Background ɣGT has been identified as a maker of systemic inflammation and cardiovascular (CV) risk. The composite index DAS28-ɣGT has been developed to allow an evaluation of both joint disease activity and CV risk. Objectives To assess the value of the DAS28-ɣGT in a population of patients with rheumatoid arthritis (RA) requesting cardiologic assessment. Methods Retrospective analysis of RA patients referred to cardio-metabolic day hospitalization in the Rheumatology department of Cochin hospital between February 2021 and January 2022. Criteria for referral were age > 50 years and presence of at least one CV risk factor. DAS28-GGT index was calculated as follows: 0,56 * √TJ-28 + 0,28 * √SJ-28 + 2 * ln (γGT) + 0,14 * GH. This index was analysed according to disease activity measured with the DAS28-CRP, CV risk assessed by the Framingham score and the decision taken by the cardiologist (requirement of complementary explorations and/or therapeutic intervention). Results We included 22 RA patients (17 women), with a mean age of 66±10 years, a disease duration of 21±12 years. Rheumatoid factor was positive in 15 patients, anti-CCP antibodies in 17, and bone erosions in 16. 15 patients received methotrexate, 13 corticosteroids (dose < 10 mg per day), 15 targeted biologic therapies and 3 JAK inhibitors. The mean DAS28-CRP was 2.5±0.9 and the mean DAS28-ɣGT was 7.90±1.90. 2 patients had a DAS28-ɣGT < 5.5, defined in our previous study as high probability of RA remission and low probability of CV risk. These two patients were in remission and their Framingham score was < 10% (low CV risk). No complementary exploration was requested by the cardiologist. 8 patients (6 women, 2 men) had a DAS28-ɣGT index between 5,5 and 7,5, defined in our previous study as high probability of RA remission or low disease activity (LDA) and increased probability of CV risk. As expected, all patients were in remission or in LDA. This population were at higher CV risk: 2 patients had a Framingham score > 20% (high risk), 3 patients a score ranging from 10 to 20% (intermediate risk), and 3 patients a score < 10%. One patient presented carotid atheroma. 4 patients required additional CV explorations and 3 patients necessitated escalation of blood hypertension therapy. Twelve patients (9 women, 3 men) had a DAS28-ɣGT index > 7,5, defined in our previous study as high probability of active RA and/or increased probability of CV risk. 4 patients were in remission, 3 were in LDA and 5 presented moderate disease activity. One patient had a Framingham score > 20%, 4 had a score ranging between 10 and 20% and 6 had a score < 10%. The score was not applicable in an 80-year-old patient. Three other patients had coronary artery disease, including a patient who presented both coronary artery disease and carotid atheroma. 5 patients requested additional CV explorations and 4 required CV therapy escalation (introduction of statin and aspirin in 2 patients and increased blood hypertension therapy in 2 patients). Among these 12 patients, 3 with the highest DAS28-ɣGT values presented CV complications: a 64-year-old woman with a DAS28-ɣGT of 12.8 (DAS28-CRP: 2.89) had carotid atheroma and intermediate lesion of the right artery on coroscanner justifying a coronarography; a 81-year-old woman with a DAS28-ɣGT of 10.67 (DAS29-CRP: 4.62) had atrial fibrillation and aortic stenosis requiring Transcatheter Aortic Valve Implantation; and a 77-year-old woman with a DAS28-ɣGT of 10.35 (DAS28-CRP: 3.89) had ischemic chest pain necessitating rapid explorations in cardiology. Conclusion The DAS28-ɣGT allowed a reliable classification of patients according to the RA activity disease and CV risk. This index may be relevant for CV risk stratification decision making to refer RA patients to a cardiologist. Its validation is in progress in a prospective cohort. References [1]Vergneault H, vandebeuque E, Codullo V, et al, J rheumatol 2020;47(12):1738-1745 Disclosure of Interests None declared

BACKGROUND In contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity. METHODS AND RESULTS CLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia, and Africa in 2009-2010, and followed up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischaemia, or prior revascularization procedure.Among 32 694 patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to ∼60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome (cardiovascular death, myocardial infarction, or stroke) with an adjusted hazard ratio of 1.28 (95% confidence interval 1.18, 1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure, and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest. CONCLUSION In patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes. CLINICALTRIALS IDENTIFIER ISRCTN43070564.

