bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incident heart failure: comparing management and outcome in primary care and hospital settings in Western Sweden 2008-2017
Authors: Chen X , Pivodic A , Schaufelberger M , Fu M 
Published: October 2024

Abstract

Background
Heart failure (HF) is a major problem in primary care (PC) and hospital care (HC). HF patients managed in these two settings may differ in their demography, comorbidities, treatment and outcomes.

Aim
We aimed to compare the patient management in PC and HC in the Västra Götaland Region (VGR) in Sweden.

Methods
The VEGA database is an administrative database includes all patients living in VGR. Patients with a first principal or contributory diagnosis of HF (I50) ≥18 years old between 2008 and 2017 were included. One-year mortality was used as the outcome.

Results
In total, 62,229 new-onset HF cases were included, with 18,722 identified only in PC and 16,651 in HC. HF patients in PC were older (80.7±10.9 vs 76.1±13.6), more women (57.1% vs 44.9%), with more hypertension, musculoskeletal and mental disorders, but less myocardial infarction. Guideline directed medical therapy was more frequently used in HC despite similar medication before HF diagnosis. Patients in HC had almost 4 times higher all-cause 1-year mortality [3.92 (3.77 - 4.08), p&lt;0.0001] compared with PC after adjustment for age and sex. Over 10-year period, despite decreasing mortality in both settings, hazard ratios for HC vs. PC were significantly increased for all patients (p for interaction 0.0004), which was more marked in female and for 70-80 years old patients.

Conclusion
Over a 10-year period, not withstanding decreasing mortality in HF patients in both PC and HC settings, differences remain between these two HF populations not only demographic profile and medications but also outcomes.
ICARUS registry: findings from the first 1595 cases of acute decompensated heart failure in a single center in a latin american country
Authors: Echeverria L E , Gomez-Ochoa S A , Rodriguez J A , Garcia-Rueda K A , Torres-Bustamante A M , Serrano-Garcia A Y , Botero D R , Cantillo-Reines M , Jurado A M , Castro K J , Pinilla K , Mendoza-Quinonez A C , Rojas M , Ortega-Solano D M , Rojas L Z 
Published: October 2024

Abstract

Introduction
Institutional aCute decompensAted HeaRt FailUre RegiStry (ICARUS) will provide information on clinical characteristics, medical practice, patterns of treatment, and outcomes of patients hospitalized with Acute Decompensated Heart Failure (ADHF) in a hospital in a middle-income country.

Objective
Describe the methodological aspects, sociodemographic, and clinical characteristics of patients hospitalized with ADHF and their short-term outcomes.

Method
Prospective cohort of patients with ADHF from the emergency service of a cardiovascular center. Descriptive statistics were used to synthesize sociodemographic characteristics, clinical characteristics during hospitalization, and outcomes.

Results
1595 patients with ADHF. The median age was 68 years (Q1=58; Q3=76), and 69.28% were men. The median hospital stay was six days (Q1=4; Q3=11), with an accumulative incidence (AI) for rehospitalization at 30 days of 8.70 % (95% CI 7.18 to 10.40%), in-hospital mortality AI of 4.33% (95% CI 3.38 to 5.44%), and a median change in the quality-of-life score like Minnesota Living with Heart Failure Questionnaire (MLHFQ) at 30 days of -20 points (Q1=-37; Q3=-5). At discharge, all patients had a percentage greater than 70% of the use of quadruple neurohormonal blockade therapy.

Conclusions
ICARUS is one of the first registries in Latin America since the indication of the use of SGLT2 inhibitors, evaluating the clinical and sociodemographic characteristics, treatment patterns, and outcomes of a preliminary cohort of 1595 patients hospitalized for ADHF. The results indicate that, at discharge, up to 82.79% of patients were receiving quadruple neurohormonal blockade therapy, which is considerably challenging to achieve in Latin America. Considering the results of the Safety, tolerability and efficacy of up-titration of Guideline-Directed Medical therapies for acute heart failure (STRONG-HF study), our study reinforces the benefit of discharge with Guideline-Directed Medical Therapy (GDMT) for heart failure from hospitalization. The use of GDMT for heart failure may have influenced our positive outcomes in terms of in-hospital mortality, improvement in quality of life, and the percentage of short-term rehospitalizations compared to similar cohorts.Proportion of HF drug group
LVEF trajectory in HFimpEF and its association with prognosis
Authors: Huang L , Zhang J , Zhang Y 
Published: October 2024

Abstract

Background
The 2021 revised Universal Definition of Heart Failure (HF) introduced the subgroup known as HF with improved ejection fraction (HFimpEF), aiming to establish a standardized definition for left ventricular ejection fraction (LVEF) improvement and emphasize the importance of longitudinally assessment of LVEF. However, there remains an insufficient characterization of the association between serial LVEF trajectory before and after impEF, and outcomes in HFimpEF.

