). Outcomes following aortic valve intervention may be linked to the presence and extent of myocardial fibrosis. Objectives This study sought to determine associations between ECV% and markers of left ventricular decompensation and post-intervention clinical outcomes. Methods Patients with severe aortic stenosis underwent CMR, including ECV% quantification using modified Look-Locker inversion recovery–based T1 mapping and late gadolinium enhancement before aortic valve intervention. A central core laboratory quantified CMR parameters. Results Four-hundred forty patients (age 70 ± 10 years, 59% male) from 10 international centers underwent CMR a median of 15 days (IQR: 4 to 58 days) before aortic valve intervention. ECV% did not vary by scanner manufacturer, magnetic field strength, or T1 mapping sequence (all p > 0.20). ECV% correlated with markers of left ventricular decompensation including left ventricular mass, left atrial volume, New York Heart Association functional class III/IV, late gadolinium enhancement, and lower left ventricular ejection fraction (p, Central Illustration

In this study, we aimed to determine if pretreatment low-density lipoprotein (LDL) levels and aortic stenosis (AS) severity alter the efficacy of lipid-lowering therapy on reducing aortic valve replacement (AVR). We used 1,687 patients with asymptomatic mild-to-moderate AS, who were randomly assigned (1:1) to 40/10 mg simvastatin/ezetimibe combination versus. placebo in the simvastatin and ezetimibe in aortic stenosis (SEAS) trial. Pretreatment LDL levels (>4 mmol/L) and peak aortic jet velocity (3 m/s) were used to partition study participants into 4 groups, which were followed for a primary endpoint of AVR. Cox regression with tests for interaction was used to study the effect of randomized treatment in each subgroup. During a median follow-up of 4.3 years (IQR 4.2 to 4.7 years; total 7,396 patient-years of follow-up), 478 (28%) patients underwent AVR and 146 (9%) died. A significant risk dependency was detected between simvastatin/ezetimibe combination, LDL levels and mild versus moderate AS on rates of AVR (p = 0.01 for interaction). In stratified analyses, randomized treatment, therefore, reduced the rate of AVR in patients with LDL levels >4 mmol and mild AS at baseline (HR 0.4; 95% CI: 0.2 to 0.9). There was no detectable effect of randomized treatment on the need for AVR in the 3 other participants subgroups. We conclude, that in a secondary analysis from a prospective randomized clinical trial, treatment with simvastatin/ezetimibe combination reduced the need for AVR in a subset of patients with mild AS and high pretreatment LDL levels (Unique identifier on clinicaltrials.gov: NCT00092677).

In this paper, we investigate the effect of real estate prices on productive investment. We build a simple theoretical framework of firms’ investment with credit rationing and real estate collateral. We show that real estate prices affect firms’ borrowing capacities through two channels. An increase in real estate prices raises the value of the firms’ pledgeable assets and mitigates the agency problem characterizing the creditor-entrepreneur relationship. It simultaneously cuts the expected profit due to the increase in the cost of inputs. While the literature only focuses on the first channel, the identification of the second channel allows for heterogeneous effects of real estate prices on investment across firms. We test our theoretical predictions using a large French database. We do find heterogeneous effects of real estate prices on productive investment depending on the position of the firms in the sectoral distributions of real estate holdings. Our preferred estimates indicate that a 10% increase in real estate prices causes a 1% decrease in the investment rate of firms in the first decile of the distribution but a 6% increase in the investment rate of firms belonging to the last decile.

Background: We evaluated whether early measurement of soluble urokinase plasminogen activator receptor (suPAR) could predict future risk of postoperative complications in initially asymptomatic patients with mild-moderate aortic stenosis (AS) undergoing aortic valve replacement (AVR) surgery.Methods: Baseline plasma suPAR levels were available in 411 patients who underwent AVR surgery during follow-up in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Cox analyses were used to evaluate suPAR in relation to all-cause mortality and the composite endpoint of postoperative complications (all-cause mortality, congestive heart failure, stroke and renal impairment) occurring in the 30-day postoperative period.Results: Patients with initially higher levels of suPAR were at increased risk of postoperative mortality with a HR of 3.5 (95% CI 1.4 to 9.0, P=0.008) and postoperative complications with a HR of 2.7 (95% CI 1.5 to 5.1, P=0.002), per doubling in suPAR. After adjusting for the European System for Cardiac Operative Risk Evaluation or Society of Thoracic Surgeons risk score, suPAR remained associated with postoperative mortality with a HR 3.2 (95% CI 1.2 to 8.6, P=0.025) and 2.7 (95% CI 1.0 to 7.8, P=0.061); and postoperative complications with a HR of 2.5 (95% CI 1.3 to 5.0, P=0.007) and 2.4 (95% CI 1.2 to 4.8, P=0.011), respectively.Conclusion: Higher baseline suPAR levels are associated with an increased risk for postoperative complications and mortality in patients with mild-moderate, asymptomatic AS undergoing later AVR surgery. Further validation in other subsets of AS individuals are warranted.Trial registration number: NCT00092677; Post-results.

