Investigation of Physical-Mechanical Properties and Microstructure of Mortars with Perlite and Thermal-Treated Materials.

This study aimed to obtain and characterize a mortar with perlite aggregate and thermal-treated materials that could substitute for Portland cement. First, the thermally treated materials were obtained by calcinating old Portland cement (OC-tt) and concrete demolition waste (CC-tt) at 550 °C, for 3 h. Second, plastic mortars with a perlite: cement volume ratio of 3:1 were prepared and tested for water absorption, mechanical strength, and thermal conductivity. The microstructure was also analyzed. Portland cement (R) was partially substituted with 10%, 30%, and 50% OC-tt. Thermal-treated materials negatively influenced the compressive and flexural strengths at 7 and 28 days. With an increase in the substitution percentage to 50%, the decrease in the compressive strength was 40% for OC-tt and 62.5% for CC-tt. The presence of 10% OC-tt/CC-tt positively influenced the water absorption. The thermal conductivity of the tested mortars was in the range of 0.37-0.48 W/m·K. SEM analysis shows the expanded perlite pores remained unbroken.

Assessment of Properties and Microstructure of Concrete with Cotton Textile Waste and Crushed Bricks.

Cotton textile waste (CW) and crushed bricks (CB) are wastes generated by the textile and construction industries that cause adverse effects on the environment. This paper explores the effect of adding 1, 2, 5, and 10 wt.% of CW and CB, instead of natural sand under 1 mm (50 to 100 vol.%), on the properties of concrete. The study included the analysis of workability, density, water absorption, thermal conductivity, mechanical strengths, and electron microscopy. The results show that the presence of CW and CB increased the water required to obtain the same slump value as reference, R. Concretes with CW provided better performance in terms of density, water absorption (for 1 wt.%), and splitting strength (for 1 to 2 wt.%). The 28 days of compressive strength decreased with increasing CW (33.3 MPa for R and 26.9 MPa for 2 wt.% of CW). The partial substitution of sand decreased the workability and density and increased the mechanical strength of concrete. The presence of both CW and CB decreased workability, density, and mechanical strengths. Regarding the ability of concrete to transfer heat, the addition of CW and CB decreased the thermal conductivity value (e.g., 0.32 W/(m·K) for 1 wt.% of CW compared to 0.37 W/(m·K) for reference).

COVID-19 crisis and the incidence of hospital admissions for psychosis in France.

OBJECTIVES: We aimed to assess the impact of the COVID-19 crisis on the occurrence of new hospital admissions for cases of psychosis in France. METHOD: We conducted a retrospective observational study from the French national PMSI database. We included patients hospitalized between 2018 and 2020 with a principal diagnosis of schizophrenia or delusional disorder with no history of psychosis in the previous 10 years. In total, we included 77,172 inpatients at crisis centers and/or in full-time hospitalization at 465 French hospitals. We assessed the number of inpatients during the year of the Covid crisis (2020) and the two years prior (2018, 2019). RESULTS: The number of inpatients in full-time hospitalization decreased gradually from 2018 to 2020 by 10.6%. This downward trend was observed in all age groups. In contrast, in crisis centers the number of inpatients increased by 13.4% between 2019 and 2020, while a 7.6% decrease was seen between 2018 and 2019. The greatest increase was observed in the 31-60-year age category, and particularly amongst 46-60-year-olds, i.e. 38.0%. CONCLUSION: The COVID-19 crisis was associated with an increase in the number of inpatients with a new episode of psychosis in crisis centers but not in full-time hospitalization. The profile of patients in crisis centers was different from that seen in preceding years and included more middle-to-late age adults. Particular attention should be given to this category of patients in the crisis environment to prevent the occurrence of new cases of psychosis in France.

Behind the scenes of the healthcare COVID-19 pandemic crisis: potential affecting factors of healthcare work sustainability in Romania during 2020-2022.

