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BACKGROUND: Voriconazole is one of the first-line therapies for invasive pulmonary aspergillosis. Drug concentrations might be significantly influenced by the use of extracorporeal membrane oxygenation (ECMO). We aimed to assess the effect of ECMO on voriconazole exposure in a large patient population. METHODS: Critically ill patients from eight centers in four countries treated with voriconazole during ECMO support were included in this retrospective study. Voriconazole concentrations were collected in a period on ECMO and before/after ECMO treatment. Multivariate analyses were performed to evaluate the effect of ECMO on voriconazole exposure and to assess the impact of possible saturation of the circuit's binding sites over time. RESULTS: Sixty-nine patients and 337 samples (190 during and 147 before/after ECMO) were analyzed. Subtherapeutic concentrations (<2 mg/L) were observed in 56% of the samples during ECMO and 39% without ECMO (p = 0.80). The median trough concentration, for a similar daily dose, was 2.4 (1.2-4.7) mg/L under ECMO and 2.5 (1.4-3.9) mg/L without ECMO (p = 0.58). Extensive inter-and intrasubject variability were observed. Neither ECMO nor squared day of ECMO (saturation) were retained as significant covariates on voriconazole exposure. CONCLUSIONS: No significant ECMO-effect was observed on voriconazole exposure. A large proportion of patients had voriconazole subtherapeutic concentrations.

BACKGROUND: Since the beginning of the pandemic, COVID-19 has been regarded as an exceptional disease. Control measures have exclusively focused on 'the virus', while failing to account for other biological and social factors that determine severe forms of the disease. AIM: We argue that although COVID-19 was initially considered a new challenge, justifying extraordinary response measures, this situation has changed - and so should our response. MAIN ARGUMENTS: We now know that COVID-19 shares many features of common infectious respiratory diseases, and can now ascertain that SARS-CoV-2 has not suddenly presented new problems. Instead, it has exposed and exacerbated existing problems in health systems and the underlying health of the population. COVID-19 is evidently not an 'extraterrestrial' disease. It is a complex zoonotic disease, and it needs to be managed as such, following long-proven principles of medicine and public health. CONCLUSION: A complex disease cannot be solved through a simple, magic-bullet cure or vaccine. The heterogeneity of population profiles susceptible to developing a severe form of COVID-19 suggests the need to adopt varying, targeted measures that are able to address risk profiles in an appropriate way. The critical role of comorbidities in disease severity calls for short-term, virus-targeted interventions to be complemented with medium-term policies aimed at reducing the burden of comorbidities, as well as mitigating the risk of transition from infection to disease. Strategies required include upstream prevention, early treatment, and consolidation of the health system.

Background. Non-flow-limiting nonculprit lesions (NCL) that contain a large lipid-rich necrotic core (nonculprit lipid-rich plaques (NC-LRP)) are most likely to cause recurrent acute coronary syndrome after ST-elevation myocardial infarction (STEMI). Near-infrared spectroscopy (NIRS) detects LRPs using the maximum 4 mm lipid-core burden index (maxLCBI4 mm). Few data are available regarding NIRS-guided therapy of these NC-LRPs, which are a potential target for preventive stenting. Bioresorbable vascular scaffold (BVS) provides local drug delivery and could facilitate plaque passivation after resorption. This study sought to assess the safety of BVS implantation in NC-LRPs and its efficacy in reducing maxLCBI4 mm at 2-year follow-up after STEMI. Methods and Results. In total, 33 non-flow-limiting NCLs from 29 STEMI patients were included in this study. Of these, 15 were LRPs and were randomly assigned to either the BVS + optimal medical therapy (OMT) arm (group 1; N = 7) or the OMT arm (group 2; N = 8). At baseline, there were no differences in plaque characteristics between groups (fractional flow reserve: 0.85 ± 0.04 vs. 0.89 ± 0.06; diameter stenosis (DS): 43.4 ± 8 vs. 40.1 ± 10.7%; plaque burden 54.98 ± 5.8 vs. 49.76 ± 8.31%; and maxLCBI4 mm 402 [348; 564] vs. 373 [298; 516]; for all comparisons between groups 1 and 2, respectively). Seven BVSs were implanted 3 ± 1 days after STEMI in six patients, without complications. At angiographic follow-up (712 [657; 740] days), a significant and similar reduction of maxLCBI4 mm was observed in both groups, with a median change of 306 [257; 377] in group 1 vs. 300 [278; 346] in group 2 . DS was significantly lower in group 1 vs. group 2 (19.8 ± 7 vs. 41.7 ± 13%, ), while plaque burden remained unchanged in both groups. Overall survival was 100%, target lesion failure was 13%, and stent thrombosis was 0%. Conclusions. BVS + OMT and OMT appear as similarly safe and effective in reducing maxLCBI4mm in NC-LRPs at 2-year follow

Au cours de la pandémie liée au COVID-19, de nombreux patients ont été admis en unité de soins intensifs, mettant en exergue le travail d’une spécialité souvent peu ou mal connue du public. L’insuffisance respiratoire présentée par ces patients, et entrant dans le cadre de la définition de l’ARDS, a nécessité des techniques d’oxygénation et de ventilation non-invasive, invasive et dans les cas les plus sévères d’une assistance extra-corporelle. Ces traitements lourds, associés à des techniques de mobilisation compliquées (décubitus ventral) et aux autres traitements usuels de soins intensifs, chez un nombre important de patients simultanés et dont le pronostic était réservé, a généré une pression importante pour les équipes au lit du malade., [Management of patients with COVID-19-related respiratory failure at the intensive care unit] During the COVID-19 pandemic, many patients have been admitted to intensive care units, thereby highlighting the work of a medical specialty that is often little or poorly known to the public. In these patients, respiratory failure, falling within the definition of acute respiratory distress syndrome, had to be managed using non-invasive and invasive oxygenation and ventilation techniques, and in the most severe cases, using extracorporeal membrane oxygenation. These heavy treatments, combined with complicated mobilization techniques (prone position) and other usual intensive care treatments, had to be delivered simultaneously to a large number of patients with a guarded prognosis, which has put under significant pressure the bedside care teams.