Impaired glucose tolerance (IGT) is associated with an increased risk of type 2 diabetes (T2DM) and cardiovascular disease. Some but not all studies have reported cardiac autonomic dysfunction in subjects with IGT and there is only one direct study of cardiac innervation in subjects with IGT. The purpose of this study was to assess global and regional cardiac sympathetic innervation and cardiac autonomic function in individuals with IGT.We undertook (123)I-mIBG scintigraphy and cardiac autonomic function in 15 subjects with IGT and 15 age and sex-matched healthy controls. Early heart to mediastinum ratio (HMR) (1.71 ± 0.17 vs 1.67 ± 0.13, P = .49), late HMR (1.73 ± 0.18 vs 1.73 ± 0.16, P = .97) and washout rate (WR) (18.6 ± 4.2 vs 19.1 ± 7.6%, P = .84), did not differ between subjects with IGT and control subjects. More detailed regional analysis revealed reduced tracer uptake at the apex, base and inferior wall in all subjects and the anterior wall in a minority of subjects. There were no differences in total score (56.6 ± 4.0 vs 53.3 ± 8.4, P = .193), modified score (48.5 ± 3.3 vs 46.2 ± 6.0, P = .215), anterior wall score (10.2 ± 1.3 vs 10.1 ± 1.6, P = .898), inferior wall score (8.9 ± 1.9 vs 7.7 ± 2.6, P = .163), basal score (18.7 ± 1.9 vs 18.2 ± 3.3, P = .636) and tests of cardiac autonomic function between the groups.Global and regional measures of MIBG uptake and washout as well as cardiac autonomic function did not differ between subjects with IGT and healthy controls.

There is increasing recognition of the need for collaboration between oncologists, acute physicians and specialists to improve the quality of care and outcomes of acutely unwell patients with cancer. At The Christie, a tertiary oncology hospital, a model has been developed to deliver acute medical and specialty support services. This delivers, among many things, a consultant-led acute medical ward round on weekdays. There has been a significant increase in the number of patients admitted to the oncology assessment unit (OAU) since its introduction, in part due to an increased number of direct discharges from the unit. Collaborative working between oncologists and acute physicians with a shared vision for high-quality care for patients has ensured that this change has been implemented smoothly. This has included development of patient flow models to optimise bed usage, so that a higher number of patients can access these specialist services.

Observational studies indicate that low-density lipoprotein (LDL) cholesterol acts as a primary contributor to an active process leading to aortic stenosis (AS) development. However, randomized clinical trials have failed to demonstrate an effect of lipid lowering on impeding AS progression. This study explored if pretreatment LDL levels and AS severity altered the efficacy of lipid-lowering therapy. The study goal was evaluated in the analysis of surviving patients with baseline data in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial of 1,873 asymptomatic patients with mild-to-moderate AS. Serially measured peak aortic jet velocity was the primary effect estimate. Linear mixed model analysis adjusted by baseline peak jet velocity and pretreatment LDL levels was used to assess effect modifications of treatment. Data were available in 1,579 (84%) patients. In adjusted analyses, lower baseline peak aortic jet velocity and higher pretreatment LDL levels increased the effect of randomized treatment (p = 0.04 for interaction). As such, treatment impeded progression of AS in the highest quartile of LDL among patients with mild AS at baseline (0.06 m/s per year slower progression vs placebo in peak aortic jet velocity, 95% confidence interval 0.01 to 0.11, p = 0.03), but not in the 3 other quartiles of LDL. Conversely, among patients with moderate AS, there was no detectable effect of treatment in any of the pretreatment LDL quartiles (all p ≥0.14). In conclusion, in a non–prespecified post hoc analysis, the efficacy of lipid-lowering therapy on impeding AS progression increased with higher pretreatment LDL and lower peak aortic jet velocity (SEAS study: NCT00092677).

