Impact of multidisciplinary team meetings on the management of venous thromboembolism. A clinical study of 142 cases.

OBJECTIVE: Numerous guidelines have been published on the management of venous thromboembolism (VTE). However, therapeutic decision-making may prove challenging in routine clinical practice. With this in mind, multidisciplinary team (MDT) meetings have been set up in Rennes University Hospital, France. This study sought to describe the situations discussed during MDT meetings and to assess whether the meetings bring about changes in the management of these patients. MATERIALS AND METHODS: A retrospective single-center study conducted at the Rennes University Hospital included cases presented from the beginning of the MDT meetings (February 2015) up to May 2017. RESULTS: In total, 142 cases were presented in 15 MDT meetings, corresponding to a mean of 10±4 cases per meeting. Of these, 129 related to VTE patients: 33 provoked VTEs, 22 unprovoked VTEs, 49 cancer-related VTEs, and 25 unspecified VTEs. MDT meetings led to significant changes in the anticoagulation type (therapeutic, prophylactic, or discontinuation) and duration, but not in the anticoagulant choice (direct oral anticoagulants, vitamin K antagonists, heparins, etc.). CONCLUSION: Requests for MDT meetings are made for all VTE types, and these meetings have an impact on VTE management.

Neutralization of EP217609, a new dual-action FIIa/FXa anticoagulant, by its specific antidote avidin: a phase I study.

INTRODUCTION: EP217609 is a representative of a new class of synthetic parenteral anticoagulants with a dual mechanism of action. It combines in a single molecule a direct thrombin inhibitor and an indirect factor Xa inhibitor. EP217609 can be neutralized by a specific antidote avidin, which binds to the biotin moiety of EP217609. PURPOSE: The primary objective was to assess the neutralization of EP217609 by avidin in healthy subjects. Secondary objectives were to define the optimal avidin monomer/EP217609 molar ratio to achieve an adequate neutralization of EP217609 and to assess the safety and tolerability of EP217609 and avidin. METHODS: Healthy subjects (n = 36) were randomized to a 3 by 3 replicated Latin square design between 3 EP217609 doses (4, 8, 12 mg) and 3 avidin monomer/EP217609 molar ratios (1:1; 2:1; 3:1). EP217609 was administered as a single intravenous bolus, and avidin as a 30-min intravenous infusion, starting 90 min after EP217609 administration. RESULTS: Overall, EP217609 and avidin were well tolerated. One subject experienced a benign and transient typical pseudo-allergic reaction. The administration of EP217609 resulted in dose-dependent increases in pharmacodynamic markers. Avidin triggered a rapid and irreversible neutralization of EP217609 without rebound effect. Adequate neutralization of the anticoagulant activity was achieved with both 2:1 and 3:1 avidin monomer/EP217609 molar ratios. All safety parameters did not show any treatment-emergent clinically relevant changes or abnormalities in any dose group. CONCLUSIONS: These results will allow further investigation in patients requiring a neutralizable anticoagulant as those undergoing cardiac surgery. STUDY REGISTRATION: EudraCT number 2010-020216-10.

Gender and age effects on risk factor-based prediction of coronary artery calcium in symptomatic patients: A Euro-CCAD study.

BACKGROUND AND AIMS: The influence of gender and age on risk factor prediction of coronary artery calcification (CAC) in symptomatic patients is unclear. METHODS: From the European Calcific Coronary Artery Disease (EURO-CCAD) cohort, we retrospectively investigated 6309 symptomatic patients, 62% male, from Denmark, France, Germany, Italy, Spain and USA. All of them underwent risk factor assessment and CT scanning for CAC scoring. RESULTS: The prevalence of CAC among females was lower than among males in all age groups. Using multivariate logistic regression, age, dyslipidaemia, hypertension, diabetes and smoking were independently predictive of CAC presence in both genders. In addition to a progressive increase in CAC with age, the most important predictors of CAC presence were dyslipidaemia and diabetes (ß = 0.64 and 0.63, respectively) in males and diabetes (ß = 1.08) followed by smoking (ß = 0.68) in females; these same risk factors were also important in predicting increasing CAC scores. There was no difference in the predictive ability of diabetes, hypertension and dyslipidaemia in either gender for CAC presence in patients aged <50 and 50-70 years. However, in patients aged >70, only dyslipidaemia predicted CAC presence in males and only smoking and diabetes were predictive in females. CONCLUSIONS: In symptomatic patients, there are significant differences in the ability of conventional risk factors to predict CAC presence between genders and between patients aged <70 and ≥70, indicating the important role of age in predicting CAC presence.