Dear Editor, Skin rashes associated with COVID‐19 include eruptions induced by drugs prescribed for management of this infection. We report a case of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome in a patient with COVID‐19. [...]

OBJECTIVES: To report current practices regarding mechanical ventilation in patients treated with extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS) and their association with 6-month outcomes. METHODS: International, multi-center, prospective cohort study of patients undergoing ECMO for ARDS during a one-year period in 23 international intensive care units (ICUs). MEASUREMENTS AND MAIN RESULTS: We collected demographics, daily pre- and per-ECMO mechanical ventilation settings and use of adjunctive therapies, ICU- and 6-month-outcome data for 350 patients (median ± standard deviation pre-ECMO PaO2/FiO2 71±34 mmHg). Pre-ECMO use of prone positioning and neuromuscular blockers were 26% and 62%, respectively. Tidal volume (6.4±2.0 vs 3.7±2.0 ml/kg), plateau pressure (32±7 vs 24±7cmH2O), driving pressure (20±7 vs. 14±4 cmH2O), respiratory rate (26±8 vs 14±6 breaths/min) and mechanical power (26.1±12.7 vs. 6.6±4.8 J/min) were markedly reduced after ECMO initiation. Six-month survival was 61%. No association was found between ventilator settings during the first 2 days of ECMO and survival in multivariable analysis. A time-varying Cox model retained older age, higher fluid balance, higher lactate, and more need for renal replacement therapy along the ECMO course as being independently associated with 6-month mortality. A higher tidal volume and lower driving pressure (likely markers of static compliance improvement) across the ECMO course were also associated with better outcomes. CONCLUSION: Ultra-protective lung ventilation on ECMO was largely adopted across medium to high case-volume ECMO centers. In contrast with previous observations, mechanical ventilation settings during ECMO did not impact patients' prognosis in this context.

OBJECTIVES: The present study aimed at investigating the respective contribution of afterload and myocardial fibrosis to pre- and post-operative left ventricular (LV) function by using stress-strain relationships. BACKGROUND: Separating the effect of myocardial dysfunction and afterload on pump performance has important implications for the prognosis and management of patients with severe aortic stenosis (AS). METHODS: A total of 101 patients with isolated severe AS (57% men; mean age 71 years) and 75 healthy control subjects underwent resting 2-dimensional and speckle-tracking echocardiography to measure global circumferential strain (GCS) and global longitudinal strain (GLS), as well as end-systolic wall stress (ESWS). Normal stress-strain relationships were constructed using control subjects' data and fitted to linear regression. End-systolic stress-strain indexes (the number of SDs from the mean regression line) were used as an afterload-independent index of myocardial function and compared with myocardial fibrosis, measured on transmural myocardial biopsies harvested at the time of surgery. RESULTS: GCS and GLS were afterload-dependent in both control subjects and patients. The GLS-ESWS relationship of patients was shifted downward compared with control subjects. Patients with reduced pre-operative end-systolic stress-strain indexes exhibited larger degrees of interstitial myocardial fibrosis than patients without (3.8 ± 2.9% vs. 8.3 ± 6.3%, p < 0.001; and 4.9 ± 4.4% vs. 9.5 ± 6.4%; p < 0.001, for GLS and GCS, respectively). By multivariate analysis, pre-operative end-systolic stress-strain indexes were the only predictors of post-operative longitudinal and circumferential end-systolic stress-strain indexes (ß = 0.49 and ß = 0.60, respectively; p < 0.001). CONCLUSIONS: Myocardial strains are afterload-dependent. In patients with severe AS, pre-operative stress-strain indexes allow identification of patients with increased myocardial fibrosis and predict the ext

AIMS: The European Society of Cardiology (ESC) EURObservational Research Programme (EORP) European Endocarditis (EURO-ENDO) registry aims to study the care and outcomes of patients diagnosed with infective endocarditis (IE) and compare findings with recommendations from the 2015 ESC Clinical Practice Guidelines for the management of IE and data from the 2001 Euro Heart Survey. METHODS AND RESULTS: Patients (n = 3116) aged over 18 years with a diagnosis of IE based on the ESC 2015 IE diagnostic criteria were prospectively identified between 1 January 2016 and 31 March 2018. Individual patient data were collected across 156 centres and 40 countries. The primary endpoint is all-cause mortality in hospital and at 1 year. Secondary endpoints are 1-year morbidity (all-cause hospitalization, any cardiac surgery, and IE relapse), the clinical, epidemiological, microbiological, and therapeutic characteristics of patients, the number and timing of non-invasive imaging techniques, and adherence to recommendations as stated in the 2015 ESC Clinical Practice Guidelines for the management of IE. CONCLUSION: EURO-ENDO is an international registry of care and outcomes of patients hospitalized with IE which will provide insights into the contemporary profile and management of patients with this challenging disease.

Pneumomediastinum work-up should focus on differentiating mediastinal organ injuries from alveolar rupture since these two causative mechanisms have a different management and prognosis. After an admission at our Emergency Department, we wanted to challenge the current classification into 'spontaneous' or 'secondary' pneumomediastinum, which reflects the clinical rather than the pathophysiological circumstances and is therefore confusing and inappropriate to our view. We propose a new work-up algorithm based on clinical risks factors and chest CT findings.