Aim: The COVID-19 pandemic represented a great disturbance for medical systems around the world, putting medical personnel on the front lines of the fight against the SARS-Cov2 virus. This fight was particularly impactful in countries with medical systems already facing various challenges, including Romania; where the pandemic unfolded in five waves that severely affected the psychological and physical well-being of medical professionals in terms of overload and continuous exposure to health threats. Against this background, our research aims to identify the mediating role of potential affecting factors of healthcare work sustainability during the change-related uncertainty conditions generated by the COVID 19 crisis. Dynamics and relations of nine carefully selected constructs were tracked along all five pandemic waves in Romania, which span from March 2020 to April 2022. The tested variables and constructs are perception of healthcare workers of their own state of health, their workplace safety, the work-family conflict, the satisfaction of basic needs, the work meaningfulness and work engagement, patient care, pandemic stress and burnout. Methods: This cross-sectional study is based on an online snowball sampling of 738 health workers from 27 hospitals. Panel research is limited to a maximum of 61 respondents for two successive waves. The analytical part is built on means comparison of analysed variables between all five pandemic waves and an in-depth model to explain the relationships between the variables. Results: The results indicate statistically significant correlations between the perception of health risks and all selected factors excluding patient care, which seems to be above the own health perception. The factors' dynamics was followed along all five pandemic waves. The developed model identified that one's health status satisfaction is a mediator of the family-work conflict and, together, of work engagement. In turn, work engagement plays a significant role in satisfying basic psychological needs and supporting work meaningfulness. Also, work meaningfulness influences the satisfaction of basic psychological needs. Discussion: Health workers with higher levels of positive perceived health are better at managing pandemic stress, burnout effects and work-family imbalances. Adaptive behaviors and attitudes towards COVID-19 pandemic threats could be identified in later pandemic waves due to the progress in terms of medical protocols and procedures.

Clinical features and outcomes of COVID-19 patients hospitalized for psychiatric disorders: a French multi-centered prospective observational study.

BACKGROUND: Patients with psychiatric disorders are exposed to high risk of COVID-19 and increased mortality. In this study, we set out to assess the clinical features and outcomes of patients with current psychiatric disorders exposed to COVID-19. METHODS: This multi-center prospective study was conducted in 22 psychiatric wards dedicated to COVID-19 inpatients between 28 February and 30 May 2020. The main outcomes were the number of patients transferred to somatic care units, the number of deaths, and the number of patients developing a confusional state. The risk factors of confusional state and transfer to somatic care units were assessed by a multivariate logistic model. The risk of death was analyzed by a univariate analysis. RESULTS: In total, 350 patients were included in the study. Overall, 24 (7%) were transferred to medicine units, 7 (2%) died, and 51 (15%) patients presented a confusional state. Severe respiratory symptoms predicted the transfer to a medicine unit [odds ratio (OR) 17.1; confidence interval (CI) 4.9-59.3]. Older age, an organic mental disorder, a confusional state, and severe respiratory symptoms predicted mortality in univariate analysis. Age >55 (OR 4.9; CI 2.1-11.4), an affective disorder (OR 4.1; CI 1.6-10.9), and severe respiratory symptoms (OR 4.6; CI 2.2-9.7) predicted a higher risk, whereas smoking (OR 0.3; CI 0.1-0.9) predicted a lower risk of a confusional state. CONCLUSION: COVID-19 patients with severe psychiatric disorders have multiple somatic comorbidities and have a risk of developing a confusional state. These data underline the need for extreme caution given the risks of COVID-19 in patients hospitalized for psychiatric disorders.

Rate and predictors of interrupted patient follow-up after first-episode psychosis - a retrospective cohort study in France.