[Hereditary thrombophilia testing and its therapeutic impact on venous thromboembolism disease: Results from a retrospective single-center study of 162 patients]. / La recherche de thrombophilie héréditaire et son impact thérapeutique dans la maladie thromboembolique veineuse : résultats d'une étude monocentrique rétrospective sur 162 patients.

INTRODUCTION: Venous thromboembolic disease is a multifactorial, frequently recurrent pathology, whose treatment is based on anticoagulation. As part of the etiological investigation, screening for an inherited thrombophilia is framed by French guidelines published in 2009. The aim of the study is to assess the contribution of inherited thrombophilias testing in common practice. METHOD: This is a retrospective single-center observational study. Over a period of a year, all records of patients who were screened for a hereditary thrombophilia were analyzed. The conformity of the indication of hereditary thrombophilia workup in balance with the guidelines, its completeness and therapeutic impact were studied. RESULTS: Of the 494 records analyzed, 225 were related to venous thromboembolism. Among them, there were 162 pulmonary embolisms or deep vein thrombosis of the lower limbs. In this subgroup, 57 % of records complied with guidelines and 69 % were complete. Thirty-four thrombophilias were highlighted: 4 protein S deficiencies, 1 protein C deficiency, 4 combined deficiencies, 17 factor V Leiden mutations and 8 factor II G20210A mutations. For one patient, hereditary thrombophilia diagnosis had profoundly changed the curative therapeutic approach. CONCLUSION: Adherence to French guidelines remains limited. In clinical practice, diagnosis of hereditary thrombophilia has little impact on the curative therapeutic approach in venous thromboembolic disease.

The coronary calcium score is a more accurate predictor of significant coronary stenosis than conventional risk factors in symptomatic patients: Euro-CCAD study.

AIMS: In this retrospective study we assessed the predictive value of the coronary calcium score for significant (>50%) stenosis relative to conventional risk factors. METHODS AND RESULTS: We investigated 5515 symptomatic patients from Denmark, France, Germany, Italy, Spain and the USA. All had risk factor assessment, computed tomographic coronary angiogram (CTCA) or conventional angiography and a CT scan for coronary artery calcium (CAC) scoring. 1539 (27.9%) patients had significant stenosis, 5.5% of whom had zero CAC. In 5074 patients, multiple binary regression showed the most important predictor of significant stenosis to be male gender (B=1.07) followed by diabetes mellitus (B=0.70) smoking, hypercholesterolaemia, hypertension, family history of CAD and age but not obesity. When the log transformed CAC score was included, it became the most powerful predictor (B=1.25), followed by male gender (B=0.48), diabetes, smoking, family history and age but hypercholesterolaemia and hypertension lost significance. The CAC score is a more accurate predictor of >50% stenosis than risk factors regardless of the means of assessment of stenosis. The sensitivity of risk factors, CAC score and the combination for prediction of >50% stenosis when measured by conventional angiogram was considerably higher than when assessed by CTCA but the specificity was considerably higher when assessed by CTCA. The accuracy of CTCA for predicting >50% stenosis using the CAC score alone was higher (AUC=0.85) than using a combination of the CAC score and risk factors with conventional angiography (AUC=0.81). CONCLUSION: In symptomatic patients, the CAC score is a more accurate predictor of significant coronary stenosis than conventional risk factors.

Attitudes of Hospital Healthcare Workers towards Influenza Vaccination in a Tertiary Hospital Setting.

