[Splenic dysfunction in sickle cell disease: An update]. / Dysfonction splénique au cours de la drépanocytose : mise au point.

The spleen filters blood cells and contributes to the immune defense. The red pulp clears the blood from altered red blood cells via its unique microcirculatory network ; while the white pulp is a secondary lymphoid organ, directly connected to the bloodstream, whose specificity is the defense against encapsulated bacteria through the production of "natural" IgM in the marginal zone. Various health conditions can cause acquired impairment of the splenic function (or hyposplenism) directly and/or through therapeutic splenectomy. Hypo/asplenia is complicated by an increased susceptibility to encapsulated germ infections, but an increased risk of thrombosis and pulmonary hypertension has also been reported after surgical splenectomy. Homozygous sickle cell disease is the most common disease associated with functional asplenia. The latter appears early in childhood likely through repeated ischemic alterations caused by the sickling of red blood cells. In addition, specific complications such as hypersplenism and acute splenic sequestration can occur and may be life-threatening. We provide here an update on the role and physiology of the spleen, which will allow a better understanding of the pathophysiology of spleen damage and its consequences in sickle cell disease.

Predictors of angiographically visible distal embolization in STEMI.

BACKGROUND: Distal embolization during primary percutaneous coronary intervention (p-PCI) in the treatment of ST-segment elevation myocardial infarction (STEMI) is associated with a poor prognosis. In this situation, thrombectomy is performed to prevent distal embolization and to restore myocardial reperfusion. The aim of our study was to determine angiographic predictors of angiographically visible distal embolization (AVDE) in patients with STEMI treated by p­PCI with thrombectomy. PATIENTS AND METHODS: This prospective study included all consecutive patients who underwent p­PCI with thrombectomy for STEMI at our institution between October 2011 and December 2014 AVDE was defined as a distal filling defect with an abrupt cut-off in one of the peripheral coronary branches of the infarct-related artery, distal to the angioplasty site. Thrombectomy was considered positive when it removed thrombi, and successful when it improved coronary flow. RESULTS: Among the 346 patients included, 59 (17%) developed AVDE during p­PCI. In multivariate analysis, the infarct-related right coronary artery (OR: 2.48, 95% CI: 1.36-4.52; p = 0.003) and a culprit lesion diameter of >3 mm (OR : 1.90, 95% CI: 1.01-3.56; p = 0.048) were identified as independent factors associated with AVDE during p­PCI with thrombectomy for STEMI. The success of thrombectomy and the Syntax score were not associated with AVDE. CONCLUSION: AVDE complicating p­PCI with thrombectomy in STEMI is frequent (17%) and a successful thrombectomy does not rule out AVDE.

[Interventional management of atrial fibrillation]. / Prise en charge interventionnelle de la fibrillation atriale.

In 2030, the European Union will include 14 to 17 million atrial fibrillation (AF) patients, with 120,000 to 215,000 new cases each year. The increase in the prevalence of this arrhythmia has led to the development of new therapeutic intervention strategies to manage the different aspects of this disease. Thus, endocavitary or epicardial ablation of AF, by radiofrequency or cryoablation, provides superior results to antiarrhythmic therapy in controlling symptoms and preventing heart failure in paroxysmal or persistent AF. In heart failure patients with advanced AF, the ablation of the atrioventricular junction associated with the implantation of a bi-ventricular pacemaker has just demonstrated its clear superiority, bringing this technique up to date. Finally, in the event of a major bleeding risk and contraindication to anticoagulants, percutaneous occlusion of the left atrium has proven its value in preventing AF-related embolic events. The future will certainly see the emergence of new technologies but also personalized strategies based on an optimal selection of the right candidates for these interventions, thanks in particular to the contribution of imaging before the procedure.

Transfusion-associated hazards: A revisit of their presentation.