Nous avons développé un indice original, le DAS28-γGT, qui pourrait avoir un intérêt pour évaluer à la fois l’activité de la polyarthrite rhumatoïde (PR) et le risque cardiovasculaire (CV) [1]. Notre objectif a été d’analyser la valeur de cet indice dans une population de PR à risque CV ayant eu évaluation récente par un cardiologue. Analyse rétrospective de l’ensemble des PR ayant été adressé en hospitalisation de jour cardio-métabolique du service de Rhumatologie de l’hôpital Cochin entre février et juin 2021. Il s’agissait de patients de plus de 50 ans présentant un ou plusieurs facteurs de risque (FDR) CV, sans notion d’évaluation cardiologique préalable. Le score DAS28-γGT (calculé à partir de la formule suivante : 0,56 * √AD-28 + 0,28 * √AG-28 + 2 * ln (γGT) + 0,14 * EVA) a été analysé en fonction de l’activité de la PR mesurée par le DAS28, du risque CV évalué par le score de Framingham et de la décision du cardiologue consulté lors de l’HDJ (explorations complémentaires, intervention thérapeutique). 14 patients atteints de PR (9 femmes), âgé de 66 ± 9 ans avec une durée de la maladie de 17 ± 9 ans ont été inclus. Les facteurs rhumatoïdes étaient positifs chez 10 patients, les ACPA chez 11 patients et 8 patients présentaient des érosions osseuses. Onze patients recevaient du méthotrexate, 9 une corticothérapie < 10 mg/jour, 8 un traitement biologique ciblé et 2 un inhibiteur de JAK. Le DAS28 était de 2,28 ± 0,90 et le DAS28-γGT de 7,60 ± 2,29. Deux patientes présentaient un score DAS28-γGT < 5,5 défini dans notre précédente étude comme étant à forte probabilité de PR en rémission et de faible risque CV. Ces 2 patientes avaient une PR en rémission. Leur score de Framingham était < 10 % (risque faible). Aucune exploration complémentaire cardiaque et intervention thérapeutique spécifique n’ont été prescrites par le cardiologue. Six patients (4 femmes, 2 hommes) présentaient un score DAS28-γGT compris entre 5,5 et 7,5 défini dans notre étude précédente comme étant à probabilité élevée de PR en rémission/faible activité et probabilité élevée de risque CV. Quatre patients étaient en rémission et 2 en faible activité de la PR. Deux patients avaient un score de Framingham > 20 % (risque élevé), 3 un score entre 10 et 20 % (risque intermédiaire) et 1 un score < 10 %. Un patient présentait un athérome carotidien. Des explorations complémentaires CV ont été demandées pour 3 patients et 2 intensifications thérapeutiques de l’HTA ont été prescrites. Six patients (3 femmes, 3 hommes) présentaient un score DAS28-γGT > 7,5 défini comme étant à probabilité élevée de PR active et/ou de risque CV. Un patient avait une PR en rémission, 2 en activité faible et 3 en activité modérée. Deux patients avaient un score de Framingham > 20 % et 4 un score entre 10 et 20 %. Des explorations complémentaires CV ont été demandées par le cardiologue pour 3 patients, incluant deux coronarographies, une intensification thérapeutique de l’HTA a été prescrite pour un patient et une patiente justifiait la prescription d’aspirine et de statine pour un athérome carotidien et une lésion intermédiaire de la coronaire droite au coroscanner. Le DAS28-γGT a permis une classification fiable des patients en fonction de l’activité de la PR et de leur risque CV. Le DAS28-γGT pourrait être utilisé pour la stratification du risque CV et la décision d’adresser un patient atteint de PR à un cardiologue. Sa validation est en cours dans des cohortes prospectives.

Le malattie cardiovascolari sono la principale causa di morte nel mondo. È stimato pari a 17,7 milioni il numero di morti per malattie cardiovascolari, ossia il 31% della mortalità globale totale. Il paziente coronarico accertato è un paziente ad alto rischio cardiovascolare. L’obiettivo della prevenzione secondaria è limitare la crescita della placca ateromatosa e l’insorgenza della sindrome coronarica acuta, al fine di limitare i sintomi e di migliorare la prognosi e la sopravvivenza. La prevenzione secondaria prevede il controllo dei fattori di rischio cardiovascolare a cui si aggiunge il trattamento farmacologico, che include inevitabilmente l’antiaggregazione piastrinica e le statine, ma anche, nel postinfarto con disfunzione ventricolare sinistra, dei betabloccanti e degli inibitori del sistema renina-angiotensina. Negli ultimi anni, le classi di farmaci si sono diversificate, come i nuovi antiaggreganti piastrinici e i nuovi anticoagulanti orali diretti. Altre sono emerse, come gli anticorpi anti-PCSK9, per abbassare il colesterolo. Sono stati, inoltre, sviluppati i trattamenti specifici dei fattori di rischio cardiovascolare. Il trattamento a lungo termine della malattia coronarica si è, quindi, evoluto fortemente verso una gestione più complessa e più personalizzata.

BACKGROUNDPrevious studies published before the era of systematic early invasive strategy have reported a higher mortality in non-ST-segment elevation myocardial infarction patients with heart failure. The aim of our study was to compare the clinical characteristics, outcomes and causes of death of patients according to their heart failure status at admission in a large non-ST-segment elevation myocardial infarction population with planned early invasive management.METHODSWe performed a post-hoc analysis of the Treatment of Acute Coronary Syndrome with Otamixaban randomised trial which included non-ST-segment elevation myocardial infarction patients with systematic coronary angiography within 72 h. Patients were categorised according to presence or absence of heart failure (Killip grade ≥2) at admission.RESULTSA total of 13,172 patients were enrolled, of whom 944 (7.2%) had heart failure. At day 30, death occurred in 213 patients (1.6%) and cardiovascular death was the dominant cause of death in both groups ((with vs without heart failure) 78.8% vs 78.4%, p = 0.94). At six months, death occurred in 90/944 (9.5%) patients with heart failure and 258/12228 patients without heart failure (2.1%) (p < 0.001). After adjustment on Global Registry of Acute Coronary Events risk score, heart failure was an independent predictor of all-cause mortality at day 30 (odds ratio: 1.58; 95% confidence interval, 1.06-2.36, p = 0.02) and at day 180 (odds ratio: 1.77; 95% confidence interval, 1.3-2.42, p < 0.001) as well as of ischaemic complications (cardiovascular death, myocardial infarction, stent thrombosis or stroke at day 30 (odds ratio: 1.28; 95% confidence interval, 1.01-1.62, p = 0.04).CONCLUSIONNon-ST-segment elevation myocardial infarction patients with heart failure at admission still have worse outcomes than those without heart failure, even with systematic early invasive strategy. Further efforts are needed to improve the prognosis of these high risk patients.

