Effect of eplerenone on clinical stability of Japanese patients with acute heart failure.

Background: In the EARLIER (Efficacy and Safety of Early Initiation of Eplerenone Treatment in Patients with Acute Heart Failure) trial, eplerenone did not reduce heart failure (HF) hospitalizations or all-cause mortality in 300 patients admitted for acute HF (AHF). However, the trial might have been underpowered for these endpoints, and a comprehensive overview of the effect of eplerenone on diuretic doses and patients' clinical stability is warranted.

Methods: The EARLIER trial included Japanese patients hospitalized for AHF randomly assigned to eplerenone or placebo over 6 months.

Efficacy of empagliflozin in heart failure with preserved versus mid-range ejection fraction: a pre-specified analysis of EMPEROR-Preserved.

The EMPEROR-Preserved trial showed that the sodium-glucose co-transporter 2 inhibitor empagliflozin significantly reduces the risk of cardiovascular death or hospitalization for heart failure (HHF) in heart failure patients with left ventricular ejection fraction (LVEF)  > 40%. Here, we report the results of a pre-specified analysis that separately evaluates these patients stratified by LVEF: preserved (≥ 50%) (n = 4,005; 66.9%) or mid-range (41-49%).

Impact of empagliflozin on decongestion in acute heart failure: the EMPULSE trial.

Aims: Effective and safe decongestion remains a major goal for optimal management of patients with acute heart failure (AHF). The effects of the sodium-glucose cotransporter 2 inhibitor empagliflozin on decongestion-related endpoints in the EMPULSE trial (NCT0415775) were evaluated.

Methods And Results: A total of 530 patients hospitalized for AHF were randomized 1:1 to either empagliflozin 10 mg once daily or placebo for 90 days.

Effects of empagliflozin on cardiovascular and renal outcomes in heart failure with reduced ejection fraction according to age: a secondary analysis of EMPEROR-Reduced.

Aims: Empagliflozin improves cardiovascular and renal outcomes in patients with heart failure (HF) and reduced ejection fraction (HFrEF), but its efficacy and safety across patient's age is not well established.

Methods And Results: We assessed the effects of empagliflozin (10 mg daily) versus placebo, on top of standard HF therapy, in symptomatic HFrEF patients with a left ventricular ejection fraction ≤40% and increased natriuretic peptides stratified by age (<65, 65-74, ≥75 years). The primary endpoint was a composite of cardiovascular death or HF hospitalization.

Interleukin-6, infection and cardiovascular outcomes in acute heart failure: Findings from the EDIFICA registry.

Aims: Interleukin-6 (IL-6) is upregulated in response to infectious and inflammatory triggers and independently predicts all-cause mortality in acute heart failure (AHF). However, the association of IL-6 with cardiovascular outcomes and its interplay with C-reactive protein and infection, a major precipitating factor in AHF, remains poorly understood.

Methods And Results: The association between IL-6 and clinical outcomes (180 days) in AHF was evaluated using a cohort of 164 patients from the EDIFICA registry.

Association of Empagliflozin Treatment With Albuminuria Levels in Patients With Heart Failure: A Secondary Analysis of EMPEROR-Pooled.

Importance: Albuminuria, routinely assessed as spot urine albumin-to-creatinine ratio (UACR), indicates structural damage of the glomerular filtration barrier and is associated with poor kidney and cardiovascular outcomes. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been found to reduce UACR in patients with type 2 diabetes, but its use in patients with heart failure (HF) is less well studied.

Objective: To analyze the association of empagliflozin with study outcomes across baseline levels of albuminuria and change in albuminuria in patients with HF across a wide range of ejection fraction levels.

Effects of Empagliflozin in Women and Men With Heart Failure and Preserved Ejection Fraction.

Background: Women and men with heart failure (HF) and preserved ejection fraction may differ in their clinical characteristics and their response to therapy. The aim of this study was to evaluate the influence of sex on the effects of empagliflozin in patients with HF and preserved ejection fraction enrolled in the EMPEROR-Preserved trial (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction).