The rate of uptake of seasonal influenza vaccination worldwide by healthcare workers (HCWs) has been suboptimal. Nationally, uptake among hospital HCWs was less than 20% prior to 2014. Indeed in our hospital following the 2010/2011 influenza season, a significant number of staff chose to have their vaccinations after the usual campaign period. The Occupational Health Department (OHD) undertook a questionnaire survey to determine the reason(s) for their late presentation. This was not anonymised, with a 21.7% participation rate (119 replied out of 548). We found 86(72.3%) HCWs believed influenza to be a serious illness, 84(70.6%) wanted to protect their family members and friends, and 64(53.8%) their patients from the infection. Nevertheless, 77(64.7%) were influenced by the recent media attention on the H1N1 influenza pandemic. We conclude external factors such as the arrival of the H1N1 pandemic continue to play an important role in influencing HCWs' attitudes towards receiving the vaccine.

EP42675, a synthetic parenteral dual-action anticoagulant: pharmacokinetics, pharmacodynamics, and absence of interactions with antiplatelet drugs.

BACKGROUND: EP42675 is a first-in-class, synthetic, parenteral, anticoagulant combining in a single molecule a direct thrombin inhibitor and an indirect factor Xa(FXa) inhibitor. OBJECTIVES: To investigate the safety, pharmacokinetics, and pharmacodynamics of EP42675 and its interaction with aspirin, clopidogrel, and unfractionated heparin (UFH). SUBJECTS AND METHODS: In study 1, healthy male subjects were administered intravenously single-ascending doses (1-10 mg) of EP42675 or placebo. In study 2, healthy male subjects were administered intravenously a single dose of 5 mg EP42675 on day 1 followed by oral administration of aspirin (100 mg) and clopidogrel (75 mg) once daily from day 8 to 21. On day 15, a second dose of 5 mg EP42675 was administered, and subjects were then randomized to receive a single dose of UFH (30 or 60 IU kg(-1) ) or placebo. RESULTS AND CONCLUSIONS: Mild bleedings were the only drug-related adverse events. EP42675 pharmacokinetics were dose-proportional and characterized by a low clearance, a small volume of distribution, a long terminal half-life. EP42675 pharmacodynamics were characterized by a long-lasting, dose-dependent increase in activated clotting time, ecarin clotting time, thrombin time, anti-FXa activity, activated partial thromboplastin time, prothrombin time, and a decrease in endogenous thrombin potential, measured by a thrombin generation test. Dose-dependent additive effects were seen with UFH on coagulation tests. EP42675 had no additive effect on the inhibition of platelet aggregation induced by aspirin and clopidogrel. These results warrant further clinical development of this new class of anticoagulant.

Should furosemide be avoided in acute right ventricular myocardial infarction?

BACKGROUND: Diuretics are conventionally prohibited in acute right ventricular myocardial infarction. AIMS: To assess the benefit of diuretics compared to fluid expansion in patients with inferior myocardial infarction extended to the right ventricule. METHODS: Of 295 patients admitted for inferior or posterior acute myocardial infarction between November 2008 and November 2010, 77 had a right ventricular extension. Among these 77 patients, 19 presented with oligoanuria (<0.5 mL/kg per hour) and no criteria for cardiogenic shock. Overall, 11 patients were treated by low dose of furosemide (40 to 80 mg) and eight received fluid expansion using isotonic saline solution. RESULTS: Baseline right ventricular dilatation and dysfunction, systolic blood pressure and heart rate were similar between the groups. Twenty-four hours after treatment, urine output was similar between the two groups but only the patients in the diuretic group improved their blood pressure (103 ± 16 mmHg versus 127 ± 20 mmHg, P < 0.001), heart rate (71 ± 15 bpm versus 76 ± 13 bpm, P = 0.03), creatinin level and alanine aminotrasferase plasmatic level. Hospitalization duration and the need of inotropic support were similar in the two groups. CONCLUSIONS: Diuretics and fluid expansion provide similar efficiency for triggering diuresis in patients with right ventricular infarction and oligoanuria but only diuretics seem to be associated with improvement in hemodynamic status and venous congestion.

Effect of heart rate reduction by ivabradine on left ventricular remodeling in the echocardiographic substudy of BEAUTIFUL.