Purpose
We aim to delineate the LVEF trajectory in patients with impEF and to discern specific LVEF trajectory pattern that portends an unfavorable prognosis.

Methods
We conducted a retrospective analysis by including hospitalized HF patients with baseline LVEF ≤ 40% and satisfactory serial echocardiographic follow-ups. ImpEF was defined as a follow-up LVEF measurement of &gt; 40% with a ≥10-point increase from baseline. Longitudinal LVEF trajectories for patients with impEF (before and after LVEF improvement) were plotted according to the clinical outcome of all-cause death using Loess curves. LVEF changes over time were analyzed by unconditional non-linear mixed-effects modeling, and compared between the groups of patients who died and those who survived using conditional non-linear mixed-effects modeling.

Results
Among the initial 923 patients with reduced LVEF, 517 had impEF. According to Loess curves and non-linear mixed-effects analysis, LVEF trajectory of impEF differed according to the clinical outcome of death. For patients who suffered all-cause death, there was a comparatively limited improvement in LVEF followed by a more rapid plateauing and decline, exhibiting an inverted U-shaped pattern with lower LVEF values towards both ends of the distribution.

Conclusions
In HFimpEF, an inverted U-shaped trajectory of LVEF, characterized by limited initial improvement followed by subsequent decline, is associated with poorer prognosis. Serial LVEF monitoring in patients with HFimpEF could help with early identification of at-risk patients.Graphical Abstract
Protein signatures associated with methylation patterns of heart failure phenotypes
Authors: Krolevets M , Ten Cate V , Buch G , Rapp S , Niehrs C , Wild P 
Published: October 2024

Abstract

Introduction
The heart failure (HF) syndrome is highly susceptible to the exposome. The interplay between DNA methylation (DNAm), surrogate for exposomal influences, and the plasma proteome in the progression and development of phenotypes of heart failure is unclear. We investigated the relation between methylation patterns of HF phenotypes and proteins signatures.

Methods
Individuals with symptomatic HF (stage C/D with HFpEF, HFmrEF and HFrEF) of the MyoVasc cohort (N=3,289) were investigated. EDTA-Plasma and DNA were extracted from peripheral blood and stored in -80°C. DNAm was measured using the Infinium MethylationEPIC v2.0 methylation array. Concentrations for 538 proteins were measured using an immuno-qPCR assay in EDTA plasma. Multivariable regression models adjusted for age and sex were used to assess the relationship between DNAm signatures and individual proteins in each phenotype. Ridge-regularized linear regression was used to generate a phenotype-specific protein-signature in relation to each methylation signature, linear regression to estimate links between protein signatures and cardiovascular traits and Cox regression relate protein signatures to clinical outcome.

Results
Data from 1,317 individuals with symptomatic HF were analyzed. After FDR adjustment, 310 proteins were significantly related to HFpEF methylation signature, 314 to HFmrEF and 266 to HFrEF. Of associated proteins, 49.9% (198) were found in all phenotypes, 8.82% (35) only in HFpEF, 12.1% (48) in HFmrEF and 4.79% (19) in HFrEF. Tumor necrosis, arterial hypertension and T-cell regulation pathways were enriched in all three phenotypes. NT-proBNP had the strongest association with HFrEF (β=0.95 [0.82-1.08], p&lt;0.0001) followed by presence of plaques in carotid artery and C-reactive protein, while left ventricular mass (LVM) had stronger association with HFpEF (β=0.22 [0.11-0.33], p=0.0001). All three signatures were associated with worsening of HF (HFpEF: HR=1.93 [1.61-2.30], p&lt;0.0001; HFmrEF: HR=1.63 [1.29-2.04], p&lt;0.0001; HFrEF: HR=1.64 [1.38-1.95], p&lt;0.0001) and all-cause death in HF (HFpEF: HR=1.93 [1.65-2.26], p&lt;0.0001; HFmrEF: HR=1.95 [1.58-2.42], p&lt;0.0001; HFrEF: HR=2.24 [1.86-2.69], p&lt;0.0001). Methylation-associated protein signatures had stronger associations with clinical outcome than the methylation signatures themselves (p &lt; 0.01).

