Impact analysis of heart failure across European countries: an ESC-HFA position paper.

Heart failure (HF) is a long-term clinical syndrome, with increasing prevalence and considerable healthcare costs that are further expected to increase dramatically. Despite significant advances in therapy and prevention, mortality and morbidity remain high and quality of life poor. Epidemiological data, that is, prevalence, incidence, mortality, and morbidity, show geographical variations across the European countries, depending on differences in aetiology, clinical characteristics, and treatment.

Distinct type I interferon responses between younger women and older men contribute to the variability of COVID-19 outcomes: Hypothesis generating insights from COVID-19 convalescent individuals.

Background/objective: Older age and male sex have been consistently found to be associated with dismal outcomes among COVID-19 infected patients. In contrast, premenopausal females present the lowest mortality among adults infected by SARS-CoV-2. The goal of the present study was to investigate whether peripheral blood type I interferon (IFN) signature and interleukin (IL)-6 serum levels -previously shown to contribute to COVID-19-related outcomes in hospitalized patients- is shaped by demographic contributors among COVID-19 convalescent individuals.

Finding acute coronary syndrome with serial troponin testing for rapid assessment of cardiac ischemic symptoms (FAST-TRAC): a study protocol.

Objective: To determine the utility of a highly sensitive troponin assay when utilized in the emergency department.

Methods: The FAST-TRAC study prospectively enrolled >1,500 emergency department patients with suspected acute coronary syndrome within 6 hours of symptom onset and 2 hours of emergency department presentation. It has several unique features that are not found in the majority of studies evaluating troponin.

Clinical significance of interleukin-18 in the course of burn injured children.

Background: Burn injury (BI) is one of the most serious causes of morbidity and mortality in the pediatric population. BI triggers an initial stage of hyperinflammation, followed by hypersecretion of both pro- and anti-inflammatory cytokines. IL- 18 is a vital pro-inflammatory cytokine, the effect of which has been investigated not only in animal models but also in adult patients.

Uric acid and sodium-glucose cotransporter-2 inhibition with empagliflozin in heart failure with reduced ejection fraction: the EMPEROR-reduced trial.

Background: The sodium-glucose cotransporter-2 inhibitor empagliflozin decreases the risk of cardiovascular death or hospitalization for heart failure (HF) in patients with HF with reduced ejection fraction. Empagliflozin reduces serum uric acid (SUA), but the relevance of this effect in patients with HF is unclear. This study aimed to investigate the effect of empagliflozin on SUA levels and the therapeutic efficacy of empagliflozin in relation to SUA.

Empagliflozin Improves Outcomes in Patients With Heart Failure and Preserved Ejection Fraction Irrespective of Age.

Background: Empagliflozin reduces cardiovascular death (CVD) or heart failure (HF) hospitalization (HFH) in patients with HF and preserved ejection fraction. Treatment effects and safety in relation to age have not been studied.

Objectives: The purpose of this study was to evaluate the interplay of age and empagliflozin effects in EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction).

Empagliflozin for Heart Failure With Preserved Left Ventricular Ejection Fraction With and Without Diabetes.

Background: Empagliflozin improves outcomes in patients with heart failure with a preserved ejection fraction, but whether the effects are consistent in patients with and without diabetes remains to be elucidated.

Methods: Patients with class II through IV heart failure and a left ventricular ejection fraction >40% were randomized to receive empagliflozin 10 mg or placebo in addition to usual therapy. We undertook a prespecified analysis comparing the effects of empagliflozin versus placebo in patients with and without diabetes.

Prevention of sudden death in heart failure with reduced ejection fraction: do we still need an implantable cardioverter-defibrillator for primary prevention?

Sudden death is a devastating complication of heart failure (HF). Current guidelines recommend an implantable cardioverter-defibrillator (ICD) for prevention of sudden death in patients with HF and reduced ejection fraction (HFrEF) specifically those with a left ventricular ejection fraction ≤35% after at least 3 months of optimized HF treatment. The benefit of ICD in patients with symptomatic HFrEF caused by coronary artery disease has been well documented; however, the evidence for a benefit of prophylactic ICD implantation in patients with HFrEF of non-ischaemic aetiology is less strong.

