Persistent High Burden of Heart Failure Across the Ejection Fraction Spectrum in a Nationwide Setting

Background Heart failure (HF) has a dramatic impact on worldwide health care systems that is determined by the growing prevalence of and the high exposure to cardiovascular and noncardiovascular events. Prognosis remains poor. We sought to compare a large population with HF across the ejection fraction (EF) spectrum with a population without HF for patient characteristics, and HF, cardiovascular, and noncardiovascular outcomes. Methods and Results Patients with HF registered in the Swedish HF registry in 2005 to 2018 were compared 1:3 with a sex-, age-, and county-matched population without HF. Outcomes were cardiovascular and noncardiovascular mortality and hospitalizations. Of 76 453 patients with HF, 53% had reduced EF, 23% mildly reduced EF, and 24% preserved EF. Compared with those without HF, patients with HF had more cardiovascular and noncardiovascular comorbidities and worse socioeconomic status. Incidence of cardiovascular and noncardiovascular events was higher in people with HF versus non-HF, with increased risk of all-cause (hazard ratio [HR], 2.53 [95% CI, 2.50-2.56]), cardiovascular (HR, 4.67 [95% CI, 4.59-4.76]), and noncardiovascular (HR, 1.49 [95% CI, 1.46-1.52]) mortality, 2- to 5-fold higher risk of first/repeated cardiovascular and noncardiovascular hospitalizations, and ~4 times longer in-hospital length of stay for any cause. Patients with HF with reduced EF had higher risk of HF hospitalizations, whereas those with HF with preserved EF had higher risk of all-cause and noncardiovascular hospitalization and mortality. Conclusions Patients with HF exert a high health care burden, with a much higher risk of cardiovascular, all-cause, and noncardiovascular events, and nearly 4 times as many days spent in hospital compared with those without HF. These epidemiological data may enable strategies for optimal resource allocation and HF trial design

Diminished levels of nasal S100A7 (psoriasin) in seasonal allergic rhinitis: an effect mediated by Th2 cytokines

<p>Abstract</p> <p>Background</p> <p>S100A7 is an antimicrobial peptide involved in several inflammatory diseases. The aim of the present study was to explore the expression and regulation of S100A7 in seasonal allergic rhinitis (SAR).</p> <p>Methods</p> <p>Nasal lavage (NAL) fluid was obtained from healthy controls before and after lipopolysaccharide (LPS) provocation, from SAR patients before and after allergen challenge, and from SAR patients having completed allergen-specific immunotherapy (ASIT). Nasal biopsies, nasal epithelial cells and blood were acquired from healthy donors. The airway epithelial cell line FaDu was used for <it>in vitro </it>experiments. Real-time RT-PCR and immunohistochemistry were used to determine S100A7 expression in nasal tissue and cells. Release of S100A7 in NAL and culture supernatants was measured by ELISA. The function of recombinant S100A7 was explored in epithelial cells, neutrophils and peripheral blood mononuclear cells (PBMC).</p> <p>Results</p> <p>Nasal administration of LPS induced S100A7 release in healthy non-allergic subjects. The level of S100A7 was lower in NAL from SAR patients than from healthy controls, and it was further reduced in the SAR group 6 h post allergen provocation. In contrast, ASIT patients displayed higher levels after completed treatment. S100A7 was expressed in the nasal epithelium and in glands, and it was secreted by cultured epithelial cells. Stimulation with IL-4 and histamine repressed the epithelial S100A7 release. Further, recombinant S100A7 induced activation of neutrophils and PBMC.</p> <p>Conclusions</p> <p>The present study shows an epithelial expression and excretion of S100A7 in the nose after microbial stimulation. The levels are diminished in rhinitis patients and in the presence of an allergic cytokine milieu, suggesting that the antimicrobial defense is compromised in patients with SAR.</p

Association between use of novel glucose-lowering drugs and COVID-19 hospitalization and death in patients with type 2 diabetes: a nationwide registry analysis