A 65-year-old woman was found unconscious (Glasgow Coma Scale 3/15) and with respiratory failure (gasping) at the pneumology ward where she had been admitted for chronic obstructive pulmonary disease (COPD) exacerbation. She had a history of psychiatric disorders treated with several psychoactive drugs and a recent traumatic lumbar vertebral fracture requiring the introduction of analgesics. [...]

BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) is an autosomal dominant lipoprotein disorder characterized by significant elevation of low-density lipoprotein cholesterol (LDL-C) and markedly increased risk of premature cardiovascular disease (CVD). Because of the very high coronary artery disease risk associated with this condition, the prevalence of FH among patients admitted for CVD outmatches many times the prevalence in the general population. Awareness of this disease is crucial for recognizing FH in the aftermath of a hospitalization of a patient with CVD, and also represents a unique opportunity to identify relatives of the index patient, who are unaware they have FH. This article aims to describe a feasible strategy to facilitate the detection and management of FH among patients hospitalized for CVD. METHODS: A multidisciplinary national panel of lipidologists, cardiologists, endocrinologists and cardio-geneticists developed a three-step diagnostic algorithm, each step including three key aspects of diagnosis, treatment and family care. RESULTS: A sequence of tasks was generated, starting with the process of suspecting FH amongst affected patients admitted for CVD, treating them to LDL-C target, finally culminating in extensive cascade-screening for FH in their family. Conceptually, the pathway is broken down into 3 phases to provide the treating physicians with a time-efficient chain of priorities. CONCLUSIONS: We emphasize the need for optimal collaboration between the various actors, starting with a "vigilant doctor" who actively develops the capability or framework to recognize potential FH patients, continuing with an "FH specialist", and finally involving the patient himself as "FH ambassador" to approach his/her family and facilitate cascade screening and subsequent treatment of relatives.

A 74-year-old woman had an atrial fibrillation (AF) ablation procedure. Three weeks later, she presented with sepsis and paresis of the left upper limb. Initial chest computed tomography (CT) was inconclusive (Fig. 1a, b). Brain magnetic resonance imaging (MRI) showed acute multiple embolic cerebral infarcts (Fig. 1c, d). An atrio-oesophageal fistula (AOF) was suspected. ECG-gated CT was performed (Fig. 1e, f), confirming the diagnosis.[...]

Dear Editor, The accessory cardiac bronchus (ACB) is the only true supernumerary variant bronchus with an incidence between 0.07% and 0.5% [1]. ACB usually originates from the inner wall of the intermediate bronchus or from the right main bronchus, almost opposite to the orifice of the right upper lobe bronchus [1], [2], [3]. To our knowledge, only a single ACB originating from a left bronchus has been reported in literature using bronchography [4]. [...]

Dear Editor, Influenza affects between two and three million people worldwide each year, with complications responsible for a significant number of excess hospitalizations in intensive care units (ICUs) [1]. Since the newsworthy 2009 A(H1N1) pandemic (pdm), publications about influenza in ICUs remain scarce, with crucial outstanding issues on prognosis factors including the timing of antiviral treatments [2, 3, 4, 5]. Here, we present a multicenter prospective study of critically ill influenza-infected patients aimed to identify prognosis factors associated with death. [...]

DESCRIPTION : A 17-year-old woman was admitted to the emergency department with a 3-day history of dyspnoea (New York Heart Association Class II) and typical pleuritic pain following a 1-week history of cough and fever. Pneumonia was diagnosed based on a chest X-ray (figure 1A), and amoxicillin–clavulanate treatment was initiated. After 48 hours, the patient developed hypotension and tachycardia. Given hypotension, ongoing fever and rising C reactive protein despite antibiotic treatment, she was referred to the intensive care unit. On admission, an echocardiography was performed. A circumferential pericardial effusion with 14 mm maximum diameter adjacent to the right ventricle was detected, without haemodynamic compromise at the time. Besides, left pleural effusion was evidenced. An ultrasound-guided thoracentesis was conducted. Pleural fluid testing revealed the following findings: white blood cells (WBC) count 11.109/Literwith 90% neutrophils, proteins 38 g/L, pH 7.36, glucose 6.3 mmol/L and lactate dehydrogenase (LDH) 492 IU/L. The culture exhibited no organism, and the cytology proved negative in terms of malignant cells.

Pathological cardiac hypertrophy, which is a compensatory mechanism established to maintain cardiac function in response to neurohormonal or mechanical stresses, becomes maladaptive with time and frequently leads to heart failure. AMP-activated protein kinase (AMPK) has been extensively described in the literature to act as a break in cardiac hypertrophy development. Its anti-hypertrophic action mostly correlates with the inhibition of several important players of cardiac hypertrophy including protein synthesis and pro-hypertrophic gene expression pathways involving the transcription factor nuclear factor of activated T cells (NFAT) and the mitogen-activated protein kinases ERK1/2. In this chapter, we describe methodologies designed to evaluate cardiomyocyte hypertrophy and its major molecular mechanisms in response to AMPK activation. Two different compounds, AICAr and the biguanide phenformin, were used to promote AMPK activation.

In the Emergency Department, chest pain triage systems are based on either clinical features or ECG recording. In this prospective, single-center, observational study, we aimed to compare the diagnostic performance of these triage systems in distinguishing acute coronary syndromes (ACS) from diseases of mild severity. Patients were sorted into the triage systems based on collected data at admission and on a systematic 12-lead ECG performed at triage. The final diagnosis was determined after a 30-day follow-up. For ACS, we determined a high-acuity triage score (Level 1 or 2) as being adequate, and for mild severity diseases a low-acuity triage score (Level 3, 4 or 5) as being adequate. The diagnostic performance of all studied systems was moderate (AUC from 0.644 to 0.694), with no statistically significant difference found between them. However, characteristics of the systems differed because the clinical-based systems had a higher sensitivity (87-91%) but lower specificity (32-39%) compared with the ECG-based system (sensitivity 62% and specificity 64%). A higher sensitivity limits the risk of a patient with acute coronary syndrome staying unsafely in the waiting room, while a higher specificity prevents overcrowding. ECG at triage also ensures that no STEMIs or high-risk NSTEMIs are missed. Based on these findings, each Emergency Depatment could more accurately select the triage system that fits their local particularities.

