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Background The prevalence and independent correlates of readmission for heart failure (HF) after transcatheter aortic valve replacement (TAVR) remain unclear in all-comers. Purpose We sought to evaluate the incidence, risk factors and clinical impact of readmission for HF after successful TAVR in an unselected patient population. Methods All patients undergoing successful TAVR in two high-volume French centers from February 2010 to December 2016 were prospectively included. Cox multivariate model was used to assess risk factors of readmission for HF over one year follow up. Results A total of 1139 patients aged 82.4 ± 7.7 years were included. Half (52.2%) were male. Transfemoral access and balloon-expandable valve were most frequently used (82.4% and 60.7% respectively). Within one-year of follow-up, 99 (8.7%) patients were readmitted for heart failure. Mortality was increased by two-fold among patients readmitted for HF vs. those without readmission (22 [22.2%] vs. 123 [11.8%], HR 1.9; 95% CI [1.2–3.1], P = 0.004). Chronic pulmonary disease (adjHR 1.8; 95% CI [1.2–2.8], P = 0.008), chronic kidney disease (adjHR 1.7; 95% CI [1.1–2.6], P = 0.01), diabetes mellitus (adjHR 1.7; 95% CI [1.1–2.5], P = 0.01), prior atrial fibrillation (adjHR 1.6; 95% CI [1.1–2.4], P = 0.02) and post-TAVR left ventricular ejection fraction (LVEF) ≤35% (adjHR 2.1 95%CI 1.2–3.7, P = 0.009) independently predicted readmission for HF. Conclusion Readmission for HF within one year of successful TAVR is frequent and associated with increased mortality. Comorbidities and post-TAVR LVEF ≤35% but not valvular-related factors are the main correlates of readmission for HF.

SummaryThe FXIII-A Leu34 genetic variant increases and accelerates fibrin stabilisation; however, its association with premature coronary artery disease (CAD) and thrombotic events remains controversial. FXIII Val34Leu genotype was determined in 242 young individuals (

Resume Introduction Il est de plus en plus frequent pour les pneumologues d’etre confrontes a des prescriptions d’antiagregants plaquettaires (AAP) chez des patients devant subir une bronchoscopie souple (BS). Il faut alors peser l’indication de la BS et les benefices qui en sont attendus au regard non seulement d’un risque hemorragique mais encore du risque thrombotique. Methodes et resultats En l’absence de recommandations consensuelles sur ce sujet, cet article passe en revue la litterature et rapporte les resultats d’une enquete realisee aupres de 138 endoscopistes membres du Groupe d’endoscopie de langue francaise. Cinq questions sont abordees : 1) risque hemorragique selon la procedure ; 2) caracteristiques des AAP actuels ; 3) risque thrombotique a l’arret du traitement par AAP ; 4) circonstances ou la BS peut-etre differee ; 5) strategie de relais therapeutique si les AAP sont interrompus. Conclusions Dans l’attente d’etudes cliniques permettant de mieux cerner les reponses a ces questions et des recommandations de pratiques professionnelles correspondantes, il est crucial que les pneumologues soient sensibilises a la necessite de systematiquement s’inquieter avant une BS de l’existence d’un traitement par AAP, d’en identifier l’indication, et de ne jamais interrompre un tel traitement sans concertation avec son prescripteur.

Background— Low-molecular-weight heparin (LMWH) is recommended in the treatment of unstable angina (UA)/non–ST-segment–elevation myocardial infarction (NSTEMI), but no relationship has ever been shown between anticoagulation levels obtained with LMWH treatment and clinical outcomes. Methods and Results— In all, 803 consecutive patients with UA/NSTEMI were treated with subcutaneous enoxaparin and were followed up for 30 days. The recommended dose of enoxaparin of 1 mg/kg BID was used throughout the population except when physicians decided on dose reduction because of a history of a recent bleeding event or because of a high bleeding risk. Anti–factor Xa activity was >0.5 IU/mL in 93% of patients; subtherapeutic anti-Xa levels (3-fold increase in mortality compared with the patients with anti-Xa levels in the target range of 0.5 to 1.2 IU/mL ( P =0.004). Multivariate analysis revealed low anti-Xa activity as an independent predictor of 30-day mortality at least as strong as age, left ventricular function, and renal function. In contrast, anti-Xa activity did not predict major bleeding complications within the range of anti-Xa levels observed in this study. Conclusions— In this large unselected cohort of patients with UA/NSTEMI patients, low anti-Xa activity on enoxaparin treatment is independently associated with 30-day mortality, which highlights the need for achieving at least the minimum prescribed anti-Xa level of 0.5 IU/mL with enoxaparin whenever possible.