AIMS: Occlusive coronary artery disease (CAD) is associated with left ventricular (LV) remodeling, LV systolic dysfunction, and heart failure. The BEAUTIFUL Echo substudy aimed to evaluate the effects of heart rate reduction with ivabradine on LV size (primary end-point: change in LV end-systolic volume index [LVESVI]) and function and the cardiac biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP). METHODS AND RESULTS: The substudy was carried out in 86 centers participating in the BEAUTIFUL study. 2D echocardiography was performed at baseline, and after 3 and 12 months in patients with stable CAD and LV systolic dysfunction receiving ivabradine or placebo at the same time-points. All data were read and analyzed centrally. Of 525 patients completing the study, 426 had adequate echocardiographic readings (n = 220 ivabradine; n = 206 placebo). Treatment with ivabradine was associated with a decrease in the primary end-point LVESVI (change from baseline to last value, -1.48 ± 13.00 mL/m(2)) versus an increase with placebo (1.85 ± 10.54 mL/m(2)) (P=0.018). There was an increase in LV ejection fraction with ivabradine (2.00 ± 7.02%) versus no change with placebo (0.01 ± 6.20%) (P=0.009). Reduction in LVESVI was related to the degree of heart rate reduction with ivabradine. There were no differences in any other echocardiographic parameters or NT-proBNP. Change in LVESVI was related to the log change in NT-proBNP in the ivabradine group only (r = 0.18, P = 0.006). CONCLUSIONS: Our observations suggest that ivabradine may reverse detrimental LV remodeling in patients with CAD and LV systolic dysfunction.

[Recommendations for training in cross-sectional cardiac imaging]. / Recommandations pour la formation en imagerie en coupes du coeur et des vaisseaux.

The recent and future advancements that are known in the field of cardiac imaging imply an optimal training of the operators. This training concerns medical specialists whether originating from radiology or cardiology. The training of the medical specialists in cardiac imaging entitles 3 main essential steps: The basic training taking place within each specialty, allowing the fellow to get acquainted with the clinical and technical basics. The specialized training, delivered principally in post-residency. This training must include an upgrading of each specialty in the domain that does not concern it (a technical base for the cardiologist, a physio-pathological and clinical base for the radiologist). It must include a specific theoretical training covering all aspects of cardiac imaging as well as practical training in a certified training centre. The continuous medical training and maintenance of skills that allow a sustained activity in the field and the obligation to regularly participate in the actions of specific validated training. The different aspects of these rules are exposed in this chapter.

[Prolongation of anti vitamin K treatment for 18 months versus placebo after 6 months treatment of a first episode of ideopathic pulmonary embolism: a mutlicentre, randomised double blind trail. The PADIS-EP Trial]. / Prolongation d'un traitement par antivitamine K pendant dix-huit mois versus placebo au décours d'un premier épisode d'embolie pulmonaire idiopathique traité six mois: un essai randomisé multicentrique en double aveugle. Essai "PADIS-EP".

BACKGROUND: After stopping a 3 to 6 months course of oral anticoagulation for a first episode of idiopathic venous thromboembolism (VTE), the risk of recurrent VTE is high (10% per year). In this setting, international guidelines recommend at least 6 months treatment. However, this recommendation is not satisfactory for the following reasons: (1) no randomized trial has compared 6 months to extended duration (2 years) anticoagulation; and (2), even though the frequency of recurrent VTE is similar after pulmonary embolism (PE) and deep vein thrombosis (DVT), the fatality rate of recurrent VTE after PE is higher than that after DVT. METHODS: A French multicentre double blind randomized trial. The main objective is to demonstrate, after a first episode of symptomatic idiopathic PE treated for 6 months using a vitamin K antagonist, that extended anticoagulation for 18 months (INR between 2 and 3) is associated with an increased benefit / risk ratio (recurrent VTE and severe anticoagulant-related bleeding) compared to placebo. The double blind evaluation is ensured using by active warfarin and placebo, and blinded INR. The protocol was approved by the ethics board of the Brest Hospital on the 7th of March 2006. For an alpha risk of 5% and a beta risk of 20%, the estimated sample size is 374 patients. EXPECTED RESULTS: This study has the potential to: (1) demonstrate that the benefit / risk ratio of extended anticoagulation for 18 months is higher than that observed with placebo in patients with a first episode of idiopathic PE initially treated for 6 months, during and after the treatment period; and (2) to validate or invalidate the contribution of isotope lung scans, lower limb Doppler ultrasound and D-Dimer at 6 months of treatment as predictors of recurrent VTE (medico-economic analysis included).