BACKGROUND:Few data are available on procedural complications of percutaneous coronary intervention (PCI) in the setting of acute coronary syndrome in the contemporary era. AIM:We sought to describe the prevalence of procedural complications of PCI in a non-ST-segment elevation acute coronary syndrome (NSTE ACS) cohort, and to identify their clinical characteristics and association with clinical outcomes. METHODS:Patients randomized in TAO (Treatment of Acute coronary syndrome with Otamixaban), an international randomized controlled trial (ClinicalTrials.gov Identifier: NCT01076764) that compared otamixaban with unfractionated heparin plus eptifibatide in patients with NSTE ACS who underwent PCI, were included in the analysis. Procedural complications were collected prospectively, categorized and adjudicated by a blinded Clinical Events Committee, with review of angiograms. A multivariable model was constructed to identify independent clinical characteristics associated with procedural complications. RESULTS:A total of 8656 patients with NSTE ACS who were enrolled in the TAO trial underwent PCI, and 451 (5.2%) experienced at least one complication. The most frequent complications were no/slow reflow (1.5%) and dissection with decreased flow (1.2%). Procedural complications were associated with the 7-day ischaemic outcome of death, myocardial infarction or stroke (24.2% vs. 6.0%, odds ratio 5.01, 95% confidence interval 3.96-6.33; P<0.0001) and with Thrombolysis In Myocardial Infarction major and minor bleeding (6.2% vs. 2.3%, odds ratio 2.79, 95% confidence interval 1.86-4.2; P<0.0001). Except for previous coronary artery bypass grafting, multivariable analysis did not identify preprocedural clinical predictors of complications. CONCLUSIONS:In a contemporary NSTE ACS population, procedural complications with PCI remain frequent, are difficult to predict based on clinical characteristics, and are associated with worse ischaemic and haemorrhagic outcomes.

effectiveness is huge and that there is an ethical obligation both of means and of results in tobacco control.Let's hope that the work of Bonaldi et al. will be followed by medico-economic analyses and by further analysis considering all health events attributable to smoking, both morbid and fatal.Let's hope that this work will be widely disseminated, motivating decision-makers to take more drastic and effective measures to fight, and thus denormalize the consumption of this poison.

L’âge et les comorbidités cardiovasculaires sont des facteurs indépendants de mortalité et d’hospitalisation en unité de soins intensifs chez les patients atteints de coronavirus 19 (COVID-19), contrairement à l’hypertension artérielle (HTA).

Las enfermedades cardiovasculares son la primera causa de mortalidad en el mundo. Se estima en 17,7 millones el número de fallecimientos imputables a las enfermedades cardiovasculares, es decir, el 31% de la mortalidad mundial total. El paciente coronario demostrado es un paciente con un riesgo cardiovascular muy alto. La prevención secundaria tiene por objetivo limitar el crecimiento de la placa de ateroma y la aparición de síndrome coronario agudo, con el fin de limitar los síntomas y mejorar el pronóstico y la supervivencia. La prevención secundaria pasa por el control de los factores de riesgo cardiovascular, al que se añade el tratamiento medicamentoso, que comprende de manera inevitable un antiagregante plaquetario y estatinas, pero también, después de un infarto con disfunción ventricular izquierda, betabloqueantes e inhibidores del sistema renina-angiotensina. A lo largo de los últimos años, las clases medicamentosas se han diversificado, como los nuevos antiagregantes plaquetarios y los nuevos anticoagulantes orales directos. Otros han visto la luz, como los anticuerpos anti-PCSK9 con un objetivo hipocolesterolemiante. Los tratamientos específicos de los factores de riesgo cardiovascular también se han desarrollado. Por lo tanto, el tratamiento prolongado del paciente coronario ha evolucionado mucho y tiende hacia un control más complejo y más personalizado.

Les bétabloquants ont révolutionné le pronostic de l’infarctus du myocarde avec un bénéfice majeur sur la mortalité. Les études randomisées validant incontestablement cet intérêt sont anciennes et remontent à une période où reperfusion coronaire, aspirine et statines ne faisaient pas partie de l’arsenal thérapeutique. Les bétabloquants ont également amélioré les symptômes angineux des coronariens stables faisant de cette classe médicamenteuse le traitement de première intention de l’angor. Mais il n’existe aucune étude randomisée validant l’intérêt pronostique des bétabloquants dans ce que l’on appelait maladie coronaire stable et qui s’intitule désormais syndrome coronaire chronique. Depuis quarante ans et avec les nombreuses innovations thérapeutiques, le spectre de toute la maladie coronaire a évolué et avec lui son pronostic. Les coronariens aujourd’hui diffèrent totalement des coronariens des années quatre-vingt. Les dernières études observationnelles ont suggéré que dans le post-infarctus sans dysfonction ventriculaire gauche, les bétabloquants étaient associés à un meilleur pronostic jusqu’à un an post-infarctus. Au-delà, ils étaient associés à un effet neutre sur le pronostic cardiovasculaire. Dans le syndrome coronaire chronique, les dernières études observationnelles ont suggéré qu’en l’absence de dysfonction ventriculaire gauche, les bétabloquants n’étaient pas associés à un meilleur pronostic. Ils ne l’étaient qu’en cas d’antécédent d’infarctus de moins d’un an. L’intérêt pronostique des bétabloquants dans la maladie coronaire a évolué. Ce changement peut être lié à une évolution de la maladie coronaire elle-même puisqu’elle s’est dissociée de l’insuffisance cardiaque avec altération de fonction ventriculaire gauche. De nouvelles études randomisées sont donc indispensables pour statuer sur le sort des bétabloquants en prévention secondaire coronaire.