The safety and efficacy of endovascular treatment of unruptured intracranial aneurysms remain undetermined. A randomized trial may be the best way to demonstrate the potential benefits of endovascular management. We propose a randomized, prospective, controlled trial comparing the incidence of subarachnoid haemorrage of patients treated by endovascular coiling as compared to conservative management. We would also study a composite outcome combining SAH and the morbidity of treatment. All patients with one or more unruptured aneurysm >> 3 mm eligible for endovascular treatment would be proposed to participate. The study would be conducted in 40–50 centres. The entire study would enrol 1800 patients, recruited over three years and followed for five years, but would be preceded by a feasibility study on 200 patients. A randomized trial comparing endovascular and conservative treatment could have an important impact on the clinical management of intracranial aneurysms

Endovascular coiling can improve the outcome of patients with ruptured intracranial aneurysms, but angiographic recurrences are frequent compared to surgical clipping. New coils or devices have been introduced to improve long-term results of endovascular treatment but none have been the object of a valid clinical trial. We have proposed a multicentric randomized double-blind study comparing radioactive and standard coil occlusion of aneurysms. The purpose of this article is to review issues that are specific to the design of clinical trials to assess embolic agents that could improve the long-term efficacy of endovascular treatment of intracranial aneurysms. The proposed trial is a randomized, multi-center, prospective, controlled trial comparing the new generation coils to standard platinum coils. Blinding, if at all possible, is preferable to minimize bias, at least for follow-up angiographic studies that should cover a period of 18 months. All patients with an intracranial aneurysm eligible for endovascular treatment would be proposed to participate. The study would enrol approximately 500 patients equally divided between the two groups, recruited within two years, to demonstrate a decrease in the recurrence rate, the primary outcome measure, from 20% to 10%. Secondary outcome measures should assure that complications, initial clinical and angiographic results remain unchanged. Independent data safety and monitoring committees are crucial to the credibility of trials and to ensure scientific rigor and objectivity. The scientific demonstration of an improved long-term efficacy, without significant compromise regarding safety, is mandatory before considering the widespread use of a new embolic device for the endovascular treatment of aneurysms.

Resume Les heparines de bas poids moleculaire (HBPM) constituent un meilleur choix que l'heparine non fractionnee (HNF) dans la prise en charge medicale de la phase aigue de l'angor instable. Leur utilisation comme traitement adjuvant de la revascularisation par angioplastie est associee a une excellente tolerance et une bonne efficacite. Leur association aux inhibiteurs de la GP IIB/IIIa semble mieux toleree qu'avec l'HNF pour une efficacite comparable. Les anti-GP Ilb/IIIa constituent un traitement adjuvant de reference pour la prevention des complications de l'angioplastie coronaire realisee a la phase aigue de l'angor instable. Leur benefice dans la prise en charge medicale de l'angor instable tout-venant reste modeste a ce jour, mais particulierement bien documentee chez les patients a tres haut risque en attente de revascularisation. L'heterogeneite de cette classe therapeutique et les differentes doses utilisees dans l'angioplastie et dans l'approche medicale peuvent expliquer en partie les resultats discordants des etudes randomisees. Les inhibiteurs des recepteurs a l'ADP sont efficaces aussi bien dans l'approche medicale qu'invasive de l'angor instable. Leur association avec les inhibiteurs de la GP Ilb/IIIa n'obere pas le benefice de ces derniers en cas de revascularisation precoce par angioplastie. Le developpement de tests biologiques evaluant ces strategies combinees est un autre defi qu'il faut relever en particulier chez les patients a haut risque hemorragique (patients âges, insuffisants renaux).

