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ObjectiveAntiphospholipid (aPL) antibodies may activate platelets and contribute to vegetation growth and embolisation in infective endocarditis (IE). We aimed to determine the value of aPL as predictors of embolic events (EE) in IE.MethodsWe studied 186 patients with definite IE (Duke-Li criteria, all types of IE) from the Nanc-IE prospective registry (2007–2012) who all had a frozen blood sample and at least one imaging procedure to detect asymptomatic or confirm symptomatic EE. Anticardiolipin (aCL) and anti-β2-glycoprotein I (β2GPI) antibodies (IgG and IgM) were assessed after the end of patients’ inclusion. The relationship between antibodies and the detection of EE after IE diagnosis were studied with Kaplan-Meier and Cox multivariate analyses.ResultsAt least one EE was detected in 118 (63%) patients (52 cerebral, 95 other locations) after IE diagnosis in 80 (time interval between IE and EE diagnosis: 5.9±11.3 days). At least one aPL antibody was found in 31 patients (17%).Detection of EE over time after IE diagnosis was more frequent among patients with anti-β2GPI IgM (log-rank P=0.0036) and that of cerebral embolisms, among patients with aCL IgM and anti-β2GPI IgM (log-rank P=0.002 and PFactors predictive of EE were anti-β2GPI IgM (HR=3.45 (1.47–8.08), P=0.0045), creatinine (2.74 (1.55–4.84), P=0.0005) and vegetation size (2.41 (1.41–4.12), P=0.0014). Those of cerebral embolism were aCL IgM (2.84 (1.22–6.62), P=0.016) and anti-β2GPI IgM (4.77 (1.79–12.74), P=0.0018).ConclusionThe presence of aCL and anti-β2GPI IgM was associated with EE, particularly cerebral ones, and could contribute to assess the embolic risk of IE.

The deficiency in methyl donors, folate and vitamin B12, increases homocysteine and produces myocardium hypertrophy with impaired mitochondrial fatty acid oxidation and increased BNP, through hypomethylation of peroxisome-proliferator-activated-receptor gamma co-activator-1α, in rat. This may help to understand better the elusive link previously reported between hyperhomocysteinemia and BNP, in human. We investigated therefore the influence of methyl donors on heart mitochondrial fatty acid oxidation and brain natriuretic peptide, in two contrasted populations.Biomarkers of heart disease, of one carbon metabolism and of mitochondrial fatty acid oxidation were assessed in 1020 subjects, including patients undergoing coronarography and ambulatory elderly subjects from OASI cohort.Folate deficit was more frequent in the coronarography population than in the elderly ambulatory volunteers and produced a higher concentration of homocysteine (19.3 ± 6.8 vs. 15.3 ± 5.6, P0.001). Subjects with homocysteine in the upper quartile (≥ 18 μmol/L) had higher concentrations of NT-pro-BNP (or BNP in ambulatory subjects) and of short chain-, medium chain-, and long chain-acylcarnitines, compared to those in the lower quartile (≤ 12 μmol/L), in both populations (P0.001). Homocysteine and NT-pro-BNP were positively correlated with short chain-, medium chain-, long chain-acylcarnitines and with acylcarnitine ratios indicative of decreased mitochondrial acyldehydrogenase activities (P0.001). In multivariate analysis, homocysteine and long chain acylcarnitines were two interacting determinants of NT-pro-BNP, in addition to left ventricular ejection fraction, body mass index, creatinine and folate.This study showed that homocysteine predicts increased NT-pro-BNP (or BNP) through a link with impaired mitochondrial fatty oxidation, in two contrasted populations.

International audience; AIMS: To improve knowledge of epidemiological data, management, and clinical outcome of acute heart failure (AHF) in a real-life setting in France. METHODS AND RESULTS: We conducted an observational survey constituting a single-day snapshot of all unplanned hospitalizations because of AHF in 170 hospitals throughout France (the OFICA survey). A total of 1658 patients (median age 79 years, 55% male) were included. Family doctors were the first medical contact in 43% of cases, and patients were admitted through emergency departments in 64% of cases. Clinical scenarios were mainly acutely decompensated HF (48%) and acute pulmonary oedema (38%) with similar clinical and biological characteristics as well as outcome. Characteristics were different and severity higher in both shock and right HF. Infection and arrhythmia were the most frequent precipitating factors (27% and 24% of cases); diabetes and chronic pulmonary disease were the most frequent co-morbidities (31% and 21%). Over 80% of patients underwent both natriuretic peptide testing and echocardiography. LVEF was preserved (>50%) in 36% of patients and associated with specific characteristics and lower severity. Median hospital stay was 13 days; in-hospital mortality was 8.2%, and independent predictors were age, blood pressure, and creatinine. Treatment at discharge in patients with reduced LVEF included ACE inhibitors/ARBs, beta-blockers, and aldosterone inhibitors in 78, 67, and 27% cases. Non-surgical devices were reported in