Aims Risk estimation is important to motivate patients to adhere to treatment and to identify those in whom additional treatments may be warranted and expensive treatments might be most cost effective. Our aim was to develop a simple risk model based on readily available risk factors for patients with stable coronary artery disease (CAD). Methods and results Models were developed in the CLARIFY registry of patients with stable CAD, first incorporating only simple clinical variables and then with the inclusion of assessments of left ventricular function, estimated glomerutar filtration rate, and haemoglobin levels. The outcome of cardiovascular death over similar to 5 years was analysed using a Cox proportional hazards model. Calibration of the models was assessed in an external study, the CORONOR registry of patients with stable coronary disease. We provide formulae for calculation of the risk score and simple integer points-based versions of the scores with associated took-up risk tables. Only the models based on simple clinical variables provided both good c-statistics (0.74 in CLARIFY and 0.80 or over in CORONOR), with no lack of calibration in the external dataset. Conclusion Our preferred model based on 10 readily available variables [age, diabetes, smoking, heart failure (HF) symptom status and histories of atrial fibrillation or flutter, myocardial infarction, peripheral arterial disease, stroke, percutaneous coronary intervention, and hospitalization for HF] had good discriminatory power and fitted well in an external dataset.

Betablockers have revolutionized the prognosis of myocardial infarction with a major benefit on mortality. The randomised studies that clearly validate this interest are old and date back to a period when coronary reperfusion, aspirin and statins were not part of the treatment. Betablockers also improved symptoms in stable coronary patients, making this drug class the first-line treatment for angina. However, there are no randomised studies validating the prognostic interest of betablockers in what used to be called stable coronary artery disease, and today kown as chronic coronary syndrome. Over the last forty years and with numerous therapeutic innovations, the spectrum and prognosis of coronary disease evolved and with it its prognosis. Coronary artery disease patients today are totally different from those of the eighties. In post-infarction without left ventricular dysfunction, the latest observational studies suggested that betablockers were associated with a better prognosis up to one-year post-infarction. Beyond that, they were associated with a neutral effect on cardiovascular prognosis. In chronic coronary syndrome, the latest observational studies suggested that in the absence of left ventricular dysfunction, betablockers were not associated with a better prognosis. They were only associated with a better prognosis in the case of a previous infarction of less than one year. The prognostic interest of betablockers in coronary disease has changed. This change might be linked to an evolution of the coronary disease itself since it has become dissociated from heart failure with impaired left ventricular function. New randomised studies are therefore essential to update the interest of betablockers in secondary coronary prevention. (C)2021 l'Academie nationale de medecine. Published by Elsevier Masson SAS. All rights reserved.

The prevalence, and prognostic implication of left bundle branch block (LBBB) in general population and patients admitted for acute myocardial infarction (MI) as been extensively studied. However, data are scarce about patients with stable coronary artery disease (CAD) and it remains unclear whether LBBB is only a marker of a severe cardiomyopathy or an independent predictor of events in these patients. We aimed to describe the prevalence, incidence and prognostic implications of LBBB in patients with stable CAD. Additionally, we aimed to describe the incidence of newly diagnosed LBBB that occurred without recent myocardial infarction. CLARIFY is an international registry of more than 30.000 patients with stable CAD. LBBB was collected at baseline and at each follow-up visit, and patients were considered to have LBBB if the length of the QRS complex was of more than 120 milliseconds. Patients with previous pacemaker implantation of internal cardiac defibrillator were excluded. The primary outcome was a composite of cardiovascular (CV) Death, MI or stroke, and secondary outcomes included hospitalization for heart failure (HF) or the need for pacemaker implantation. From the 23.457 patients with available data regarding LBBB status, 1.041 (4.4%) had LBBB at baseline and 1.237 (5.3%) had at least one LBBB assessed during 5-year follow-up. Only 21 patients with newly diagnosed LBBB overtime, had a documented MI the same year. Compared to patients without LBBB, patients with LBBB had a higher risk profile regarding age (67.2±10.1 versus 63.6±10.4 years, p<0.0001), history of coronary artery bypass grafting (29.2% vs 23.7%, p<0.0001), diabetes (35.1% vs 28.4%, p<0.0001), and HF (25.2% vs 16.8%, p<0.0001) (Table). In unadjusted analysis, patients with LBBB had a higher risk of primary outcome (13.4% vs 8.7%, p<0.0001) and each secondary outcome. In multivariate analysis taking into account several possible confounders, there was no difference in the rate of CV death, MI or stroke between LBBB or no-LBBB patients (adjusted HR 1.04, 95% CI 0.85–1.29). However, patients with LBBB had a higher rate of pacemaker implantation (adjusted HR 2.21, 95% CI 1.55–3.15, p<0.0001) and hospitalization for HF (adjusted HR 1.53, 95% CI 1.25–1.88, p<0.0001) (Figure). Outcomes according to LBBB status The prevalence of LBBB in patients with stable CAD was 4.4% and 5.3% with 5-year follow-up. The overwhelming majority of newly diagnosed LBBB were not contemporary of documented myocardial infarction. LBBB was not associated with a higher rate of major adverse cardiovascular events, including all cause mortality but with a higher risk of pacemaker implantation and hospitalization for heart failure. To our knowledge this is the first study reporting such results in a broad population of stable CAD patients. None