Echocardiographic assessment of the incidence of mechanical complications during the early phase of myocardial infarction in the reperfusion era: a French multicentre prospective registry.

BACKGROUND: Since the early reports on the incidence of mechanical complications of acute myocardial infarction (AMI) assessed by echocardiography published in the 1980s, the management of patients with AMI has changed considerably, in particular with the progressive development of early revascularisation. METHODS: The aim of this multicentre study was to assess the incidence of mechanical complications of AMI in the reperfusion era. Nine-hundred and eight consecutive patients were included. Echocardiography was performed on admission and at discharge. Seventy-eight percent of patients were revascularised at the acute phase. RESULTS: The following incidence rates of mechanical complications were observed: mitral regurgitation 28%, secondary to left ventricular (LV) remodelling (43%) or papillary muscle dysfunction (57%); pericardial effusion 6.6%, more frequent after anterior AMI and associated with a lower ejection fraction (EF); LV thrombus 2.4%, mainly after anterior AMI and associated with a lower EF (38+/-10% vs. 48+/-12%; p<0.001); early infarct expansion 4%; septal rupture 0.6%; and acute free wall rupture 0.8%. The following factors were independently associated with the occurrence of mechanical complications by multivariate logistic regression analysis: lack of early revascularisation (OR 3.48, 95%CI 1.36-8.95; p<0.001), LV-EF<50% (OR 1.95, 95%CI 1.42-2.67; p<0.001), Killip class>II (OR 1.91, 95%CI 1.27-2.87; p<0.002) and age > or =70 years (OR 1.42, 95%CI 1.03-1.97; p<0.03). CONCLUSION: This study demonstrates the favourable prognostic influence of early revascularisation as shown by the low incidence of mechanical complications after AMI, and underlines the persistent relationship between the development of these complications and depressed LV function.

Adverse reaction to Bacille-Calmette-Guérin vaccine in a HIV positive healthcare worker.

BACKGROUND: The Bacille-Calmette-Guérin (BCG) vaccine is used in Mycobacterium tuberculosis prophylaxis in at risk tuberculin-negative healthcare workers. Its use is contraindicated however in individuals with HIV infection. AIMS: We herein highlight the case of a healthcare worker who developed a localised reaction at a BCG vaccination site and who was subsequently found to be HIV positive. CONCLUSION: This case emphasises the importance of eliciting risk factors for immunocompromise in individuals for whom BCG vaccination is being considered.

Prospective evaluation of the '4Ts' score and particle gel immunoassay specific to heparin/PF4 for the diagnosis of heparin-induced thrombocytopenia.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a severe disease that is often difficult to diagnose. A clinical scoring system, the '4Ts' score, has been proposed to estimate its probability before laboratory testing, and a particle gel immunoassay (H/PF4 PaGIA) has also been developed for rapid detection of HIT antibodies. AIM: To evaluate the performance of both methods when HIT is suspected clinically. METHODS: Two hundred thirteen consecutive patients were included in four centers. The probability of HIT was evaluated using the 4Ts score blind to antibody test results. HIT was confirmed only when the serotonin release assay (SRA) was positive. RESULTS: The risk of HIT was evaluated by the 4Ts score as low (LowR), intermediate (IR) or high (HR) in 34.7%, 60.6% and 4.7% of patients, respectively. The negative predictive value (NPV) of the 4Ts score was 100%, as the SRA was negative in all LowR patients. PaGIA was negative in 176 patients without HIT (99.4%, NPV) and the negative likelihood ratio (LR-) was 0.05. PaGIA was positive in 37 patients, including 21 with HIT (positive predictive value = 56.8%), with a positive LR of 11.4. A negative PaGIA result decreased the probability of HIT in IR patients from 10.9% before assay to 0.6%, whereas a positive result did not substantially increase the likelihood for HIT. CONCLUSION: The use of the 4Ts score with PaGIA appears to be a reliable strategy to rule out HIT.

[Evaluation of left ventricular function: echocardiography, MRI or CT?]. / Evaluation de la fonction ventriculaire gauche: échocardiographie, IRM ou scanner?