Alhough cardiogenic shock (CS) after acute myocardial infarction (AMI) is more common in elderly patients, information on the epidemiology of these patients is scarce. This study aimed to assess the trends in prevalence, characteristics, management, and outcomes of elderly patients admitted with CS complicating AMI between 1995 and 2010, using data from the FAST-MI programme.We analysed the incidence and 1-year mortality of CS in four nationwide French surveys carried out 5 years apart from 1995 to 2010, including consecutive AMI patients over 1-month periods. Among the 10 610 patients, 3389 were aged ≥75 years, of whom 9.9% developed CS. The prevalence of CS decreased in elderly patients from 11.6% in 1995 to 6.7% in 2010 (P = 0.02). Over the 15-year period, the characteristics of elderly patients with CS changed, with more diabetes, hypertension, and hypercholesterolaemia. The use of PCI increased markedly in elderly patients with and without CS, reaching 51% and 59%, respectively, in 2010. In addition, medical therapy also evolved, with more patients receiving antithrombotic agents, beta-blockers, and statins. Over time, 1-year mortality decreased by 32% among elderly patients with CS but remained high (59% in 2010). ST-segmet elevation myocardial infarction and previous AMI were independent correlates of increased 1-year death, while study period was associated with decreased mortality (2010 vs, 1995: hazard ratio 0.40, 95% confidence interval 0.27-0.61, P0.001), along with early use of PCI.Cardiogenic shock in elderly patients with AMI remains a major clinical concern. However, 1-year mortality declined in these patients, a decrease potentially mediated by broader use of PCI and the improvement of global patient management.

Cardiomyopathies occur by mechanisms that involve inherited and acquired metabolic disorders. Both folate and vitamin B12 deficiencies are associated with left ventricular dysfunction, but mechanisms that underlie these associations are not known. However, folate and vitamin B12 are methyl donors needed for the synthesis of S-adenosylmethionine, the substrate required for the activation by methylation of regulators of energy metabolism. We investigated the consequences of a diet lacking methyl donors in the myocardium of weaning rats from dams subjected to deficiency during gestation and lactation. Positron emission tomography (PET), microscope and metabolic examinations evidenced a myocardium hypertrophy, with cardiomyocyte enlargement, disturbed mitochondrial alignment, lipid droplets, decreased respiratory activity of complexes I and II and decreased S-adenosylmethionine:S-adenosylhomocysteine ratio. The increased concentrations of triglycerides and acylcarnitines were consistent with a deficit in fatty acid oxidation. These changes were explained by imbalanced acetylation/methylation of PGC-1α, through decreased expression of SIRT1 and PRMT1 and decreased S-adenosylmethionine:S-adenosylhomocysteine ratio, and by decreased expression of PPARα and ERRα. The main changes of the myocardium proteomic study were observed for proteins regulated by PGC-1α, PPARs and ERRα. These proteins, namely trifunctional enzyme subunit α-complex, short chain acylCoA dehydrogenase, acylCoA thioesterase 2, fatty acid binding protein-3, NADH dehydrogenase (ubiquinone) flavoprotein 2, NADH dehydrogenase (ubiquinone) 1α-subunit 10 and Hspd1 protein, are involved in fatty acid oxidation and mitochondrial respiration. In conclusion, the methyl donor deficiency produces detrimental effects on fatty acid oxidation and energy metabolism of myocardium through imbalanced methylation/acetylation of PGC-1α and decreased expression of PPARα and ERRα. These data are of pathogenetic relevance to perinatal cardiomyopathies.

Summarymethylenetetrahydrofolate reductase polymorphism (MTHFR C677T) is an established determinant of homocysteine plasma level (t-Hcys) while its association with coronary artery disease (CAD) seems to be more limited. In contrast, the association of the substitutions A2756G of methionine synthase (MTR), A66G of methionine synthase reductase (MTRR) and C776G of transcobalamin (TCN) to both t-Hcys and CAD needs to be evaluated further. The objective was to evaluate the association of these polymorphisms with t-Hcys and CAD in a French population. We investigated the individual and combined effects of these polymorphisms and of vitamin B12 and folates with t-Hcys in 530 CAD patients and 248 matched healthy controls. t-Hcys was higher in the CAD group than in controls (11.8 vs 10.4 μM, P median and MTRR AA genotype were two significant independent predictors of CAD with respective odds ratios of 3.1 (95 % CI: 1.8-5.1, P

