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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).

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.

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.

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

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.

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.

Objectives The aim of the study was to examine the predictive value of QRS duration and morphology during watchful waiting in asymptomatic patients with aortic stenosis (AS). Background QRS duration and morphology are associated with poor prognosis in many different populations, but the predictive value, particularly of the risk of sudden cardiac death (SCD), in asymptomatic patients with AS has not been well studied. Methods Data were obtained in asymptomatic AS patients randomized to simvastatin/ezetimibe combination versus placebo in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study. The impact of QRS duration, evaluated as a categorical variable of = 100 ms (excluding bundle branch block [BBB]) and QRS morphology in those with BBB, on cardiovascular morbidity and mortality was assessed by adjusting for clinical and echocardiographic covariates. Results QRS data were available in 1,542 patients who were followed for a mean of 4.3 +/- 0.8 years (6,631 patient-years of follow-up). There were 68 cardiovascular deaths (4.6%), including 27 SCDs (1.8%). QRS duration was = 100 ms in those without BBB in 144 (9.3%), and 102 (6.6%) in those with BBB. In multivariable analyses, those with QRS duration >= 100 ms had, compared with those with QRS duration

Mitral stenosis is nearly always a consequence of rheumatic heart disease. It is characterised by a narrowed valve orifice that obstructs flow from left atrium to left ventricle causing a rise in left atrial pressure and left atrial enlargement. Longstanding elevation of left atrial pressures may cause secondary pulmonary hypertension. Breathlessness is the most common symptom. Atrial fibrillation is common. Patients in atrial fibrillation require tight control of heart rate and should be anticoagulated. Patients with moderate or severe symptoms should be offered balloon mitral valvuloplasty if the anatomy is suitable or valve replacement if it is not. Mitral regurgitation may be due to a number of different aetiologies of which degenerative valve disease is the most common. Asymptomatic patients with good left ventricular function can be followed with regular echocardiography but should be considered for surgery at the first sign of symptoms or impaired left ventricular function. Valve repair is superior to replacement in most degenerative valves. Other aetiologies include ischaemic and rheumatic disease. Acute ischaemic regurgitation due to papillary muscle rupture is a surgical emergency. Chronic ischaemic regurgitation is more common and results from distortion of the mechanism of mitral valve closure. Moderate or severe ischaemic regurgitation should be corrected in patients undergoing coronary bypass surgery. Severe symptomatic ischaemic regurgitation may require surgery in its own right. Many ischaemic valves can be repaired. Most incompetent rheumatic valves require replacement.

Objectives The aim of this analysis was to assess the diagnostic importance of pressure recovery in evaluation of aortic stenosis (AS) severity. Background Although pressure recovery has previously been demonstrated to be particularly important in assessment of AS severity in groups of patients with moderate AS or small aortic roots, it has never been evaluated in a large clinical patient cohort. Methods Data from 1,563 patients in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study was used. Inner aortic diameter was measured at annulus, sinus, sinotubular junction, and supracoronary level. Aortic valve area index (AVAI) was calculated by continuity equation and pressure recovery and pressure recovery adjusted AVAI (energy loss index [ELI]), by validated equations. Primarily, sinotubular junction diameter was used to calculate pressure recovery and ELI, but pressure recovery and ELI calculated at different aortic root levels were compared. Severe AS was identified as AVAI and ELI ≤0.6 cm 2 /m 2 . Patients were grouped into tertiles of peak transaortic velocity. Results Pressure recovery increased with increasing peak transaortic velocity. Overestimation of AS severity by unadjusted AVAI was largest in the lowest tertile and if pressure recovery was assessed at the sinotubular junction. In multivariate analysis, a larger difference between AVAI and ELI was associated with lower peak transaortic velocity (beta = 0.35) independent of higher left ventricular ejection fraction (beta = –0.049), male sex (beta = –0.075), younger age (beta = 0.093), and smaller aortic sinus diameter (beta = 0.233) (multiple R 2 = 0.18, p < 0.001). Overall, 47.5% of patients classified as having severe AS by AVAI were reclassified to nonsevere AS when pressure recovery was taken into account. Conclusions For accurate assessment of AS severity, pressure recovery adjustment of AVA must be routinely performed. Estimation of pressure recovery at the sinotubular junction is suggested.