Abstract —The glycoprotein IIb/IIIa receptor inhibitor abciximab has been shown to facilitate the rate and the extent of pharmacological thrombolysis with recombinant tissue plasminogen activator (rtPA) in patients with acute myocardial infarction. However, the underlying mechanisms remain not fully determined. We sought to demonstrate that this facilitating effect of abciximab could be related to its potential to modify the clot architecture and the clot physical properties. Compared with fibrin-rich clots, platelets dramatically modified the in vitro properties of the fibrin network, leading to a significant increase of the permeability ( K s ) and the viscoelasticity (G′) indexes but also leading to the appearance of platelet aggregates (surface area [S.ag]). These modifications resulted in a 2.6-fold decrease of the fibrinolysis rate when rtPA (1 nmol/L) was added before the initiation of clotting. Adding aspirin (100 μg/mL) or abciximab (0.068 μmol/L) before the clotting of platelet-rich clots (PRCs) lowered K s by 50% and 70%, respectively ( P P P P P P K s (35%, P P =NS) and resulted in a 27% ( P

IntroductionMuch is known about the fibrinolytic system that converts fibrin-bound plasminogen to the active protease, plasmin, using plasminogen activators, such as tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator. Plasmin then cleaves fibrin at specific sites and generates soluble fragments, many of which have been characterized, providing the basis for a molecular model of the polypeptide chain degradation.1-3 Soluble degradation products of fibrin have also been characterized by transmission electron microscopy, yielding a model for their structure.4 Moreover, high resolution, three-dimensional structures of certain fibrinogen fragments has provided a wealth of information that may be useful in understanding how various proteins bind to fibrin and the overall process of fibrinolysis (Doolittle, this volume).5,6 Both the rate of fibrinolysis and the structures of soluble derivatives are determined in part by the fibrin network structure itself. Furthermore, the activation of plasminogen by t-PA is accelerated by the conversion of fibrinogen to fibrin, and this reaction is also affected by the structure of the fibrin. For example, clots made of thin fibers have a decreased rate of conversion of plasminogen to plasmin by t-PA, and they generally are lysed more slowly than clots composed of thick fibers.7-9 Under other conditions, however, clots made of thin fibers may be lysed more rapidly.10 In addition, fibrin clots composed of abnormally thin fibers formed from certain dysfibrinogens display decreased plasminogen binding and a lower rate of fibrinolysis.11-13 Therefore, our increasing knowledge of various dysfibrinogenemias will aid our understanding of mechanisms of fibrinolysis (Matsuda, this volume).14,15 To account for these diverse observations and more fully understand the molecular basis of fibrinolysis, more knowledge of the physical changes in the fibrin matrix that precede solubilization is required. In this report, we summarize recent experiments utilizing transmission and scanning electron microscopy and confocal light microscopy to provide information about the structural changes occurring in polymerized fibrin during fibrinolysis. Many of the results of these experiments were unexpected and suggest some aspects of potential molecular mechanisms of fibrinolysis, which will also be described here.

Non-ST elevation (NSTE) myocardial infarction and unstable angina are the most common clinical presentations of acute coronary syndrome (ACS). Platelet activation is central to the pathogenesis of NSTE-ACS and consensus guidelines that advocate early revascularization supported by intensive antiplatelet therapy. This review examines the drugs used concurrently with aspirin as dual antiplatelet therapy in the NSTE-ACS setting. Clopidogrel represented an important therapeutic advance. However, variations in platelet response and a relatively slow onset of action compromise outcomes with clopidogrel. Evidence reviewed in this article shows that in NSTE-ACS patients, ticagrelor and prasugrel are more effective than clopidogrel and are relatively well tolerated, with an acceptable and manageable bleeding risk. The literature suggests several differences between ticagrelor and prasugrel that should allow clinicians to better tailor treatment to the patient. Head-to-head comparisons are now needed to compare directly the risks and benefits of ticagrelor and prasugrel in NSTE-ACS. Further studies also need to address other outstanding issues such as the benefits and risks of prasugrel pre-treatment and to stratify efficacy and tolerability according to diabetes mellitus (DM) and other co-morbidities. In the meantime, the issues discussed in this review should enhance clinicians' ability to optimize and individualize NSTE-ACS treatment, thereby further reducing the morbidity and mortality associated with this common cardiovascular condition.

