Proteomic biomarkers and pathway analysis for progression to heart failure in three epidemiological representative cohorts.

Aims: Biomarkers associated with asymptomatic ventricular dysfunction might improve risk stratification and identify pathways leading to heart failure (HF). We explored the association between proteomic biomarkers and left ventricular hypertrophy (LVH), diastolic dysfunction (DD) and incident HF in three population-based cohorts.

Methods And Results: A chip was used to measure 92 protein biomarkers in blood samples from >1500 Malmö Preventive Project (MPP) participants, of whom 514 had LVH (34%), 462 had DD (32.

Dapagliflozin and quality of life measured using the EuroQol 5-dimension questionnaire in patients with heart failure with reduced and mildly reduced/preserved ejection fraction.

Aims: Although much is known about the usefulness of heart failure (HF)-specific instruments for assessing patient well-being, less is known about the value of generic instruments for the measurement of health-related quality of life (HRQL) in HF. The aim of this study was to assess the relationship between the EuroQol 5-dimension 5-level (EQ-5D-5L) visual analogue scale (VAS) and index scores, clinical characteristics, and outcomes in patients with HF and the effect of dapagliflozin on these scores.

Methods And Results: We performed a patient-level pooled analysis of the DAPA-HF and DELIVER trials, which investigated the effectiveness and safety of dapagliflozin in patients with HF and reduced ejection fraction (HFrEF) and mildly reduced/preserved ejection fraction (HFmrEF/HFpEF), respectively.

Dapagliflozin and Timing of Prior Heart Failure Hospitalization: A Patient-Level Meta-Analysis of DAPA-HF and DELIVER.

Background: Patients recently hospitalized for heart failure (HF) are at a higher risk of adverse clinical outcomes, but they may experience a greater absolute and relative benefit from effective therapies than individuals who are considered more "stable."

Objectives: The authors examined the effects of dapagliflozin according to the timing of prior HF hospitalization in a patient-level pooled analysis of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure).

Methods: A total of 11,007 patients were randomized in DAPA-HF and DELIVER.

Prognostic Models for Mortality and Morbidity in Heart Failure With Preserved Ejection Fraction.

Importance: Accurate risk prediction of morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF) may help clinicians risk stratify and inform care decisions.

Objective: To develop and validate a novel prediction model for clinical outcomes in patients with HFpEF using routinely collected variables and to compare it with a biomarker-driven approach.

Design, Setting, And Participants: Data were used from the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial to derive the prediction model, and data from the Angiotensin Receptor Neprilysin Inhibition in Heart Failure With Preserved Ejection Fraction (PARAGON-HF) and the Irbesartan in Heart Failure With Preserved Ejection Fraction Study (I-PRESERVE) trials were used to validate it.

Cost-effectiveness of dapagliflozin for patients with heart failure across the spectrum of ejection fraction: A pooled analysis of DAPA-HF and DELIVER data.

Aim: To assess the cost-effectiveness of dapagliflozin in addition to usual care, compared with usual care alone, in a large population of patients with heart failure (HF), spanning the full range of left ventricular ejection fraction (LVEF).

Methods And Results: Patient-level data were pooled from HF trials (DAPA-HF, DELIVER) to generate a population including HF with reduced, mildly reduced and preserved LVEF, to increase statistical power and enable exploration of interactions among LVEF, renal function and N-terminal pro-B-type natriuretic peptide levels, as they are relevant determinants of health status in this population. Survival and HF recurrent event risk equations were derived and applied to a lifetime horizon Markov model with health states defined by Kansas City Cardiomyopathy Questionnaire total symptom score quartiles; costs and utilities were in the UK setting.

Galectin-4 is associated with diabetes and obesity in a heart failure population.

An association between high Galectin-4 (Gal-4) and prevalence of diabetes in subjects with heart failure (HF) has previously been reported. The purpose of this study was to confirm these findings, as well as to further investigate this association, in a Swedish HF population. In addition, a second aim was to explore Gal-4's association with obesity and biomarkers of metabolism and heart failure.

Efficacy of Dapagliflozin According to Heart Rate: A Patient-Level Pooled Analysis of DAPA-HF and DELIVER.