Valvular heart disease, particularly aortic stenosis and mitral regurgitation, accounts for a large proportion of cardiology practice, and their prevalence is predicted to increase. Management of the asymptomatic patient remains controversial. Biomarkers have been shown to have utility in the management of cardiovascular disease such as heart failure and acute coronary syndromes. In this state-of-the-art review, we examine the current evidence relating to natriuretic peptides as potential biomarkers in aortic stenosis and mitral regurgitation. The natriuretic peptides correlate with measures of disease severity and symptomatic status and also can be used to predict outcome. This review shows that natriuretic peptides have much promise as biomarkers in common valvular heart disease, but the impact of their measurement on clinical practice and outcomes needs to be further assessed in prospective studies before routine clinical use becomes a reality.

Asymptomatic aortic stenosis (AS) carries risk of heart failure and sudden death during watchful waiting. However, it remains unclear whether NT-proBNP, and its change from last year, in asymptomatic aortic valve stenosis (AS) predicts outcome. We evaluated 1577 asymptomatic AS patients from the

Low-Flow Aortic Stenosis in Asymptomatic Patients: Valvular–Arterial Impedance and Systolic Function From the SEAS SubstudyDana Cramariuc, Giovanni Cioffi, Ashild E. Rieck, Richard B. Devereux, Eva...

The improvement in left-ventricular ejection fraction (LVEF) in response to beta blockers is heterogeneous in patients with heart failure due to ischaemic heart disease, possibly indicating variations in the myocardial substrate underlying left-ventricular dysfunction. We investigated whether improvement in LVEF was associated with the volume of hibernating myocardium (viable myocardium with contractile failure).We did a double-blind, randomised trial to compare placebo and carvedilol for 6 months in individuals with stable, chronic heart failure due to ischaemic left-ventricular systolic dysfunction. We enrolled 489 patients, of whom 387 were randomised. Patients were designated hibernators or non-hibernators according to the volume of hibernating myocardium. The primary endpoint was change in LVEF, measured by radionuclide ventriculography, in hibernators versus non-hibernators, on carvedilol compared with placebo. Analysis was by intention to treat.82 patients dropped out of the study because of adverse events, withdrawal of consent, or failure to complete the investigation. Thus, 305 (79%) were analysed. LVEF was unchanged with placebo (mean change -0.4 [SE 0.9] and -0.4 [0.8] for non-hibernators and hibernators, respectively) but increased with carvedilol (2.5 [0.9] and 3.2 [0.8], respectively; p0.0001 compared with baseline). Mean placebo-subtracted change in LVEF was 3.2% (95% CI 1.8-4.7; p=0.0001) overall, and 2.9% (0.7-5.1; p=0.011) and 3.6% (1.7-5.4; p=0.0002) in non-hibernators and hibernators, respectively. Effect of hibernator status on response of LVEF to carvedilol was not significant (0.7 [-2.2 to 3.5]; p=0.644). However, patients with more myocardium affected by hibernation or by hibernation and ischaemia had a greater increase in LVEF on carvedilol (p=0.0002 and p=0.009, respectively).Some of the effect of carvedilol on LVEF might be mediated by improved function of hibernating or ischaemic myocardium, or both. Medical treatment might be an important adjunct or alternative to revascularisation for patients with hibernating myocardium.