Adjustment costs impair the optimal allocation of production factor across firms. In this paper, we use the cost associated with corporate relocation to explore the effect of the adjustment costs of the premises size on factor demand. We rely on the tax on realized capital gains on real estate asset, which entails varying real estate adjustment costs across firms, to empirically study the effect of these frictions on firms' behaviour. We develop a general equilibrium model, with heterogeneous firms, that sheds light on the implication of the level of the fixed costs associated with the adjustment of real estate on the change in firms' labor demand following productivity shocks. This model predicts that employment growth of firms facing positive productivity shocks shrinks with the level of the frictions. Confronting these results using French firm-level data over the period 1994-2013, we find that higher adjustment costs constrain relocation and reduce job creation of the most dynamic firms. The highlighted frictions have noticeable macroeconomic effects.

Through a time-varying VAR model with drifting parameters and stochastic volatilities (Cogley and Sargent, 2005, Primiceri, 2005), we explore nonlinearities on the French housing and credit markets, which give rich insights on the persistent bubble of the 2000s. While the price increase took place during a period of low shock variance, shock persistence increased during this period, as well as the elasticity relative to demography and income. Low reactivity of the housing stock to housing prices may create construction bottlenecks and explain these nonlinearities. However, even though our framework is very flexible, part of the price increase remains unexplained.

Background Patients with aortic stenosis ( AS ) often have concomitant hypertension. Antihypertensive treatment with a β‐blocker (Bbl) is frequently avoided because of fear of depression of left ventricular function. However, it remains unclear whether antihypertensive treatment with a Bbl is associated with increased risk of cardiovascular events in patients with asymptomatic mild to moderate AS . Methods and Results We did a post hoc analysis of 1873 asymptomatic patients with mild to moderate AS and preserved left ventricular ejection fraction in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study. Propensity‐matched Cox regression and competing risk analyses were used to assess risk ratios for all‐cause mortality, sudden cardiac death, and cardiovascular death. A total of 932 (50%) patients received Bbl at baseline. During a median follow‐up of 4.3±0.9 years, 545 underwent aortic valve replacement, and 205 died; of those, 101 were cardiovascular deaths, including 40 sudden cardiovascular deaths. In adjusted analyses, Bbl use was associated with lower risk of all‐cause mortality (hazard ratio 0.5, 95% confidence interval 0.3‐0.7, P P P =0.004). This was confirmed in competing risk analyses (all P AS severity (all P >0.1). Conclusions In post hoc analyses Bbl therapy did not increase the risk of all‐cause mortality, sudden cardiac death, or cardiovascular death in patients with asymptomatic mild to moderate AS . A prospective study may be warranted to determine if Bbl therapy is in fact beneficial. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00092677.

Mitral stenosis (MS) has become less common in developed countries following the declining incidence of rheumatic fever, but it remains a major health problem worldwide. Atrial fibrillation is a common accompaniment and may trigger the onset of pulmonary oedema. Medical treatment is aimed at control of atrial fibrillation and prevention of thromboembolism. Patients with symptoms and a valve area

Objective The aim of the current study was to identify predictors of paraprosthetic aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) and examine its influence on short/medium-term mortality using the UK TAVI Registry. TAVI is an effective treatment for high-risk patients with severe symptomatic aortic stenosis (AS), but paraprosthetic AR has been associated with increased in-hospital and mid-term mortality. Methods Between January 2007 and December 2011, 2584 TAVI procedures were performed in the UK. Patients undergoing ‘valve-in-valve’ procedures, patients with aortic regurgitation as the primary pathology and with no recorded severity of AR were excluded from this analysis (n=144). In total, therefore, 2440 patients were included. Balloon-expandable and self-expanding devices were implanted in 52.7 and 47.2%, respectively, using either transfemoral (67.7%) or non-transfemoral, surgical access (32.3%). Results Postprocedural AR was observed in 68%, mild AR in 57% and moderate-severe in 10%. A large aortic annulus, high preprocedural transaortic gradient, and use of self-expanding valve were independent predictors of moderate-severe AR. Moderate-severe (but not mild) AR was associated with increased mortality, and this relationship appeared significant for the balloon-expandable but not the self-expanding device. Conclusions Our data suggest that a large aortic annulus, high preprocedural transaortic gradient, and use of the self-expanding valve predict moderate-severe AR after TAVI. Such a degree of AR is associated with a significantly worse outcome with the balloon-expandable, but not with the self-expanding valve. Further studies are needed to verify this and explore potential mechanisms.

