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Resume Introduction Des reactions paradoxales de type « sarcoidose-like » ont ete rapportees apres traitement par anti-Tumor Necrosis Factor α (anti-TNFα). Les presentations cliniques sont variees mais le plus souvent comportent une atteinte mediastino-pulmonaire typique. Plus rarement, des localisations granulomateuses isolees ont ete decrites pouvant toucher differents organes, posant un probleme diagnostic. Cas clinique Nous rapportons le cas d’une reaction granulomateuse paradoxale de la valve mitrale chez un patient de 26 ans, traite par etanercept pour une polyarthrite rhumatoide (PR). Devant la persistance de signes d’activite de la maladie, malgre un traitement associant leflunomide, et faible corticotherapie, un traitement par etanercept a ete ajoute. Ce patient n’avait pas d’antecedent de tuberculose, ni de contage tuberculeux et le scanner thoracique etait normal. Apres 3 mois d’etanercept, une remission etait obtenue mais a 6 mois, sont survenues des cephalees avec scotomes du champ visuel droit et des vertiges sans fievre. L’IRM cerebrale a revele 3 infarctus recents. L’echographie cardiaque a montre une masse mobile sur la valve mitrale posterieure, evocatrice de vegetation. Le taux de proteine C reactive etait de 8 mg/L et tous les prelevements a la recherche d’un agent infectieux etaient negatifs. Le leflunomide et l’etanercept ont ete arretes, une antibiotherapie probabiliste debutee et une resection avec plastie de la valve mitrale realisee 2 jours plus tard. L’analyse histologique de la valve a revele de volumineux granulomes epithelioides non caseeux a centre necrotique « de type suppure ». Apres avoir elimine une endocardite infectieuse, une sarcoidose, une valvulite rhumatismale et une reaction de type lupus induit par les anti-TNF, le diagnostic de reaction paradoxale aux anti-TNF a ete retenu. Apres 4 semaines d’antibiotherapie le patient n’avait pas de recidive cardiaque ni de sequelle neurologique. En revanche, il a presente une nouvelle poussee de PR. Apres discussion collegiale, un traitement par tocilizumab a ete instaure en monotherapie sans traitement antibiotique preventif. Apres 2 ans de recul, le patient etait toujours en remission sous ce traitement. Conclusion Ce cas illustre la possibilite d’une reaction paradoxale granulomateuse isolee limitee a une valve cardiaque au cours d’un traitement par anti-TNF, ici l’etanercept.

Aims To estimate the effect of prophylactic angiotensin-converting enzyme inhibitors (ACEi) on survival in Duchenne muscular dystrophy (DMD). Methods and results We analysed the data from the French multicentre DMD Heart Registry (ClinicalTrials.gov: NCT03443115). We estimated the association between the prophylactic prescription of ACEi and event-free survival in 668 patients aged 8 to 13 years, with normal left ventricular function, using (i) a Cox model with intervention as a time-dependent covariate, (ii) a propensity-based analysis comparing ACEi treatment vs. no treatment, and (iii) a set of sensitivity analyses. The study outcomes were overall survival and hospitalizations for heart failure (HF) or acute respiratory failure. Among the 668 patients included in the DMD Heart Registry, 576 (mean age 6.1 ± 2.8 years) were eligible for this study, of whom 390 were treated with ACEi prophylactically. Death occurred in 53 patients (13.5%) who were and 60 patients (32.3%) who were not treated prophylactically with ACEi, respectively. In a Cox model with intervention as a time-dependent variable, the hazard ratio (HR) associated with ACEi treatment was 0.49 [95% confidence interval (CI) 0.34–0.72] and 0.47 (95% CI 0.31–0.17) for overall mortality after adjustment for baseline variables. In the propensity-based analysis, 278 patients were included in the treatment group and 834 in the control group, with 18.5% and 30.4% 12-year estimated probability of death, respectively. ACEi were associated with a lower risk of death (HR 0.39; 95% CI 0.17–0.92) and hospitalization for HF (HR 0.16; 95% CI 0.04–0.62). All other sensitivity analyses yielded similar results. Conclusion Prophylactic ACEi treatment in DMD was associated with a significantly higher overall survival and lower rates of hospitalization for HF.

Background An accurate estimation of the duration of atrial fibrillation is critical for its safe management. Recent studies suggested that copeptin, carbohydrate antigen-125, galectin-3 and growth differentiation factor-15 are increased in atrial fibrillation. We examined the ability of these markers to identify patients presenting with atrial fibrillation of ≤48 versus >48 h duration. Methods Retrospective analysis of a prospective study that included patients with atrial fibrillation of known duration. Results A total of 98 patients were analysed, 47 with atrial fibrillation ≤48 h and 51 with >48 h. In patients presenting with atrial fibrillation of ≤48 versus >48 h duration, the mean carbohydrate antigen-125 concentration was 16.9 ± 12.5 versus 30.9 ± 36.3 U/mL ( P = 0.01), and growth differentiation factor-15 concentration was 1320 ± 889 versus 2608 ±2163 pg/mL ( P Conclusion The plasma concentrations of carbohydrate antigen-125, growth differentiation factor-15 and copeptin, but not galectin-3, are higher in patients presenting with atrial fibrillation of >48 h duration than in those with atrial fibrillation ≤48 h. The ability to discriminate recent atrial fibrillation offered by carbohydrate antigen-125 and growth differentiation factor-15 seems high.