Cannabinoid hyperemesis syndrome (CHS) is a clinical condition that was first described in 2004. The syndrome may occasionally be observed in long-term cannabis users and is characterized by a set of features: severe cyclic nausea and vomiting, recurrent epigastric or periumbilical pain, relief of symptoms with hot baths, and cannabis use cessation. The pathophysiology is not fully understood but is probably related to Cannabinoid-1 (CB-1) receptors dysregulation. On the other hand, there is also growing epidemiological evidence that cannabis smoking may trigger acute coronary syndrome (ACS) in young men. We describe the case of 41-year-old man with a long history of cannabis smoking who not only complained of recurrent epigastric but also of retrosternal pain. He had undergone several negative radiological or endoscopic investigations. During the last episode, electrocardiographic and echocardiographic changes were consistent with takotsubo cardiomyopathy. However, the patient was readmitted very soon with a ST-elevation myocardial infarction related to coronary vasospasm. While the link between CHS and ACS is not established, CHS patients with atypical pain should be investigated carefully to exclude any serious cardiac event.

L’angioplastie occupe une place centrale dans le traitement de l’infarctus du myocarde, diminuant la mortalité. Le traitement de choix du STEMI est l’angioplastie primaire. Etant donné l’occlusion complète de l’artère coronaire, la reperfusion par angioplastie est une urgence et doit être réalisée dans les 60 à 90 minutes après le premier contact médical. Tous les acteurs de la chaine de soins doivent joindre leurs efforts pour réduire les délais de traitement. La stratégie de traitement est différente pour le patient souffrant d’un infarctus NSTEMI. Dans la plupart des cas, la lésion responsable de l’infarctus n’est pas totalement occlusive. Le délai de prise en charge est moins un enjeu majeur. La stratégie de revascularisation, y compris par angioplastie, doit être discutée en Heart Team après une évaluation précise du risque du patient et plus particulièrement de ses comorbidités.

L’arrivée des nouveaux anticoagulants a ouvert une porte vers une nouvelle indication qui est la prévention secondaire en postsyndrome coronarien aigu. Les premiers résultats mettent en évidence une réduction de récidive d’évènement cardiovasculaire et de mortalité, avec toutefois un risque hémorragique accru. Par ailleurs, avec l’avènement des nouveaux antiagrégants dans le syndrome coronarien aigu, le clinicien est amené à rencontrer des patients associant ces deux thérapeutiques : antiagrégation (simple ou double) et anticoagulation. Les premières études montrent une majoration du risque hémorragique lorsque le traitement conventionnel de la fibrillation auriculaire est donné conjointement au traitement du syndrome coronarien aigu. Dès lors, bon nombre d’études sont en cours afin d’évaluer cette association et les doses les plus adaptées tant du point de vue de l’efficacité que du risque hémorragique.

OBJECTIVES: Cardiac transplantation using hearts from donors after circulatory death (DCD) is critically limited by the unavoidable warm ischaemia and its related unpredictable graft function. Inasmuch as hypothermic machine perfusion (MP) has been shown to improve heart preservation, we hypothesized that MP could enable the use of DCD hearts for transplantation. METHODS: We recovered 16 pig hearts following anoxia-induced cardiac arrest and cardioplegia. Grafts were randomly assigned to two different groups of 4-h preservation using either static cold storage (CS) or MP (Modified LifePort© System, Organ Recovery Systems©, Itasca, Il). After preservation, the grafts were reperfused ex vivo using the Langendorff method for 60 min. Energetic charge was quantified at baseline, post-preservation and post-reperfusion by measuring lactate and high-energy phosphate levels. Left ventricular contractility parameters were assessed both in vivo prior to ischaemia and ex vivo during reperfusion. RESULTS: Following preservation, the hearts that were preserved using CS exhibited higher lactate levels (57.1 ± 23.7 vs 21.4 ± 12.2 µmol/g; P < 0.001), increased adenosine monophosphate/adenosine triphosphate ratio (0.53 ± 0.25 vs 0.11 ± 0.11; P < 0.001) and lower phosphocreatine/creatine ratio (9.7 ± 5.3 vs 25.2 ± 11; P < 0.001) in comparison with the MP hearts. Coronary flow was similar in both groups during reperfusion (107 ± 9 vs 125 ± 9 ml/100 g/min heart; P = ns). Contractility decreased in the CS group, yet remained well preserved in the MP group. CONCLUSION: MP preservation of DCD hearts results in improved preservation of the energy and improved functional recovery of heart grafts compared with CS.

We report and discuss the case of a 51-year-old patient undergoing elective laparoscopic surgery for pheochromocytoma after 10 days of medical pre-treatment. After anaesthetic induction, a deep level of anaesthesia could not prevent the onset of repeated hypertensive peaks, followed by severe hypotensive periods. Once the surgical incision was made, the patient developed acute pulmonary oedema along with significant oxygen desaturation. The decision was made to stop the surgery and transfer the patient to the intensive care unit (ICU) for further support and management. Unfortunately, additional monitoring and symptomatic treatment did not help haemodynamic stabilisation. In the absence of any external stimulation or medical support, the oscillation of blood pressure (BP) continued with peaks every 20 minutes up to 300 mmHg systolic blood pressure (SBP) and falls down to 30 mmHg SBP. The patient also sustained two episodes of cardiac arrest from which he recovered. Facing this unmanageable situation, a decision was made after a multi-disciplinary discussion to go back to surgery in order to remove the source of adrenergic stimulation. Surgery by laparotomy was performed and catecholamine substitution was provided. Nevertheless, after tumour removal, BP dropped leading to a third cardiac arrest that was successfully managed. Following a 10-day stay in the ICU, the patient left with subsequent cardiac stabilisation and full recovery.