Viral investigations were performed during 4 winter seasons (88/89, 89/90, 92/93, 93/94) in children attending day-care centers (DCCs) in the Rhone Département in eastern France. Over the total observation period of 4 winter seasons, 780 children were screened with a nasal swab for the presence of viruses. Of those, 230 (29.5%) had a positive viral culture. The viruses identified were respiratory syncytial virus (RSV), influenza A and B virus, parain-fluenza virus, coronavirus, rhinovirus, adenovirus and enterovirus. During that time, 83 epidemic events in 47 DCC were recorded. A particular virus was judged to be causally related to an epidemic if the identical virus was isolated in ≥ 3 children during the same outbreak of respiratory diseases. Thus, in 51 cases (61.4%) of all epidemics, the following viruses were responsible for an epidemic: RSV (n = 23), coronavirus (n = 10) (only during the season of 1993-1994), influenza A virus (n = 6), rhinovirus (n = 4), enterovirus (n = 4), adenovirus (n = 3) and parainfluenza virus (n = 1). Except for the somewhat surprising accumulation of coronavirus epidemics during the winter of 1993-1994, there were only minor seasonal variations from one year to another. As expected, RSV accounted for about one third of all respiratory tract infections in children attending DCCs and was therefore the most important single causative agent. These results are compared with data from children who did not attend a DCC and were cared for in a private practice. During the winter of 1989-1990, the viral epidemiological survey was performed at the same time and in parallel to a double-blind, placebo-controlled clinical study investigating the efficacy of OM-85 BV, an immunoactive bacterial extract. This study, enrolling 423 children attending DCCs demonstrated a protective effect of OM-85 BV in significantly reducing the risk of recurrent infections of the upper respiratory tract during the treatment period with the compound. 34% of all participating children (75 in the verum group, 70 in the placebo group) were enrolled in an additional virological study. In these patients, RSV was isolated 10 times in the placebo group, but only 5 times in the treated group (p < 0.05) and influenza A virus was present in 4 children in the placebo group, but only in 1 infant in the verum group giving a total of 14 positive virologie results in the placebo group versus 6 in the verum group (p < 0.05). Despite the small numbers of children investigated for their virologie status during respiratory infectious outbreaks, there was a statistically significant difference in the prevalence of virus carriers in favor of the children treated with OM-85 BV. These results corroborate the clinical findings.

Recurrent upper respiratory tract infections in children have an important socioeconomic impact, with consequences on both the quality of life of the children, the possible medical sequelae and the inherent direct and indirect costs. The possibility to prevent these infections is limited in the absence of specific vaccines against microorganisms responsible for most of the respiratory tract infections (i.e. respiratory syncitial virus, adenovirus, rhinovirus). Immunoactive bacterial extracts that stimulate the nonspecific component of the immune system may protect against a large variety of microorganisms that enter the body by the oral and respiratory pathway; they may, therefore, play an important role with regard to this preventive action. OM-85 BV is an IBE that has been used in children who suffer from repeated infections to prevent the occurrence of new episodes (secondary prevention). In this condition, the drug has been shown to be effective in protecting children against recurrent airway infections. Its use as a primary preventive agent to prevent the development of repeated infections in children attending day-care centers (a very high-risk environment for repeated infections), however, did not show a similar efficacy. The risk of havingor = 4 episodes of upper respiratory tract infections over a period of 7.5 months was 26.7% in the verum group and 33.8% in the placebo group (relative risk 0.79, confidence interval 0.59-1.06]. In an exploratory analysis concentrating on the 3-month treatment period, however, a 48% reduction of the risk of presentingor = 3 episodes was observed. Furthermore, this exploratory analysis showed a strong correlation between drug efficacy and age of the children.(ABSTRACT TRUNCATED AT 250 WORDS)