Heart transplantation now offers an effective means of improving the quality of life and survival of selected patients with heart disease. Despite limited availability of donor organs the number of heart transplantation procedures worldwide continues to increase. 1 Geographically, recipients may be some distance away from their supervising center and present to hospitals that are more local. The dissemination of information relating to their clinical care is therefore important. Echocardiography is playing an increasingly important role in the investigation of these patients. Its specific role in the noninvasive evaluation of the heart transplant recipient will be summarized in this review, which will be applicable exclusively to adult orthotopic tramplantation. No reference will be made to the less commonly performed heterotopic procedure or pediatric transplantation.

Right ventricular (RV) dysfunction determines prognosis in patients with chronic pulmonary disease. We examined the relative prognostic potential of measures of systolic, diastolic, and global RV function in 87 patients with chronic pulmonary disease. Systolic function was evaluated by measuring RV dimensions, diastolic function by pulsed wave Doppler of the tricuspid flow profile, and global function by the Tei index. After 15.5 months follow-up, 47 patients had died. Univariate analysis demonstrated that both clinical and echocardiographic variables predicted survival. In the multivariate model both RV end-diastolic diameter index and velocity of late diastolic filling were independent predictors of survival. Receiver operator characteristic analysis demonstrated that a composite model combining these 2 measures provided the most powerful prognostic information. Echocardiographic indices of RV function identify patients with pulmonary disease at high risk and provide incremental prognostic information over and above that supplied by clinical data. (J Am Soc Echocardiogr 2002;15:633-9.)

We hypothesized that increased myocardial oxygen consumption (MOC) may be a predictor of heart failure (HF) in mild-to-moderate aortic stenosis (AS). MOC was available in 1,623 (87%) of 1,873 patients in the Simvastatin in Ezetimibe in Aortic Stenosis study with asymptomatic mild-to-moderate AS.

ECG signs of myocardial abnormality provide independent prognostic information in asymptomatic aortic stenosis (AS). It is unknown if the sum of ECG abnormalities further improves discriminatory power for prediction of cardiovascular outcomes. Patients with complete 12-lead ECGs in the simvastatin/

The value of land in the balance sheet of French firms correlates positively with their hiring and investment flows. To explore the relationship between these variables, we develop a macroeconomic model with firms that are subject to both credit and labor market frictions. The value of collateral is driven by the forward-looking dynamics of the land price, which reacts endogenously to fundamental and non-fundamental (sunspot) shocks. We calibrate the model to French data and find that land price shocks give rise to significant amplification and hump-shaped responses of investment, vacancies and unemployment that are in line with the data.

Background: Carvedilol reduces mortality and improves symptoms and ejection fraction in ischemic heart failure, but its mode of action is not well defined and not all patients respond to treatment The aim of the CHRISTMAS (Carvedilol Hibernation Reversible Ischaemia Trial, Marker of Success) study is to examine whether hibernation may be a significant factor determining this response. This paper describes the methodology and the rationale for the choice of the nuclear cardiology and echocardiography imaging techniques used in the study. Methods and results: The CHRISTMAS study is a double-blind, randomised, parallel group, multinational study of oral carvedilol versus placebo in patients with chronic stable heart failure due to left ventricular systolic dysfunction from coronary artery disease. The study aims to randomise 400 patients who are on optimal treatment. Two parallel groups will be randomised to carvedilol or placebo, namely 200 with hibernating myocardium at baseline and 200 matched patients without. The presence of hibernation is defined from a mismatch between regional contractile function and regional viability, measured by echocardiography (severe segmental asynergy) and nitrate prepared resting Tc99m-MIBI myocardial perfusion imaging (segmental activity >60%). The primary treatment-related end-point of the study is the comparison of the mean change, from baseline to the final visit, in radionuclide-determined left ventricular ejection fraction in patients on placebo with those on carvedilol, between the groups designated as hibernating and non-hibernating. Other end-points being examined include the prevalence of hibernation in heart failure, the relationship between the volume of hibernating myocardium and the ejection fraction response, the prevalence of reversible ischemia in heart failure, and the comparison of echo with gated SPECT. To date, 303 patients have been screened and 251 patients randomised in the study. The study aims to report in 2000. Conclusions: The CHRISTMAS study addresses the issue of whether the presence of hibernation is a predictor of the ejection fraction response to carvedilol in heart failure. It also examines the potential role of medical therapy in hibernation as well as a number of other end-points. The study may potentially lead to an important new role for nuclear cardiology in heart failure, and demonstrates important synergy between cardiac imaging and the pharmaceutical industry.