As a therapy or a support to other therapies, despite being largely beneficial to patients in general, transfusion it is not devoid of some risks. In a moderate number of cases, patients may manifest adverse reactions, otherwise referred to as transfusion-associated hazards (TAHs). The latest French 2016 haemovigilance report indicates that 93% of TAHs are minor (grade 1), 5.5% are moderate (grade 2) and 1.6% are severe (grade 3), with only five deaths (grade 4) being attributed to transfusion with relative certainty (imputability of level [or grade] 1 to 3). Health-care providers need to be well aware of the benefits and potential risks (to best evaluate and discuss the benefit-risk ratio), how to prevent TAHs, the overall costs and the availability of alternative therapeutic options. In high-income countries, most blood establishments (BEs) and hospital blood banks (HBBs) have developed tools for reporting and analysing at least severe transfusion reactions. With nearly two decades of haemovigilance, transfusion reaction databases should be quite informative, though there are four main caveats that prevent it from being fully efficient: (ai) reporting is mainly declarative and is thus barely exhaustive even in countries where it is mandatory by law; (aii) it is often difficult to differentiate between the different complications related to transfusion, diseases, comorbidities and other types of therapies in patients suffering from debilitating conditions; (aiii) there is a lack of consistency in the definitions used to describe and report some transfusion reactions, their severity and their likelihood of being related to transfusion; and (aiv) it is difficult to assess the imputability of a particular BC given to a patient who has previously received many BCs over a relatively short period of time. When compiling all available information published so far, it appears that TAHs can be analysed using different approaches: (bi) their pathophysiological nature; (bii) their severity; (biii) the onset scheme; (biv) a quality assessment (preventable or non-preventable); (bv) their impact on ongoing therapy. Moreover, TAHs can be reported either in a non-integrative or in an integrative way; in the latter case, presentation may also differ when issued by a blood establishment or a treating ward. At some point, a recapitulative document would be useful to gain a better understanding of TAHs in order to decrease their occurrence and severity and allow decision makers to determine action plans: this is what this review attempts to make. This review attempts to merge the different aspects, with a focus on the hospital side, i.e., how the most frequent TAHs can be avoided or mitigated.

Use of artesunate in non-malarial indications.

INTRODUCTION: Artesunate and other artemisinin derivatives are used in various infectious and non-infectious diseases. We aimed to analyze available data on artesunate and artemisinin derivatives activity in humans and their potential clinical benefits in non-malarial indications. MATERIAL AND METHODS: Literature review performed on PubMed and the Cochrane Library databases using the PRISMA method. We analyzed studies published in English from January 2008 to August 2017 using the same indicators of drug efficacy. RESULTS: We included 19 studies performed in humans (1 meta-analysis, 1 literature review, 4 randomized controlled trials, 3 prospective controlled trials, 3 prospective uncontrolled trials, 2 exploratory phase 1 or 2 trials, 1 case series, and 4 case reports). Artesunate and artemisinin derivatives demonstrated efficacy in the treatment of schistosomiasis in combination with praziquantel (P=0.003). Artesunate monotherapy was less effective than praziquantel alone (P<0.001) probably because its activity only affects the early stages of Schistosoma parasites. Artesunate monotherapy could be interesting as a chemoprophylactic drug against schistosomiasis (P<0.001). Findings seem promising but are still controversial in the treatment of multidrug-resistant CMV infections. Studies do not conclude on artesunate and artemisinin derivatives efficacy in the treatment of cervix, breast, colorectal, and lung cancers. CONCLUSION: Artesunate and artemisinin derivatives in combination with praziquantel were effective against schistosomiasis, and could be used as a chemoprophylactic drug alone. They could be interesting as anti-CMV and anti-tumor treatment. Additional trials in humans are required to assess the efficacy of artesunate and artemisinin derivatives in diseases other than malaria.

Post-treatment haemolysis in African children with hyperparasitaemic falciparum malaria; a randomized comparison of artesunate and quinine.