This population-based prospective cohort study compared the risk of recurrent infections in children attending family day care ( or = 40 children) DCCs. The parents of a total of 1,242 children participated in the study (97% of the families initially contacted). An infectious episode was defined as the acute occurrence of a new symptom lasting for at least 48 h and resulting in specific treatment. Two episodes were counted as such only if they were separated by a symptom-free week. Surveillance was under the responsibility of a nursing director and was similar for all three types of DCCs. During the 8.5-month follow-up period, 3,639 infectious episodes were recorded. Compared to those in family day-care, children attending small DCCs presented a higher risk for > or = 6 total infectious episodes [odds ratio (OR) = 2.4; 95% confidence interval (CI) = 1.6-3.7]; > or = 5 upper respiratory tract infections (OR = 2.2; 95% CI = 1.4-3.4); > or = 2 episodes of otitis media (OR = 2.6; 95% CI = 1.0-2.6); > or = 2 episodes of conjunctivitis (OR = 4.1; 95% CI = 2.1-8.2); and > or = 2 episodes of croup (OR = 4.1; 95% CI = 1.6-10.9). The risk for children attending large DCCs was intermediate between those in family day care and those in small DCCs.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine the incidence, type and possible association with mortality of major bleeding in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) treated with an invasive strategy using predominantly the radial approach and triple antiplatelet therapy.In the multicentre randomised ABOARD Study, 352 patients with NSTE-ACS were randomised to an 'immediate percutaneous coronary intervention (PCI)' strategy or a strategy of PCI on the 'next working day'. Radial access was predominantly used in this study population. The present subanalysis evaluated the occurrence of major bleeding complications and their association with mortality at 1 month.Patients were treated with a triple antiplatelet therapy using high loading and maintenance doses of clopidogrel and abciximab in 99% of patients receiving PCI. The trans-radial approach was used in the vast majority of patients (84%). During the first 30 days, major bleeding complications (STEEPLE definition) occurred in 5.4% of patients (n=19), with no difference between immediate and delayed intervention. The most common bleeding complications were occult bleeding (36.8% of bleeding, n=7/19) and overt gastrointestinal bleeding (21% of bleeding, n=4/19). Patients with major bleeding had a higher peak concentration of creatinine during hospitalisation (mean±SD, 170±169 vs 97±57 μmol/l; p=0.005) and a 1-month mortality of 26.3%, much higher than patients without bleeding (0.6%, p0.0001). Major bleeding was strongly associated with 30-day mortality (OR 50.3; 95% CI 10.1 to 249.7; p0.0001).Despite the predominant use of the radial approach, major bleeding (essentially occult and gastrointestinal) remains a common complication, which is highly associated with mortality in patients with NSTE-ACS treated with optimal antithrombotic therapy.

Objective— Hypofibrinolysis promotes atherosclerosis progression and recurrent ischemic events in premature coronary artery disease. We investigated the role of fibrin physical properties in this particular setting. Methods and Results— Biomarkers of recurrent thrombosis and premature coronary artery disease (CAD) were measured in 33 young post–myocardial infarction patients with angiographic-proven CAD and in 33 healthy volunteers matched for age and sex. Ex vivo plasma fibrin physical properties were assessed by measuring fibrin rigidity and fibrin morphological properties using a torsion pendulum and optical confocal microscopy. The fibrinolysis rate was derived from continuous monitoring of the viscoelastic properties after addition of lytic enzymes. Young CAD patients had a significant increase in plasma concentration of fibrinogen, von Willebrand factor, plasminogen activator inhibitor type 1, and lipoprotein(a) as compared with controls ( P P =0.002), made of numerous ( P =0.002) and shorter fibers ( P =0.04), and lysed at a slower rate than that of controls ( P =0.03). Fibrin stiffness was an independent predictor for both premature CAD and hypofibrinolysis. Conclusions— This first detailed study of clot properties in such a group of patients demonstrated that abnormal plasma fibrin architecture is an important feature of both premature CAD and fibrinolysis rate. The determinants of this particular phenotype warrant further investigation.