On 15th April 2019, Parisians watched in shock as Notre-Dame de Paris, the iconic cathedral that has towered over their city for almost 900 years, was engulfed in flames. Although flames destroyed the spire and considerably weakened the structure, no human lives were lost. However, as some amounts of lead volatilized and deposited in the surrounding areas, fears of potential intoxication began to rise. We investigated the impact of this fire on the blood lead levels of adults in Paris according to the distance between the cathedral and where they live or work. The geometric mean of blood lead levels of the study population was 1.49μg/dl (95% CI [1.38–1.62]) with a prevalence of blood lead levels≥5.0μg/dL of 5.0%. Despite the early legitimate fears of intoxication, the fire that destroyed a significant part of the Notre-Dame cathedral did not increase the blood lead levels of adults living and working in the vicinity.

Although most majority of COVID-19 cases are mild as shown in a recent issue of this journal,1Chen J. Qi T. Liu L. Ling Y. Qian Z. Li T. et al.Clinical progression of patients with COVID-19 in Shanghai, China.J Infect. 2020; 80 (Epub 2020 Mar 19PMID: 32171869): e1-e6https://doi.org/10.1016/j.jinf.2020.03.004Abstract Full Text Full Text PDF PubMed Scopus (539) Google Scholar some patients with initial mild to moderate forms of COVID-19, complain of persistent or resurgent symptoms.2Carfì A. Bernabei R. Landi F. Carfì A. et al.Gemelli Against COVID-19 Post-Acute Care Study GroupPersistent symptoms in patients after acute COVID-19.JAMA. 2020; 324 (PMID: 32644129): 603-605https://doi.org/10.1001/jama.2020.12603Crossref PubMed Scopus (2652) Google Scholar Our aim was to describe the clinical, biological and imaging profile of such patients in order to suggest a classification of the symptoms and raise hypotheses about their pathophysiology. We established in May 2020, in COCHIN HOTEL DIEU Hospital of Paris, an out-patient clinic for adult patients with persistent and/or recurrent symptoms after a confirmed COVID-19 and performed a cross-sectional monocenter survey on consecutive patients presenting:1Chen J. Qi T. Liu L. Ling Y. Qian Z. Li T. et al.Clinical progression of patients with COVID-19 in Shanghai, China.J Infect. 2020; 80 (Epub 2020 Mar 19PMID: 32171869): e1-e6https://doi.org/10.1016/j.jinf.2020.03.004Abstract Full Text Full Text PDF PubMed Scopus (539) Google Scholar an initial symptomatic COVID-19 infection virologically confirmed by either a positive SARS-CoV-2 RNA RT-PCR or positive SARS-CoV-2 serology,2Carfì A. Bernabei R. Landi F. Carfì A. et al.Gemelli Against COVID-19 Post-Acute Care Study GroupPersistent symptoms in patients after acute COVID-19.JAMA. 2020; 324 (PMID: 32644129): 603-605https://doi.org/10.1001/jama.2020.12603Crossref PubMed Scopus (2652) Google Scholar who developed prolonged COVID symptoms defined as persistent symptoms (> 2 months after the first day of the initial episode) or resurgent symptoms (at least 3 weeks after the 1st episode). The presence of another obvious cause of symptoms was an exclusion criteria. Clinical characteristics (previous history, COVID symptoms, physical examination) were collected on a structured questionnaire. A SARS-COV-2 serology was routinely requested. SARS-COV-2 RT-PCR assay on nasopharyngeal swabs and other bioassays were requested based on symptoms. Ethics approval was granted by the local Institutional Review Board of Henri-Mondor Hospital (00011558, Approval number 2020-088). All patients included provided an informed consent. Characteristics of the patients were described by n (%) for categorical data and mean (standard deviation SD) or median (inter-quartile range IQR) for continuous data as appropriate. Among 70 consecutive patients with a documented SARS-CoV-2 infection, median age was 45 (range 23–75), 78.6% were female. During the initial episode of COVID-19, the most frequent symptoms were fever, anosmia, headaches and asthenia. Six (8.6%) patients were hospitalized and 2 required oxygen support (Table 1).Table 1Demographic characteristics of the 70 patients presenting with persistent and/or re merging late symptoms of COVID after a documented SARS COV 2 infection.CharacteristicsAvailable dataAll patientsClinical characteristicsAge, years7045 [36–51]Male, No. (%)7015 (21.4)Female, No. (%)7055 (78.6)ProfessionHealthcare worker, No. (%)6919 (27.5)Other, No. (%)6950 (72.5)BMI, kg/m²5323.0 [21.1–27.2]Allergy6934 (49.3)Respiratory allergy, No. (%)6212 (19.4)Asthma, No. (%)623 (3.2)Medicinal allergy6210 (14.5)Other allergy, No622 (2.9)Autoimmune disease, No. (%)709 (12.9)Personal705 (7.1)Familial704 (5.7)Anxiety or psychiatric history703 (4.3)Smoking, No. (%)662 (3.0)Sport practicing, No. (%)5125 (49.0)Virologic confirmation of the 1st SARS COV 2 infectionPositive SARS-CoV-2 RT-PCR positive in rhino pharyngeal swabs4727 (57.4)Positive SARS-CoV-2 IgG positive antibodies6964 (92.3)Positive SARS-CoV-2 RT-PCR and serology27Only a positive SARS-CoV-2 RT-PCR6Only a positive SARS-CoV-2 serology37Values are median [inter-quartile range] or number (percentage %). BMI: Body Mass Index; COVID-19: Coronavirus Disease 2019; No.: number. Open table in a new tab Values are median [inter-quartile range] or number (percentage %). BMI: Body Mass Index; COVID-19: Coronavirus Disease 2019; No.: number. A symptom-free interval was noted between the first episode and the following episodes in 32/65 cases with a mean interval of 25 days (SD=20). During the prolonged phase, 54.3% patients had symptoms that persisted from the 1st episode, 50% that disappeared and reappeared and 75.7% presented new symptoms that were absent during the 1st episode appeared. Characteristics of late symptoms could be classified in 7 main categories (Fig. 1):­Major fatigue or exhaustion for 51 patients (72.9%)­Neurological symptoms, in 54 (77.1%). Those were divided into neuro-cognitive disorders (such as memory, mood or attention disorders), headaches, sensory disturbances (such as balance disorders, tingling, burning sensations and neurogenic pains), or others (swallowing or speech disorders, thermoregulation disorders).­Cardiothoracic symptoms in 50 patients (71.4%): chest pain and tightness, palpitations, cough, dyspnea.­Muscular or/and articular pains for 20 (25.7%).­ENT symptoms: persistent or recurrent anosmia, hyposmia and/or dysgeusia for 21 (30%).­Gastro-intestinal symptoms for 17 (24.3%): diarrhea, nausea/vomiting, epigastric or abdominal pain.