BACKGROUND: Patient adherence to follow-up after a first episode of psychosis (FEP) is currently a major challenge. Patient's early adherence reduces the risk of relapse and improves their prognosis in the short and long term. The primary goal of our study was to determine the incidence of treatment disengagement at 1-year follow-up in patients with first-episode schizophrenia, schizophreniform or schizoaffective disorder. The secondary goal was to assess the factors associated with treatment disengagement in this patient population. METHODS: We conducted a monocentric retrospective study of 136 patients in France. Relevant information was collected on sociodemographic, pre-morbidities and co-morbidities data, as well as the management and treatment characteristics at 1.3 and 12 months. Survival analysis was used to assess the association between clinical variables, management and treatment disengagement. RESULTS: Eighty-four patients (62%) have interrupted their medical follow-up at 1 year, 16% at 1 month and 34% at 3 months. A higher number of out-patient appointments after a FEP was associated with better adherence (HR:0.85 p < .0001 95% IC = [0.0-0.9]). Initial management seems to play an important role. Involuntary admissions (HR:7.14 p = .015 95% IC = [1.48-34.52]) and total number of admissions (HR:6.86 p < .0001 95% IC = [2.47-19.05]) predict disengagement at 1 month while an increased number of out-patient appointments at 3 months predicts adherence (HR:0.60 p < .0001 95% IC = [0.00-0.74]). Being a single parent is associated with disengagement at 3 months (HR:15.51 p = .022 95% IC = [1.49-161.65]). CONCLUSIONS: Incidence of disengagement is high. It might be necessary to change our management in order to develop out-patient or day-admission care and intensify care for patients at risk.

Sex differences in circulating proteins in heart failure with preserved ejection fraction.

BACKGROUND: Many patients with heart failure with preserved ejection fraction (HFpEF) are women. Exploring mechanisms underlying the sex differences may improve our understanding of the pathophysiology of HFpEF. Studies focusing on sex differences in circulating proteins in HFpEF patients are scarce. METHODS: A total of 415 proteins were analyzed in 392 HFpEF patients included in The Metabolic Road to Diastolic Heart Failure: Diastolic Heart Failure study (MEDIA-DHF). Sex differences in these proteins were assessed using adjusted logistic regression analyses. The associations between candidate proteins and cardiovascular (CV) death or CV hospitalization (with sex interaction) were assessed using Cox regression models. RESULTS: We found 9 proteins to be differentially expressed between female and male patients. Women expressed more LPL and PLIN1, which are markers of lipid metabolism; more LHB, IGFBP3, and IL1RL2 as markers of transcriptional regulation; and more Ep-CAM as marker of hemostasis. Women expressed less MMP-3, which is a marker associated with extracellular matrix organization; less NRP1, which is associated with developmental processes; and less ACE2, which is related to metabolism. Sex was not associated with the study outcomes (adj. HR 1.48, 95% CI 0.83-2.63), p = 0.18. CONCLUSION: In chronic HFpEF, assessing sex differences in a wide range of circulating proteins led to the identification of 9 proteins that were differentially expressed between female and male patients. These findings may help further investigations into potential pathophysiological processes contributing to HFpEF.

Enhanced clinical phenotyping by mechanistic bioprofiling in heart failure with preserved ejection fraction: insights from the MEDIA-DHF study (The Metabolic Road to Diastolic Heart Failure).

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome for which clear evidence of effective therapies is lacking. Understanding which factors determine this heterogeneity may be helped by better phenotyping. An unsupervised statistical approach applied to a large set of biomarkers may identify distinct HFpEF phenotypes.Methods: Relevant proteomic biomarkers were analyzed in 392 HFpEF patients included in Metabolic Road to Diastolic HF (MEDIA-DHF). We performed an unsupervised cluster analysis to define distinct phenotypes. Cluster characteristics were explored with logistic regression. The association between clusters and 1-year cardiovascular (CV) death and/or CV hospitalization was studied using Cox regression.Results: Based on 415 biomarkers, we identified 2 distinct clusters. Clinical variables associated with cluster 2 were diabetes, impaired renal function, loop diuretics and/or betablockers. In addition, 17 biomarkers were higher expressed in cluster 2 vs. 1. Patients in cluster 2 vs. those in 1 experienced higher rates of CV death/CV hospitalization (adj. HR 1.93, 95% CI 1.12-3.32, p = 0.017). Complex-network analyses linked these biomarkers to immune system activation, signal transduction cascades, cell interactions and metabolism.Conclusion: Unsupervised machine-learning algorithms applied to a wide range of biomarkers identified 2 HFpEF clusters with different CV phenotypes and outcomes. The identified pathways may provide a basis for future research.Clinical significanceMore insight is obtained in the mechanisms related to poor outcome in HFpEF patients since it was demonstrated that biomarkers associated with the high-risk cluster were related to the immune system, signal transduction cascades, cell interactions and metabolismBiomarkers (and pathways) identified in this study may help select high-risk HFpEF patients which could be helpful for the inclusion/exclusion of patients in future trials.Our findings may be the basis of investigating therapies specifically targeting these pathways and the potential use of corresponding markers potentially identifying patients with distinct mechanistic bioprofiles most likely to respond to the selected mechanistically targeted therapies.

