0198: Global and regional echocardiographic strain to assess early phase of hypertrophic cardiomyopathy due to sarcomeric mutations

ObjectiveHypertrophic cardiomyopathy (HCM) is a genetic disease with delayed cardiac expression. Our objective was to characterize global and regional LV myocardial strain by two-dimensional imaging in sarcomeric HCM families and hypothesized that early systolic dysfunction, before hyper-trophic stage, may be diagnosed by this technique.Methods and resultsWe analyzed 81 adults: HCM patients with LV hypertrophy (LVH+, n=38), mutation carriers without LV hypertrophy (LVH/G+, n=20), and normal control subjects (n=23). We calculated global longitudinal strain (GLS), regional peak longitudinal strain and the Echo/TDI score (combination of 3 parameters about remodeling and pulse TDI). Age, sex ratio and body surface area were not significantly different between groups. Maximal 2D wall thickness of left ventricle was 10.1±1.6mm in LVH-/G+and not different from controls (9.9±1.2mm). We observed that LV GLS was not different in LVH-/G+as compared to controls (–21.6%±3.2 vs –23.5%±3.3) but was reduced in HCM patients (–15.3%±4.5) although a normal ejection fraction. Interestingly, regional peak longitudinal strain was similar in LVH-/G+and controls except antero-septo-basal segment strain that was decreased in LVH-/G+as compared to controls (–15.6%±7.2 vs –20.0%±3.9, p=0.025). A cut-off of –16% for abnormal strain of antero-septo-basal segment identified LVH-/G+subjects with a sensitivity of 47% and a specificity of 90%. The Echo/TDI score was different in LVH-/G+as compared to controls (p=0.0008) and sensitivity of previous defined cut-off was 83% for identification of LVH-/G+. All LVH-/G+subjects with abnormal regional strain, except one, had abnormal Echo/TDI score.ConclusionWe observed that regional longitudinal strain, but not global strain, was significantly reduced at early stage of HCM. This tool may be useful for clinical evaluation of relatives in daily practice, but does not provide significant additional information as compared to the Echo/TDI score

064 Temporal trends in prescription rates of recommended treatments in chronic heart failure outpatients: a comparison of three French surveys IMPACT RECO I, II & III

BackgroundRecent registries have shown that recommended drugs for the treatment of congestive heart failure (CHF) remain under-prescribed in daily practice.AimsTo compare prescription rates of CHF drugs in three French surveys Impact Reco I, II and III.MethodsWe included outpatients followed by private cardiologists: 1947 in Impact Reco I (2005), 1974 in Impact Reco II (2005/2006) and 1574 in Impact Reco III (2007), with NYHA class II-IV heart failure and a left ventricular ejection fraction < 40%, and we compared treatment modalities. Recommended treatments and target doses were defined according to ESC guidelines.ResultsThere was an improvement in both the rate of prescription, and in the proportion of patients reaching target dose or 50% of target dose of ACE I, ARBs and beta blockers (see table).ConclusionWe observed an improvement with time in the management of CHF outpatients with an increase in prescription rates of recommended CHF drugs, as well as in the dosage used for ACE-I, ARB and beta-blockers,PrescriptionIMPACT I 2005IMPACT II 2005/2006IMPACT III 2007Global population191719741574ACE INumber patients with prescriptionN (%)1361 (71.0)1349 (68.3)1099 (70.2)Target dose%48.757.3*52.3•50% Target dose%80.484.5*88.4†,•ARBsNumber patients with prescriptionN (%)395 (20.6)592 (30.0)*516 (33.3)†,•Target dose%9.17.420.7†,•50% Target dose%52.949.768.6†,•BetablockersNumber patients with prescriptionN (%)1245 (65.2)1382 (70.0)*1229 (78.3)†,•Target dose%18.423.4*25.7†50% Target dose%47.353.5*59.9†•*: p<0.05 Impact II vs I•: p<0.05 Impact III vs II†: p<0.05 Impact III vs Ialthough there is still room for improvement particularly for beta blockers. These encouraging findings suggest a better awareness and implementation of ESC guidelines by French private cardiologists