­Skin and vascular symptoms in 10 (14.4%). Other symptoms included odynophagia, low-grade fever, rhinorrhea, conjunctivitis suppress. The majority of the patients (n = 63, 90%) had more than three categories of symptoms. The course of symptoms was intermittent in 42.9% of the cases, alternating symptoms-free intervals of a few days or hours with sudden relapses, often worsening after physical or intellectual exercise. During the prolonged COVID-19 phase, the SARS-CoV-2 RT-PCR was still positive in rhino pharyngeal swabs in 11/43 patients and remained positive more than 3 months for 3 subjects (Supplementary Fig. S1). SARS-CoV-2 serology was positive in most of the cases (n = 64/69, 92.8%). Inflammatory proteins (C reactive protein, ferritin, IL-6 levels) were in the normal range or slightly elevated in 10% of the patients. Autoimmune antibodies were absent in 90% patients (data not shown). Cardiac echography and/or MRI, led to the diagnosis of pericarditis and/or myopericarditis in 9 cases. Cerebral CT scan and/or MRI were normal, except in 4 cases. An inflammation of olfactive bulbs was occasionally found in case of persistent or recurrent anosmia. It was striking that these patients had essentially made a benign form of COVID-19 and consisted mainly of young women. The phenotype was dominated by a major fatigue, associated with neurological and cardiovascular symptoms. If some cases may have been related to the involvement of an organ (pericarditis, myocarditis), some symptom groupings in a same patient were suggestive of an autonomic dysfunction. Another striking finding was that the RT-PCR was occasionally detected in rhino pharyngeal swabs during the prolonged episodes although no patient was immunosuppressed and the majority had developed antibodies against SARS-CoV-2. Unfortunately we were not able to perform viral culture (supplementary Fig. S1). The pathophysiology of the persistence of symptoms is currently unknown and probably non univocal. Those observations made us raise several hypotheses. The first one is a viral persistence in the host. The virus could continue to replicate in usual sites, as shown in our study and a few previous series.3Kang H. Wang Y. Tong Z. Liu X. Retest positive for SARS-CoV-2 RNA of "Recovered" patients with COVID-19: persistence, sampling issues, or re-infection?.JMV. 2020; https://doi.org/10.1002/jmv.26114Crossref Scopus (90) Google Scholar,4Goussef M. Penot P. Gallay L. Batisse D. Bouiller K. Collarino R. et al.Clinical recurrences of COVID-19 symptoms after recovery: viral relapse, reinfection or inflammatory rebound?.J Infect. 2020; (S0163-4453(20)30454-0)Abstract Full Text Full Text PDF Scopus (197) Google Scholar It might also have spread elsewhere, via neurological or vascular invasion, in cells reported to express ACE2 receptors such as endothelial cells.5Hamming I. Timens W. Bulthuis M. Lely A. Navis G. van Goor H Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis.J Pathol. 2004; 203: 631-637Crossref PubMed Scopus (4144) Google Scholar A second hypothesis is that of a reinfection. Although a rare event, several cases evidenced by a phylogenetically distinct strain of SARS COV-2, have now been demonstrated.6To K.K., Hung I.F., Ip J.D., Chu A.W., Chan W.M., Tam A.R., Fong C.H., et al. COVID-19 re-infection by a phylogenetically distinct SARS-coronavirus-2 strain confirmed by whole genome sequencing. Clin Infect Dis.;ciaa1275. doi:10.1093/cid/ciaa1275.Google Scholar, 7Van Elslande J., Vermeersch P., Vandervoort K., Wawina-Bokalanga K., Vanmechelen B., Wollants E., et al. Symptomatic SARS-CoV-2 reinfection by a phylogenetically distinct strain, Clin Infect Dis, ciaa1330, https://doi.org/10.1093/cid/ciaa1330.Google Scholar, 8Tillett R., Sevinsky J., Hartley P., Kerwin H., Crawford N., Gorzalski A., et al. Genomic evidence for a case of reinfection with SARS-CoV-2 (2020). Available at SSRN: https://ssrn.com/abstract=3680955 or http://dx.doi.org/10.2139/ssrn.3680955.Google Scholar These reinfections have been shown to occur several months after the 1st episode. Knowing that our population consisted of 27% of health care workers, the hypothesis of a reinfection cannot be excluded. However, the difference in clinical profile between the first infection and the prolonged symptoms does not favor of this hypothesis. A third hypothesis could be that of an inadequate immune response leading to an auto inflammatory chronic condition in genetically predisposed individual. A last hypothesis is that of a condition similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). After SARS epidemic in Hong Kong, a follow-up study of 233 patients infected with SARS showed that 27% met the diagnostic criteria for ME/CSF.9Lam M.H. Wing Y.K. Yu M.W. Leung C.M. Ma R.C. Kong A.P. et al.Mental morbidities and chronic fatigue in severe acute respiratory syndrome survivors: long-term follow-up.Arch Intern Med. 2009; 169 (https://doi.org/): 2142-2147https://doi.org/10.1001/archinternmed.2009.384Crossref PubMed Scopus (477) Google Scholar A subset of patients with prolonged COVID-19 symptoms have symptoms that overlap with ME/CFS. Finally, we cannot exclude at this stage the possibility of a post-traumatic stress induced by the COVID-19 pandemic and/or exacerbated by these symptoms themselves. One strength of this study it that it focused on patients tested positive for SARS-COV-2 infection, in order to reduce the risk of attributing to COVID 19 symptoms that could be of psycho somatic origin. All our patients filled the same questionnaire and were explored similarly in case of neurological symptoms with a cerebral CT scan and/or MRI and a neurologist advice, and in case cardiothoracic symptoms with an echography and/or a cardiac MRI if needed. The limitations are linked to its small sample. Our description could be possibly the tip of the iceberg, only the most affected patients being inclined to visit the clinic. Moreover, our design did not allow us to determine the prevalence of prolonged symptoms. A few recent data establish that more than 20% of patients will present with prolonged symptoms at least for three months among which the fatigue is the predominant symptom although none of them has described precisely the profile of clinical symptoms.2Carfì A. Bernabei R. Landi F. Carfì A. et al.Gemelli Against COVID-19 Post-Acute Care Study GroupPersistent symptoms in patients after acute COVID-19.JAMA. 2020; 324 (PMID: 32644129): 603-605https://doi.org/10.1001/jama.2020.12603Crossref PubMed Scopus (2652) Google Scholar,10Tenforde M.W. Kim S.S. Lindsell C.J. Billig Rose E. Shapiro N.I. Files D.C. et al.Duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health care systems network – United States, March–June 2020.MMWR Morb Mortal Wkly Rep. 2020; 69 (PMID: 32730238; PMCID: PMC7392393): 993-998https://doi.org/10.15585/mmwr.mm6930e1Crossref PubMed Google Scholar In conclusion, although prolonged manifestations of COVID-19 are mostly subjective, the repetition of similar neurological and cardiothoracic complaints and the fact that we observed objective cases of myopericarditis suggests that there is a real prolonged COVID-19 entity. We believe that is crucial to promptly report our results to the scientific community as these patients have an urgent need to be taken into account and supported. While waiting to find a virological, immune or inflammatory and/or genetic signature that could explain the symptoms, it is difficult to recommend a treatment. Standardized and multidisciplinary investigations and a cohort follow-up are urgently needed in order to precisely assess the prevalence of such symptoms after COVID-19, better understand their pathophysiology and natural evolution and evaluate therapeutic approaches. All the authors have read and agreed with the paper's content. No authors have financial or personal conflicts. Neither the work nor any part of its essential substance, tables or figures have been or will be published or submitted to another scientific journal or are being considered for publication elsewhere. The authors would like to thank Mrs Yannie CUVILLIER for technical assistance. We thank all patients who participated in the study. We thank Nicolas DUMESGES for linguistic revision. This study was not sponsored by any external financial support