In patients admitted for acute myocardial infarction, the communication and transition from specialists to primary care physicians is often delayed, and the information imparted to subsequent healthcare providers (HCPs) may be sub-optimal. A French group of cardiologists, lipidologists and diabetologists decided to establish a consensus to optimize the discharge letter after hospitalization for acute myocardial infarction. The aim is to improve both the timeframe and the quality of the content transmitted to subsequent HCPs, including information regarding baseline assessment, procedures during hospitalization, residual risk, discharge treatments, therapeutic targets and follow-up recommendations in compliance with European Society of Cardiology guidelines. A consensus was obtained regarding a template discharge letter, to be released within two days after patient’s discharge, and containing the description of the patient’s history, risk factors, acute management, risk assessment, discharge treatments and follow-up pathway. Specifically for post acute MI patients, tailored details are necessary regarding the antithrombotic regimen, lipid-lowering and anti-diabetic treatments, including therapeutic targets. Lastly, the follow-up pathway needs to be precisely mentioned in the discharge letter. Additional information such as technical descriptions, imaging, and quality indicators may be provided separately. A template for a standardized discharge letter based on 8 major headings could be useful for implementation in routine practice and help to improve the quality and timing of information transmission between HCPs after acute MI.

This study aimed to determine the results of INR monitoring in patients on vitamin K antagonists (VKAs) and the time in therapeutic range (TTR) in 'real-world' settings.Retrospective analysis of 836,857 INR measurements performed in adults from February 2010 to August 2015 in two districts in the French Brittany region.Of the 836,857 INR measurements, 94.9% were ordered by general practitioners and 2.0% by cardiologists. The number of tests increased by 10-year age categories up to the age-group of 80-90 years. The number of INR measurements increased from 169,636 in 2011 to 176,184 in 2012, but then decreased slightly to 162,597 in 2013 and 164,427 in 2014. Mean coefficient of variation of INR was 19.0%, and mean TTR was 29.0%. TTR was higher in women than in men (31% vs. 18%), in older than in younger patients (19.1% at 40 years and 38.6% at 100 years) and in patients with arrhythmias than in those with deep vein thrombosis/pulmonary embolism (44.4% versus 19.4%) (p 10VKAs are still frequently prescribed in this era of direct oral anticoagulants. The low TTR cannot be explained by inadequate INR monitoring.

Background Despite widespread investigation into the incidence of acute myocardial infarction during the COVID-19 pandemic and associated lockdown, no study has examined the situation's impact on blood pressure (BP) levels. Methods Measurements of BP and heart rate (HR) were obtained from persons living in the Paris urban area using connected home BP monitors (accessible to patients and health providers through a secured server). Three time periods of e-Health recordings were compared: during the pandemic prior to the lockdown, during the lockdown and the same time period in 2019. Results A total of 297,089 BP recordings from 2,273 participants (age 56.3±12.8 years, 81.1% male) were made. During confinement, systolic BP gradually decreased by 3 mmHg (−2.4 to −3.9), and diastolic BP, by 1.5 mmHg (−1.4 to −2.2) (all p Conclusion Among a very large cohort, we observed a significant decrease in home BP measured with e-Health devices during the first lockdown period. This study emphasizes the research potential of e-Health during the Covid crisis. Funding Acknowledgement Type of funding sources: None. Changes in BP during the French Lockdown

Background Natriuretic peptides (NPs) are widely used in the diagnosis and risk stratification of heart failure (HF).NPs may have a reduced discriminative ability in the subgroup of elderly patients. Methods We examined all biological tests performed from February 2010 to August 2015 in two districts in the French Brittany. We report the “real-world” use of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in an elderly population and examine the measured concentration and potential impact of the cut-off value's selection. Results From a total of 3,606,432 tests ordered in 557,650 adult patients, 56,653 included at least one NT-proBNP measurement. NT-proBNP measurements gradually increased by 10-y age categories up to 80–90 y, and 39,828 (70.3%) of all measurements have been done in patients ≥75y. NT-proBNP concentrations increased with advanced age (Pearson's correlation coefficient: 0.2; p75y (p Conclusion Among a very large cohort, we observed that NT-proBNP is increasingly measured in elderly patients. NT-proBNP concentrations increase with age, and the selection of the threshold value markedly impacts the proportion of “low” versus “high” results. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Roche Diagnostics Proportion (in %) of low NT-proBNP

International audience; Background: Despite widespread investigation into the incidence of acute myocardial infarction during the coronavirus disease 2019 (COVID-19) pandemic and associated lockdown, no study has examined the situation's impact on blood pressure (BP) levels. Methods: Measurements of BP and heart rate (HR) were obtained from persons living in the Paris urban area using connected home BP monitors (accessible to patients and health providers through a secured server). Three time periods of e-health recordings were compared: during the pandemic before the lockdown, during the lockdown, and the same time period in 2019. Results: A total of 297,089 BP recordings from 2,273 participants (age 56.3 ± 12.8 years, 81.1% male) were made. During confinement, systolic BP gradually decreased by 3 mmHg (-2.4 to -3.9), and diastolic BP by 1.5 mmHg (-1.4 to -2.2) (all p < 0.001); this decrease was greater for participants with higher BP (p < 0.0001 each). No significant variation in HR was noted. Conclusion: Among a very large cohort, we observed a significant decrease in home BP measured with e-health devices during the first lockdown period. This study emphasizes the research potential of e-health during the COVID-19 crisis.