257 A novel polysaccharide-based porous scaffold for cell delivery into the infarcted heart

BackgroundCellular cardiomyoplasty has been proposed as an attractive strategy to repair myocardial damage. One of the crucial point is the optimal delivery strategy. In the present study, we examined the use of an implantable porous scaffold for promoting bone marrow-derived mesenchymal stem cells (MSCs) survival and functions in a rat model of acute myocardial infarction.Methods and ResultsCardiac patch was based on biodegradable polysaccharides porous scaffold. After ligation of the left anterior coronary artery, the fate of 1x106 GFP+ MSC administered either using cellularized scaffold implantation or direct injection was examined at 1 and 2 months. The number of residual GFP+ cells in the sample studied was estimated on the basis of the fluorescence emitted by a defined number of GFP+ cells used for calibration. Cellularized scaffold allowed a more efficient delivery and the difference with direct injection was significant at 2 months, with respectively 2100±1300×103 and 215±85x103 residual GFP+ cells (p<0.03). Cardiac tissue levels of matrix metalloproteinase-2 and -9 mRNA were similar whatever the administration conditions but a slight increase in the local production of vascular endothelial growth factor was observed at 2 months after patch implantation in comparison to direct injection (p<0.05). In animals having received MSC implemented on scaffold, clusters of GFP+ cells, mainly phenotypically consistent with immature MSC cells, were detected in the peri-infarct area. The increased survival using scaffold was not translated in an improved myocardial remodelling and functions with no significant difference in the LVEDD, LVESD, and FS between the 2 groups as in comparison with animals implanted with non cellularized scaffold.ConclusionsThese findings demonstrate that the implantation of cellularized grafts is safe and effective for delivering mesenchymal stem cells into damaged myocardium, and results in a better cellular engraftment compared to direct injection

Acute respiratory failure in the elderly: etiology, emergency diagnosis and prognosis

INTRODUCTION: Our objectives were to determine the causes of acute respiratory failure (ARF) in elderly patients and to assess the accuracy of the initial diagnosis by the emergency physician, and that of the prognosis. METHOD: In this prospective observational study, patients were included if they were admitted to our emergency department, aged 65 years or more with dyspnea, and fulfilled at least one of the following criteria of ARF: respiratory rate at least 25 minute(-1); arterial partial pressure of oxygen (PaO(2)) 70 mmHg or less, or peripheral oxygen saturation 92% or less in breathing room air; arterial partial pressure of CO(2 )(PaCO(2)) ≥ 45 mmHg, with pH ≤ 7.35. The final diagnoses were determined by an expert panel from the completed medical chart. RESULTS: A total of 514 patients (aged (mean ± standard deviation) 80 ± 9 years) were included. The main causes of ARF were cardiogenic pulmonary edema (43%), community-acquired pneumonia (35%), acute exacerbation of chronic respiratory disease (32%), pulmonary embolism (18%), and acute asthma (3%); 47% had more than two diagnoses. In-hospital mortality was 16%. A missed diagnosis in the emergency department was noted in 101 (20%) patients. The accuracy of the diagnosis of the emergency physician ranged from 0.76 for cardiogenic pulmonary edema to 0.96 for asthma. An inappropriate treatment occurred in 162 (32%) patients, and lead to a higher mortality (25% versus 11%; p < 0.001). In a multivariate analysis, inappropriate initial treatment (odds ratio 2.83, p < 0.002), hypercapnia > 45 mmHg (odds ratio 2.79, p < 0.004), clearance of creatinine < 50 ml minute(-1 )(odds ratio 2.37, p < 0.013), elevated NT-pro-B-type natriuretic peptide or B-type natriuretic peptide (odds ratio 2.06, p < 0.046), and clinical signs of acute ventilatory failure (odds ratio 1.98, p < 0.047) were predictive of death. CONCLUSION: Inappropriate initial treatment in the emergency room was associated with increased mortality in elderly patients with ARF

Repurposing Metformin in Nondiabetic People With HIV:Influence on Weight and Gut Microbiota

Background. People with HIV (PWH) taking antiretroviral therapy (ART) may experience weight gain, dyslipidemia, increased risk of non-AIDS comorbidities, and long-term alteration of the gut microbiota. Both low CD4/CD8 ratio and chronic inflammation have been associated with changes in the gut microbiota of PWH. The antidiabetic drug metformin has been shown to improve gut microbiota composition while decreasing weight and inflammation in diabetes and polycystic ovary syndrome. Nevertheless, it remains unknown whether metformin may benefit PWH receiving ART, especially those with a low CD4/CD8 ratio. Methods. In the Lilac pilot trial, we recruited 23 nondiabetic PWI I receiving ART for more than 2 years with a low CD4/CD8 ratio ( Results. Metformin decreased weight in PWH, and weight loss was inversely correlated with plasma levels of the satiety factor GDF-15. Furthermore, metformin changed the gut microbiota composition by increasing the abundance of anti-inflammatory bacteria such as butyrate-producing species and the protective Akkermansia muciniphila. Conclusions. Our study provides the first evidence that a 12-week metformin treatment decreased weight and favored anti-inflammatory bacteria abundance in the microbiota of nondiabetic ART-treated PWH. Larger randomized placebo-controlled clinical trials with longer metformin treatment will be needed to further investigate the role of metformin in reducing inflammation and the risk of non-AIDS comorbidities in ART-treated PWH