Background: Annular non-planarity, the "saddle-shape" of the mitral valve (MV) annulus, plays a role in minimizing leaflet stress and preserving valve function. Aortic valve (AV) repair/sparing procedures are increasingly used to treat aortic regurgitation (AR). The impact of these procedures on MV geometry and function is unknown. Methods: 2D and 3D transesophageal echocardiography (TEE) of the MV was acquired pre-operatively and immediately after surgery in 30 patients with severe AR and/or aortic root dilatation (Group 1 (n=10): bicuspid AV undergoing AV repair and valve-sparing root replacement with AV reimplantation; Group 2 (n=10): tricuspid AV undergoing AV repair and AV reimplantation; Group 3 (n=10): isolated AV cusp repair) and in 10 controls (Group 4). MV morphology was assessed by dedicated quantification software (fig. 1). Results: Comorbidities were similar in all groups. Groups 1, 2 and 3 had increased LV end-diastolic volumes compared to group 4 (214±90, 193±56, 180±55 vs. 86± 28ml for groups 1, 2, 3 and 4, respectively; p<0.001); LVEF was similar (59.5 ± 6.2%). The baseline dimensions of the ventriculo-aortic junction and sinuses of Valsalva were larger in groups 1 and 2 vs. groups 3 and 4 (p<0.0001). AV and MV parameters are summarized (table). Pre-operative MV parameters did not differ from those of normal subjects. The annular height and annular height to commissural width ratio (AHCWR) significantly decreased after surgery in groups 1 and 2, as did the tenting area. Significant changes in the coaptation depth and mitro-aortic angle were only found in group 1. Conclusions: AV repair/sparing procedures alter the MV geometry, including the non-planarity of the annulus and the depth of coaptation of the leaflets, especially among patients with a bicuspid AV undergoing AV reimplantation. These alterations could have long-term implications on MV function.

Les progrès médicaux et chirurgicaux permettent actuellement à la majorité des patients atteints de cardiopathies congénitales d’atteindre l’âge adulte. Cet article revoit les principales cardiopathies congénitales et leur évolution à l’âge adulte, [What must be known about congenital cardiopathies in adults] Medical and surgical progress currently allows a majority of patients with congenital heart disease to reach adulthood. This article sought to review the main congenital heart diseases and their evolution during adult life.

This chapter describes the history of mechanical circulatory, available paracorporeal or implantable systems, indications for mechanical circulatory support, patient selection and management, complications and future perspectives.

In the last thirty years, numerous linguists have stressed the discourse functions of adverbials. More specifically, sentence-initial temporal and spatial adverbials are often seen as signals that highlight the beginning of a new discourse unit for which they provide the setting. These expressions are thus supposed to affect the reading processes. This paper reports psycholinguistic experiments in which the impact on comprehension of sentence-initial adverbials has been specifically studied. In the first section, we summarize the two discourse functions these adverbials should play according to linguistic theories: signalling the beginning of a new textual unit (the segmenting function) and setting the frame of reference for the whole textual unit that they preface (the framing function). The main conclusion is that inserting an adverbial in sentence-initial position must be seen as a strategic decision of the author of the text for the benefit of the reader. In the next sections, we report several experiments that show that, contrarily to sentence-final adverbials, sentence-initial adverbials enable readers to initiate a set of procedures specific to a topic change and induce them to keep in active memory the setting expressed by the adverbial so that it can regulate the processes of knowledge mobilization required for the interpretation of the sentences that are under its scope. In the conclusion, several avenues for further development are discussed

A 19-year-old man was admitted with acute dyspnoea. Physical examination revealed subcutaneous emphysema in the cervical and thoracic area. This was further confirmed by the total body computed tomography that also demonstrated mediastinal emphysema. Epidural pneumatosis of the thoracis spine was also evident. There was no history of trauma, but well of a recent oral ecstasy consumption during a techno rave party, associated with intense dancing and jumping. Clinical course was favourable with conservative therapy.

Introduction: The improved outcomes of third-generation continuous-flow left ventricular assist devices (CF-LVAD) in bridge-to-transplant and the high attrition rate among patients awaiting an allograft have raised the question whether CF-LVADs are better than the waiting list for transplant eligible patients. Hypothesis: we assessed the hypothesis that survival after LVAD is improved compared to waiting list in adult patients listed in UNOS status II. Methods: We identified all patients >18 years of age in the Organ Procurement and Transplantation Network (OPTN) database listed for their first heart transplant in the US in UNOS status II with no mechanical circulatory support at time of listing and not candidates to multi-organ transplant between January 2011 and March 2014. Of 2468 patients listed during the study period, 208 patients received a third-generation CF-LVAD. CF-LVAD and NO-LVAD patients were then matched 1:2 by mean of the closest-neighbor Propensity Score and survival of the matched groups was estimated with the Kaplan-Meier method. Results: One hundred and ninety CF-LVAD patients were PS-matched with 380 NO-LVAD patients. The matched groups were similar for several baseline characteristics (p=ns). In the CF-LVAD subgroup, 158 patients (83.2%) were transplanted, 21 (11.1%) were still on support and on the list, and 11 patients (5.8%) died or were delisted. In the NO-LVAD group, 314 patients (82.6%) were transplanted, 48 (12.6%) were still on the list and 18 patients (4.7%) died or were delisted. Freedom from death or delisting with CF-LVAD was 80.5% versus 85.5% of NO-LVAD patients at 18 months postoperatively (p=0.4). Cumulative survival considering also the post-transplant period was similar in the two groups at 24 months since listing (80.4% CF-LVAD versus 79.4% NO-LVAD, p=0.3). Conclusions: In conclusion, heart transplant candidates listed in status II and supported with CF-LVAD have shown a similar survival on the waiting list compared to candid