BACKGROUND: Parenteral artesunate is the treatment of choice for severe malaria. Recently, haemolytic anaemia occurring 1 to 3 weeks after artesunate treatment of falciparum malaria has been reported in returning travellers in temperate countries. METHODS: To assess these potential safety concerns in African children, in whom most deaths from malaria occur, an open-labelled, randomized controlled trial was conducted in Kinshasa, Democratic Republic of Congo. 217 children aged between 6 months and 14 years with acute uncomplicated falciparum malaria and parasite densities over 100,000/µL were randomly allocated to intravenous artesunate or quinine, hospitalized for 3 days and then followed for 42 days. RESULTS: The immediate reduction in haemoglobin was less with artesunate than with quinine: median (IQR) fall at 72 h 1.4 g/dL (0.90-1.95) vs. 1.7 g/dL (1.10-2.40) (p = 0.009). This was explained by greater pitting then recirculation of once infected erythrocytes. Only 5% of patients (in both groups) had a ≥ 10% reduction in haemoglobin after day 7 (p = 0.1). One artesunate treated patient with suspected concomitant sepsis had a protracted clinical course and required a blood transfusion on day 14. CONCLUSIONS: Clinically significant delayed haemolysis following parenteral artesunate is uncommon in African children hospitalised with acute falciparum malaria and high parasitaemias. TRIAL REGISTRATION: ClinicalTrials.gov ; Identifier: NCT02092766 (18/03/2014).

Mechanical clearance of red blood cells by the human spleen: Potential therapeutic applications of a biomimetic RBC filtration method.

During their lifespan, circulating RBC are frequently checked for their deformability. This mechanical quality control operates essentially in the human spleen. RBC unable to squeeze though narrow splenic slits are retained and cleared from the blood circulation. Under physiological conditions this prevents microvessels from being clogged by senescent, rigid RBC. Retention of poorly deformable RBC is an important determinant of pathogenesis in malaria and may also impact the clinical benefit of transfusion. Modulating the splenic retention of RBC has already been proposed to support therapeutic approaches in these research fields. To this aim, the development of microplates for high throughput filtration of RBC through microsphere layers (microplate-based microsphiltration) has been undertaken. This review focuses on potential therapeutic applications provided by this technology in malaria chemotherapy and transfusion.

[Hyper-reactive malarial splenomegaly]. / Splénomégalie palustre hyper-réactive.

Hyper-reactive malarial splenomegaly is a rare and severe form of chronic malaria. This condition is a common cause of splenomegaly in endemic areas. The pathophysiology of hyper-reactive malarial splenomegaly involves an intense immune reaction (predominantly B cell-driven) to repeated/chronic infections with Plasmodium sp. The diagnosis may be difficult, due to a poorly specific clinical presentation (splenomegaly, fatigue, cytopenias), a long delay between residence in a malaria-endemic area and onset of symptoms, and a frequent absence of parasites on conventional thin and thick blood smears. A strongly contributive laboratory parameter is the presence of high levels of total immunoglobulin M. When the diagnostic of hyper-reactive malarial splenomegaly is considered, search for anti-Plasmodium antibodies and Plasmodium nucleic acids (genus and species) by PCR is useful. Diagnosis of hyper-reactive malarial splenomegaly relies on the simultaneous presence of epidemiological, clinical, biological and follow-up findings. Regression of both splenomegaly and hypersplenism following antimalarial therapy allows the differential diagnosis with splenic lymphoma, a common complication of hyper-reactive malarial splenomegaly. Although rare in Western countries, hyper-reactive malarial splenomegaly deserves increased medical awareness to reduce the incidence of incorrect diagnosis, to prevent progression to splenic lymphoma and to avoid splenectomy.

Surveillance of leishmaniases in France, 1999 to 2012.