Background— Oral antiplatelet agents (OAAs) can prevent further vascular events in cardiovascular disease. How prior use or recent discontinuation of OAA affects clinical presentation of acute coronary syndromes (ACS) and clinical outcomes (death, myocardial infarction [MI]) is unclear. Methods and Results— We studied and followed up for up to 30 days a cohort of 1358 consecutive patients admitted for a suspected ACS; of these, 930 were nonusers, 355 were prior users of OAA, and 73 had recently withdrawn OAA. Nonusers were at lower risk, more frequently presented with ST-elevation MI on admission, and more frequently had Q-wave MI at discharge than prior users (36.6% versus 17.5%, P P P =NS). In addition, prior users experienced more major bleeds within 30 days compared with nonusers (3.4% versus 1.4%, respectively; P =0.04). Recent withdrawers were admitted on average 11.9±0.8 days after OAA withdrawal. Interruption was primarily a physician decision for scheduled surgery (n=47 of 73). Despite a similar cardiovascular risk profile, recent withdrawers had higher 30-day rates of death or MI (21.9% versus 12.4%, P =0.04) and bleedings (13.7% versus 5.9%, P =0.03) than prior users. After multivariate analysis, OAA withdrawal was found to be an independent predictor of both mortality and bleedings at 30 days. Conclusions— Among ACS patients, prior users represent a higher-risk population and present more frequently with non–ST-elevation ACS than nonusers. Although patients with a recent interruption of OAA resemble those chronically treated by OAA, they display worse clinical outcomes.

Background— A few studies have suggested that von Willebrand factor (vWF) or plasminogen activator inhibitor-1 (PAI-1) can be associated with outcomes of acute coronary syndromes. The present study was designed to assess the acute release of these markers in ST-segment elevation myocardial infarction (STEMI) and their relations to death. Methods and Results— In 153 consecutive patients with STEMI, vWF and PAI-1 antigens were measured on admission (H0) and 24 hours later (H24). At 30 days, the death rate was 7.2%. Heart failure (Killip stage ≥3) on admission was present in 13.7% of patients. The acute release of PAI-1 (H24−H0, in ng/mL) and of vWF (H24−H0, in %) was dramatically higher in patients who died than in those who survived (46.9±26.3 versus −0.6±2.8 ng/mL, P =0.0001 and 65.8±20.0% versus 10.0±5.1%, P =0.004 for PAI-1 and vWF, respectively) and in patients developing heart failure compared with those without (24.8±10.1 versus −1.1±3.3 ng/mL, P =0.004 and 47.3±11.0% versus 8.1±5.6%, P =0.005 for PAI-1 and vWF, respectively). The release of PAI-1 correlated weakly with the left ventricular ejection fraction ( R =−0.195, P =0.01) and the peak of troponin ( R =0.149, P =0.045). Postangioplasty TIMI-3 flow and the acute release of PAI-1 were the only 2 independent predictors of death at 30 days. Conclusions— The acute release of vWF and PAI-1 over the first 24 hours of STEMI is associated with death and heart failure. The acute rise of PAI-1 is also a strong independent predictor of death at 30 days.

We have transmitted 1.5 Tbit/s over a deployed line of 4000 km of NZDSF using only C-band EDFAs with 25 GHz spacing and NRZ modulation format. The average performance obtained correspond to a 4.8 dB margin for a system designed with Enhanced 7% redundancy FEC scheme based on concatenated Reed-Solomon code. This experiment demonstrates for the first time the industrial feasibility of a 1.5 Tbit/s regional network transmission which is compatible with 0.4 (bit/s)/Hz. The use of NRZ format has two advantages. The first one is a low cost and compact terminal equipment due to less modulation stages compared to RZ or CRZ. The second one is a better compatibility with high channel density allowing simpler and lower cost repeaters for a given capacity. Furthermore, the demonstration of the excellent robustness of NRZ format over NZDSF allow direct field deployment or upgrades.

We report the first demonstration of 340 Gb/s, 50 GHz DWDM straight-line transmission over 6380 km with performance fully consistent with transatlantic plant installation.

Summary form only given. We have demonstrated the feasibility of high performance nonlinear but nonsoliton transmission in the normal dispersion regime. This kind of nonlinear nonsoliton transmission can be an alternative way to conventional or soliton systems. Further work will be needed to assess the real viability of such systems, mainly in the scope of wavelength-division multiplexing transmissions.

