Empagliflozin to elderly and obese patients with increased risk of developing heart failure: Study protocol for the Empire Prevent trial program.

Introduction: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have previously demonstrated cardioprotective properties in patients with type 2 diabetes, suggesting a preventive effect on heart failure (HF). The Empire Prevent trial program investigates the therapeutic potential for HF prevention by evaluating the cardiac, metabolic, and renal effects of the SGLT2 inhibitor empagliflozin in patients with increased risk of developing HF, but without diabetes or established HF.

Methods: The Empire Prevent trial program is an investigator-initiated, double-blind, randomized clinical trial program including elderly and obese patients (60-84 years, body mass index >28 kg/m) with at least one manifestation of hypertension, cardiovascular or chronic kidney disease, but no history of diabetes or HF.

Thoracentesis to alleviate pleural effusion in acute heart failure: study protocol for the multicentre, open-label, randomised controlled TAP-IT trial.

Introduction: Pleural effusion is present in half of the patients hospitalised with acute heart failure. The condition is treated with diuretics and/or therapeutic thoracentesis for larger effusions. No evidence from randomised trials or guidelines supports thoracentesis to alleviate pleural effusion due to acute heart failure.

Specialized heart failure clinics versus primary care: Extended registry-based follow-up of the NorthStar trial.

Background: Whether continued follow-up in specialized heart failure (HF) clinics after optimization of guideline-directed therapy improves long-term outcomes in patients with HF with reduced ejection fraction (HFrEF) is unknown.

Methods And Results: 921 medically optimized HFrEF patients enrolled in the NorthStar study were randomly assigned to follow up in a specialized HF clinic or primary care and followed for 10 years using Danish nationwide registries. The primary outcome was a composite of HF hospitalization or cardiovascular death.

Effects of empagliflozin on erythropoiesis in heart failure: data from the Empire HF trial.

Aims: It remains unknown whether the consistently observed increase in haematocrit with sodium-glucose cotransporter 2 inhibitors is caused by diuresis-associated haemoconcentration or increased erythropoiesis. We aimed to investigate the early effect of empagliflozin on erythropoiesis and iron metabolism in patients with heart failure with reduced ejection fraction (HFrEF).

Methods And Results: The Empire HF was a double-blind, randomized, placebo-controlled trial.

The effect of empagliflozin on contractile reserve in heart failure: Prespecified sub-study of a randomized, double-blind, and placebo-controlled trial.

Background: Sodium-glucose co-transporter-2 inhibitors improve cardiac structure but most studies suggest no change in left ventricular (LV) systolic function at rest. Whether sodium-glucose co-transporter-2 inhibitors improve LV contractile reserve is unknown. We investigated the effect of empagliflozin on LV contractile reserve in patients with heart failure (HF) and reduced ejection fraction.

[Infective endocarditis].

Infective endocarditis (IE) is one of the most severe infectious diseases with an in-hospital mortality of 20-25%. Several studies have shown, that the incidence of IE is increasing, and that patients now are older with a higher burden of comorbidities than previously. The diagnostic work-up is mainly based upon the presence of bacteraemia and echocardiography.

The effect of empagliflozin on growth differentiation factor 15 in patients with heart failure: a randomized controlled trial (Empire HF Biomarker).

Background: Plasma growth differentiation factor-15 (GDF-15) biomarker levels increase in response to inflammation and tissue injury, and increased levels of GDF-15 are associated with increased risk of mortality in patients with heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter-2 (SGLT2) inhibitors, which improve outcome in HFrEF, have been shown to increase plasma GDF-15 in diabetic patients. We aimed to investigate the effect of empagliflozin on GDF-15 in HFrEF patients.

Associations of Empagliflozin With Left Ventricular Volumes, Mass, and Function in Patients With Heart Failure and Reduced Ejection Fraction: A Substudy of the Empire HF Randomized Clinical Trial.

Importance: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) improve outcomes in patients with heart failure and a reduced ejection fraction (HFrEF). The association with cardiac remodeling has not been investigated.

Objective: To investigate the outcome of the SGLT2i empagliflozin, compared with placebo, on cardiac remodeling in patients with HFrEF.

Effects of empagliflozin on estimated extracellular volume, estimated plasma volume, and measured glomerular filtration rate in patients with heart failure (Empire HF Renal): a prespecified substudy of a double-blind, randomised, placebo-controlled trial.

Background: SGLT2 inhibitors are a promising treatment option in patients with heart failure and reduced ejection fraction. We aimed to investigate the effects of empagliflozin on estimated extracellular volume, estimated plasma volume, and measured glomerular filtration rate (GFR) in patients with heart failure and reduced ejection fraction.

Methods: Empire HF Renal was a prespecified substudy of the investigator-initiated, double-blind, randomised, placebo-controlled Empire HF trial.

Twelve weeks of treatment with empagliflozin in patients with heart failure and reduced ejection fraction: A double-blinded, randomized, and placebo-controlled trial.

Aims: To investigate the effect of the sodium-glucose co-transporter-2 inhibitor empagliflozin on N-terminal pro-b-type natriuretic peptide (NT-proBNP) in patients with heart failure (HF) and reduced ejection fraction (HFrEF).

Methods And Results: Empire HF was an investigator-initiated, multi-center, double-blinded, placebo-controlled, randomized trial. Patients with mildly symptomatic HFrEF, mean (standard deviation (SD)) age 64 (11) years, 85% male, and mean left ventricular ejection fraction 29% (8), on recommended HF therapy were assigned to receive either empagliflozin 10 mg once daily or placebo for 12 weeks.