Leishmaniasis is endemic in the south of France, where autochthonous disease is caused by Leishmania infantum, and affects both humans and dogs. The prevalence of canine leishmaniasis is between 3 and 66% depending on the region and the methods used. Human leishmaniases are also imported into France, mainly from French Guiana and North Africa. The surveillance of autochthonous and imported human leishmaniases is based on passive notification to the National Reference Centre for Leishmaniases (NRCL) created in 1998. Between 1999 and 2012, 317 autochthonous and 1,154 imported cases were notified to the NRCL. The average number of autochthonous cases notified per year was 22.6, mainly cases of visceral leishmaniasis (84.5%). All cases were infected in the south of France. Leishmaniasis incidence is 0.22 per 100,000 inhabitants in the endemic area. Imported cases were more frequent (annual mean of 82.4 cases) and consisted predominantly in cutaneous leishmaniasis (CL) cases (91%), essentially L. major CL imported from Maghreb and Sub-Saharan Africa, and L. guyanensis CL from French Guiana. This national notification system allowed a better understanding of the incidence and distribution of the disease; it is also useful to assess the temporal-spatial evolution of the disease in France, which appears relatively stable.

Travelers with cutaneous leishmaniasis cured without systemic therapy.

BACKGROUND: Cutaneous leishmaniasis (CL) is a disfiguring but not life-threatening disease. Because antileishmanial drugs are potentially toxic, the World Health Organization (WHO) recommends simple wound care or local therapy as first-line treatment, followed or replaced by systemic therapy if local therapy fails or cannot be performed. METHODS: To determine the feasibility and impact of the recommended approach, we analyzed the results of a centralized referral treatment program in 135 patients with parasitologically proven CL. RESULTS: Infections involved 10 Leishmania species and were contracted in 29 different countries. Eighty-four of 135 patients (62%) were initially treated without systemic therapy. Of 109 patients with evaluable charts, 23 of 25 (92%) treated with simple wound care and 37 of 47 (79%) treated with local antileishmanial therapy were cured by days 42-60. In 37 patients with large or complex lesions, or preexisting morbidities, or who had not been cured with local therapy, the cure rate with systemic antileishmanial agents was 60%. Systemic adverse events were observed in 15 patients, all receiving systemic therapy. CONCLUSIONS: In this population of CL patients displaying variable degrees of complexity and severity, almost two-thirds of patients could be initially managed without systemic therapy. Of these, 60 were cured before day 60. The WHO-recommended stepwise approach favoring initial local therapy therefore resulted in at least 44% of all patients being cured without exposure to the risk of systemic adverse events. Efforts are needed to further simplify local therapy of CL and to improve the management of patients with complex lesions and/or preexisting comorbidities.

[Admissions to a coronary care unit for severe iatrogenic conditions: a prospective study of 7244 patients]. / Les admissions pour iatrogénie sévère en unité de soins intensifs de cardiologie: étude prospective sur 7244 patients.

INTRODUCTION: Iatrogenic complications are defined as adverse drug reactions or complications induced by non-drug interventions, such as cardiac devices or stimulation techniques. Iatrogenic complications occurring during hospital stay are known to be associated with increased hospital length of stay and mortality. Only few data are available on iatrogenic as cause of hospital admission, particularly in coronary care unit. In patient admitted in coronary care unit for iatrogenic, we aimed: (a) to analyse their prevalence, type and characteristics, (b) to analyse their in-hospital length of stay and mortality and (c) to evaluate the predictive factors of severity and mortality. METHODS: From 1st April 2008 to 31 January 2012, all the consecutive admissions caused by iatrogenic complications at the coronary care unit were prospectively included and classified in two groups: (1) pharmacological iatrogenic (beta-blockers, digoxin, calcium channel blockers, cordarone, several antiarrhythmic , anticoagulants, antiplatelets and others), (2) non-pharmacological iatrogenic (pacemaker, cardioverter-defibrillator, radiofrequency, coronary angiography and cardiac surgery including valve surgery). We excluded patients with intentional overdose. We also compared patients according to the severity (group 1: patients who just need a monitoring; and group 2: patients for whom there was invasive procedure or for whom we used vasoactive amine). RESULTS: Among 7244 patients admitted in coronary care unit during the inclusion period, 250 (3.4%) were admitted for iatrogenic complication, 136 in pharmacological group and 114 in non-pharmacological group. In non-pharmacological group, there was more men: 73.7% vs. 47.8% (P < 0.001), patients are younger: 67.3 ± 13.2 vs. 75.4 ± 15.8 (P < 0.001) and are more severe: 80.4% in group 2 vs. 69.4% (P = 0.05). The mortality in this group tends to be more important. According to the severity, there is no difference about drugs: 7.4 ± 3.4 vs. 6.8 ± 2.9 (P = 0.184) and are staying longer in hospital: 4.7 ± 3.2 days vs. 3.4 ± 2.4 (P = 0.009) for coronary care unit length of stay and 15 ± 13.7 vs. 10 ± 9.8 (P = 0.003) for total length of stay. CONCLUSION: Iatrogenic represent a non-negligible cause of admission in coronary care unit, which associated with significant mortality (8.8%) and with a trend toward a higher length of stay. Further studies are needed to determinate the origin of mortality and to better characterize patients at risk of iatrogenic.

