Association between loop diuretic dose changes and outcomes in chronic heart failure: observations from the ESC-EORP Heart Failure Long-Term Registry

[Abstract] Aims. Guidelines recommend down-titration of loop diuretics (LD) once euvolaemia is achieved. In outpatients with heart failure (HF), we investigated LD dose changes in daily cardiology practice, agreement with guideline recommendations, predictors of successful LD down-titration and association between dose changes and outcomes. Methods and results. We included 8130 HF patients from the ESC-EORP Heart Failure Long-Term Registry. Among patients who had dose decreased, successful decrease was defined as the decrease not followed by death, HF hospitalization, New York Heart Association class deterioration, or subsequent increase in LD dose. Mean age was 66±13 years, 71% men, 62% HF with reduced ejection fraction, 19% HF with mid-range ejection fraction, 19% HF with preserved ejection fraction. Median [interquartile range (IQR)] LD dose was 40 (25–80) mg. LD dose was increased in 16%, decreased in 8.3% and unchanged in 76%. Median (IQR) follow-up was 372 (363–419) days. Diuretic dose increase (vs. no change) was associated with HF death [hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.12–2.08; P = 0.008] and nominally with cardiovascular death (HR 1.25, 95% CI 0.96–1.63; P = 0.103). Decrease of diuretic dose (vs. no change) was associated with nominally lower HF (HR 0.59, 95% CI 0.33–1.07; P = 0.083) and cardiovascular mortality (HR 0.62 95% CI 0.38–1.00; P = 0.052). Among patients who had LD dose decreased, systolic blood pressure [odds ratio (OR) 1.11 per 10 mmHg increase, 95% CI 1.01–1.22; P = 0.032], and absence of (i) sleep apnoea (OR 0.24, 95% CI 0.09–0.69; P = 0.008), (ii) peripheral congestion (OR 0.48, 95% CI 0.29–0.80; P = 0.005), and (iii) moderate/severe mitral regurgitation (OR 0.57, 95% CI 0.37–0.87; P = 0.008) were independently associated with successful decrease. Conclusion. Diuretic dose was unchanged in 76% and decreased in 8.3% of outpatients with chronic HF. LD dose increase was associated with worse outcomes, while the LD dose decrease group showed a trend for better outcomes compared with the no-change group. Higher systolic blood pressure, and absence of (i) sleep apnoea, (ii) peripheral congestion, and (iii) moderate/severe mitral regurgitation were independently associated with successful dose decrease

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%

Total IgE and allergen-specific IgE and IgG antibody levels in sera of atopic dermatitis affected and non-affected Labrador- and Golden retrievers

Canine atopic dermatitis (CAD) is an allergic skin disease associated with IgE and IgG antibodies (Ab) to environmental allergens. The aim of this study was to determine which other factors influence serum Ab levels in CAD-affected and non-affected dogs as this has only been poorly investigated in dogs so far. Total and allergen-specific IgE levels and Dermatophagoides farinae (DF)-specific IgG1 and IgG4 were measured by ELISA in sera of 145 CAD-affected and 271 non-affected Labrador- and Golden retrievers. A multivariable logistic regression analysis including the factors age, breed, gender, castration, clinical CAD status and allergen-specific immunotherapy (ASIT) was performed. Golden retrievers had more frequently total (OR=1.87, 95% CI=1.26-2.87, p<0.01) and specific IgE levels above the threshold value than Labrador retrievers, suggesting that genetic factors influence IgE levels in dogs. Castration was generally associated with low Ab levels (OR=0.43-0.65, p<0.05). Surprisingly, dogs with CAD did not have increased odds for high IgE against any of the allergens tested. ASIT with DF was associated with high DF-specific IgG1 (OR=4.32, 95% CI 1.46-12.8, p<0.01) but was not associated with DF-specific IgG4 or decreased IgE levels. Further studies are needed to understand the role of allergen-specific IgE in CAD and of IgG1 in ASIT