Empathy and Burnout - A Cross-Sectional Study Among Mental Healthcare Providers in France.

Previous studies have established a correlation between empathy and burnout among healthcare providers. The aim of this study is to explore whether empathy - the ability to understand what another person is experiencing, was related to mental healthcare staffs' burnout. We performed a descriptive, cross-sectional, observational study among medical and nursing mental healthcare staff working in the district of Moselle, France. Participants completed a survey including The French versions of the Jefferson Scale of Empathy (JSPE) and The Maslach Burnout Inventory-Human Services Survey (MBI-HSS). The sample included 241 (n=241) participants (N=420, response rate=51.7%). 187 (77.6%) respondents had low burnout, 43 (17.8%) had intermediate burnout and 11 (4.6%) had high burnout. 41 (17%) had low empathy, 156 (64.7) had moderate empathy and 44 (18.3%) scored high. Empathy scores were positively correlated with scores of personal accomplishment of the MBI-HSS (r=0.2; p<0.001), but negatively correlated with scores of depersonalization (r=-0.2; p<0.003). Highest means of depersonalization (DP) (M=8.7; SD=6.8; p<0.009) and lowest means of compassionate care (M=40.05; SD=7.9; p=0.0001) were found among forensic psychiatric security units staff. Participation in the Omega educational program was associated with lower scores of EE on the MBI-HSS survey (mean score 14.7 versus a mean score of 19.7 for nonparticipants). Empathic mental healthcare providers have lower levels of burnout. Forensic psychiatric staff showed low means of compassionate care and high depersonalization. Interventions designed to foster attributes and skills such as empathy, resilience, and perception of security may be an essential step in reducing and preventing burnout.

[Identification of abuse/dependence cases by the French addictovigilance network (FAN): A pilot study of the addictovigilance center and the psychotherapeutic center of Nancy (France)]. / Identification de cas d'abus/dépendance par le réseau français d'addictovigilance : une étude pilote du CEIP-A et du Centre psychothérapique de Nancy.

OBJECTIVES: France is the only European country with a dedicated addictovigilance network (French addictovigilance network [FAN]). However, the reporting of cases of abuse/dependence is insufficient. In an attempt to overcome this under-reporting, data from the medical information systems program (PMSI) is regularly used to identify cases. Since addictions are frequently associated with psychiatric comorbidities, a pilot study was conducted for the first time in a psychiatric hospital. It aims, through a PMSI request, to identify the sociodemographic characteristics and psychiatric diagnoses of patients consuming psychoactive substances (PAS) and the PAS types consumed. METHODS: This is a retrospective observational study conducted over a nine-month period at the psychotherapeutic center of Nancy (CPN). The codes used for the PMSI request are those of the international classification of diseases, tenth revision (ICD-10), codes F10 to F19 that characterize mental and behavioral disorders associated with the use of PAS. Cases presenting the four criteria necessary for an addictovigilance notification: (1) identified notifier, (2) identified patient, (3) known consumed product (s) and (4) presence of an effect related to the abuse/dependence of PAS; were retained and analyzed. RESULTS: On an initial number of 252 cases, 82 cases of abuse/dependence were retained. The selected sample is predominantly male (67%). Cannabis (29%) and heroin (15%) are the most common illicit PAS. Regarding drugs, the consumption of benzodiazepines, a predominantly female phenomenon, is observed in 34% of subjects. Sixty-four per cent of the subjects were diagnosed "disorders related to the use of PAS", 14% as neurotic disorders, 9% as schizophrenia and 5% as of the mood disorders. CONCLUSION: This study identified a significant number of potentially reportable cases to the French Addictovigilance Network and demonstrated the interest of investigating cases of abuse/dependence in a psychiatric hospital.