To the Editor: In October 2013, autochthonous transmission of chikungunya was detected in the Caribbean area, which resulted in the current epidemic of chikungunya in the Western Hemisphere (1). The chikungunya virus strain that caused this epidemic belongs to the Asian lineage, not to the strain descending from the East/Central/South African (ECSA) lineage that spread in the Indian Ocean region after 2004. This ECSA lineage was reported mainly to cause long-lasting musculoskeletal and rheumatic disorders in chikungunya virus–infected patients (2–8). In 1984 in South Africa, Brighton and Simson reported post-chikungunya destructive polyarthritis (6). Twenty years later, the arthritogenic pathogenesis of viruses in the ECSA chikungunya virus lineage was confirmed after outbreaks in the Indian Ocean region (2–5,7,8). Because >870,000 suspected cases of chikungunya have occurred during the past 12 months in the Western Hemisphere (http://www.paho.org/hq/index.php?option=com_content&view=article&id=9436), it is crucial to know whether infection with the epidemic Asian strain will cause chronic inflammatory and potentially destructive rheumatism. We report post-chikungunya rheumatoid arthritis from Saint Martin, the epicenter of the current epidemic. A 70-year-old woman (artist–painter) in Saint Martin sought treatment in June 2014 for joint pains and disabilities persisting after chikungunya. Her medical history included high blood pressure, hypothyroidism, and 3 dengue infections. During October 2013, the patient had high-grade fever, intense fatigue, and a maculopapular troncular exanthema without lymphadenopathy. Five days later, she had distal polyarthritis (joint pain and swelling) in interphalangeal joints, wrists, and ankles without plantar involvement. Recent infection with chikungunya virus was confirmed (IgM and IgG against chikungunya virus was detected in 2 blood samples), and recent dengue was excluded according to the criteria of the National Reference Center on Arboviral Diseases (http://www.niaid.nih.gov/labsandresources/resources/dmid/wrceva/Pages/default.aspx). Despite initial brief improvement, the patient never totally recovered and subsequently chronic polyarthritis developed, which involved >10 joints, including interphalangeal joints, wrists, and knees. Nonsteroidal antiinflammatory drugs did not relieve the diffuse pain, stiffness, and swelling. She was given oral corticotherapy (20 mg/day) beginning in January 2014. She was referred to another hospital in France 5 months later because of treatment failure. She reported continuous pain in the left knee and wrists and multiple tenosynovitis on flexors and extensors of the fingers (Figure). She did not report any fever or axial, shoulder, or hip pain. Radiographs of the involved joints showed no abnormalities. Figure Swollen and stiff hands of a 70-year-old woman with post-chikungunya rheumatoid arthritis 10 months after acute infection with chikungunya virus, Saint Martin. The patient had mild inflammation (C-reactive protein level 13 mg/L, fibrinogen level 3.4 g/L) but no specific autoimmunity (results were negative for anticitrullinated peptide antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, and antinuclear antibodies). Serologic results for viruses other than chikungunya virus were negative or indicated past vaccination. The patient’s condition met the 2010 American College of Rheumatology/European League against Rheumatism criteria for rheumatoid arthritis (https://www.rheumatology.org/practice/clinical/classification/ra/ra_2010.asp), and the only cause observed for this disease was acute chikungunya. For this corticosteroid-resistant, seronegative, and nondestructive post-chikungunya rheumatoid arthritis, methotrexate was prescribed at a weekly low dose after exclusion of contraindications, but the patient was not followed-up after she returned to Saint Martin. The reported case was caused by chikungunya virus infection during an epidemic in Saint Martin in October 2013. This unfavorable post-chikungunya outcome of chronic inflammatory rheumatism 8 months later indicates a probable course of post-chikungunya disorders in the Western Hemisphere, as has already been observed in Africa and Asia. Previous outbreaks in Reunion and India offer insights regarding patients’ post-chikungunya chronic status with long-lasting pain and disability, impaired quality of life, and extensive treatment (2,3,9). The spectrum of post-chikungunya rheumatic and musculoskeletal disorders includes multiple tendinitis and tenosynovitis, plantar fasciitis, mechanical disbalance in susceptible joints, tunnel syndromes, edematous polyarthralgia, rheumatoid arthritis, and psoriatic arthritis (2,4,5). Although the proportion of patients with chronic disease has decreased, post-chikungunya chronic inflammatory rheumatism, mostly rheumatoid arthritis, develops in ≈5% of these patients (8). These patients had a poor prognosis and were given disease-modifying anti-rheumatic drugs (DMARDs), despite the postinfectious origin of rheumatism (4,5). Patients with post-chikungunya rheumatoid arthritis should benefit from methotrexate, which is recommended for treatment of classic rheumatoid arthritis (10). In our experience, resistance to or dependence on corticosteroids beyond the third month after disease onset is highly evocative of post-chikungunya chronic inflammatory rheumatism. This finding requires early treatment with DMARDs to control the inflammatory process, prevent bone erosions, and prevent inevitable side effects of prolonged corticotherapy. To date, the efficacy of different DMARDs for treatment of post-chikungunya chronic inflammatory rheumatism has not been evaluated. Therefore, physicians should follow the international guidelines for treatment of classic rheumatoid arthritis and psoriatic polyarthritis, which recommend methotrexate as first-line treatment for patients fulfilling chronic inflammatory rheumatism criteria after 3 months of evolution. We found that the Asian strain of chikungunya virus has induced arthritic disorders in the Western Hemisphere. Thus, a possible increase in post-chikungunya rheumatoid arthritis should not be overlooked. Physicians and public health authorities should prepare a response to the patients’ post-chikungunya stage in the epidemic areas. Clinical vigilance is recommended to identify patients with unfavorable outcomes 3 months after disease onset and for those in whom post-chikungunya chronic inflammatory rheumatism develops and who require specific treatment. Detailed guidelines for diagnosis and treatment of these patients with chronic rheumatoid arthritis are needed.