Background: Although elevated resting heart rate (HR) is associated with a higher risk of cardiovascular events in patients with heart failure with reduced ejection fraction in sinus rhythm (SR), the relationship between HR and outcomes among patients with heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction and in those with atrial fibrillation (AF) is uncertain. The aims of this study were to examine the association between baseline HR and outcomes across the range of left ventricular ejection fraction, in patients with and without AF, and evaluate the effect of dapagliflozin according to HR.

Methods: A patient-level pooled analysis of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure; heart failure with reduced ejection fraction) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure trial; heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction) trials.

Heart failure, chronic obstructive pulmonary disease and efficacy and safety of dapagliflozin in heart failure with mildly reduced or preserved ejection fraction: Insights from DELIVER.

Aim: Chronic obstructive pulmonary disease (COPD) is common in heart failure with a mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and is associated with worse outcomes. In a pre-specified analysis of DELIVER, we investigated the relationship between COPD status and outcomes, and the efficacy and safety of dapagliflozin, compared with placebo, according to COPD status.

Methods And Results: Patients with severe pulmonary disease (including COPD) were excluded from the trial.

Efficacy of Dapagliflozin According to Geographic Location of Patients With Heart Failure.

Background: Because clinical characteristics and prognosis vary by geographic region in patients with heart failure (HF), the response to treatment may also vary. A previous report suggested that the efficacy of sodium-glucose cotransporter-2 inhibitor efficacy in heart failure with reduced ejection fraction (HFrEF) may be modified by region.

Objectives: The goal of this study was to examine the efficacy and safety of dapagliflozin in patients with HF according to geographic region.

The cost-effectiveness of dapagliflozin in heart failure with preserved or mildly reduced ejection fraction: A European health-economic analysis of the DELIVER trial.

Aims: To determine the cost-effectiveness of dapagliflozin, added to usual care, in patients with heart failure (HF) with mildly reduced or preserved ejection fraction for the UK, German and Spanish payers using detailed patient-level data from the Dapagliflozin Evaluation to Improve the LIVEs of Patients with Preserved Ejection Fraction Heart Failure (DELIVER) trial.

Methods And Results: A lifetime Markov state-transition cohort model was developed. Quartiles of the Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) defined health states and monthly transition count data informed transition probabilities.

Efficacy and Safety of Dapagliflozin According to Frailty in Patients With Heart Failure: A Prespecified Analysis of the DELIVER Trial.

Background: Frailty is increasing in prevalence. Because patients with frailty are often perceived to have a less favorable risk/benefit profile, they may be less likely to receive new pharmacologic treatments. We investigated the efficacy and tolerability of dapagliflozin according to frailty status in patients with heart failure with mildly reduced or preserved ejection fraction randomized in DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure).

Dapagliflozin for heart failure according to body mass index: the DELIVER trial.

Aims: Obesity is common and associated with unique phenotypic features in heart failure with preserved ejection fraction (HFpEF). Therefore, understanding the efficacy and safety of new therapies in HFpEF patients with obesity is important. The effects of dapagliflozin were examined according to body mass index (BMI) among patients in the Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure trial.

Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction.

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death among patients with chronic heart failure and a left ventricular ejection fraction of 40% or less. Whether SGLT2 inhibitors are effective in patients with a higher left ventricular ejection fraction remains less certain.

Methods: We randomly assigned 6263 patients with heart failure and a left ventricular ejection fraction of more than 40% to receive dapagliflozin (at a dose of 10 mg once daily) or matching placebo, in addition to usual therapy.

Galectin-4 levels in hospitalized versus non-hospitalized subjects with obesity: the Malmö Preventive Project.

Background: Obesity is strongly associated with the development of cardiovascular disease (CVD). However, the heterogenous nature of obesity in CVD-risk is still poorly understood. We aimed to explore novel CVD biomarkers and their possible association with presumed unhealthy obesity, defined as hospitalized subjects with obesity (HO).

Physical Inactivity Is Associated With Post-discharge Mortality and Re-hospitalization Risk Among Swedish Heart Failure Patients-The HARVEST-Malmö Study.

Background: Several studies have examined the role of physical activity as a predictor of heart failure (HF) mortality and morbidity. Here, we aimed to evaluate the role of self-reported physical activity as an independent risk factor of post-discharge mortality and re-hospitalization in patients hospitalized for HF, as well as study the association between physical activity and 92 plasma proteins associated with cardiovascular disease (CVD).