Heart rate, pulse pressure and mortality in patients with myocardial infarction complicated by heart failure.

OBJECTIVE: To assess the relationship between heart rate (HR), pulse pressure (PP), and their association with mortality in a population of high-risk patients following acute myocardial infarction (MI). METHODS: We performed an analysis in 22,398 patients included in "The High-Risk Myocardial Infarction Database Initiative", a database of clinical trials evaluating pharmacologic interventions in patients with MI complicated by signs of heart failure (HF) or left ventricular dysfunction. We found an interaction between HR and PP. Based on median HR and median PP, patients were divided in four categories: (1) HR < 75 bpm and PP ≥ 50 mm Hg (reference), (2) HR < 75 bpm and PP < 50 mm Hg, (3) HR ≥ 75 bpm and PP ≥ 50 mm Hg, and (4) HR ≥ 75 bpm and PP < 50 mm Hg. The association between these categories and outcomes was studied using a Cox proportional hazard model. RESULTS: After a median follow-up of 24 (18-33) months, 3561 (16%) patients died of all-causes and 3048 (14%) patients of cardiovascular (CV) causes. In multivariate analysis, patients from the fourth category had the highest risk of all-cause mortality (hazard ratio of 1.69; 95% CI: 1.53-1.86) and CV mortality (hazard ratio of 1.78; 95% CI: 1.60-1.97). CONCLUSIONS: There is an interaction between HR and PP in patients with HF following MI, with the highest risk being conferred by a clinical status with both an elevated HR and a lower PP. These findings identify a high-risk population likely to require an aggressive diagnostic and management strategy.

A history of diabetes predicts outcomes following myocardial infarction: an analysis of the 28 771 patients in the High-Risk MI Database.

AIMS: To examine the impact of diabetes mellitus on long-term clinical outcomes in patients with myocardial infarction (MI) complicated by clinical signs of heart failure (HF) or left ventricular dysfunction (LVD). METHODS AND RESULTS: The High-Risk MI Database consists of individual data from 28 771 patients and was created by merging four large recent randomized clinical trials (VALIANT, EPHESUS, OPTIMAAL, and CAPRICORN) that each examined the impact of pharmacological interventions following MI in patients with evidence of HF or LVD. The mean age of patients was 65 years, 70% were male, and almost 94% Caucasian. Overall, 7368 (26%) had a history of diabetes. All the major outcomes were adjudicated by independent end-point committees. Strong and highly significant associations were found with all major clinical outcomes. Diabetes was associated with an increased risk for all-cause death [adjusted hazard ratio (HR) 1.37; confidence interval (CI) 1.28-1.46; P < 0.001]. The higher risk for all-cause death was largely mediated by higher risk for cardiovascular death (adjusted HR 1.38; CI 1.27-1.48; P < 0.001) predominantly due to a substantially increased risk for fatal re-infarction (adjusted HR 1.78; CI 1.42-2.23; P < 0.001). Additionally, diabetes was associated with an increased risk for hospitalizations, particularly HF hospitalization (adjusted HR 1.50; CI 1.39-1.63; P < 0.001). There were also elevated risks for composite outcomes, particularly death or hospitalization due to HF (adjusted HR 1.48; CI 1.38-1.59; P < 0.001). CONCLUSION: The risk for adverse outcomes associated with diabetes remains elevated even after debut of coronary artery disease in patients with MI complicated by clinical signs of HF or LVD. This association is particularly strong for HF-related outcomes.