Background Natriuretic peptides have broad indications during heart failure and the detection of left ventricular dysfunction in high-risk patients. They can also be used for the diagnosis/management of other cardiac diseases. However, very little is known regarding their use in routine practice. Methods We examined all biological tests performed from February 2010 to August 2015 in two districts from the French Brittany, covering 13,653 km2 and including 22,265 physicians. We report the settings and conditions of N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements (the only locally natriuretic peptide available). Results From a total of 3,606,432 tests requested in 557,650 adult (older than 20 years) patients, only 56,653 (1.6%) included at least one NT-proBNP measurement. NT-proBNP measurements gradually increased, from 9188 in 2011 to 12,938 in 2014 ( P Conclusion Among a very large cohort, we observed that natriuretic peptides remain largely undermeasured. NT-proBNP is mostly measured in elderly patients, and its interpretation may be hazardous in up to 16% of all individuals because no measurement of creatinine was associated to NT-proBNP.

Background: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation. Methods: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as (1) sudden cardiac death or (2) implantable cardioverter defibrillator–treated or hemodynamically unstable VTA. The prognostic model was derived using the Fine-Gray regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (SD) or medians [interquartile range]. Results: We included 444 patients, 40.6 (14.1) years of age, in the derivation sample and 145 patients, 38.2 (15.0) years, in the validation sample, of whom 86 (19.3%) and 34 (23.4%) experienced LTVTA over 3.6 [1.0–7.2] and 5.1 [2.0–9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, nonmissense LMNA mutation, first degree and higher atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction (https://lmna-risk-vta.fr). In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711–0.842), and the calibration slope 0.827. In the external validation sample, the C-index was 0.800 (0.642–0.959), and the calibration slope was 1.082 (95% CI, 0.643–1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA in comparison with the guidelines-based approach. Conclusions: In comparison with the current standard of care, this risk prediction model for LTVTA in laminopathies significantly facilitated the choice of candidates for implantable cardioverter defibrillators. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03058185.

Heart failure (HF) has high event rates, mortality, and is challenging to manage in clinical practice. Clinical management is complicated by complex therapeutic strategies in a population with a high prevalence of comorbidity and general frailty. In the last four years, an abundance of research has become available to support multidisciplinary management of heart failure from within the hospital through to discharge and primary care as well as supporting diagnosis and comorbidity management. Within the hospital setting, recent evidence supports sacubitril-valsartan combination in frail, deteriorating or de novo patients with LVEF ≤ 40%. Furthermore, new strategies such as SGLT2 inhibitors and vericiguat provide further benefit for patients with decompensating HF. Studies with tafamidis report major clinical benefits specifically for patients with ATTR cardiac amyloidosis, a remaining underdiagnosed and undertreated disease. New evidence for medical interventions supports his bundle pacing to reduce QRS width and improve haemodynamics as well as ICD defibrillation for non-ischemic cardiomyopathy. The Mitraclip reduces hospitalisations and mortality in patients with symptomatic, secondary mitral regurgitation and ablation reduces mortality and hospitalisations in patients with paroxysmal and persistent atrial fibrillation. In end-stage HF, the 2018 French Heart Allocation policy should improve access to heart transplants for stable, ambulatory patients and, mechanical circulatory support should be considered to avoid deteriorating on the waiting list. In the community, new evidence supports that improving discharge education, treatment and patient support improves outcomes. The authors believe that this review fills the gap between the guidelines and clinical practice and provides practical recommendations to improve HF management.

Objective: The Covid-19 pandemic has been associated with a marked reduction in the incidence of cardiovascular diseases. The main objective of the study was to quantify the changes in blood pressure (BP) and heart rate (HR) prior to and after initiation of the lockdown Design and method: A big data analysis of BP and HR measurements recorded during the lockdown period versus measurements during the Covid-19 period prior to con finement as well as versus measurements recorded in 2019. All participants were from the Paris urban area. Subjects used a Withings connected home blood pressure monitor and had at least one measurement prior to and during the lockdown and in 2019 Results: A total of 297,089 BP recordings were available from 2273 participants (age 56.3±12.8 years, 81.1% male). Recording frequency was similar before and during the lockdown. BP gradually decreased during the first 4 weeks of con finement reaching a decrease of 3 mmHg (-2.4 to-3.9) in systolic BP (SBP) and 1.5 mmHg (-1.4 to-2.2) in diastolic BP (DBP) from week 4 to week 7 (all p