The objective of this article is to clarify the advantages and limits of echocardiography, MRI, and CT for the determination of left ventricular (LV) function, emphasising the importance of evaluating global ventricular function. MRI is the reference technique, owing to its precision, reproducibility, and innocuous nature. However, echography is performed much more frequently because it is more widely available and easier to carry out. It is our reference technique in everyday practice. More recently, synchronised multi-slice tomodensitometry has provided dynamic reconstructed images of the left ventricle throughout the cardiac cycle, offering a succession of short axis views covering the entire volume of the ventricle. These acquisitions, in addition to non-invasive coronary angiography, allow the LV ejection fraction to be determined. With MRI, study of the LV function does not require any contrast medium to be injected and makes use of effective semi-automatic segmentation programs.

Bypassing the emergency room reduces delays and mortality in ST elevation myocardial infarction: the USIC 2000 registry.

OBJECTIVE: To study the impact on outcomes of direct admission versus emergency room (ER) admission in patients with ST-segment elevation myocardial infarction (STEMI) DESIGN: Nationwide observational registry of STEMI patients SETTING: 369 intensive care units in France. INTERVENTIONS: Patients were categorised on the basis of the initial management pathway (direct transfer to the coronary care unit or catheterisation laboratory versus transfer via the ER). MAIN OUTCOME MEASURES: Delays between symptom onset, admission and reperfusion therapy. Mortality at five days and one year. RESULTS: Of 1204 patients enrolled, 66.9% were admitted direct and 33.1% via the ER. Bypassing the ER was associated with more frequent use of reperfusion (61.7% v 53.1%; p = 0.001) and shorter delays between symptom onset and admission (244 (interquartile range 158) v 292 (172) min; p < 0.001), thrombolysis (204 (150) v 258 (240) min; p < 0.01), hospital thrombolysis (228 (156) v 256 (227) min, p = 0.22), and primary percutaneous coronary intervention (294 (246) v 402 (312) min; p < 0.005). Five day mortality rates were lower in patients who bypassed the ER (4.9% v 8.6%; p = 0.01), regardless of the use and type of reperfusion therapy. After adjusting for the simplified Thrombolysis in Myocardial Infarction (TIMI) risk score, admission via the ER was an independent predictor of five day mortality (odds ratio 1.67, 95% confidence interval 1.01 to 2.75). CONCLUSIONS: In this observational analysis, bypassing the ER was associated with more frequent and earlier use of reperfusion therapy, and with an apparent survival benefit compared with admission via the ER.

High risk hypertensives: pre-hospital management of acute myocardial infarction--results from the French nationwide registry USIC 2000.

OBJECTIVE: To assess the use of mobile coronary care units (MCU) in hypertensive patients previously treated for cardiovascular diseases in comparison with those with no history of cardiovascular disease and to estimate the influence of the use of MCU on cardiovascular outcome in this population. PATIENTS: We used a nationwide prospective registry of all patients admitted for AMI in French intensive care units in 2000. Patients without history of hypertension or patients admitted with pulmonary oedema or cardiogenic shock were excluded. Men (N = 514) and women (N = 291) were analysed separately. RESULTS: The proportion of patients with history of myocardial infarction, peripheral artery disease and stroke was not significantly higher in subjects who used physician-staffed MCU as compared with patients with no history of myocardial infarction, peripheral artery disease or stroke. In each sex, revascularization (pre hospital fibrinolysis, in hospital fibrinolysis or coronary angioplasty) were more frequent in patients who used MCU. Also, one year cardiovascular mortality was lower in men who used MCU. CONCLUSION: Known high risk hypertensive patients did not use physician-staffed MCU more than subjects free of such condition. Education of hypertensive patients at risk during routine visits is required to increase of the use of physician-staffed MCU in case of symptoms suggestive of AMI.

Major impact of admission glycaemia on 30 day and one year mortality in non-diabetic patients admitted for myocardial infarction: results from the nationwide French USIC 2000 study.

OBJECTIVE: To analyse the short and long term prognostic significance of admission glycaemia in a large registry of non-diabetic patients with acute myocardial infarction. METHODS: Assessment of short and long term prognostic significance of admission blood glucose in a consecutive population of 1604 non-diabetic patients admitted to intensive care units in France in November 2000 for a recent (