Incidence, determinants, and prognostic significance of hyperkalemia and worsening renal function in patients with heart failure receiving the mineralocorticoid receptor antagonist eplerenone or placebo in addition to optimal medical therapy: results from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF).

BACKGROUND: Mineralocorticoid receptor antagonists improve outcomes in patients with systolic heart failure but may induce worsening of renal function (WRF) and hyperkalemia (HK). We assessed the risk factors for mineralocorticoid receptor antagonist-related WRF and for HK, as well as the association between HK and WRF with clinical outcomes in the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF). METHODS AND RESULTS: Serial changes in estimated glomerular filtration rate and in serum potassium were available in 2737 patients during a median 21-month follow-up. HK variably defined as serum K>4.5, 5, or 5.5 mmol/L occurred in 74.7%, 32.5%, and 8.9% patients enrolled in EMPHASIS-HF, respectively. WRF defined as a decrease in estimated glomerular filtration rate>20% or >30% from baseline occurred in 27% and 14% of patients, respectively. Patients assigned eplerenone displayed modest and early but significant and persistent (1) rise in serum potassium and (2) reduction in estimated glomerular filtration rate when compared with those assigned placebo. In multivariate analyses, eplerenone was associated with a higher incidence of WRF and HK, which were interrelated and also associated with baseline patient characteristics (eg, age≥75 years, hypertension, diabetes mellitus, nonwhite race, ejection fraction<30%, and treatment with an antiarrythmics drug or loop diuretic). Eplerenone retained its survival benefits without any significant interaction with the association between HK>5.5 mmol/L only and WRF and worse outcomes. CONCLUSIONS: In patients with heart failure receiving optimal therapy, WRF and HK were more frequent when eplerenone was added, but their occurrence did not eliminate the survival benefit of eplerenone. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00232180.

Heart rate: a prognostic factor and therapeutic target in chronic heart failure. The distinct roles of drugs with heart rate-lowering properties.

Heart rate not only predicts outcome but may also be a therapeutic target in patients with chronic heart failure. Several classes of pharmacological agents can be used to modulate heart rate, including beta-blockers, ivabradine, digoxin, amiodarone, and verapamil. Choice of agent will depend on heart rhythm, co-morbidities, and disease phenotype. Beneficial and harmful interactions may also exist. The aim of this paper is to summarize the current body of knowledge regarding the relevance of heart rate as a prognostic factor (risk marker) and particularly as a therapeutic target (risk factor) in patients with chronic heart failure, with a special focus on ivabradine, a novel agent that is currently the only available purely bradycardic agent.

Effectiveness of a multidimensional home nurse led heart failure disease management program--a French nationwide time-series comparison.

BACKGROUND: The purpose of this study was to assess the effectiveness of a disease management program (DMP) in heart failure (HF) on the incidence of HF hospitalizations and related costs in a real-world population-based setting. METHODS: Insuffisance CArdiaque en LORraine (ICALOR), a DMP for HF was established in 2006 in the French region of Lorraine. Patients were enrolled after an index HF hospitalization. They received educational and home-visit monitoring programs by HF-trained nurses. General physicians received automatic alerts about patients' significant clinical or biological changes. We used the ICALOR and the national diagnostic related group databases to conduct a comparison of time-series trends in HF hospitalizations in France. The economic impact was obtained using the national scale of costs in France. RESULTS: The median age of the 1222 patients recruited before 2010 was 76 years, and 65% were male. Upon enrollment, patients essentially presented with NYHA class II (n=537, 48%) or class III (n=359, 32%) symptoms. One-year mortality rate was 20.3%. The implementation of the ICALOR program was associated with a reduction in HF hospitalizations in Lorraine estimated by an absolute difference between the number of hospitalizations observed in the Lorraine region and that expected had it been similar to that observed in the whole country of -7.19% in 2010. The estimated annual hospital cost saved by ICALOR was €1,927,648 in 2010. CONCLUSION: Coordinated DMP of HF might improve outcome cost-effectively when implemented in a real-world population setting, and was associated in Lorraine with a substantial modification of the trend of HF hospitalizations.