Left atrial (LA) size and function change with chronically increased left ventricular (LV) filling pressures. It remains unclear whether these variations in LA parameters can predict new-onset atrial fibrillation (AF) in asymptomatic patients with aortic stenosis (AS).Data were obtained in asymptomatic patients with mild-to-moderate AS (2.5 ≤ transaortic Doppler velocity ≤ 4.0m/s), preserved LV ejection fraction (EF), no previous AF, and were enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis study. Peak-aortic velocity, LA(max) volumeLAmin volume were measured by echocardiography. LA conduit (LA(con)) volume was defined as LV stroke volume-LA stroke volume. LA function was expressed as LA-EF (LA(max)-LAmin volume/LA(max)).In the 1159 patients included, new-onset AF occurred in 71 patients (6.1%) within a mean follow-up of 4.2 ± 0.9 years. Mean age was 66 ± 9.7 years, aortic valve area index 0.6 ± 0.2 cm(2)/m(2), LV mass 99.2 ± 29.7 g/m(2), LA(max) volume 34.6 ± 12.0 mL/m(2), LAmin volume 17.9 ± 9.3 mL/m(2), LA-EF 50 ± 15% and LA(con) volume 45 ± 21 mL/m(2). Baseline LAmin volume predicted new-onset AF in Cox multivariable analysis (HR:2.3 [95%CI:1.3-4.4], P0.01), and added prognostic information on AF development beyond conventional risk factors (likelihood ratio, P0.01). In comparison of c-indexes LAmin volume was superior to all other LA measurements. Net reclassification index improved by 15.9% when adding LAmin volume to a model with classic risk factors for AF (P=0.01).LAmin volume independently predicted new-onset AF in patients with asymptomatic AS and was superior to LA-EF, LA(con) and LA(max) volumes and conventional risk factors.

Infective endocarditis (IE) is uncommon but important because it is difficult to manage and universally fatal unless appropriately treated. The estimated incidence is 3–10 episodes each year per 100 000 population.1 In industrially developed countries, IE increasingly occurs in older adults with intracardiac devices (pacemakers and implantable defibrillators), replacement heart valves and medical interventions such as haemodialysis.2–4 Younger age groups are also affected, particularly intravenous drug users and those with adult congenital heart disease.5 Staphylococci are now the most common causative organisms in international series and streptococci the second most common.6 Resistance to antimicrobial agents, particularly vancomycin, is increasing.1 ,7 Patients with IE remain in hospital for a median of 4–6 weeks8 ,9 and approximately a half require inpatient cardiac surgery.1 ,10 ,11 The inhospital mortality rate is about 20%8 ,12 but varies widely according to age, comorbidity, heart failure, the presence of prosthetic material and the organism.13 For example, in prosthetic valve IE with associated renal failure, the reported mortality may be 40%–50%14 ,15 and with severe heart failure as high as 64%.15 The outcome can be improved by prompt diagnosis and antibiotic therapy and by early surgery when indicated.8 ,10 ,16 ,17 Despite this, the diagnosis may be delayed, mistakes may be made in the type, duration or dose of antibiotic18 or the antibiotic may be started before blood cultures are obtained.11 Patients are still frequently referred to a specialist only at an advanced stage with heart failure6 ,11 ,18–20 or may not receive surgery even when indicated.8 As expected, non-compliance with guidelines is associated with a worse outcome.20 A multidisciplinary team (MDT) approach is increasingly seen as best practice where decision …