Background: Several previous studies have demonstrated that, in patients with severe aortic stenosis (SAS), chronic pressure overload hypertrophy frequently results in reduced longitudinal function as assessed by tissue Doppler or speckle tracking echocardiography (STE). The aim of the present study was to determine the relative contribution of structural (interstitial fibrosis) and functional (afterload) alterations in this process and to evaluate the implications thereof for functional recovery after aortic valve replacement (AVR). Methods: 34 patients with isolated SAS underwent pre-operative resting conventional echocardiography and STE, to calculate end-systolic wall stress (ESS) and to measure global longitudinal strain (GLS) and left ventricular ejection fraction (LVEF). At the time of AVR, a per-operative transmural biopsy was obtained in every patient, to quantify the degree of interstitial fibrosis. Echocardiographic functional parameters were reassessed 6 months after AVR. Results: Compared to age-matched normal controls, SAS patients exhibited significantly reduced GLS (-12.5 ± 3.9% vs -18.2 ± 1.5% p<0.0001) and LVEF (57 ± 13 vs 66 ± 4%, p=0.026). With univariate analysis, pre-operative GLS was found to correlate significantly with LVEF (r=0.70, p<0.0001), interstitial fibrosis (r=-0.60, p=0.0002), LV mass (r=-0.52, p=0.002) and ESS (r=-0.61, p=0.0001). Using stepwise multiple regression analysis, only the degree of interstitial fibrosis and ESS were found to be independent correlates of pre-operative GLS (r=0.74). Interestingly,unstressed pre-operative GLS, extrapolated as GLS at zero stress, correlated well with interstitial fibrosis (r=0.51) and predicted GLS at the 6-months post-operative follow-up (r=0.55). Conclusions: In patients with SAS, reduced longitudinal function results from both excessive afterload and structural tissue alterations (interstitial fibrosis). Unstressed pre-operative GLS was found to be a reasonable correlate of tissue fibros

AIMS: The aim of this study was to evaluate predictors of recovery after balloon aortic valvuloplasty (BAV) among patients with aortic stenosis and depressed left ventricular ejection fraction (LVEF). Predictors for recovery after BAV are not clearly defined. B-type natriuretic peptide (BNP) predicts outcome after surgical and transcatheter aortic valve replacement. METHODS AND RESULTS: Among 151 consecutive patients treated in our institution by BAV, a total of 59 with poor LVEF underwent an echocardiography at 1 month. In these 59 patients, LVEF significantly improved in 22 patients (group 1) from 27 ± 5% to 45 ± 6% (P<.0001) and remained unchanged in 37 patients (group 2) from 29 ± 8% to 30 ± 11% (P=NS). BNP plasma levels at 24 hours only decreased in group 1 from 2170 ± 967 pg/mL to 1208 ± 662 pg/mL (P=.001). By multivariate analysis, BNP reduction >300 pg/mL was the strongest independent predictor of LVEF improvement at 30 days (hazard ratio, 5.459; 95% confidence interval, 1.580-18.860; P=.007). Kaplan-Meier analysis showed that 1-year survival after BAV was significantly higher in patients of group 1 than in group 2 (95 ± 4% vs 51 ± 8%, respectively; P=.02). CONCLUSIONS: BAV in patients with poor left ventricular function resulted in LVEF improvement at 30 days in 37% of cases, which was detected by a reduction of BNP levels already seen at 24 hours. Survival at 1 year was significantly higher in patients with such an improved LVEF after BAV.

Objectives: The purpose of this study was to evaluate the impact of focal fibrosis (FF) assessment by delayed-enhanced cardiac magnetic resonance (DE-CMR) on survival in patients with severe aortic stenosis (AS) treated by aortic valve replacement (AVR). Background: Prior studies have shown that DE-CMR predicts survival in severe aortic valve disease. However in context of curative surgery, FF impact is less known as well as influence of coronary status. Methods: The authors prospectively evaluated survival of 180 consecutive patients (118 males, age 72±9.5 years) with AVR undergoing DE-CMR. One hundred twenty four patients underwent isolated AVR, whereas 56 patients received associated coronary artery bypass graft (CABG). Results: Over the 3-year median follow-up, 21 patients died. Mean FF percentage was higher in patients with events versus those without (3.9±5.1 vs. 1.5±2.6, 0.001). Kaplan-Meier analyses revealed that higher degrees of FF were associated with worse long-term survival after AVR with or without associated CABG (chi-square = 3.58, p 0.05; chi-square = 4.15, p 0.04, respectively). On multivariable cox analysis, FF (hazard ratio [HR]: 1.12 (1.0-1.2), 95% confidence interval [CI]: 1.0 to 1.2, p < 0.004) and New York Heart Association functional class (HR: 2.0, 95% CI: 1.1 to 3.5, p < 0.01) were identified as strong independent determinants of poor prognosis. In patients with AS, there were 3 findings for FF distributed as follows between patients with events versus those without: no enhancement (67 vs. 42, p <0.02), infarct pattern (22 vs. 33, p =NS), and midwall enhancement (10 vs. 23, p =NS). However after exclusion of 67 patients with CAD history, prognostic value of FF was decreased (log rank=NS). Conclusions: With or without revascularization, presence of FF by DE-CMR is an independent predictor of mortality in patients AVR with AS. DE-CMR provides additional information in the evaluation of preoperative risk particularly for patients with CAD his