Intersite variations of a battery of biomarkers at different levels of biological organisation in the estuarine endobenthic worm Nereis diversicolor (Polychaeta, Nereididae).

The ragworm Nereis diversicolor has been proposed as a sentinel species for the assessment of estuarine sediment quality. The aim of this study was to test the responsiveness of the worms using a battery of biomarkers in specimens from a moderately contaminated site (Loire estuary, Fr.) and a comparatively cleaner site (Bay of Bourgneuf, Fr.) as a reference site. Ragworms were collected on 7 occasions from April 2008 to October 2009 for the determination of biochemical (GST, AChE, digestive enzymes), physiological (energy reserves (glycogen, lipids and proteins), relationship between length and weight), and behavioural (feeding and burrowing) biomarkers. The biomarker responses were tentatively interpreted in terms of the concept of cascading events potentially responsible for local depletion/extinction of populations submitted to chemical stress. Impairments of AChE and amylase activities, feeding rate, energy reserve concentrations (glycogen and lipids), and the relationship between length and weight showed up differences between the reference site and the Loire estuary despite the latter being far from the most contaminated estuary in France or internationally. However, no links could be established in the Loire estuary ragworms between effects at infra-individual and individual levels, nor with worm population density, even though a small oil spill had occurred in the Loire estuary only one month before the beginning of sampling.

Impact of obesity on the prognostic value of the N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with acute myocardial infarction.

OBJECTIVE: To examine the influence of obesity on the predictive value of the pro-B-type natriuretic peptide (NT-proBNP) assay in acute myocardial infarction. DESIGN: Prospective observational study. SETTING: All intensive care units in one region of France. Patients 2217 consecutive patients admitted for an acute myocardial infarction matched with respect to age, gender, Killip class and renal function. MAIN OUTCOME MEASURE: Cardiovascular death at one year. RESULTS: There were three groups (according to body mass index (BMI): obese, overweight and normal) of 739 matched patients. Median levels of NT-proBNP were considerably lower in high BMI patients, by about 20% in overweight and by 60% in obese patients, compared with normal BMI patients. An inverse relationship between the propeptide values and BMI was found in the overall study population (r = -0.20, p < 0.0001), and for both genders. In multivariate linear regression, BMI as a continuous variable was a predictor of the log NT-proBNP level, even when adjusted for potential confounders. CV mortality at 1-year follow-up was similar for the three BMI groups (p = 0.691). In multivariate logistic regression analysis, log NT-proBNP predicted mortality in normal (OR (95% CI) 3.48 (2.00 to 6.12)) and overweight (OR (95% CI) 3.96 (1.95 to 8.06)) patients, even when adjusted for confounders (GRACE risk score, left ventricular ejection fraction). However, in obese patients, propeptide levels failed to retain their independent prognostic value (OR (95% CI) 1.34 (0.86 to 2.08)). CONCLUSIONS: In this large population of patients with myocardial infarction, circulating NT-proBNP levels were considerably lower in obese patients; the significance of the propeptide level as an independent prognostic factor is severely compromised.