Korozní chování povrchu silicidu titanu v přítomnosti peroxidu vodíku: Tvorba sub-μm kuliček na bázi TiOx, nanokompozitních fází TiOx / SiOx a mezoporézní sítě TiOx / SiOx

Dosud neprozkoumaná koroze povrchu silicidu titanu (Ti5Si3) okyseleným peroxidem vodíku je zajímavá díky svému potenciálnímu využití při zlepšování osseointegrace titanových implantátů potažených silicidy titanu. Detailní charakterizace produktů koroze pomocí FTIR, Ramanovy a XP spektroskopie, elektronové mikroskopie, XRD, BET a techniky rozptylu světla umožňují rozpoznání hydratovaných nanokompozitních fází TiOx / SiOx (x≤2) složených ze segregovaných amorfních fází SiOx a sítě na bázi TiOx obsahující vazby Ti-O-Si a -O-O. ¨ Vzhled TiOx síťoví závisí na rozsahu peroxidace. Méně postupující peroxidace poskytuje submikronové kuličky na bázi Tild, které po žíhání vyvíjejí anatasová nahozena, která odolávají do teploty 800 °C. Výraznější peroxidace produkuje větší mesoporézní tělíska na bázi TiOx, která se desintegrují po působení ultrazvuku na entity o velikosti mikrometrů. Navrhovaný mechanismus povrchové koroze vyplývá z komplementárního použití analytických technik. Jednokroková produkce bioaktivních (hydratovaných TiOx a SiOx) druhů je vhodná pro další výzkum osseointegrace mírně zkorodovaných titanových implantátů potažených Ti5Si3.silicid titanu, peroxid vodíku, mikrofáze SiOx, nanofáze TiOx a SiOx, mezoporézní a mikroporézní částice na bázi TiOxSo far unexplored corrosion of titanium silicide (Ti5Si3) surface with acidified hydrogen peroxide is of interest due to its potential use in improving osseointegration of titanium implants coated by titanium silicides. Detailed examination of corrosion products by FTIR, Raman and XP spectroscopy, electron microscopy, XRD, BET and light scattering techniques allows recognition of hydrated nanocomposite TiOx/SiOx (x≤2) phases composed of segregated amorphous SiOx species and TiOx–based networks containing Ti-O-Si and -O-O- bonds. The appearance of the TiOx networks depends on the extent of peroxidation. A less progressed peroxidation yields sub- μm-sized TiOx-based spheres which upon annealing develop anatase nanograins withstanding 800° C. A more progressed peroxidation produces larger mesoporous TiOx-based bodies which disintegrate upon sonication into micrometer-sized entities. The proposed mechanism of surface corrosion is based on the complementary use of analytical techniques. The one-step production of bioactive (hydrated TiOx and SiOx) species deserves to be explored in osseointegration studies of slightly corroded Ti5Si3-coated titanium implants

Two loci on chromosome 5 are associated with serum IgE levels in Labrador retrievers

Crosslinking of immunoglobulin E antibodies (IgE) bound at the surface of mast cells and subsequent mediator release is considered the most important trigger for allergic reactions. Therefore, the genetic control of IgE levels is studied in the context of allergic diseases, such as asthma, atopic rhinitis, or atopic dermatitis (AD). We performed genome-wide association studies in 161 Labrador Retrievers with regard to total and allergen-specific immunoglobulin E (IgE) levels. We identified a genome-wide significant association on CFA 5 with the antigen-specific IgE responsiveness to Acarus siro. We detected a second genome-wide significant association with respect to the antigen-specific IgE responsiveness to Tyrophagus putrescentiae at a different locus on chromosome 5. A. siro and T. putrescentiae both belong to the family Acaridae and represent so-called storage or forage mites. These forage mites are discussed as major allergen sources in canine AD. No obvious candidate gene for the regulation of IgE levels is located under the two association signals. Therefore our studies offer a chance of identifying a novel mechanism controlling the host's IgE response