Objective To study the mortality profile of patients with rheumatoid arthritis (RA) in France. Methods Data were collected between 2000 and 2011 from the French Epidemiological Center for the Medical Causes of Death database; all death certificates from adults that either mentioned RA as an underlying cause of death (UCD) or as an associated cause of death (ACD) were evaluated using multiple-cause-of-death analysis. The different causes of death and their frequency were reported, together with the ratio of observed/expected number of death (O/E ratio) to measure the strength of association between RA listed as an ACD and the corresponding UCD. Results During the study period, 13,208 deaths related to RA were identified. The mean ± SD age at death was 79 ± 9 years (51% with ≥80 years) and the female/male ratio was 3.2. When RA was the UCD ( n = 4597), the main causes of death were cardiovascular (29%) and infectious diseases (22%). When RA was an ACD ( n = 8611), the most common UCDs were cardiovascular diseases (35%), neoplasms (14%), respiratory disease (9%), and infectious diseases (7%). The overall O/E ratio was >1 for infectious (3.58), respiratory (1.38), and cardiovascular diseases (1.25), but was Conclusion We provide the most recent national multiple-cause-of-death analysis assessing the mortality profile of RA patients. Our results show that mortality related to cardiovascular, respiratory, and infectious diseases is highly associated with RA. These data support the need to expand new strategies to prevent infectious and cardiovascular diseases in order to improve survival of RA patients.

Background An accurate estimate of the duration of atrial fibrillation (AF) is critical for its safe and successful management. We examined the ability of midregional pro–atrial natriuretic peptide (MR-proANP) to identify patients presenting with AF of ≤48 vs >48 h in duration. Methods We prospectively studied 106 patients presenting with AF of known duration. We examined the predictive values of MR-proANP and N-terminal pro–brain natriuretic peptide (NT-proBNP) in the detection of recent-onset AF, in addition to other factors identified by multiple variable analyses. Results In patients presenting with AF of ≤48 vs >48 h in duration, the median MR-proANP plasma concentration was 147.7 [95.3–197.4] pmol/L vs 220.4 [154.0–303.1] pmol/L (P Conclusions A score based on a model including heart rate, dyspnea, and plasma MR-proANP concentration was helpful in identifying AF of ≤48 h in duration.

Background Right Ventricular (RV) involvement during inferior acute myocardial infarction (AMI) was known to be associated with poor outcome, but might have been mitigated by recent therapeutics. The aim of study was to determine the characteristics and outcomes of patients with RVAMI compared to isolated inferior AMI. Methods This is an observational study that enrolled consecutive patients with RVAMI; age-sex matched patients with isolated inferior AMI served as controls. Results A total of 51 patients with RVAMI were studied (male 39, age 63 ± 16) and compared to 39 age-sex matched patients with isolated inferior AMI. Atherosclerosis risk factors, previous MI and treatment at presentation were similar in both groups. Primary coronary angioplasty was successful in > 90% in both groups. When compared to patients with isolated inferior AMI, patients with RVAMI had more frequent cardiogenic shock at presentation (35% versus 0%, P P Conclusion RVAMI is still associated with high in-hospital mortality. The severity of initial presentation is not a prognostic factor. Mortality rates after discharge increased very slowly and similarly in both groups.

The presence of a normal atrial electrical activity together with the absence of mechanical atrial activity has been reported after successful cardioversion and is named atrial stunning. In this observation, we report the existence of left but not right atrial stunning.

Objectives: Copeptin and high-sensitivity cardiac troponin (HS-cTn) assays improve the early detection of non-ST-segment elevation myocardial infarction (NSTEMI). Their sensitivities may, however, be reduced in very early presenters.Setting: We performed a post hoc analysis of three prospective studies that included patients who presented to the emergency department for chest pain onset (CPO) of less than 6 hours.Participants: 449 patients were included, in whom 12% had NSTEMI. CPO occurred 4 hours in 146 patients. The prevalence of NSTEMI was similar in all groups (9%, 13% and 12%, respectively, p=0.281).Measures: Diagnostic performances of HS-cTn and copeptin at presentation were examined according to CPO. The discharge diagnosis was adjudicated by two experts, including cardiac troponin I (cTnI). HS-cTn and copeptin were blindly measured.Results: Diagnostic accuracies of cTnI, cTnI +copeptin and HS-cardiac troponin T (HS-cTnT) (but not HS-cTnT +copeptin) lower through CPO categories. For patients with CPO, DC-2009-1052.

The new paradigm of the big data raises many expectations, particularly in the field of health. Curiously, even though medical biology laboratories generate a great amount of data, the opportunities offered by this new field are poorly documented. For better understanding the clinical context of chronical disease follow-up, for leveraging preventive and/or personalized medicine, the contribution of big data analytics seems very promising. It is within this framework that we have explored to use data of a Breton group of laboratories of medical biology to analyze the possible contributions of their exploitation in the improvement of the clinical practices and to anticipate the evolution of pathologies for the benefit of patients. We report here three practical applications derived from routine laboratory data from a period of 5 years (February 2010-August 2015): follow-up of patients treated with AVK according to the recommendations of the High authority of health (HAS), use of the new troponin markers HS and NT-proBNP in cardiology. While the risks and difficulties of using algorithms in the health domain should not be underestimated - quality, accessibility, and protection of personal data in particular - these first results show that use of tools and technologies of the big data repository could provide decisive support for the concept of "evidence based medicine".