[Impact of the angles and the age of the thrombus on efficacity of thromboaspiration device. A bench study]. / Impact du diamètre et de l'âge du thrombus sur la thromboaspiration. Étude expérimentale.

INTRODUCTION: Coronary thrombectomy is usually used to treat acute coronary syndrome. Many studies evaluated its benefit in this context however, it is still unknown if coronary characteristics are predictive of success or failure. The aim of our laboratory bench study was to evaluate the impact of angiographic characteristics on the thromboaspiration efficiency. METHODS: Glass tubes of 150 mm in the length were used, with five diameters: 2; 2.6; 3; 3.6 and 4 mm; and for each diameter, three angulations: no angulation; 90° and 120°. Blood sample were taken from healthy subject and thrombi of 3 and 6 hours old were performed, with a constant volume for each test. Thromboaspirations were performed with an Export(®) catheter (Medtronic). The primary endpoint was total thrombectomy. A total of 240 thromboaspirations were performed. RESULTS: A total thrombectomy was obtained for 71.2% of the tests. It was achieved more frequently with the smaller diameter, respectively: 100% for 2 mm, 81.3% for 2.6 mm, 89.6% for 3 mm vs 54.2% for 3.6 mm and 31.3% for 4 mm (P<0.001). No differences were observed between the 2 thrombi ages (73.3% for the 3 hours old thrombi and 69.2% for the 6 hours old thrombi, P = 0.476), nor between the three tube's angulations (77.5% for no angle, 66.3% for 90° and 70.0% for 120°, P = 0.278). RESULTS AND CONCLUSION: This study shows an impact of the coronary diameters on the rate of thromboaspiration success with an Export(®) catheter. Beyond 3 mm of diameter, the rate of success is divided by 2: for diameters less or equal to 3 mm, 90.3% of success vs 42.7% for diameters greater than 3 mm (P<0.001). There is no difference of efficiency between the 3 and 6 hours old thrombi, neither between the tube's angulations. However, this is a preliminary and further works are needed to clarify how to optimize the aspiration and the impact of other catheters.

The free oxygen radicals test (FORT) to assess circulating oxidative stress in patients with acute myocardial infarction.

BACKGROUND AND AIM: Reactive oxygen species (ROS) play an important role in the pathogenesis of many diseases including cardiovascular diseases. Several methods have been developed for the direct or indirect measurement of oxygen free radical and its by-products. The current study was designed to validate the new free oxygen radicals test (FORT) and to investigate the potential relationships between ROS and clinical or biological factors in male patients with acute myocardial infarction (AMI). METHODS: We analysed FORT values in samples from 66 patients with AMI. RESULTS: FORT values ranged from 324 to 1198 FORT units, with a median value of 581 (494-754) FORT units. In univariate analysis, FORT values were positively related only to LVEF <40% (p=0.005), levels of CRP (r=0.438, p<0.001) and peak CK (r=0.274, p=0.028). Multiple linear regression analysis showed that CRP (p=0.023), LVEF <40% (p<0.001) and the presence of diabetes (p=0.039) were independent predictors of serum FORT values. This statistical model can explain 45% of the variance in FORT values (R(2)=0.45). CONCLUSIONS: The FORT is a simple tool to assess circulating ROS in routine clinical practice. Oxidative conditions such as inflammation and diabetes are the major determinants of FORT values in patients with AMI.

Assessment of the influence of confounding factors (weight, salinity) on the response of biomarkers in the estuarine polychaete Nereis diversicolor.