Direct-acting oral anticoagulants (DOACs) are easier to use, safer than and as effective as vitamin K antagonists (VKA) in the treatment of non-valvular AF (NVAF). Because of their favourable safety profile and easier use than VKAs, DOACs as anti-thrombotic therapy may have a role in the management of chronic coronary syndromes (CCS). To date, few studies have evaluated DOACs in this setting. Initial studies have focused on patients receiving DOACs for NVAF undergoing acute or elective percutaneous coronary intervention who additionally require dual antiplatelet therapy (DAPT). Rivaroxaban 15 mg once daily plus a P2Y12 inhibitor compared with a VKA regimen was associated with a reduction of bleedings (HR 0.59; 95% CI [0.47–0.76]; p<0.001). Rivaroxaban 2.5 mg twice daily plus DAPT up to 12 months followed by rivaroxaban 15 mg once daily plus P2Y12 inhibitor showed similar results. Dabigatran 110 mg twice daily plus a P2Y12 inhibitor versus a VKA regimen was associated with a reduction of bleedings (HR 0.52; 95% CI [0.42–0.63]; p<0.001), after a mean follow-up of 14 months. A dabigatran 150 mg regimen showed similar results. Apixaban 5 mg twice daily plus a P2Y12 inhibitor versus a VKA regimen confirmed at 6 months the safety of DOACs with a reduction of bleedings (HR 0.69; 95% CI [0.58–0.81]; p<0.001 for non-inferiority and superiority). Edoxaban 60 mg once daily plus a P2Y12 inhibitor was non-inferior to a VKA regimen on bleeding outcomes (major bleeding or non-major clinically relevant non-major bleeding) after a 12-month follow-up (HR 0.83; 95% CI [0.65–1.05]; p=0.001 for non-inferiority; p=0.1154 for superiority). Meta-analysis of these four trials confirmed the safety of DOACs regarding bleeding outcomes, but showed a trend toward stent thrombosis for dual antithrombotic therapy using DOACs versus triple antithrombotic therapy using VKAs. DOACs may show promise in the management of high-risk patients with chronic coronary syndromes. In these patients, rivaroxaban 2.5 mg twice daily in addition to aspirin was shown to reduce the composite outcome of cardiovascular death, stroke or MI compared to aspirin alone (HR 0.76; 95% CI [0.66–0.86]; p<0.001). All-cause death, cardiovascular death and stroke were also significantly lower. This benefit was at the cost of an increase in non-fatal bleeding.