Objective Digital ulcers (DU) are a burden in systemic sclerosis (SSc). Microangiopathy is a cardinal feature of SSc that plays a critical role in the development of DU. However, whether injury of medium or large vessels also contributes to DU in SSc remains controversial. Methods To measure concomitantly in SSc patients with and without active DU: (i) the Augmentation Index of the reflected wave (Aix_75) by radial applanation tonometry, an index of small and medium arterial function; (II) the aortic pulse wave velocity (PWV), a marker of large vessel injury (aortic stiffness). Results Sixty-three consecutive SSc patients were included (49 females, aged 60 [49–65] years, disease duration of 8.5 [5–13] years), including 10 (15.9%) with active DU. Patients with active DU versus those without had increased Aix_75 (35% [28–38] versus 28% [20–34], P = 0.041) whereas no difference existed in PWV (7.0 m/s [6.7–10.1] versus 7.6 m/s [6.8–8.7], P = 0.887), in systolic, diastolic, as well as aortic pulse pressure ( P = 0.126, 0.592, and 0.161, respectively). When compared to patients in the low tertile, patients having Aix_75 in the highest tertile had 10-fold more DU (OR = 10.23; 95% CI 1.12 to 93.34, P = 0.039). Conclusion The presence of DU is associated with increased Aix_75 whereas there is no relation with PWV. These data suggest that small and medium arteries are involved in the occurrence of DU whether large vessel stiffness does not contribute. Whether Aix_75 is predictive of further DU remained to be studied.

Heart involvement in systemic sclerosis (SSc) is a strong prognostic factor. Our aim was to examine left ventricle (LV) and right ventricle (RV) involvement.We examined LV and RV, systolic and diastolic functions, using echocardiography and Tissue-Doppler echocardiography (TDE) indexes, in a cohort of 212 consecutive SSc patients seen during a 9-month period at 2 institutions (Paris, France and Los Angeles, USA). They were compared to 50 healthy controls.When compared to controls, SSc patients had consistently impaired RV indices that include reduced RV contractility (p0.001), larger right atrial area (p = 0.027) and overall RV diastolic dysfunction (25% of SSc patients versus 0% of controls; p0.001). Patients also exhibited alterations in LV contractility and diastolic function (p0.001 each). In multivariate analysis, RV contractility as expressed by the TDE S(T) parameter was associated with TDE LV contractility S(M) (p = 0.030), DLCO (p = 0.013) whereas RV diastolic impairment was associated with systolic pulmonary artery pressure (p = 0.015). A subgroup of 27 patients had proven pulmonary arterial hypertension (PAH); comparison between SSc-PAH versus SSc free of PAH patients revealed reduced LV diastolic function (transmitral E/A ratio, p = 0.045 and E(A)10 cm/s, p = 0.029), reduced overall RV contractility (21.5% versus 4.5%; p = 0.03) and reduced RV diastolic function (transtricuspid E/A ratio; p = 0.014 and 68% versus 29% with impaired function; p = 0.001).Our data show that RV is commonly affected in SSc with predominant impaired diastolic function. Several factors, including primary heart, lung vascular disease and pulmonary hypertension, contribute to such impairment.

Objective To measure plasma concentrations of high-sensitivity cardiac troponin T (HS-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with systemic sclerosis (SSc; scleroderma) and age- and sex-matched healthy control subjects, and to examine the contribution of traditional cardiovascular risk factors and SSc features to the concentrations of these 2 cardiac biomarkers. Methods Plasma HS-cTnT and NT-proBNP concentrations were measured using the electrochemiluminescence method and sandwich immunoassay, respectively. Results The study group comprised 161 unrelated patients with SSc and 213 matched control subjects. HS-cTnT and NT-proBNP plasma levels were significantly increased in SSc patients compared with controls (both P 14 ng/liter. Increased NT-proBNP concentrations were associated only with the presence of precapillary pulmonary hypertension (P Conclusion HS-cTnT and NT-proBNP concentrations are increased in patients with SSc, even in those who are free of cardiovascular risk factors. These easily obtained biomarkers may be useful for systematic evaluation and stratification of SSc patients, especially to identify those at risk of pulmonary hypertension.

SummaryCardiac troponin (cTn) assays have quickly gained in analytical sensitivity to become what are termed ‘high-sensitivity cardiac troponin’ (hs-cTn) assays, bringing a flurry of dense yet incomplete literature data. The net result is that cTn assays are not yet standardized and there are still no consensus-built data on how to use and interpret cTn assay results. To address these issues, the authors take cues and clues from multiple disciplines to bring responses to frequently asked questions. In brief, the effective use of hs-cTn hinges on knowing: specific assay characteristics, particularly precision at the 99th percentile of a reference population; factors of variation at the 99th percentile value; and the high-individuality of hs-cTn assays, for which the notion of individual kinetics is more informative than straight reference to ‘normal’ values. The significance of patterns of change between two assay measurements has not yet been documented for every hs-cTn assay. Clinicians need to work hand-in-hand with medical biologists to better understand how to use hs-cTn assays in routine practice.