Aims: To assess the accuracy of the recently proposed echocardiographic classification system of aortic stenosis (AS), and to evaluate differences between patients with high (HG) and low gradient (LG) and normal (NF) and low flow (LF) AS in terms of AS severity, LV remodeling and fibrosis using cardiovascular magnetic resonance (CMR). Methods and results: 128 consecutive patients (73±11 years, 95 male) with aortic valve area (AVA) <0.6 cm/m2 and ejection fraction >50% by echocardiography underwent evaluation of planimetric AVA, phase contrast indexed stroke volume (SVI), left ventricular hypertrophy, and focal fibrosis by CMR. Using <40 mm Hg, and SVI <35 ml/m2 as criteria for LG and LF respectively, 69 (54%) patients were HG/NF, 28 (22%) HG/LF, 17 (13%) LG/NF, and 14 (11%) LG/LF AS. Measurements of LVOT area, SVI and AVA correlated well between echocardiography and CMR (r=0.7, 0.61, 0.65, respectively; p<0.001 for all). Planimetric AVA by MRI was less severe in LF/LG (0.54±0.08 cm2/m2) and NF/LG (0.61±0.08 cm2/m2) than in HG/LF (0.46±0.07 cm2/m2, p<0.05) AS. Also indexed mass was less in LF/LG (75±12 g/m2) and LG/NF (81±18 g/m2) than in HG/LF (100±27 g/m2, p<0.05) AS. All groups of AS had predominantly concentric hypertrophy remodeling, and similar amounts of focal fibrosis (1.6±3.9%, 1.5±2.2%, 0.8±0.7% and 1.0±1.3% for HG/NF HG/LF, LG/NF and LG/LF groups respectively p=NS) Conclusions: CMR confirmed that echocardiographic classification system of AS was overall accurate. Patients with paradoxical LG/LF and LG/NF AS had less severe AS severity, less hypertrophy and similar remodeling and similar amount of focal fibrosis than HG/LF AS.

Nous rapportons le cas d’une patiente de 49 ans ayant développé un syndrome d’encéphalopathie postérieure réversible (PRES) 7 jours après transplantation cardiaque. La symptomatologie, l’imagerie caractéristique et les hypothèses pathophysiologiques de cette entité sont discutés à la lumière de la littérature récente.

OBJECTIVES: Studies have emphasized the importance of normal fibrinogen concentrations in surgical patients. The primary hypothesis of this study was that fibrinogen levels significantly decrease in on-pump coronary artery bypass graft (CABG) surgery versus off-pump coronary artery bypass graft (OPCAB) surgery. The second objective was to show that ROTEM (TEM International, GmbH, Munich, Germany) rapidly detects these abnormalities compared with standard tests. DESIGN: A prospective, nonrandomized study. SETTING: A university hospital. PARTICIPANTS: Forty-two and 62 patients in the CABG and OPCAB groups, respectively, undergoing first-time bypass surgery were included. INTERVENTIONS: CABG versus OPCAB surgery. MEASUREMENTS AND MAIN RESULTS: Routine coagulation tests and ROTEM values were measured before anesthesia (T0), after the first dose of heparin (T1), after protamine (T2), upon intensive care unit arrival (T3), and 4 hours postoperatively (T4). The outcome measures were followed until 4 hours postoperatively. Fibrinogen concentrations were significantly lower in the CABG versus the OPCAB group at T2 (170 ± 44 v 243 ± 73 mg/dL, p < 0.001) and T3 (179 ± 42 v 232 ± 68 mg/dL, p < 0.001). This was confirmed by significantly lower FIBTEM maximal clot firmness values at T2 (9 ± 4 v 14 ± 5 mm, p < 0.001) and T3 (9 ± 4 v 13 ± 6 mm, p < 0.001). In the CABG group, patients received significantly more transfusions of all blood products except fresh frozen plasma. CONCLUSIONS: Fibrinogen concentration significantly decreases after cardiopulmonary bypass. ROTEM helps in its fast detection.

Rivaroxaban is one of the new oral anticoagulants (NOACs) (recommended as reference treatments when a long-term anticoagulation is needed). It has many potential advantages in comparison with Vitamin K Antagonists (VKA). It has a predictable anticoagulant effect and does not theoretically require biological monitoring. It is also characterized by less food and drug interactions. However, due to major risks associated with over- and under-dosage, its optimal use in patients should be carefully followed by health care professionals. The aim of this article is to provide recommendations for pharmacists on the practical use of Xarelto® in its different approved indications. This document is adapted from the practical user guide of rivaroxaban which was developed by an independent group of Belgian experts in the field of thrombosis and haemostasis.

OBJECTIVE: Preliminary data showed an increase in endogenous erythropoietin (EPO) concentrations after acute normovolemic hemodilution (ANH) in patients undergoing coronary artery bypass graft (CABG) surgery. Numerous studies have shown the organ protective properties of EPO. The aim of this study was to investigate the cardioprotective effects of these increased EPO concentrations that resulted from ANH during cardiac surgery. DESIGN: A prospective, randomized, blind study. SETTING: A university hospital. PARTICIPANTS: A total of 93 patients undergoing isolated CABG surgery with or without cardiopulmonary bypass (CPB). INTERVENTIONS: Subjects with CPB were randomized into the control (C) or ANH group. Those in the off-pump coronary artery bypass group underwent no treatment. In the ANH group, a precalculated amount of blood was withdrawn and replaced by colloids after the induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters were recorded intra- and postoperatively. Troponin concentrations were measured as a routine parameter postoperatively. Upon intensive care unit arrival, the EPO levels were higher in the ANH group than in the C group. There was no significant difference between the troponin values of the C and the ANH groups at 4 hours postoperatively. CONCLUSIONS: In patients undergoing CABG surgery on CPB, an increase in endogenous EPO concentrations in the physiologic range has no cardioprotective effects.