Beta-blockers (BB) are frequently avoided in aortic stenosis (AS) patients because of fear of depression of left ventricular function. We evaluated if BB increased the risk of cardiovascular events in patients with mild to moderate AS. Post-hoc analysis from the Simvastatin and Ezetimibe in Aortic

Observational data indicate a possible effect of statin therapy on reducing risk of lens opacities. 1,873 patients with asymptomatic aortic stenosis and no history of diabetes, coronary heart disease or other serious comorbidities were randomized (1:1) to double-blind 40 mg simvastatin plus 10 mg

long axis dynamics of the human left ventricle. Br Heart J [19] Cutler BS, Wheeler HB, Paraskos JA, Cardullo PA. Applicability 1990;63:215–20. and interpretation of electrocardiographic stress testing in patients [13] Gibson DG, Brown D. Measurement of instantaneous left ventricular with peripheral vascular disease. Am J Surg 1981;141:501–6. dimension and filling rate in man using echocardiography. Br Heart [20] Arous EJ, Baum PL, Cutler BS. The ischemic exercise test in J 1973;35:1141–9. patients with peripheral vascular disease. Arch Surg 1984;119:780– [14] Crawford E, Bomberger R, Glaese D, Saleh A, Russel W. Aorto3. iliac occlusive disease. Factors influencing survival and function [21] Henein MY, Das SK, O’Sullivan C, Kakkar VV, Gillbe CE, Gibson following reconstruction operation over a twenty year period. DG. Effect of acute alterations in afterload on left ventricular Surgery 1981;90:1055–67. function in patients with combined coronary artery and peripheral [15] Brown O, Hollier L, Pairolero P, Kazmier F, McCready R. Abdomivascular disease. Heart 1996;75:151–8. nal aortic aneurysm and coronary artery disease. Arch Surg [22] Heyndrickx GR, Millard RW, McRitchie RJ, Maroko PR, Vatner SF. 1981;116:1484–8. Regional myocardial functional and electrophysiological alterations [16] Mamode N, Cobbe S, Pollock JG. Infarcts after surgery: assessment after brief coronary artery occlusion in conscious dogs. J Clin Invest of patients before operation can reduce the risk. Br Med J 1975;56:978–85. 1995;310:1215–6. [23] Henein MY, Anagnostopoulos C, Das SK, O’Sullivan C, Under[17] Tomatis LA, Fierens EE, Verbrugge GP. Evaluation of surgical risk wood SR, Gibson DG. Left ventricular long axis disturbances as in peripheral vascular disease by coronary arteriography: a series of predictors for thallium perfusion defects in patients with known 100 cases. Surgery 1972;71:429–35. peripheral vascular disease. Heart 1998;79:295–300. [18] Hertzer NR, Young JR, Kramer JR et al. Routine coronary angiography prior to elective aortic reconstruction: results of selective myocardial revascularization in patients with peripheral vascular disease. Arch Surg 1979;114:1336–44.

We describe a previously healthy man who presented with features consistent with Wegener's granulomatosis. While undergoing investigation, he developed acute respiratory failure, thought to represent progression of his vasculitis. Open lung and sinus biopsies were performed to obtain the diagnosis. Vasculitis was confirmed on the paranasasl biopsy, and the lung biopsy showed pneumonia due to Legionella pneumophila, an association not previously reported in Wegener's granulomatosis. If immunosuppressive therapy had been started without making the diagnosis of Legionella pneumonia on lung biopsy, the patient might well have succumbed to the infection.