Conclusion
This study revealed protein signatures associated with methylation patterns of HF phenotypes that shared common and unique features for HF phenotypes. Important common pathways were enriched in tumour necrosis, arterial hypertension and regulation of T cells. However, important differences between phenotypes were also revealed, e.g. NT-proBNP was strongly associated with the HFrEF protein signature and LVM with the HFpEF signature. The methylation-associated protein signatures emphasise the possible exposomal influence on HF syndrome.
A streamlined protocol for exercise right heart catheterisation for the diagnosis of heart failure with preserved ejection fraction
Authors: Selvadurai M V , Dagan M , Mariani J , Vizi D , Dewar E M , Kaye D M , Nanayakkara S 
Published: October 2024

Abstract

Background
Heart failure with preserved ejection fraction (HFpEF) can be a challenging diagnosis. The gold standard diagnostic test is exercise right heart catheterisation (eRHC), with HFpEF confirmed if pulmonary capillary wedge pressure (PCWP) &gt;15mmHg at rest or ≥25mmHg with exercise. However, many centres do not perform eRHC and the current, well-established, nine-minute eRHC protocol can be time consuming and costly.

Purpose
We sought to determine whether an abbreviated 3-minute eRHC protocol is sufficient for accurate diagnosis of HFpEF, thus allowing simplification, reduced patient risk and costs, and broader uptake of eRHC across centres.

Methods
Patients undergoing eRHC between 09/09/2008 and 18/07/2023 at a tertiary hospital in Australia were retrospectively analysed. Haemodynamic measurements at three minutes of exercise were correlated with peak measurements.

Results
Overall cohort of n=532, with a mean age of 64 ± 12 years, and 60% female. Compared to PCWP ≥25mmHg at peak exercise, measurement of PCWP at 3 minutes yielded an area under the receiver-operating characteristic curve of 0.92±0.01, P&lt;0.0001. PCWP ≥25mmHg at 3 minutes has a high specificity (97%) but moderate sensitivity (65%) for diagnosis of HFpEF; PCWP ≥21 mmHg at 3 minutes has good specificity (83%) and sensitivity (85%) for predicting peak PCWP ≥25mmHg. Using the 3-minute protocol with PCWP cut-off of 21mmHg, 86% of participants were correctly diagnosed (Figure 1). There were strong positive correlations in PCWP (R2=0.6922), cardiac output (R2=0.5543) and pulmonary vascular resistance (R2=0.6516) between 3 minutes and peak exercise (Figure 2).

Conclusions
Abbreviated 3-minute eRHC protocol has good diagnostic potential in HFpEF, with strong correlations in haemodynamics, when compared to peak exercise. This suggests that simplification of the current HFpEF protocol to 3 minutes exercise could be a valid strategy to enable improved uptake and maximise resource utilisation while maintaining diagnostic accuracy.Figure 1.Sankey plot of PCWP valuesFigure 2.Haemodynamics during eRHC
The role of angiotensin II and endothelin receptor antibodies in COVID19 patients with HFpEF
Authors: Cherneva Z H , Marchev S , Jelev L , Markova P , Girchev R , Cherneva R 
Published: October 2024

Abstract

Background
The infection caused by the coronavirus SARS-COV-2, is associated with an unusual pattern of organ damage in comparison to other viral-induced pathologies. A theory of autoimmunity induced by ACE-2/SARS-COV-2 spike protein complex or its degradation products, was proposed as a possible explanation for the versatile and multiorgan damage in COVID-19.

Aim
The aim of the study is to determine whether antibodies against angiotensin II receptor type 1 (AT1R) or endothelin-1 receptor type A (ETAR) do exist in plasma of COVID -19 patients with heart failure with preserved ejection fraction and whether they correlate to the severity of the disease.

Methods
A total of 61 patients with COVID-19 and heart failure with preserved ejection fraction and 48 controls (free of COVID19) with heart failure with preserved ejection fraction were included. Patients were divided into two groups: patients with severe disease (admitted at the intensive care (n=30)), patients with milder clinical presentation that remained in the general therapeutical department (n=31). The plasma levels of IL-6 and auto-antibodies against AT1R or ETAR in peripheral blood were measured and compared between COVID19 patients with severe and milder disease and age matched controls. Clinical and standard laboratory parameters were also collected and their association with the research biomarkers was analysed.

Results
Auto-antibodies against AT1R were significantly increased in severe disease course (median 19.60 U/mL, IQR 4.8-34.75) compared to milder disease (median 10.95 U/mL, IQR 7.69 – 17.67, p=0.017) and the control group (median 6.79 U/mL, IQR 5.10 – 14.05, p&lt; 0.001). ETAR antibody titers were also significantly increased in severe disease (median 14.52, IQR 6.76-32.94), compared to milder disease course (median 8.73 U/mL, IQR 6.59 –13.45, p=0.023) and to the control group (median 6.64, IQR 6.79 – 17.92, p &lt;0.001). The same was the trend regarding IL-6 antibodies. Severe disease (median 12.11 U/mL, IQR 5.59–19.38); milder disease disease (median 8.64U/mL, IQR 1.84 – 14.13, p=0.039); control group (median 4.28U/mL, IQR 0.11–1.43, p&lt;0.001).Both AT1R and ETAR correlated to IL-6 plasma levels. The results did not show association with the concomitant therapy.