Background: Central Pulse Wave Velocity (PWV) is considered to be the gold standard measurement of arterial stiffness. In healthy subjects, cardiovascular risk factors such as age, hypertension, diabetes and end-stage renal disease are associated with increased central (Carotid-Femoral) and peripheral (Femoral-Ankle) PWV. However, little is known about PWV in patients with peripheral arterial disease and pathological Ankle-Brachial Index (ABI). The aim of this study was to study central and peripheral PWV in a population with various degree of peripheral arterial disease. Methods: Central and peripheral PWV were measured in sixty-two hospitalized patients. Half were admitted for symptomatic peripheral vascular disease and the remainder for cardiac or carotid disease. The population was classified on basis of the Framingham-derived risk score for claudicants and on the ABI. For all patients, PWV was assessed on electrocardiogram-ultrasonographic images acquired at the four following sites: carotid, radial, femoral and tibial arteries. Results: Carotid-Femoral PWV increased significantly with the Framingham-derived global risk score (p < 0.0001) but Femoral-Ankle PWV did not. With respect to the Ankle-Brachial Index, Carotid-Femoral and Femoral-Ankle PWV significantly increased (p = 0.05 and p = 0.02 respectively) with the severity of peripheral arterial scoring. Conclusions: These results confirm that central PWV is the best indicator of general atherosclerosis, even in the presence of peripheral arterial disease. Both central and peripheral PWV can be considered as indicators of the severity of peripheral vascular disease. © 2011 Association for Research into Arterial Structure and Physiology.

Assault chemical burns are uncommon in northern Europe. Besides local toxicity, systemic manifestations are possible after strong acid exposure. A 40-year-old woman was admitted 1 h after a criminal assault with sulfuric acid. The total burned surface area was 35%, third degree. Injury was due to sulfuric acid (measured pH 0.9) obtained from a car battery. Immediate complications were obstructive dyspnea and metabolic acidosis. The admission arterial pH was 6.92, with total bicarbonate 8.6 mEq/l and base deficit 23.4 mEq/l. The correction of metabolic acidosis was achieved after several hours by the administration of bicarbonate and lactate buffers. The patient developed several burns-related complications (sepsis and acute renal failure). Cutaneous projections of strong acids may cause severe metabolic acidosis, particularly when copious irrigation and clothes removal cannot be immediately performed at the scene.

Refractory hypercapnia with severe acidosis appeared in a 67-year-old man who presented with lung fibrosis and a left pneumothorax as delayed complications of bleomycin chemotherapy for advanced grade lymphoma. Due to failure of noninvasive ventilation using a high-flow nasal cannula oxygen system, the patient was mechanically ventilated with two ventilators at different settings, after intubation with a double-lumen tube. As he had a poor haematological prognosis, extracorporeal membranous oxygenation was not considered. To remove some amount of carbon dioxide, we used a simplified method based on a veno-venous hemofiltration circuit coupled to a paediatric oxygenator and an air/oxygen blender. The efficacy on carbon dioxide removal was modest, with a percentage of CO2 total extraction ranging from 10.5 to 20.4%, but the system was immediately available, well tolerated and not very expensive.

Exercise capacity is improved in patients supported with continuous flow rotary blood pumps (RP). The aim of this study was to investigate the mechanisms underlying this improvement. Ten patients implanted with a RP underwent cardiopulmonary exercise testing (CPET) at 6 months after surgery with hemodynamic and metabolic measurements (RP group). A group of 10 matched heart failure patients were extracted from our heart transplant database, and the results of their last CPET before transplantation were used for comparison (heart failure [HF] group). Peak VO(2) was significantly higher in RP than in HF patients (15.8 ± 6.2 vs. 10.9 ± 3 mL O(2)/kg.min) reaching 52 ± 16% of their predicted peak VO(2). The total output measured by a Swan-Ganz catheter increased from 5.6 ± 1.6 to 9.2 ± 1.8 L/min in the RP group and was significantly higher at rest and at peak exercise than in the HF group, whose output increased from 3.5 ± 0.4 to 5.6 ± 1.6 L/min. In the RP group, the estimated pump flow increased from 5.3 ± 0.4 to 6.2 ± 0.8, whereas the native cardiac output increased from 0.0 ± 0.5 to 3 ± 1.7 L/min. Cardiac output at peak exercise was inversely correlated with age (r = -0.86, P = 0.001) and mean pulmonary artery pressure (r = -0.75, P = 0.012). Maximal exercise capacity is improved in patients supported by RP as compared to matched HF patients and reaches about 50% of the expected values. Both a spontaneous increase of pump flow at constant pump speed and an increase of the native cardiac output contribute to total flow elevation. These findings may suggest that an automatic pump speed adaptation during exercise would further improve the exercise capacity. This hypothesis should be examined.

Safe use of cyclosporine (CsA) in solid organ transplantation relies on regular whole-blood drug monitoring. Several promising immmunoassays, e.g. the antibody-conjugated magnetic immunoassay (ACMIA) method, were developed and commercialized during recent years to compete with liquid chromatography coupled to tandem mass spectrometry, which remains the reference method but is labor-intensive. We describe the occurrence of interference in the monitoring of whole-blood CsA after transplantation when using the ACMIA method and discuss the potential mechanisms involved in such interference. Clinically unexpected results of whole-blood CsA require immediate reassessment by another technique to prevent the risk of CsA underdosage and graft rejection.