Colostrum is required for the postnatal ontogeny of small intestine innate lymphoid type 2 cells and successful anti‐helminth defences

No abstract available

Estimation and application of the thermodynamic properties of aqueous phenanthrene and isomers of methylphenanthrene at high temperature

Estimates of standard molal Gibbs energy (ΔGf°) and enthalpy (ΔHf°) of formation, entropy (S°), heat capacity (Cp°) and volume (V°) at 25 °C and 1 bar of aqueous phenanthrene (P) and 1-, 2-, 3-, 4- and 9-methylphenanthrene (1-MP, 2-MP, 3-MP, 4-MP, 9-MP) were made by combining reported standard-state properties of the crystalline compounds, solubilities and enthalpies of phenanthrene and 1-MP, and relative Gibbs energies, enthalpies and entropies of aqueous MP isomers from published quantum chemical simulations. The calculated properties are consistent with greater stabilities of the β isomers (2-MP and 3-MP) relative to the α isomers (1-MP and 9-MP) at 25 °C. However, the metastable equilibrium values of the abundance ratios 2-MP/1-MP (MPR) and (2-MP + 3-MP)/(1-MP + 9-MP) (MPI-3) decrease with temperature, becoming <1 at ~375–455 °C. The thermodynamic model is consistent with observations of reversals of these organic maturity parameters at high temperature in hydrothermal and metamorphic settings. Application of the model to data reported for the Paleoproterozoic Here’s Your Chance (HYC) Pb–Zn–Ag ore deposit (McArthur River, Northern Territory, Australia) indicates a likely effect of high-temperature equilibration on reported values of MPR and MPI-3, but this finding is contingent on the location within the deposit. If metastable equilibrium holds, a third aromatic maturity ratio, 1.5 × (2-MP + 3-MP)/(P + 1-MP + 9-MP) (MPI-1), can be used as a proxy for oxidation potential. Values of log aH2(aq) determined from data reported for HYC and for a sequence of deeply buried source rocks are indicative of more reducing conditions at a given temperature than those inferred from data reported for two sets of samples exposed to contact or regional metamorphism. These results are limiting-case scenarios for the modeled systems that do not account for effects of non-ideal mixing or kinetics, or external sources or transport of the organic matter.Nevertheless, quantifying the temperature dependence of equilibrium constants of organic reactions enables the utilization of organic maturity parameters as relative geothermometers at temperatures higher than the nominal limits of the oil window

EClinicalMedicine

BACKGROUND: As mortality remains high for patients with Ebola virus disease (EVD) despite new treatment options, the ability to level up the provided supportive care and to predict the risk of death is of major importance. This analysis of the EVISTA cohort aims to describe advanced supportive care provided to EVD patients in the Democratic Republic of the Congo (DRC) and to develop a simple risk score for predicting in-hospital death, called PREDS. METHODS: In this prospective cohort (NCT04815175), patients were recruited during the 10(th) EVD outbreak in the DRC across three Ebola Treatment Centers (ETCs). Demographic, clinical, biological, virological and treatment data were collected. We evaluated factors known to affect the risk of in-hospital death and applied univariate and multivariate Cox proportional-hazards analyses to derive the risk score in a training dataset. We validated the score in an internal-validation dataset, applying C-statistics as a measure of discrimination. FINDINGS: Between August 1(st) 2018 and December 31(th) 2019, 711 patients were enrolled in the study. Regarding supportive care, patients received vasopressive drug (n = 111), blood transfusion (n = 101), oxygen therapy (n = 250) and cardio-pulmonary ultrasound (n = 15). Overall, 323 (45%) patients died before day 28. Six independent prognostic factors were identified (ALT, creatinine, modified NEWS2 score, viral load, age and symptom duration). The final score range from 0 to 13 points, with a good concordance (C = 86.24%) and calibration with the Hosmer-Lemeshow test (p = 0.12). INTERPRETATION: The implementation of advanced supportive care is possible for EVD patients in emergency settings. PREDS is a simple, accurate tool that could help in orienting early advanced care for at-risk patients after external validation. FUNDING: This study was funded by ALIMA

Atlas of the clinical genetics of human dilated cardiomyopathy

[Abstract] Aim. Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort. Methods and results. In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is considerably high. Of note, we find that >38% of patients have compound or combined mutations and 12.8% have three or even more mutations. When comparing patients recruited in the eight participating European countries we find remarkably little differences in mutation frequencies and affected genes. Conclusion. This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide a sound database of the genetic causes of DCM.Hôpitaux de Paris; PHRC AOM0414