Les manifestations persistantes ou résurgentes de COVID-19 survenant plus de 2 à 3 semaines après un premier épisode sont extrêmement diverses et encore mal connues. Une consultation post-COVID a été ouverte à l'Hôtel-Dieu depuis mai 2020 pour les patients (pts) souffrant de symptômes prolongés ou résurgents de COVID. Un recueil était fait selon un questionnaire préétabli, après obtention de l'accord oral des pts. Ils étaient inclus en cas de diagnostic d'infection confirmée à SARS-COV-2 et après exclusion d'un diagnostic différentiel. Le diagnostic de COVID était retenu devant : RT-PCR et/ou une sérologie positive et/ou scanner thoracique initial typique de COVID et/ou contact avec un cas confirmé par PCR associé à 2 signes majeurs (anosmie, toux, fièvre, dyspnée). Parmi les 58 pts vus en consultation entre le 20 mai et le 12 juin 2020, 26 avaient un diagnostic de COVID confirmé par RT-PCR (n = 15), sérologie (n = 8), scanner thoracique typique (n = 1) et/ou présence de deux signes majeurs avec contage (n = 2). Il s'agissait de 19 (73,1 %) femmes et 7 (26,9 %) hommes, d'âge moyen 46 ans (22–75). Quatre sur 23 (15,4 %) pts avaient un antécédent de pathologie auto-immune et 11 (42,3 %) un terrain d'allergie. Les symptômes initiaux les plus fréquemment retrouvés étaient : fièvre (n = 19, 73,1 %), toux (n = 18, 69,2 %), anosmie (n = 17, 65,4 %) et céphalées (n = 16, 61,5 %). Seuls 4/23 (17,4 %) pts ont été hospitalisés. Un intervalle libre entre le 1er épisode et les épisodes suivants a été noté dans 11 cas avec une durée de 13 ± 10 jours, en moyenne. Lors du 2e épisode une persistance des symptômes du premier épisode était notée dans 11 cas, une réapparition de ces mêmes symptômes dans 16 cas et l'apparition de symptômes différents dans 18 cas. Lors des épisodes tardifs, les symptômes étaient intermittents dans 35 % des cas (n = 7/20). 22 patients (84,6 %) étaient apyrétiques. Les symptômes les plus fréquents rapportés étaient : – au moins 1 symptôme neurologique (21 pts, 80,7 %) : psychocognitifs à type de troubles de la mémoire, de la concentration, de l'humeur, somnolence (n = 17) ; sensoriels à type de céphalées, trouble de l'équilibre, fourmillements, brûlure et douleur neurogène (n = 35) ; trouble de la déglutition et de l'élocution (n = 2) et dysrégulation thermique (n = 2) dont 4 ont eu une IRM cérébrale qui est redevenue normale ; – des symptômes cardiovasculaires, pour 20 pts (76,9 %), à type d'oppression et douleurs thoraciques, palpitations, dyspnée d'effort et toux ayant conduit au diagnostic de péricardite et/ou myocardite (n = 5 cas) ; – et une asthénie souvent majeure (16 cas, 61,5 %). La PCR SARS-COV-2 était souvent négative (n = 14/21, 66,7 %) lors que la sérologie SARS-COV-2 était le plus souvent positive (15/23, 65,2 %). Les myopéricardites évoquent un syndrome post infectieux de nature dysimmunitaire, tandis que des recherches approfondies doivent être menées sur les atteintes neurologiques pour lesquelles une atteinte virale directe ne peut être exclue.