Conclusion
In conclusion, we establishеd the presence of AT1R and ETAR autoantibodies in COVID-19 patients with heart failure with preserved ejection fraction. They correlated to IL-6 plasma levels (systemic inflammation) and are associated with severe form of the disease.
Construction of an inflammatory, nutritional, and metabolic prognostic risk score in patients with heart failure with preserved ejection fraction: a machine learning-based approach
Authors: Feng J , Huang L , Li X , Xin A , Wang C , Zhang J , Zhang Y 
Published: October 2024

Abstract

Background
Chronic inflammation, malnutrition, and metabolic syndrome contribute to the underlying mechanisms of heart failure with preserved ejection fraction (HFpEF). Inflammatory, nutritional, and metabolic biomarkers often interact with each other and affect the prognosis of patients.

Purpose
We aimed to identify the most predictive indicators from a pool of 21 biomarkers encompassing inflammation, nutritional status, as well as lipid, glucose, thyroid, and uric acid metabolism. Subsequently, predictive biomarkers were used to develop a risk score to enhance risk prediction for patients with HFpEF.

Methods
We included patients diagnosed with HFpEF and without infective or systemic disease. The primary outcome was all-cause mortality. We employed the Least Absolute Shrinkage and Selection Operator (LASSO) regression to screen the biomarkers. A machine learning-based approach was utilized to fine-tune the optimal model parameters. Additionally, we generated 1000 bootstrapping datasets to identify biomarkers recurring above a 95% frequency in repetitions, which were then employed to formulate the biomarker risk score. The discrimination of incorporating the risk score into the basic model was evaluated using 100 iterations of 5-fold cross-validation to assess the predictive efficacy.

Results
Among the 1311 included patients (with a median age of 64 years and 42.6% female), 363 patients (27.7%) experienced mortality over a median follow-up period of 2.7 years. The final risk score model was derived from 5 biomarkers—albumin (ALB), red blood cell distribution width-standard deviation (RDW-SD), lymphocytes, triiodothyronine (T3), and uric acid—each selected in over 95% of 1000 bootstrapping iterations. Integration of this risk score into the basic model notably enhanced discrimination (∆C-index=0.015, 95% CI 0.005-0.023) and reclassification (IDI: 3.3%, 95% CI 1.7%-5.8%; NRI: 15.2%, 95% CI 6.5%-22.5%) for risk stratification. In time-dependent receiver operating characteristic (ROC) analysis, the mean area under the curve (AUC) of the risk score was 0.688, 0.710, and 0.738 at 1, 3, and 5 years post-discharge, respectively, in the cross-validation sets. Incorporating the risk score into the basic model significantly improved the AUC at 1, 3, and 5 years (DeLong test P-value&lt;0.05). Furthermore, in multivariable Cox regression, the risk score demonstrated an independent association with all-cause mortality (HR: 1.81, 95% CI 1.51-2.16, P&lt;0.001 per 1 score increase).

Conclusions
A risk score derived from 5 commonly used inflammatory, nutritional, thyroid and uric acid metabolic biomarkers can effectively identify high-risk patients with HFpEF. This approach supports the development of potential individualized management strategies for patients with HFpEF.Study population and model constructionPredictive performance of the risk score
Prognostic value of circulating glypican-4 in patients with chronic heart failure with reduced ejection fraction
Authors: Schwegel N , Santner V , Zach D K , Hoeller V , Wallner M , Muendlein A , Brandtner E M , Leiherer A , Drexel H , Mader A , Von Lewinski D , Ablasser K , Kolesnik E , Zirlik A , Verheyen N 
Published: October 2024

Abstract

Background
Chronic heart failure is one of the leading causes of hospitalization and mortality worldwide, with an ever-increasing prevalence. Glypican-4 (GPC4) is a cell surface protein part of the endothelial glycocalyx which is actively released into the circulation in the context of ischemia, inflammation, neurohumoral activity, and shear stress. The current literature on the association between circulating GPC4 and heart failure is limited and its prognostic value on top of established risk markers in chronic heart failure is unknown.

Purpose
In the present study, we aim to investigate the prognostic value of circulating GPC4 on clinical outcomes in a contemporary cohort of patients with stable chronic heart failure with reduced ejection fraction (HFrEF).