Aims Type 2 diabetes (T2DM) in patients with coronavirus disease-19 (COVID-19) is associated with a worse prognosis. We separately investigated the associations between the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and dipeptidyl peptidase-4 inhibitors (DPP-4i), and the risk of COVID-19 hospitalization and death. Methods and results Patients with T2DM registered in the Swedish National Patient Registry and alive on 1 February 2020 were included. 'Incident severe COVID-19' was defined as the first hospitalization and/or death from COVID-19. A modified Poisson regression approach was applied to a 1:1 propensity score-matched population receiving vs. not receiving SGLT2i, GLP-1 RA, and DPP-4i to analyse the associations between their use and (I) incident severe COVID-19 and (II) risk of 30-day mortality in patients hospitalized for COVID-19. Among 344 413 patients, 39 172 (11%) were treated with SGLT2i, 34 290 (10%) with GLP-1 RA, and 53 044 (15%) with DPP-4i; 9538 (2.8%) had incident severe COVID-19 by 15 May 2021. SGLT2i and DPP-4i were associated with a 10% and 11% higher risk of incident severe COVID-19, respectively, whereas there was no association for GLP-1 RA. DPP-4i was also associated with a 10% higher 30-day mortality in patients hospitalized for COVID-19, whereas there was no association for SGLT2i and GLP-1 RA. Conclusion SGLT2i and DPP-4i use were associated with a higher risk of incident severe COVID-19. DPP-4i use was associated with higher 30-day mortality in patients with COVID-19, whereas SGLT2i use was not. No increased risk for any outcome was observed with GLP-1 RA

A module-based analytical strategy to identify novel disease-associated genes shows an inhibitory role for interleukin 7 Receptor in allergic inflammation

<p>Abstract</p> <p>Background</p> <p>The identification of novel genes by high-throughput studies of complex diseases is complicated by the large number of potential genes. However, since disease-associated genes tend to interact, one solution is to arrange them in modules based on co-expression data and known gene interactions. The hypothesis of this study was that such a module could be a) found and validated in allergic disease and b) used to find and validate one ore more novel disease-associated genes.</p> <p>Results</p> <p>To test these hypotheses integrated analysis of a large number of gene expression microarray experiments from different forms of allergy was performed. This led to the identification of an experimentally validated reference gene that was used to construct a module of co-expressed and interacting genes. This module was validated in an independent material, by replicating the expression changes in allergen-challenged CD4⁺cells. Moreover, the changes were reversed following treatment with corticosteroids. The module contained several novel disease-associated genes, of which the one with the highest number of interactions with known disease genes, <it>IL7R</it>, was selected for further validation. The expression levels of <it>IL7R </it>in allergen challenged CD4⁺cells decreased following challenge but increased after treatment. This suggested an inhibitory role, which was confirmed by functional studies.</p> <p>Conclusion</p> <p>We propose that a module-based analytical strategy is generally applicable to find novel genes in complex diseases.</p

Association of Coronary Microvascular Dysfunction With Heart Failure Hospitalizations and Mortality in Heart Failure With Preserved Ejection Fraction:A Follow-up in the PROMIS-HFpEF Study

Background: Coronary microvascular dysfunction (CMD) is common in heart failure with preserved ejection fraction (HFpEF). We assessed the association of CMD with hospitalization and mortality in HFpEF. Methods and Results: We assessed the 1-year outcomes in patients from the PROMIS-HFpEF study, a prospective observational study of patients with chronic stable HFpEF undergoing coronary flow reserve measurements. Outcomes were (1) time to cardiovascular (CV) death/first HF hospitalization, (2) CV death/recurrent HF hospitalizations, (3) all-cause death/first HF hospitalization, and (4) first and (5) recurrent all-cause hospitalizations. CMD was defined as coronary flow reserve of Conclusions: In this exploratory assessment of the prognostic role of CMD in HFpEF, CMD was independently associated with primarily CVand HF-specific events. The high prevalence of CMD and its CV and HF specific prognostic role suggest CMD may be a potential treatment target in HFpEF

Eligibility for vericiguat in a real-world heart failure population according to trial, guideline and label criteria:Data from the Swedish Heart Failure Registry

Aim: We investigated the eligibility for vericiguat in a real-world heart failure (HF) population based on trial, guideline and label criteria. Methods and results: From the Swedish HF registry, 23 573 patients with HF with reduced ejection fraction (HFrEF) enrolled between 2000 and 2018, with a HF duration ≥6 months, were considered. Eligibility for vericiguat was calculated based on criteria from (i) the Vericiguat Global Study in Subjects with Heart Failure and Reduced Ejection Fraction (VICTORIA) trial; (ii) European and American guidelines on HF; (iii) product labelling according to the Food and Drug Administration and European Medicines Agency. Estimated eligibility for vericiguat in the trial, guidelines, and label scenarios was 21.4%, 47.4%, and 47.4%, respectively. Prior HF hospitalization within 6 months was the criterion limiting eligibility the most in all scenarios (met by 49.1% of the population). In the trial scenario, other criteria meaningfully limiting eligibility were elevated N-terminal pro-B-type natriuretic peptide levels and nitrate use. In all scenarios, eligibility was higher among patients hospitalized for HF at baseline (44.3% vs. 21.4% [trial scenario] and 97.3% vs. 47.4% [guideline/label scenarios] for hospitalized vs. non-hospitalized patients). Overall, eligible patients were older, had more severe HF, more comorbidities, and consequently higher cardiovascular mortality and HF hospitalization rates compared with ineligible patients across all scenarios. Conclusion: In a large and contemporary real-world HFrEF cohort, we estimated that 21.4% of patients would be eligible for vericiguat according to the VICTORIA trial selection criteria, 47.4% based on guidelines and labelling. Eligibility for vericiguat translated into the selection of a population at high risk of morbidity/mortality.</p