Biomarkers for the prediction of heart failure and cardiovascular events in patients with type 2 diabetes: a position statement from the Heart Failure Association of the European Society of Cardiology.

Knowledge on risk predictors of incident heart failure (HF) in patients with type 2 diabetes (T2D) is crucial given the frequent coexistence of the two conditions and the fact that T2D doubles the risk of incident HF. In addition, HF is increasingly being recognized as an important endpoint in trials in T2D. On the other hand, the diagnostic and prognostic performance of established cardiovascular biomarkers may be modified by the presence of T2D.

Osteoprotegerin and MTHFR gene variations in rheumatoid arthritis: association with disease susceptibility and markers of subclinical atherosclerosis.

We aimed to explore whether the rs2073618 variant (G1181C) of the osteoprotegerin (OPG) gene and the methylenetetrahydrofolate reductase (MTHFR) rs1801131 (A1298AC) and rs1801133 (C677T) gene polymorphisms contribute to rheumatoid arthritis (RA) susceptibility and RA related subclinical atherosclerosis. Overall 283 RA patients and 595 healthy controls (HC) were genotyped for common variants of the OPG and MTHFR genes using PCR based assays. Clinical and laboratory parameters were recorded following thorough chart review.

Prognostic Implications of N-Terminal Pro-B-Type Natriuretic Peptide and High-Sensitivity Cardiac Troponin T in EMPEROR-Preserved.

Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) are associated with disease severity and outcomes among patients with heart failure (HF) with preserved ejection fraction.

Objectives: The authors evaluated associations between both biomarkers and clinical outcomes in the EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction) trial.

Methods: Of 5,988 study participants, 5,986 (99.

Neurometabolic Alterations in Motor Neuron Disease: Insights from Magnetic Resonance Spectroscopy.

Magnetic resonance spectroscopy (MRS) has contributed important academic insights in motor neuron diseases (MNDs), particularly in amyotrophic lateral sclerosis (ALS). Over the past three decades momentous methodological advances took place, including the emergence of high-field magnetic resonance imaging (MRI) platforms, multi-voxel techniques, whole-brain protocols, novel head-coil designs, and a multitude of open-source imaging suites. Technological advances in MRS are complemented by important conceptual developments in MND, such as the recognition of the importance of extra-motor brain regions, multi-timepoint longitudinal study designs, assessment of asymptomatic mutation carriers, description of genotype-associated signatures, and the gradual characterisation of non-ALS MND phenotypes.

Scleroderma-specific autoantibodies: Should they be included in the diagnostic work-up for Sjögren's syndrome?

Objectives: Sicca complaints are a frequent reason for rheumatologic consultation. Testing for specific antibodies against Ro/SSA and La/SSB antigens and minor salivary gland (MSG) biopsy are among the main tools implemented in the diagnostic work-up. Anticentromere antibodies and sicca manifestations are frequently detected in Sjögren's syndrome (SS) and systemic sclerosis (SSc), respectively.

Outcomes with empagliflozin in heart failure with preserved ejection fraction using DELIVER-like endpoint definitions.

Aims: To report data from EMPEROR-Preserved according to prespecified endpoints of DELIVER.

Methods And Results: In order to assess the impact of DELIVER-like definition on EMPEROR-Preserved outcomes, the following differences were reconciled: (1) the primary outcome in DELIVER added urgent heart failure (HF) visits to cardiovascular death or HF hospitalizations; (2) the EMPEROR-Preserved trial did not require documentation of physical findings or laboratory tests for confirming a HF hospitalization and it included events of 12-24 h if intensification of treatment was not only oral diuretics; (3) DELIVER excluded undetermined causes of deaths from the primary endpoint; (4) the composite renal endpoint in DELIVER included a sustained ≥50% decline in estimated glomerular filtration rate and incorporated renal death; and (5) DELIVER will assess outcomes in the overall population and in patients with ejection fraction (EF) <60% separately. Using the endpoint definitions from DELIVER, the primary outcome overall occurred in 13.

Distinct pathophysiological pathways in women and men with heart failure.

Aims: Clinical differences between women and men have been described in heart failure (HF). However, less is known about the underlying pathophysiological mechanisms. In this study, we compared multiple circulating biomarkers to gain better insights into differential HF pathophysiology between women and men.