Ischemic Preconditioning Improves Microvascular Endothelial Function in Remote Vasculature by Enhanced Prostacyclin Production.

BACKGROUND The mechanisms underlying the effect of preconditioning on remote microvasculature remains undisclosed. The primary objective was to document the remote effect of ischemic preconditioning on microvascular function in humans. The secondary objective was to test if exercise also induces remote microvascular effects.

Accelerated treatment of endocarditis-The POET II trial: Rationale and design of a randomized controlled trial.

Background: The optimal antibiotic treatment length for infective endocarditis (IE) is uncertain. International guidelines recommend treatment duration of up to 6 weeks for patients with left-sided IE but are primarily based on historical data and expert opinion. Efficacies of modern therapies, fast recovery seen in many patients with IE, and complications to long hospital stays challenge the rationale for fixed treatment durations in all patients.

Empagliflozin in heart failure patients with reduced ejection fraction: a randomized clinical trial (Empire HF).

Background: Data from recent cardiovascular outcome trials in patients with type 2 diabetes (T2D) suggest that sodium-glucose cotransporter 2 (SGLT2) inhibitors can prevent development of heart failure (HF) and prolong life in patients without HF. Ongoing event-driven trials are investigating whether the same effect is present in patients with well-defined HF. The mechanism behind the effect of SGLT2 inhibitors in patients with T2D and the potential effect in patients with overt HF is presently unknown.

Galectin-3 and fibulin-1 in systolic heart failure - relation to glucose metabolism and left ventricular contractile reserve.

Background: Heart failure (HF) patients with diabetes (DM) have an adverse prognosis and reduced functional capacity, which could be associated with cardiac fibrosis, increased chamber stiffness and reduced left ventricular (LV) contractile reserve. Galectin-3 (Gal-3) and fibulin-1 are circulating biomarkers potentially reflecting cardiac fibrosis. We hypothesize that plasma levels of Gal-3 and fibulin-1 are elevated in HF patients with DM and are associated with reduced LV contractile reserve in these patients.

Effect of extended follow-up in a specialized heart failure clinic on adherence to guideline recommended therapy: NorthStar Adherence Study.

Aims: The optimal duration of a public heart failure (HF) clinic programme is unknown. This substudy of the NT-proBNP stratified follow-up in outpatient heart failure clinics (NorthStar) trial was designed to evaluate the effect of extended follow-up in an outpatient HF clinic on long-term adherence to guideline-based therapy.

Methods And Results: Patients with HF with reduced EF on optimal medical therapy (n = 921) were randomized to either extended follow-up in the HF clinic (n = 461) or discharge to primary care (n = 460) and followed for a median of 4.

Haemodynamic response during low-dose dobutamine infusion in patients with chronic systolic heart failure: comparison of echocardiographic and invasive measurements.

Aims: To investigate whether left ventricular (LV) systolic shortening velocity (s'), diastolic lengthening velocity (e'), and non-invasively estimated LV filling pressure (E/e') during low-dose dobutamine echocardiography (LDDE) reflect invasive measures of cardiac output and pulmonary capillary wedge pressure (PCWP) in stable patients with chronic systolic heart failure.

Methods And Results: Fourteen patients with heart failure (aged 65 ± 8 years, LVEF 36 ± 8%) underwent simultaneous tissue Doppler echocardiography and invasive measurements of cardiac output and PCWP by right heart catheterization at rest and during dobutamine infusion at rates of 10 and 20 µg/kg/min. Cardiac output increased from rest to peak dobutamine (4.

Abnormal glucose metabolism is associated with reduced left ventricular contractile reserve and exercise intolerance in patients with chronic heart failure.

Aims: To investigate the associations between glucose metabolism, left ventricular (LV) contractile reserve, and exercise capacity in patients with chronic systolic heart failure (HF).

Methods And Results: From an outpatient HF clinic, 161 patients with systolic HF were included (mean age 70 ± 10 years, 69% male, 59% had ischaemic heart disease, mean LV ejection fraction (LVEF) 37 ± 9%). Thirty-four (21%) patients had known diabetes mellitus (DM).

Extended heart failure clinic follow-up in low-risk patients: a randomized clinical trial (NorthStar).

Background: Outpatient follow-up in specialized heart failure clinics (HFCs) is recommended by current guidelines and implemented in most European countries, but the optimal duration of HFC programmes has not been established. Nor is it known whether all or only high-risk patients, e.g.

Prediction of outcome by highly sensitive troponin T in outpatients with chronic systolic left ventricular heart failure.

Our aim was to assess the prognostic impact of a high-sensitivity cardiac troponin T (hs-cTnT) assay in an outpatient population with chronic systolic left ventricular heart failure (HF). Four hundred sixteen patients with chronic HF and left ventricular ejection fraction ≤ 45% were enrolled in a prospective cohort study. In addition to hs-cTnT, plasma amino-terminal pro-B-type natriuretic peptide was measured at baseline.

Cardiovascular events in thyroid disease: a population based, prospective study.

No consensus exists whether subclinical thyroid disease should be treated or just observed. Untreated overt thyroid disease is associated with increased risk of cardiovascular disease, and this study was conducted to assess the risk of cardiovascular events in subclinical thyroid disease. The population-based prospective study was conducted in Denmark.