Methods: Four-hundred-and-thirty-four patients hospitalized for HF (mean age 75 years; 32% women) were screened for physical activity derived from questionnaires in the Swedish national public health survey.

Proteomic and Metabolomic Characterization of Metabolically Healthy Obesity: A Descriptive Study from a Swedish Cohort.

Method: Associations between different biomarkers (proteomics, lipidomics, and metabolomics) coupled to either MHO or metabolically unhealthy obese (MUO) individuals were analyzed through principal component analysis (PCA). Subjects were identified from a subsample of 416 obese individuals, selected from the Malmö Diet and Cancer study-Cardiovascular arm (MDCS-CV,  = 3,443). They were further divided into MHO ( = 143) and MUO ( = 273) defined by a history of hospitalization, or not, at baseline inclusion, and nonobese subjects (NOC,  = 3,027).

Antibodies against phosphorylcholine in hospitalized versus non-hospitalized obese subjects.

Obesity associates with reduced life expectancy, type 2 diabetes, hypertension and cardiovascular disease, and is characterized by chronic inflammation. Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein, dead cells and some microorganisms. Antibodies against PC (anti-PC) have anti-inflammatory properties.

The Shrunken pore syndrome is associated with poor prognosis and lower quality of life in heart failure patients: the HARVEST-Malmö study.

Aims: This study aimed to investigate the association between the 'Shrunken pore syndrome' (SPS) and risk of death, 30 day rehospitalization, and health-related quality of life (QoL) in heart failure (HF) patients. SPS is characterized by a difference in renal filtration between cystatin C and creatinine, resulting in a low eGFR /eGFR ratio.

Methods And Results: A total of 373 patients hospitalized for HF [mean age 74.

Self-care Management Intervention in Heart Failure (SMART-HF): A Multicenter Randomized Controlled Trial.

Background: Self-care behavior is important in avoiding hospitalization for patients with heart failure (HF) and refers to those activities performed with the intention of improving or restoring health and well-being, as well as treating or preventing disease. The purpose was to study the effects of a home-based mobile device on self-care behavior and hospitalizations in a representative HF-population.

Methods And Results: SMART-HF is a randomized controlled multicenter clinical trial, where patients were randomized 1:1 to receive standard care (control group [CG]) or intervention with a home-based tool designed to enhance self-care behavior (intervention group [IG]) and followed for 240 days.

Proteins linked to atherosclerosis and cell proliferation are associated with the shrunken pore syndrome in heart failure patients: Shrunken pore syndrome and proteomic associations.

Purpose: The "Shrunken pore syndrome" (SPS) is characterized by a difference in renal filtration between cystatin C and creatinine, resulting in a low eGFR /eGFR -ratio. Studies have demonstrated a high risk for cardiovascular morbidity and mortality for patients with SPS. In this discovery study, we explored associations between SPS and proteins implicated in cardiovascular disease and inflammation in patients with heart failure.

Impaired cerebral oxygenation in heart failure patients at rest and during head-up tilt testing.

Aims: Heart failure (HF) confers potentially negative effects on the brain and autonomic nervous system. The measurement cerebral tissue oxygen saturation (SctO ) may aid in understanding such effects. We aimed to investigate if compensated HF affects SctO at rest and during orthostatic challenge.

Cognitive test results are associated with mortality and rehospitalization in heart failure: Swedish prospective cohort study.

Aims: We aimed to search for associations between cognitive test results with mortality and rehospitalization in a Swedish prospective heart failure (HF) patient cohort.

Methods And Results: Two hundred and eighty-one patients hospitalized for HF (mean age, 74 years; 32% women) were assessed using cognitive tests: Montreal Cognitive Assessment (MoCA), A Quick Test of Cognitive speed, Trail Making Test A, and Symbol Digit Modalities Test. The mean follow-up time censored at rehospitalization or death was 13 months (interquartile range, 14) and 28 months (interquartile range, 29), respectively.

High circulating levels of midregional proenkephalin A predict vascular dementia: a population-based prospective study.

Midregional Pro-enkephalin A (MR-PENK A) and N-terminal Protachykinin A (NT-PTA) have been associated with vascular dementia. However, the longitudinal relationship between these biomarkers and incident dementia has not been fully investigated. In the population-based Malmö Preventive Project, circulating levels of MR-PENK A and NT-PTA were determined in a random sample of 5,323 study participants (mean age: 69 ± 6 years) who were followed-up over a period of 4.