Background— Extracellular matrix expansion is a key element of ventricular remodeling and a potential therapeutic target. Cardiovascular magnetic resonance (CMR) T 1 -mapping techniques are increasingly used to evaluate myocardial extracellular volume (ECV); however, the most widely applied methods are without histological validation. Our aim was to perform comprehensive validation of (1) dynamic-equilibrium CMR (DynEq-CMR), where ECV is quantified using hematocrit-adjusted myocardial and blood T 1 values measured before and after gadolinium bolus; and (2) isolated measurement of myocardial T 1 , used as an ECV surrogate. Methods and Results— Whole-heart histological validation was performed using 96 tissue samples, analyzed for picrosirius red collagen volume fraction, obtained from each of 16 segments of the explanted hearts of 6 patients undergoing heart transplantation who had prospectively undergone CMR before transplantation (median interval between CMR and transplantation, 29 days). DynEq-CMR–derived ECV was calculated from T 1 measurements made using a modified Look-Locker inversion recovery sequence before and 10 and 15 minutes post contrast. In addition, ECV was measured 2 to 20 minutes post contrast in 30 healthy volunteers. There was a strong linear relationship between DynEq-CMR–derived ECV and histological collagen volume fraction ( P r =0.745; P r 2 =0.555 and between-subject: r =0.945; P r 2 =0.893; for ECV calculated using 15-minute postcontrast T 1 ). Correlation was maintained throughout the entire heart. Isolated postcontrast T 1 measurement showed significant within-subject correlation with histological collagen volume fraction ( r =−0.741; P r 2 =0.550 for 15-minute postcontrast T 1 ), but between-subject correlations were not significant. DynEq-CMR–derived ECV varied significantly according to contrast dose, myocardial region, and sex. Conclusions— DynEq-CMR–derived ECV shows a good correlation with histological collagen volume fraction throughout the whole heart. Isolated postcontrast T 1 measurement is insufficient for ECV assessment.

Background— Aortic valve area index adjusted for pressure recovery (energy loss index [ELI]) has been suggested as a more accurate measure of aortic stenosis (AS) severity, but its prognostic value has not been determined in a prospective study. Methods and Results— The relation between baseline ELI and rate of aortic valve events and combined total mortality and hospitalization for heart failure resulting from the progression of AS was assessed by multivariate Cox regression and reclassification analysis in 1563 patients with initial asymptomatic AS in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. During 4.3 years follow-up, a total of 498 aortic valve events and 181 combined total mortalities and hospitalizations for heart failure caused by the progression of AS occurred. In Cox regression analyses, 1-cm 2 /m 2 lower baseline ELI predicted a 2-fold higher risk both for aortic valve events and for combined total mortality and hospitalization for heart failure independently of baseline peak aortic jet velocity or mean aortic gradient and independently of aortic root size (all P Conclusions— In asymptomatic AS patients without known atherosclerotic disease or diabetes mellitus, ELI provides independent and additional prognostic information to that derived from conventional measures of AS severity, suggesting that ELI should be measured in such patients. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00092677.

We examined pulmonary artery pressure (PAP) characteristics of CF adults, studied clinical correlates and long-term survival.Comprehensive clinical data were collected and Doppler echocardiography was used to estimate PAP in 109 stable CF adults and 50 healthy controls.CF patients had lower day and night-time oxygen status, elevated CRP and BNP, and elevated PAP (27.7(13.2, 62.8) mmHg patients v 17.9(11.3, 30.9) mmHg controls, p0.001). Even patients with mild pulmonary disease had raised PAP. PAP measurements strongly correlated with arterial partial pressure of oxygen (PaO(2), r=-0.673, p0.001), and FEV(1) percentage predicted (FEV(1)%, r=-0.642, p0.001) which were both independent predictors of PAP. At 10 year follow up PAP measurements were related to survival but FEV(1)% and PaO(2) were both stronger predictors of death.PAP is raised in CF adults and correlates with pulmonary disease severity. Unlike PaO(2) and FEV(1)%, it does not appear to be an independent prognostic marker.