Aims Duchenne muscular dystrophy (DMD), an inherited X-linked muscular disease, is associated with dilated cardiomyopathy that is responsible for death in 40% of patients. Our objective was to determine whether inotropic reserve is predictive of LV trend over time. Methods and results A total of 69 DMD patients (age 12.2 ± 2.3 years) were investigated. At baseline, LVEF and the presence of inotropic reserve (defined as an increase in LVEF >10% during dobutamine infusion) were investigated using radionuclide ventriculography. During follow-up (FU), LVEF was remeasured after a mean 29 ± 19 months delay. In the whole population, mean LVEF was 58 ± 8% at baseline and declined to 54 ± 11% during FU (P = 0.004). At baseline, 21 patients (30.4%) had LVEF 45% or 55% at baseline. Conclusion Inotropic reserve assessment allows the distinction of DMD patients who will vs. those who will not show a deterioration in LVEF, thus offering a sensitive approach for delineating the presence and progression of cardiovascular disease in these patients.

Cardiac involvement contributes to the severity of SSc and should carefully be investigated and managed in SSc patients. Although it is commonly sub-clinical, once symptomatic it has a poor prognosis. Several complementary tools (circulating biomarkers, electrocardiography, echocardiography, scintigraphy or MRI) allow the assessment of all the various cardiac structures (endocardium, myocardium and pericardium) and heart function. Treatment remains empirical but cardiac trials in SSc can add data to the treatment of this complication.

Background Pacemakers (PM) and implantable cardioverter defibrillators (ICD) may be indicated for sudden death prevention in myotonic dystrophy type 1 (DM1), however the risk of complications after the placement of these devices is unknown. Objective To compare the rate of device-related complications between PM and ICD implantations in patients with DM1. Methods Among 914 patients with DM1 included in the DM1 Heart Registry between January 2000 and January 2010, we retrospectively selected 23 patients who were implanted with an ICD and matched them to 46 controls with a PM on age, gender, and year of device placement. Results Over a 6 years follow-up period, we observed device-related complications in 9 ICD recipients (inappropriate shocks in 5, lead dysfunction in 5, infection in 2) and in 3 PM recipients (lead dysfunction in 3). Patients with an ICD had, compared to those with a PM, higher rates of complications (39.1% vs. 6.5%, p = 0.0006) and more frequent complications requiring hospitalisation and/or re-intervention (respectively 30.4% and 21.7% vs. 0%). Conclusion Our study shows a higher risk of device-related complications after the implantation of an ICD than for a PM in patients presenting with DM1.

ObjectivesTo determine the causes of death and risk factors in systemic sclerosis (SSc).MethodsBetween 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation.ResultsWe identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile.ConclusionCombining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients’ survival.

Aims The aim of this study was to determine whether angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-II receptor blocker (ARB) use is associated with lower rates of cardiovascular events in patients with stable coronary artery disease (CAD) but without heart failure (HF) receiving contemporary medical management. Methods and results Using data from the Reduction of Atherothrombosis for Continued Health (REACH) registry, we examined, using propensity score approaches, relationships between cardiovascular outcomes and ACEI/ARB use (64.1% users) in 20 909 outpatients with stable CAD and free of HF at baseline. As internal control, we assessed the relation between statin use and outcomes. At 4-year follow-up, the risk of cardiovascular death, MI, or stroke (primary outcome) was similar in ACEI/ARB users compared with non-users (hazard ratio, 1.03; 95% confidence interval [CI], 0.91–1.16; P = 0.66). Similarly, the risk of the primary outcome and cardiovascular hospitalization for atherothrombotic events (secondary outcome) was not reduced in ACEI/ARB users (hazard ratio, 1.08; 95% CI, 1.01–1.16; P = 0.04), nor were the rates of any of its components. Analyses using propensity score matching yielded similar results, as did sensitivity analyses accounting for missing covariates, changes in medications over time, or analysing separately ACEI and ARB use. In contrast, in the same cohort, statin use was associated with lower rates for all outcomes. Conclusions Use of ACEI/ARB was not associated with better outcomes in stable CAD outpatients without HF. The benefit of ACEI/ARB seen in randomized clinical trials was not replicated in this large contemporary cohort, which questions their value in this specific subset.

L’evolution rapide des methodes de dosage des troponines cardiaques (cTn) vers une meilleure sensibilite analytique (cTn de haute sensibilite ou cTn HS) s’accompagne de nombreuses donnees de la litterature, mais encore incompletes. En l’absence de standardisation des cTn et de donnees consensuelles sur l’utilisation et l’interpretation des resultats, les auteurs de cette revue proposent, a partir d’une revue de la litterature, et de facon multidisciplinaire, des elements de reponses aux questions frequemment posees. En conclusion, le bon usage des cTn HS repose sur la connaissance : 1) des caracteristiques propres de la methode utilisee, en particulier de la precision obtenue au 99e percentile d’une population de reference ; 2) des facteurs de variation de la valeur du 99e percentile ; 3) de la forte individualite des dosages de cTn HS, pour lesquels la notion de cinetique individuelle est plus informative que la simple reference a des valeurs usuelles. La significativite des variations entre deux dosages n’est pas encore documentee pour toutes les methodes HS. La collaboration entre cliniciens et biologistes est necessaire a une meilleure utilisation des troponines au quotidien.