Paradoxical Reasoning: An fMRI Study.

Paradoxes are a special form of reasoning leading to absurd inferences in contrast to logical reasoning that is used to reach valid conclusions. A functional MRI (fMRI) study was conducted to investigate the neural substrates of paradoxical and deductive reasoning. Twenty-four healthy participants were scanned using fMRI, while they engaged in reasoning tasks based on arguments, which were either Zeno's like paradoxes (paradoxical reasoning) or Aristotelian arguments (deductive reasoning).

Epidemiology and age-related mortality in critically ill patients with intra-abdominal infection or sepsis: an international cohort study.

Objective: To describe epidemiology and age-related mortality in critically ill older adults with intra-abdominal infection.

Methods: A secondary analysis was undertaken of a prospective, multi-national, observational study (Abdominal Sepsis Study, ClinicalTrials.gov #NCT03270345) including patients with intra-abdominal infection from 309 intensive care units (ICUs) in 42 countries between January and December 2016.

Earlier Age at Menarche Is Associated with Body Fat and Negative Body Image in Adult Life.

Earlier age at menarche is one of the well-documented antecedents of a range of adverse health effects in adulthood including obesity and psychopathological effects. Yet, few researchers have examined the potential association of menarcheal age with body fat distribution, self-perception, and body image. We retrospectively tested a sample (N = 392) of adult women (18-80 years) to examine the associations of age at menarche with body composition and body image indices.

Hematological Abnormalities in COVID-19 Disease: Association With Type I Interferon Pathway Activation and Disease Outcomes.

Increased expression of interferon (IFN)-stimulated genes (ISGs) in peripheral blood, has been previously reported in viral infections, as well as in autoimmune disorders, in association with reduced leukocyte and platelet counts. Though cytopenias are common in patients with COVID-19 disease and predict severe outcomes, the underlying mechanisms have not been fully elucidated. In the current study, we aimed to determine the prevalence of hematological abnormalities in the setting of active COVID-19 infection and to explore whether they associate with disease outcomes and activation of type I IFN pathway.

Autoimmune pulmonary alveolar proteinosis in children.

In childhood, a multitude of causes lead to pulmonary alveolar proteinosis (PAP), an excessive surfactant accumulation in the alveolar space, limiting gas exchange. Autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) causing autoimmune PAP, the principal aetiology in adults, are rare. In this first case series on autoimmune PAP, we detail the presentation and management issues of four children.

Responder analysis for improvement in 6-min walk test with ferric carboxymaltose in patients with heart failure with reduced ejection fraction and iron deficiency.

Aim: Improving functional capacity is a key goal in heart failure (HF). This pooled analysis of FAIR-HF and CONFIRM-HF assessed the likelihood of improvement or deterioration in 6-min walk test (6MWT) among iron-deficient patients with chronic HF with reduced ejection fraction (HFrEF) receiving ferric carboxymaltose (FCM).

Methods And Results: Data for 760 patients (FCM: n = 454; placebo: n = 306) were analysed.

Mineralocorticoid Receptor Antagonists and Empagliflozin in Patients With Heart Failure and Preserved Ejection Fraction.

Background: Mineralocorticoid receptor antagonists (MRAs) may be beneficial in reducing heart failure (HF) hospitalizations in patients with HF with preserved ejection fraction. The effect of sodium-glucose cotransporter 2 inhibitors in patients with HF with preserved ejection fraction according to MRA background therapy has not been reported.

Objectives: The aim of this study was to examine the effect of empagliflozin in MRA users and nonusers in the EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction) trial.

Influence of atrial fibrillation on efficacy and safety of omecamtiv mecarbil in heart failure: the GALACTIC-HF trial.

Aims: In GALACTIC-HF, the cardiac myosin activator omecamtiv mecarbil compared with placebo reduced the risk of heart failure events or cardiovascular death in patients with heart failure with reduced ejection fraction. We explored the influence of atrial fibrillation or flutter (AFF) on the effectiveness of omecamtiv mecarbil.

Methods And Results: GALACTIC-HF enrolled patients with New York Heart Association (NYHA) Class II-IV heart failure, left ventricular ejection fraction ≤35%, and elevated natriuretic peptides.