IntroductionLe stress mental est considéré comme un facteur de risque des maladies cardiovasculaires. Le stress mental est associé avec une stimulation sympathique. L’insuffisance cardiaque est caractérisée par une activation du système sympathique et par une augmentation des cytokines pro-inflammatoires. L’IL1-β est une cytokine pro-inflammatoire, mais elle est aussi rélarguée lors l’exposition a un stress mental. L’activité de cette cytokine peut être modifiée par des polymorphismes sur le cluster IL-1. Cette étude examine l’hypothèse que un stress mental conduit à une augmentation des marqueurs inflammatoires chez les patients avec une dysfonction systolique ventriculaire gauche (DSVG), et que cette augmentation est associée aux polymorphismes des cytokines.Méthodes5 polymorphismes étudiés : IL1A -889, IL1β-511, ILRN VTRN, TNFA -308 and IL6 -174 en 570 patients, 77.5 % hommes, âge moyenne 66 ans, 42.1 % avec une DSVG. Le model « stress mental » était l’examen coronarographique (T1). Trois temps de IL-1β étaient mesurés en basal (T0 et T2) et un en période de stress (T1). IL-1β était mésurée dans la salive.RésultatsEn période basale les concentrations de l’IL-1 étaient significativement inférieures que en T1 p

The aim of this study was to compare alcohol consumption and biological markers for alcoholism in a population of 23 men (57 +/- 8 years) admitted to hospital with idiopathic dilated cardiomyopathy (DCM), and a control group of 46 men (54 +/- 8 years) with coronary artery disease, matched for age. The DCM group had a higher daily alcohol consumption (82 g/day vs. 30 g/day, P0.0002). This difference was greater for the consumption of wine (63 g/day in the DCM group vs. 24 g/day in the control group, P0.002). Duration of regular daily alcohol consumption was longer in DCM patients (34 years vs. 22 years, P0.01) as well as duration of heavy alcohol consumption (60 g/day) (25 years vs. 10 years, P0.001). Among the biological markers, only the serum levels of immunoglobulin A were significantly increased in the DCM group (3.7 g/l vs. 2.7 g/l, P0.03). In this French population, alcohol is strongly linked to DCM. Biological markers appear to be poor predictors of alcohol intoxication in this so-called 'idiopathic' myocardial disease.

Right ventricular function was studied by means of a thermodilution catheter before, during and after percutaneous transluminal angioplasly of the proximal right (group 1, n = 8), left anterior descending (group 2, n = 8) or left circumflex (group 3, n = 8) coronary artery. All patients had evidence of myocardial ischemia, with single-vessel disease affecting the proximal segment of one of the three major coronary arteries; no patient had had a previous myocardial infarction and all had normal cardiac function at baseline study.Cardiac index decreased during balloon inflation, Mean pulmonary artery pressure was unaffected in group 1 but increased in group 2 (from 19 ± 5 to 31 ± 11 mm Hg, p < 0.01) and in group 3 (from 19 ± 2 to 22 ± 5 mm Hg, p < 0.05). Right ventricular ejection fraction decreased from 62 ± 9% to 52 ± 10% (p < 0.01) in group 1 and from 64 ± 7% to 44 ± 10% (p < 0.005) in group 2, and returned to normal within 2 min after balloon deflation in both groups. In group 3, right ventricular ejection fraction was unchanged during balloon inflation (58 ± 5% at baseline, 58 ± 9% at 60 s, p = NS).Therefore, brief occlusion of the proximal segments of the left anterior descending or right coronary artery results in marked alteration of right ventricular performance that is probably caused by right ventricular free wall ischemia in the right coronary group and by the concomitant effects of septal ischemia and increased right ventricular afterload in the left anterior descending artery group. Right ventricular dysfunction might be an additional mechanism of altered cardiac function in patients with acute myocardial infarction caused by occlusion of the proximal left anterior descending or right coronary artery.

The effects on left ventricular function of transient myocardial ischemia induced by balloon inflation during percutaneous transluminal coronary angioplasty (PTCA) have been extensively studied. 1–3 Right ventricular (RV) function, however, is also an important determinant of global cardiac function. The present study assesses RV ejection fraction by thermodilution measurements, during and immediately after transient myocardial ischemia caused by PTCA of the proximal right coronary artery.