International audience; In patients admitted for acute coronary syndrome (ACS), the guidelines of the European Society of Cardiology give a Class I, Level A recommendation for the prescription of high-intensity statins to be initiated as early as possible, regardless of the low-density lipoprotein cholesterol (LDL-C) level. Although statins are widely prescribed after ACS, the intensity of therapy and the proportion of patients achieving target LDL-C values are often not in line with recommendations due to a lack of compliance with guidelines by the physicians, a lack of compliance with treatment or poor tolerance by patients, and poor dose adaptation. In this context, a group of French physicians came together to define strategies to facilitate and improve the management of lipid-lowering therapy after ACS. This paper outlines the scientific rationale for the use of statins at the acute phase of ACS, the utility of ezetimibe, the measurement of LDL-C during the course of ACS, the opportunities for detecting familial hypercholesterolaemia and the results of the consensus for the management of lipid-lowering therapy, illustrated in two decision-making algorithms.

Objective.To measure concentrations of high-sensitivity cardiac troponin (HS-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with rheumatoid arthritis (RA) and to examine correlates.Methods.The plasma concentrations of HS-cTnT and NT-proBNP were measured in consecutive patients with RA and compared to values obtained from age-matched and sex-matched healthy controls.Results.We included 236 unrelated patients with RA (192 females, 57 ± 13 yrs) and 213 controls (170 females, 55 ± 15 yrs). Seventy-one patients with RA were free of cardiovascular (CV) risk factors. HS-cTnT and NT-proBNP concentrations were significantly higher in the total cohort of patients with RA (p = 0.03 and p < 0.0001, respectively) and in the subgroup free of CV risk factors (p = 0.02 and p < 0.0001, respectively) compared to controls. In addition, both the total cohort of patients with RA and the subgroup free of CV risk factors were more likely to have levels above the cutoff concentrations of HS-cTnT (p = 0.003 and p = 0.007, respectively) and NT-proBNP (p = 0.0001 and p < 0.0001, respectively) than controls. Patients with RA and increased C-reactive protein (CRP) levels had higher HS-cTnT (p = 0.03) and NT-proBNP (p = 0.02) concentrations. HS-cTnT levels positively correlated with the 28-joint Disease Activity Score (DAS28-CRP; r = 0.2, p = 0.020). Multivariate logistic regression analysis indicated that increased HS-cTnT levels were independently associated with a DAS28-CRP > 5.1 (OR 11.8; 95% CI 1.6–35.5) and a body mass index > 30 kg/m2 (OR 2.7; 95% CI 1.3–5.5).Conclusion.HS-cTnT and NTproBNP are increased in patients with RA, independent of CV risk factors. The association between HS-cTnT, NT-proBNP, and CRP, together with the correlation between HS-cTnT and disease activity, support the link between myocardial injury/dysfunction and inflammation.

Measurements of cardiac troponins (cTn) are yet considered the gold standard method in patients with chest pain. Very recently, high-sensitivity (hs)cTn emerged and allow to measure very low concentrations of cTn. The aim of these assays was the better detection of patients with acute myocardial infarction (AMI). The threshold value should be the 99th percentile of the method, which corresponds to the concentration obtained from 99% of a reference population. These assays improve the detection of patients with elevated cTn concentrations. All patients with increased hs-cTn concentration above the 99th percentile should be considered at high risk of future clinical event when compared to patients with lower concentration. However, these elevated concentrations are not necessarily related to AMI due to coronary artery plaque rupture and superimposed thrombus. In order to understand adequately cTn measurement, the physician should base his interpretation on the context, the cTn concentration, variations during serial sampling, and the possible existence of a coexistent disease characterized by increased cTn concentrations.

Background Concerns have been raised about possible gender disparities in cardiac investigations and/or outcome. This study sought to examine and compare the diagnostic and prognostic performance of selected cardiac biomarkers in women versus men. Methods In a prospective, multicenter cohort of patients with acute chest pain cardiac troponin T (cTnT) (fourth-generation Roche assay), high-sensitivity cTnT (hs-cTnT), and copeptin were measured at presentation. Results Of 1,247 patients, 420 were women and 827 were men. Although the rate of acute myocardial infarction was similar in women (14.5%) and men (16.6%, P = .351), women more frequently had cardiac but noncoronary causes of chest pain (17.4% vs 10.8%, P = .001) and less frequently had unstable angina (8.8% vs 16.6%, P = .002) than men. Diagnostic accuracy as quantified by the area under the receiver operating characteristic curve (AUC) for acute myocardial infarction in women was 0.90 (95% CI 0.84-0.95) for cTnT, which was lower than the AUC for hs-cTnT alone (0.94, 95% CI [0.91-0.98]), the combination of cTnT with copeptin (0.96, 95% CI [0.94-0.98]) or the combination of hs-cTnT with copeptin (0.96, 95% CI [0.93-0.98]) ( P = .008, P = .006, and P = .002, respectively). Prognostic accuracy as quantified by the AUCs for 1-year mortality was 0.69 (0.56-0.83), 0.86 (0.79-0.93), 0.87 (0.81-0.94), and 0.87 (0.80-0.94), respectively. No relevant gender differences in AUCs were observed. Conclusion The diagnostic and prognostic performance of cTnT, hs-cTnT, and copeptin is as good in women as in men. High-sensitivity cTnT and the combination of cTnT and copeptin outperform cTnT alone, both in women and men.