Association between resting heart rate, chronotropic index, and long-term outcomes in patients with heart failure receiving ß-blocker therapy: data from the HF-ACTION trial.

AIMS: The aim of this study was to assess the association between resting heart rate (HR), chronotropic index (CI), and clinical outcomes in optimally treated chronic heart failure (HF) patients on ß-blocker therapy. METHODS AND RESULTS: We performed a sub-study in 1118 patients with HF and reduced ejection fraction (EF < 35%) included in the HF-ACTION trial. Patients in sinus rhythm who received a ß-blocker and who performed with maximal effort on the exercise test were included. Chronotropic index was calculated as an index of HR reserve achieved, by using the equation (220-age) for estimating maximum HR. A sensitivity analysis using an equation developed for HF patients on ß-blockers was also performed. Cox proportional hazards models were fit to assess the association between CI and clinical outcomes. Median (25th, 75th percentiles) follow-up was 32 (21, 44) months. In a multivariable model including resting HR and CI as continuous variables, neither was associated with the primary outcome of all-cause mortality or hospitalization. However, each 0.1 unit decrease in CI <0.6 was associated with 17% increased risk of all-cause mortality (hazard ratio 1.17, 95% confidence interval 1.01-1.36; P = 0.036), and 13% increased risk of cardiovascular mortality or HF hospitalization (hazard ratio 1.13, 1.02-1.26; P = 0.025). Overall, 666 of 1118 (60%) patients had a CI <0.6. Chronotropic index did not retain statistical significance when dichotomized at a value of ≤ 0.62. CONCLUSION: In HF patients receiving optimal medical therapy, a decrease in CI <0.6 was associated with adverse clinical outcomes. Obtaining an optimal HR response to exercise, even in patients receiving optimal ß-blocker therapy, may be a therapeutic target in the HF population.

Statin therapy and clinical outcomes in myocardial infarction patients complicated by acute heart failure: insights from the EPHESUS trial.

AIMS: Several clinical trials have shown that in patients with acute myocardial infarction (MI), statin therapy improves cardiovascular (CV) outcomes, but in these trials patients with acute heart failure (HF) were excluded or only a few were included. In patients with chronic HF, statin therapy does not reduce all-cause or CV mortality. We aimed to assess the association between statin therapy and clinical outcomes in the setting of acute HF with systolic dysfunction complicating acute MI. METHODS AND RESULTS: We performed a post-hoc analysis in 6632 patients included in the EPHESUS trial. The mean age of patients was 64 years and 71% were male. Overall, 47% of patients had a statin prescribed at baseline. Cox regression models and a secondary analysis using propensity score matching were fit to assess the association between statin prescription and clinical outcomes. During a mean follow-up of 16 ± 7 months, all-cause death occurred in 385 (12%) patients with and in 647 (18%) patients without a statin (P < 0.001). After extensive adjustment, the risk of all-cause death was 20% lower in patients on statin [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.69-0.92, P = 0.001]. This positive association was mostly due to a lower risk of CV death (HR 0.76, 95% CI 0.65-0.88, P = 0.0002). In contrast, statin use was associated with a higher risk of non-CV hospitalizations (HR 1.16, 95% CI 1.02-1.33, P = 0.02). CONCLUSION: Our results suggest that patients with acute HF complicating acute MI may benefit from being on statin therapy. Prospective clinical trials are required to validate these findings.

Hypo- and hyperglycemia predict outcome in patients with left ventricular dysfunction after acute myocardial infarction: data from EPHESUS.