Aims OFICA is a nationwide, observational study of characteristics, management and outcome of acute heart failure (AHF) during hospitalization as well as after discharge. Methods A single-day snapshot was performed on 12 March 2009 in French public and privates hospitals. Investigators were encouraged to include all hospitalized patients with a diagnosis of AHF, irrespective of the time of admission. Planned hospitalizations and cardiac surgery setting were excluded. Relevant data was recorded about medical journeys and outcome was assessed after discharge. Results The survey included 1817 patients (77 ± 13y, 45% females) in 170 centers from cardiology wards (58%) as well intensive care units (18%) and internal medicine (24%). Before definitive admission at hospital, most patients were firstly examined by family doctors (41%) or cardiologist (18%). Mobile medical units were required in 33% of cases and patients were admitted in cardiac intensive care unit in 41% of cases. In-hospital mortality was 8.8%. Most survivors were discharged at home (66%) or in rehabilitation centers (5%) or in nursing homes (19%). Patients were followed by family doctors in 63% of cases, private cardiologists in 33% and hospital doctors in 32%; only 5% were included in HF networks or ambulatory HF units. At 3 months, the rate of allcause death was 17.8% and the rate of hospitalization was 30.9%. Conclusion The OFICA survey is a valuable tool for analyzing AHF in the real life because of a large inclusion of unselected patients in different types of hospitals as well as departments. Family doctors play an important role as a first step management before admission as well after discharge while use of rehabilitation centers or HF units is marginal. High rates of death as well as hospitalization are observed in the short-term follow-up.

The deficiency in methyl donors is prevalent in the perinatal period of life and in aging. Dietary methyl donors, folate and vitamin B12, influence the cellular content in Sadenosylmethionine and S-adenosylhomocysteine and increases homocysteine. The link between methyl donors and energy metabolism is not known, despite their role in pathways related to epigenetics and synthesis of methylated molecules. We evaluated the consequences of a diet lacking methyl donors, in myocardium of weaning rats from dams subjected to deficiency during gestation and lactation. The deficient diet increased plasma homocysteine and myocardium Sadenosylhomocysteine. The results evidenced a hypertrophic cardiomyopathy with a global deficit in fatty acid oxidation with increased plasma acylcarnitines. The links between one-carbone metabolism, mitochondrial fatty acid oxidation and cardiomyopathy were ascertained by correlations between hyperhomocysteinemia, short-, medium- and long-chain acylcarnitines, and type-B natriuretic peptide. Methyl donor deficiency may be an aggravating condition of cardiomyopathy by impairing fatty acid oxidation through altered expression of PPAR[alpha] and ERR[alpha] and imbalanced acetylation/methylation of PGC1[alpha]. Finally, in a clinical study we sshowed that the Hcy and Apo A-I were two metabolic factors that influence the « anckle brachial index » in an ambulatory aged Sicilian population. The influence of homocysteine on Apo A-I and HDL metabolism provides new insights on its role on vascular diseases, at a cross-point between atherosclerosis and atherothrombosis, La carence en donneurs de méthyle est assez fréquente dans la période périnatale et au cours du vieillissement. Les donneurs de méthyle alimentaires, l'acide folique et la vitamine B12, influencent la teneur cellulaire en S-adénosylméthionine et S-adénosylhomocystéine et en homocystéine. Le lien entre les donneurs de méthyle et le métabolisme énergétique n'est pas connu, en dépit de leur rôle dans les voies liées à l'épigénétique et la synthèse de molécules méthylées. Nous avons évalué les conséquences d'un régime alimentaire déficient donneur de méthyle, dans le myocarde des ratons au moment du sevrage, soumis à une carence durant la gestation et la lactation. Le régime carencé augmente l'homocystéine plasmatique et S-adénosylhomocystéine myocardique. Les résultats mettent en évidence une cardiomyopathie hypertrophique et un déficit global de l'oxydation des acides gras avec acylcarnitines plasmatiques. Les liens entre le métabolisme des mono-carbones, l'oxydation mitochondriale des acides gras et de cardiomyopathie ont été constatées par des corrélations entre l'homocystéine et les acylcarnitines et le peptide natriurétique de type B. La carence en donneurs de méthyl peut être une condition aggravante de la cardiomyopathie en altérant l'oxydation des acides gras à travers une expression modifiée de PPAR[alpha] et ERR[alpha] et un déséquilibre de l'acétylation / méthylation de PGC1[alpha]. Nous avons montré que l'Hcy et Apo A-I ont été deux facteurs métaboliques déterminants de l'ABI dans une population ambulatoire de volontaires âgés d'une région rurale de la Sicile. L'influence négative de l'Hcy sur Apo A-I et sur le métabolisme des HDL ouvre des nouvelles perspectives sur l'implication de l'Hcy dans la physiopathologie de l'athérothrombose