Objectives: To determine the long-term incidence of cardiac life-threatening complications and death in patients with the m.3243A>G mutation, and to identify cardiac prognostic factors. Methods: We retrospectively included patients carrying the m.3243A>G mutation who were admitted to the Neuromuscular Disease Clinic of Pitie Salpetriere Hospital between January 1992 and December 2010. We collected information relative to their yearly neurologic and cardiac investigations, their mutation load in blood, urine, and muscle at initial admission, and the occurrence of cardiac life-threatening adverse events and death during follow-up. Results: Forty-one patients (median age = 47 years [36–55 years], men = 13) were included, of whom 38 had clinical manifestations of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and 3 were asymptomatic. One patient had a personal history of cardiac transplantation. Cardiac investigations displayed left ventricular hypertrophy, left ventricular dysfunction, or both abnormalities in 18 patients, along with Wolff-Parkinson-White syndrome in 7, conduction system disease in 4, and atrial fibrillation in 1. Over a median 5-year (3–9 years) follow-up period, 11 patients died, including 3 due to heart failure; 7 had life-threatening adverse events, including 6 hospitalizations for severe heart failure and 1 resuscitated cardiac arrest. By multivariate analysis, left ventricular hypertrophy was the only parameter independently associated with occurrence of cardiac adverse events. Conclusion: Patients with the m.3243A>G mutation have a high incidence of cardiac death and life-threatening adverse events. Left ventricular hypertrophy was the only parameter independently associated with occurrence of these events.

Objectives Cardiovascular involvement is a major contributor to mortality in systemic sclerosis (SSc). We examined whether N-terminal pro-brain natriuretic peptide (NT-proBNP) is a reliable predictor of mortality in SSc. Methods and results This multicentre prospective cohort study included 523 patients presenting with SSc, whose mean age was 54 ± 13 years, mean disease duration 8 ± 9 years, and diffuse cutaneous form in 168. Plasma NT-proBNP was measured at baseline and the patients were followed yearly. Overall mortality was measured at 3 years. At baseline, cardiovascular involvement was present in 37 patients, including 17 with pulmonary artery hypertension (PAH) and 20 with a left ventricular ejection fraction (LVEF)

Summary Atrial fibrillation (AF) occurs in 5–9% of patients treated with ibrutinib for chronic lymphocytic leukaemia (CLL); the clinical consequences and optimal management are unclear. We retrospectively studied 56 CLL patients who received ibrutinib and developed AF. Median time to onset was 3·8 months. AF was persistent in 35/56 (62%) cases despite treatment. Clinical consequences included: three episodes of severe cardiac failure (one fatal) and one stroke; eight non-thrombocytopenic patients (14%) experienced severe bleeding adverse events. Altogether, ibrutinib was permanently discontinued in 26/56 cases (46%). Data to guide optimal management are lacking and clinical practice guidelines are urgently needed.

Summary Background Hospitalization for worsening/acute heart failure is increasing in France, and limited data are available on referral/discharge modalities. Aim To evaluate patients’ journeys before and after hospitalization for this condition. Methods On 1 day per week, between October 2014 and February 2015, this observational study enrolled 260 consecutive patients with acute/worsening heart failure in all 10 departments of cardiology and four of the departments of geriatrics in the Greater Paris University Hospitals. Results First medical contact was an emergency unit in 45% of cases, a general practitioner in 16% of cases, an emergency medical ambulance in 13% of cases and a cardiologist in 13% of cases; 78% of patients were admitted directly after first medical contact. In-hospital stay was 13.2 ± 11.3 days; intensive care unit stay (38% of the population) was 6.4 ± 5 days. In-hospital mortality was 2.7%. Overall, 63% of patients were discharged home, whereas 21% were transferred to rehabilitation units. A post-discharge outpatient visit was made by only 72% of patients within 3 months (after a mean of 45 ± 28 days). Only 53% of outpatient appointments were with a cardiologist. Conclusion Emergency departments, ambulances and general practitioners are the main points of entry before hospitalization for acute/worsening heart failure. Home discharge occurs in two of three cases. Time to first patient post-discharge visit is delayed. Therefore, actions to improve the patient journey should target primary care physicians and emergency structures, and efforts should be made to reduce the time to the first visit after discharge.