Background —Abciximab plus aspirin improves the TIMI 3 flow rate of the infarct-related artery in patients treated with either percutaneous coronary intervention or thrombolysis. The present study investigated whether the reperfusion efficacy of abciximab relates to modifications of clot architecture in patients admitted for acute myocardial infarction (AMI). Methods and Results —A total of 23 AMI patients in the Abciximab before Direct angioplasty and stenting in Myocardial Infarction Regarding Acute and Long term follow-up (ADMIRAL) trial received, in a double-blind fashion, either abciximab (n=13) or placebo (n=10) before primary stenting. Viscoelastic (G′ in dyne/cm 2 ) and morphological (mean platelet aggregate surface area [SAG] in μm 2 ) indexes of ex vivo platelet-rich clots (PRC) were assessed in a double-blind fashion before and after the bolus administration of abciximab or placebo. G′ and SAG reflect the mechanical and morphological impact of activated platelets on the PRC fibrin network, respectively. Abciximab administration reduced G′ by 63% ( P =0.0001) and SAG by 65% ( P =0.0007), and no effect was seen in the placebo group. These abciximab-related changes increased fibrin exposure as a consequence of the platelet-aggregate surface reduction and may have improved endogenous fibrinolysis. These effects were identified in all patients, independent of previous heparin administration. Conclusions —Abciximab dramatically reduces platelet aggregate size and increases the fibrin accessibility of ex vivo PRC in AMI patients. These modifications could participate in the better coronary artery patency observed with abciximab.

Contexte Le traitement preventif des anevrismes non rompus demeure controverse. L’efficacite du traitement endovasculaire a prevenir les episodes hemorragiques est encore inconnue. Methodes Nous avons revu les donnees disponibles de la litterature, ainsi que nos resultats du traitement endovasculaire dans notre centre. Nous avons retenu divers scenarios pertinents a l’elaboration des hypotheses de travail necessaires a la planification d’une etude clinique. Etude proposee Nous proposons une etude prospective, randomisee, multicentrique, controlee, comparant les evenements hemorragiques survenant au decours d’un traitement endovasculaire ou conservateur des anevrismes non rompus de plus de 3 mm. Le recrutement de 1200-1300 patients dans 30-40 centres en 3 ans, serait suivis d’une periode d’observation de 5 ans. L’hypothese principale serait une diminution des evenements hemorragiques de 5 ou 4 % a 1 %. Il serait egalement possible de demontrer une diminution globale de la morbimortalite de 15 a 10 %. Les objectifs secondaires de l’etude seraient une meilleure estimation de l’histoire naturelle des lesions referees pour traitement endovasculaire et du risque lie a ce traitement, ainsi qu’une evaluation du cout et des benefices de cette approche. L’etude principale serait precedee d’une phase initiale d’evaluation de la faisabilite sur 200 patients qui permettrait egalement de juger de la credibilite des hypotheses, en particulier au niveau de la morbidite liee au traitement. Conclusion Une etude randomisee est laborieuse mais sa realisation demeure possible. Elle est la seule capable de prouver l’efficacite relative du traitement.

Ultrastructural perturbations resulting from defects in polymerization of fibrinogen Dusart, a congenital dysfibrinogenemia with the amino acid substitution A alpha 554 arginine to cysteine, were investigated by a variety of electron microscope studies. Polymerization of this mutant fibrinogen on addition of thrombin is impaired, producing clots with decreased porosity and increased resistance to fibrinolysis, resulting in thrombotic complications in the family members with this dysfibrinogenemia. Electron microscopy of rotary-shadowed individual molecules revealed that, in contrast to control fibrinogen, most of the alpha C domains of fibrinogen or fibrin Dusart appeared to be free-swimming appendages that do not exhibit intra- or intermolecular interactions either with each other or with the central domains. The location of albumin on the alpha C domains was demonstrated by electron microscopy using anti-albumin antibodies. Electron microscopy of negatively contrasted fibrin Dusart fibers indicated that they were less ordered than control fibers and had additional mass visible. Electron microscopy of freeze-dried, unidirectionally shadowed fibers showed that they were twisted with a shorter pitch. Scanning electron microscopy revealed that intact clots were made up of thin fibers with many branch points and very small pore sizes. The viscoelastic properties of Dusart fibrin clots measured with a torsion pendulum indicated a marked increase in stiffness consistent with the structural observations.