The influences of salinity and body size on biochemical (activities of glutathione-S-transferase, lactate dehydrogenase (LDH), acetylcholinesterase and digestive enzymes amylase and CMCase), physiological (feeding and egestion rates, energy reserves) and behavioural (burrowing speed) biomarkers were examined in the infaunal polychaete Nereis diversicolor. Only a few biomarkers were affected, including increased egestion rate and activities of CMCase and LDH at higher salinity, and higher egestion rate in larger worms. These findings reinforce the status of N. diversicolor as a robust sentinel species for estuaries which are environments that are particularly productive but also particularly at risk.

[Antiplatelet agents in acute coronary syndromes. Data from the main clinical trials]. / Les anti-agrégants plaquettaires au cours du syndrome coronarien aigu. Données des grandes études.

Cardiovascular disease is the leading cause of early death and morbidity in developed countries and is becoming a growing problem in many developing countries. Currently, anti-coagulants play a major role in the management of the acute phase in association or not with reperfusion strategies. The combination of clopidogrel and aspirin, in accordance with the results of large randomized trials, is the treatment of reference. However two new drugs, a thienopyridine (prasugrel), and a cyclo-pentyl-triazolo-pyridine (ticagrelor) have shown their interest in major studies in comparison with clopidogrel. As a result, several effective P2Y12 receptor antagonist anti-platelet agents are now available in the therapeutic arsenal, and the cardiologist have to tailored the best drug scheme according the balance between the risk of hemorrhage and the benefits with regard to the ischemia to determine the optimal prescription for every patient.

Prognostic value of N-terminal pro-brain natriuretic peptide in elderly people with acute myocardial infarction: prospective observational study.

OBJECTIVE: To examine the influence of age on the predictive value of N-terminal pro-brain natriuretic (NT-proBNP) peptide assay in acute myocardial infarction. DESIGN: Prospective observational study. SETTING: All intensive care units in one French region. PARTICIPANTS: 3291 consecutive patients admitted for an acute myocardial infarction, from the RICO survey (a French regional survey for acute myocardial infarction). MAIN OUTCOME MEASURE: Cardiovascular death at 1 year. RESULTS: Among the 3291 participants, mean age was 68 (SD 14) years and 2356 (72%) were men. In the study population, the median NT-proBNP concentration was 1053 (interquartile range 300-3472) pg/ml. Median values for age quarters 1 to 4 were 367 (119-1050), 696 (201-1950), 1536 (534-4146), and 3774 (1168-9724) pg/ml (P<0.001). A multiple linear regression analysis was done to determine the factors associated with the pro-peptide concentrations in the overall population. NT-proBNP was mainly associated with age, left ventricular ejection fraction, creatinine clearance, female sex, hypertension, diabetes, and anterior wall infarction. At one year's follow-up, 384 (12%) patients had died from all causes and 372 (11%) from cardiovascular causes. In multivariate analysis, NT-proBNP remained strongly associated with the outcome, beyond traditional risk factors including creatinine clearance and left ventricular ejection fraction, in each age group except in the youngest one (<54 years) (P=0.29). The addition of NT-proBNP significantly improved the performance of the statistical model in the overall study population (-2log likelihood 3179.58 v 3099.74, P<0.001) and in each age quarter including the upper one (1523.52 v 1495.01, P<0.001).The independent discriminative value of NT-proBNP compared with the GRACE score was tested by a diagonal stratification using the median value of the GRACE score and NT-proBNP in older patients (upper quarter). Such stratification strikingly identified a high risk group-patients from the higher NT-proBNP group and with a high risk score-characterised by a risk of death of almost 50% at one year. CONCLUSIONS: In this large contemporary non-selected cohort of patients with myocardial infarction, NT-proBNP concentration had incremental prognostic value even in the oldest patients, above and beyond the GRACE risk score and traditional biomarkers after acute myocardial infarction. These data further support the potential interest of clinical trials specifically assessing NT-proBNP measurement as a guide to current treatment strategies, as well as novel strategies, in older patients with acute myocardial infarction.