Methods
Symptomatic outpatients with stable chronic HFrEF were consecutively enrolled in a prospective cohort study. Circulating serum GPC4 levels were assessed using an enzyme-linked immunosorbent at baseline. Patient outcomes were retrieved from medical and health insurance records.

Results
We enrolled 205 patients with a median (interquartile range) age of 66 (59-74) years, with 22% females. Median left ventricular ejection fraction (LVEF) was 37 (30-43)%, median estimated glomerular filtration rate (eGFR) was 64 (48-80) ml/min/1,73 m2, median N-terminal pro-brain natriuretic peptide (NT-proBNP) was 964 (336-2173) pg/ml, median interleukin 6 (IL6) was 4.7 (3.2-7.9) pg/ml, and median GPC4 was 1553 (1034-1950) pg/ml.
During a median follow-up of 4.7 (4.0-5.3) years, 46 patients (22%) were hospitalized due to worsening heart failure (WHF), 18 patients (9%) died of cardiovascular (CV) cause, and 58 patients (28%) died of any cause. In univariate Cox-regression, serum GPC4 levels predicted WHF (HR 1.57, 95%CI 1.29-1.92, p&lt;0.001), CV death (HR 2.07, 95%CI 1.56-2.74, p&lt;0.001), and all-cause mortality (HR 1.93, 95%CI 1.59-2.34, p&lt;0.001). The association between serum GPC4 levels and both, CV death (HR 1.69, 95%CI 1.04-2.86, p=0.048) and all-cause mortality (HR 1.56, 95%CI 1.14-2.14, p=0.006) remained significant in a multivariable Cox-regression model adjusted for age, sex, eGFR, IL6, NT-proBNP, and LVEF.

Conclusion
In patients with stable chronic HFrEF, circulating GPC4 is significantly associated with cardiovascular outcome and is an independent predictor of all-cause mortality. The potential prognostic value in clinical routine of GPC4 should be addressed in prospective studies.
Prognostic value of soluble urokinase plasminogen activator receptor (suPAR) in patients admitted with acute heart failure
Authors: Kandiah A , Taraldsen I , El-Sheikh M , Olsen El Caidi N , Dencker Wisborg F , Dahlgaard Hove J , Grand J 
Published: October 2024

Abstract

Introduction
The inflammatory marker, soluble urokinase plasminogen activator receptor (suPAR), has emerged as a promising prognostic biomarker of heart failure (HF). Higher levels of suPAR in plasma are indicative of hospital readmissions and mortality. Currently little is known about suPAR-values upon admission in patients with acute heart failure (AHF).

Purpose
This study investigates the prevalence of elevated suPAR and prognostic value in patients hospitalized with AHF.

Methods
In this prospective cohort study, all patients ≥ 18 years old admitted at the Emergency Department at a large University Hospital in Denmark, were consecutively included from March 10, 2020, to March 31, 2022. The follow-up period was 365 days. The biomarker suPAR was measured in all patients upon admission (median time from admission to suPAR measurement was two hours (IQR 3: 3,9-6,9)). Patient data was extracted from the electronic patient record system, and a cardiologist adjudicated whether the patients had AHF. Patients were stratified according to validated cut-off values of suPAR above or below 6 ng/mL. Kaplan-Meier survival analysis and Cox Regression were used to assess the association between suPAR levels and one-year mortality outcomes.

Results
A total of 408 (5%) AHF patients, from a total population of 6,715, were included in the study. 40 patients were excluded due to missing suPAR-values and the final analysis comprised of 368 AHF patients. Among AHF patients upon admission, the mean suPAR value was 6.2 ng/mL (standard deviation [SD] = 4.8 ng/mL), and non-AHF patients had a mean value of 4.5 ng/mL (SD = 3.1 ng/mL).
A suPAR level above 6 ng/mL was significantly associated with mortality (figure 1), log-rank test p-value &lt; 0.0001. Furthermore, Cox regression analysis demonstrated that elevated suPAR levels were independently associated with increased risk of mortality with a hazard ratio (HR): 2.09 (95% CI: 1.59-2.90), p-value &lt; 0.001 after adjusting for potential confounders: age, sex, atrial fibrillation, Chronic Obstructive Pulmonary Disease, and Creatinine levels.

Conclusion
The inflammatory biomarker suPAR measured upon hospital admission in AHF patients is significantly associated with one-year mortality in patients admitted with AHF. The potential of suPAR as a valuable prognostic marker in AHF is offering clinicians a tool to identify high-risk patients and tailor management strategies, accordingly, thereby improving patient outcomes.Figure 1 - 1 year mortality