Title Aldosterone receptor blockade at presentation for ST elevation myocardial infarction is associated with a reduction in potentially lethal ventricular arrhythmia. Purpose To assess the benefit of aldosterone receptor blockade on admission for primary PCI for STEMI. Methods 806 consecutive patients admitted within 12 hours after onset of a STEMI for primary PCI were studied. The latest 111 patients were systematically treated by 200 mg IV potassium canrenonate at presentation, followed by soludactone 25 mg daily during the hospital stay. The association between aldosterone receptor blockade and in-hospital death, ischemic events and ventricular arrhythmia was assessed using a logistic model adjusted on age, Killip class and reperfusion status. Follow-up was completed in 97% and 96% of patients at 30 days and 6 months. Results Results are depicted in the table. Baseline characteristics were not different between the 2 groups (age 63 ± 14 vs 62 ± 15, successful reperfusion 87% vs 90% and Killip class IV 5% in both groups).Aldosterone receptor blockade was associated with significantly lower rates of ventricular arrhythmia with an adjusted OR of 0.18 (95%CI 0.07–0.47) and 0.25 (95%CI 0.11–0.57) for the ventricular tachycardia and ventricular tachycardia or fibrillation respectively, and a trend towards lower rates of resuscitated cardiac arrest and high grade atrioventricular block. Mortality rates at 30 days (6 vs 6.7%) and 6 months (6.8 vs 7%) were comparable between the groups. Conclusions Aldosterone receptor blockade at presentation for STEMI is associated with a marked reduction of the risk of potentially lethal ventricular arrhythmia. These findings underline the anti-arrhythmic effect of aldosterone blockade and the need for adequately sized randomized trials to assess the benefit of such strategy on major cardiovascular events. No aldosterone blockade (n = 695) Aldosterone blockade (n = 111) p In-hospital Death 5.3% 6.31% NS Ressucitated cardiac arrest 7.2% 6.4% NS Death or ressucitated cardiac arrest 8.4% 7.3% NS Recurrent ischemia 5% 3.6% NS V tach-V Fib 25.6% 7.3% V tach 24.6% 5.45% High grade AV block 5.8% 1.8% 0.08

Aim We evaluated the rates, types and prognosis impact of bleeding complications in all-comers presenting with STEMI treated with aggressive antithrombotic treatment and radial access for primary PCI. Methods Consecutive STEMI patients (n=695) were evaluated for bleeding complications using a web-based registry (e-PARIS). In-hospital bleedings were adjudicated using various definitions (TIMI, GUSTO, STEEPLE). In-hospital ischemic events were the composite of MI, stroke and recurrent ischemia leading to urgent revascularization. Results Mean age was 63+/-14 years, 531 (76.4%) were male, 142 (20.4%) diabetic, 141 (20.3%) had known coronary disease. In this non-selected, high risk population, 5.2% had cardiogenic choc on admission, 3.7% had pre-hospital cardiac arrest, 49.4% had multivessel disease and in 45.2% the left anterior descending artery or left main was the culprit artery. Radial access (88%) was used as often as possible as well as abciximab (82%). The loading dose of clopidogrel ranged from 300 to 900mg. Pre-hospital fibrinolysis was used in 5.9%. Cardiac assist devices (IABP, ECMO, Tandem Heart) all requiring a femoral access, were used in 7.5% of patients. In-hospital death rate was 5.3%. In-hospital bleeding rates varied widely according to the definitions used: 2.3%, 1.4%, 5.3%, 9.2% and 10.8% with TIMI Major, GUSTO Severe, TIMI Major & Minor, GUSTO Severe & Moderate or STEEPLE Major, respectively. One year mortality according to bleeding or ischemic events are shown in the figure. The most frequent TIMI Major Bleeding (MB) complications were gastrointestinal (GI) (44%) and assistance device related (33%) MB. Conclusions Although bleeding rates vary a lot with the definitions used, major or minor bleedings strongly relate to 1-yr mortality after primary PCI and weigh at least as much as recurrent ischemic complications. The most frequent MB with radial primary PCI is GI bleeding. Download : Download full-size image