BACKGROUND: Hyperglycemia predicts death in cardiovascular disease, but intensive glucose-lowering strategies increase mortality rates in diabetes. The present analysis investigated the prognostic value of postadmission blood glucose (BG) concentration on clinical outcomes in high-risk patients with heart failure after acute myocardial infarction. METHODS AND RESULTS: A total of 6,496 patients from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) were categorized into 4 groups by plasma glucose concentration: ≤4.5 mmol/L (hypoglycemia), 4.5-5.5 mmol/L (normoglycemia), 5.5-8.3 mmol/L (elevated glucose level), and >8.3 mmol/L (severe hyperglycemia). We evaluated the time to all-cause death (primary end point) and time to cardiovascular death or hospitalization (secondary end point). Hypo- and severe hyperglycemia were prevalent in 509 (8%) and 1,588 (24%) patients, respectively. There was a U-shaped relationship between BG level and incidence of all-cause death (11.8% in patients with normoglycemia vs 15.1% and 19.9% in those with hypo- and severe hyperglycemia; P < .001). The incidence of the secondary end point was increased only in hyperglycemic patients (36% vs 23% in normoglycemic patients; P < .001). In multivariate Cox regression analysis, hypoglycemia (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.06-1.81; P = .002) and severe hyperglycemia (HR 1.52, CI 1.27-1.83; P < .0001) proved to be strong predictors of all-cause death. There was no significant interaction between eplerenone treatment and blood glucose levels regarding clinical outcomes. CONCLUSIONS: In heart failure after acute myocardial infarction, both hypo- and hyperglycemia at the postacute phase identify patients with increased risk of death during long-term follow-up.

Can we prevent or treat renal dysfunction in chronic heart failure?

We aimed to summarize the predictors of renal dysfunction and present strategies to prevent and/or treat renal dysfunction in Chronic Heart Failure (CHF). Several factors may predict renal dysfunction in CHF, including older age, comorbidities (anemia, hypertension, diabetes), severity of underlying heart disease (systolic and diastolic dysfunction, central venous pressure) as well as certain therapies in specific circumstances (diuretics, nonsteroid acute inflammatory drugs, and renine-angiotensin-aldosterone (RAAS) inhibitors). Thus, prevention of renal dysfunction is possible in CHF by treating comorbidities and underlying heart disease as well as by monitoring therapies with potential toxic renal effect. At present, there is no specific treatment for renal dysfunction, but several new entities are under investigation. In conclusion, prevention of renal dysfunction is possible in CHF, but treatment is still under investigation. New studies are necessary to establish whether a specific algorithm may be used to prevent renal dysfunction in CHF patients.

Determinants and consequences of renal function variations with aldosterone blocker therapy in heart failure patients after myocardial infarction: insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study.

BACKGROUND: We evaluated the effect of the selective mineralocorticoid receptor antagonist eplerenone on renal function and the interaction between changes in renal function and subsequent cardiovascular outcomes in patients with heart failure and left ventricular systolic dysfunction after an acute myocardial infarction in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). METHODS AND RESULTS: Serial changes in estimated glomerular filtration rate (eGFR) were available in 5792 patients during a 24-month follow-up. Patients assigned to eplerenone had a decline in eGFR with an adjusted mean difference of -1.4±0.3 mL · min(-1) · 1.73 m(-2) compared with placebo (P<0.0001), an effect that appeared within the first month (-1.3±0.4 mL · min(-1) · 1.73 m(-2)) and persisted throughout the study. Overall, 914 patients experienced a decline in eGFR >20% in the first month, 16.9% and 14.7% in the eplerenone and placebo groups, respectively (odds ratio, 1.15; 95% confidence interval, 1.02-1.30; P=0.017). In multivariate analyses, determinants of this early decline in eGFR were female sex, age ≥65 years, smoking, left ventricular ejection fraction <35%, and use of eplerenone and loop diuretic. An early decline in eGFR by >20% was associated with worse cardiovascular outcomes independently of baseline eGFR and of the use of eplerenone, which retained its prognostic benefits even under these circumstances. CONCLUSIONS: In patients with heart failure after acute myocardial infarction and receiving standard medical care, an early decline in eGFR is not uncommon and is associated with poor long-term outcome. Eplerenone induced a moderately more frequent early decline in eGFR, which did not affect its clinical benefit on cardiovascular outcomes.