Association between potassium level and outcomes in heart failure with reduced ejection fraction: a cohort study from the Swedish Heart Failure Registry

AimsHyperkalaemia and hypokalaemia are common in heart failure and associated with worse outcomes. However, the optimal potassium range is unknown. We sought to determine the optimal range of potassium in patients with heart failure and reduced ejection fraction (5.0- mmol/L. Potassium 5.0- mmol/L were more common with lower estimated glomerular filtration rate and heart failure of longer duration and greater severity. The potassium level associated with the lowest hazard risk for mortality at 30- days, 12 months, and maximal follow- up was 4.2- mmol/L, and there was a steep increase in risk with both higher and lower potassium levels. In adjusted strata analyses, lower potassium was independently associated with all- cause mortality at 12 months and maximal follow- up, while higher potassium levels only increased risk at 30- days.ConclusionIn this nationwide registry, the relationship between potassium and mortality was U- shaped, with an optimal potassium value of 4.2- mmol/L. After multivariable adjustment, hypokalaemia was associated with increased long- term mortality but hyperkalaemia was associated with increased short- term mortality.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162724/3/EJHF1757-sup-0001-APPS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162724/2/ejhf1757_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162724/1/ejhf1757.pd

Liver Injury Indicating Fatty Liver but Not Serologic NASH Marker Improves under Metformin Treatment in Polycystic Ovary Syndrome

Objective. Polycystic ovary syndrome (PCOS) is associated with obesity and insulin resistance (IR), key features of nonalcoholic steatohepatitis (NASH). Cytokeratin 18 fragments (M30) have been established as a serum marker for NASH. The insulin sensitizer metformin improves hepatic IR. This study evaluates the influence of MF on serologic NASH (sNASH) in patients with PCOS. Patients and Methods. In 89 patients, metabolic parameters, liver injury indicating fatty liver (LIFL), and M30 were assessed at baseline and after metformin treatment. Patients with initial IR were subdivided into dissolved (PCOS-exIR) and persistent IR (PCOS-PIR) after treatment and compared to an initially insulin sensitive PCOS group (PCOS-C). Results. Improvement of LIFL prevalence could be seen in PCOS-C and PCOS-exIR compared to PCOS-PIR (−19.4, resp., −12.0% versus 7.2%, Chi2 = 29.5, P<0.001) without change in sNASH prevalence. In PCOS-PIR, ALT levels increased significantly accompanied by a nominal, nonsignificant M30 increase. Conclusions. Metformin improves LIFL in subgroups of patients with PCOS without influencing sNASH. This could either indicate a missing effect of metformin on NAFLD or slowed disease progression. Further studies are needed to elucidate NAFLD in the context of PCOS and potential therapeutic options

Eligibility for dapagliflozin and empagliflozin in a real-world heart failure population

Background: We investigated eligibility for dapagliflozin and empagliflozin in a real-world heart failure (HF) cohort based on selection criteria of DAPA-HF, DELIVER, and EMPEROR trials. Methods and Results: Selection criteria were applied to the Swedish HF registry out-patient population according to three scenarios: (i) a “trial scenario” applying all selection criteria; (ii) a “pragmatic scenario” applying the most clinically relevant criteria; (iii) a “label scenario” following the regulatory agencies labels. Of 49,317 patients, 55% had ejection fraction (EF)&lt;40% and were assessed for eligibility based on DAPA-HF and EMPEROR-Reduced, 45% had EF≥40% and were assessed based on EMPEROR-Preserved and DELIVER. Eligibility using trial, pragmatic and label scenarios was: 35%, 61% and 80% for DAPA-HF; 31%, 55% and 81% for EMPEROR-Reduced; 30%, 61% and 74% for DELIVER; 32%, 59% and 75% for EMPEROR-Preserved. Main selection criteria limiting eligibility were HF duration and NT-proBNP. Eligible patients had more severe HF, more comorbidities, higher use of HF treatments and higher mortality/morbidity. Conclusions: In a real-world HF setting, eligibility for SGLT2i was similar whether selection criteria from DAPA-HF or EMPEROR-Reduced were applied in HFrEF, or EMPEROR-Preserved or DELIVER in HFpEF. These data might help stakeholders assessing the consequences of future trial eligibility