Methods: The effects of empagliflozin on the primary outcome of cardiovascular death or hospitalization for HF and on secondary outcomes (including total HF hospitalization, cardiovascular and all-cause mortality, and Kansas City Cardiomyopathy Questionnaire scores) were compared in women and men in the overall cohort and in subgroups defined by left ventricular ejection fraction (41%-49%, 50%-59%, and ≥60%).

Renal effects of empagliflozin in patients hospitalized for acute heart failure: from the EMPULSE trial.

Aim: The sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin improved clinical outcomes in patients hospitalized for acute heart failure. In patients with chronic heart failure, SGLT2 inhibitors cause an early decline in estimated glomerular filtration rate (eGFR) followed by a slower eGFR decline over time than placebo. However, the effects of SGLT2 inhibitors on renal function during a hospital admission for acute heart failure remain largely unknown.

Effect of empagliflozin on circulating proteomics in heart failure: mechanistic insights into the EMPEROR programme.

Aims: Sodium-glucose co-transporter 2 (SGLT2) inhibitors improve cardiovascular outcomes in diverse patient populations, but their mechanism of action requires further study. The aim is to explore the effect of empagliflozin on the circulating levels of intracellular proteins in patients with heart failure, using large-scale proteomics.

Methods And Results: Over 1250 circulating proteins were measured at baseline, Week 12, and Week 52 in 1134 patients from EMPEROR-Reduced and EMPEROR-Preserved, using the Olink® Explore 1536 platform.

Biomarker-driven prognostic models in chronic heart failure with preserved ejection fraction: the EMPEROR-Preserved trial.

Aims: Biomarker-driven prognostic models incorporating N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) in heart failure (HF) with preserved ejection fraction (HFpEF) are lacking. We aimed to generate a biomarker-driven prognostic tool for patients with chronic HFpEF enrolled in EMPEROR-Preserved.

Methods And Results: Multivariable Cox regression models were created for (i) the primary composite outcome of HF hospitalization or cardiovascular death, (ii) all-cause death, (iii) cardiovascular death, and (iv) HF hospitalization.

Uric acid and sodium-glucose cotransporter-2 inhibition with empagliflozin in heart failure with reduced ejection fraction: the EMPEROR-reduced trial.

Background: The sodium-glucose cotransporter-2 inhibitor empagliflozin decreases the risk of cardiovascular death or hospitalization for heart failure (HF) in patients with HF with reduced ejection fraction. Empagliflozin reduces serum uric acid (SUA), but the relevance of this effect in patients with HF is unclear. This study aimed to investigate the effect of empagliflozin on SUA levels and the therapeutic efficacy of empagliflozin in relation to SUA.

Management of dyslipidemia and atherosclerotic cardiovascular risk in prediabetes.

Prediabetes affects at least 1 in 3 adults in the U.S. and 1 in 5 in Europe.

Empagliflozin for Heart Failure With Preserved Left Ventricular Ejection Fraction With and Without Diabetes.

Background: Empagliflozin improves outcomes in patients with heart failure with a preserved ejection fraction, but whether the effects are consistent in patients with and without diabetes remains to be elucidated.

Methods: Patients with class II through IV heart failure and a left ventricular ejection fraction >40% were randomized to receive empagliflozin 10 mg or placebo in addition to usual therapy. We undertook a prespecified analysis comparing the effects of empagliflozin versus placebo in patients with and without diabetes.

Early changes in estimated glomerular filtration rate post-initiation of empagliflozin in EMPEROR-Reduced.

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) may induce an early post-initiation decrease of estimated glomerular filtration rate (eGFR), which does not impact the SGLT2i benefits. The occurrence, characteristics, determinants, and clinical significance of an initial eGFR change among patients with heart failure with reduced ejection fraction require further study. In this study we aimed to describe eGFR change from randomization to week 4 (as percent of change relative to randomization) and assess its impact in EMPEROR-Reduced.

The association between markers of type I collagen synthesis and echocardiographic response to spironolactone in patients at risk of heart failure: findings from the HOMAGE trial.

Aims: Procollagen type I C-terminal propeptide (PICP) and procollagen type III N-terminal propeptide (PIIINP) are markers reflecting collagen synthesis in cardiac fibrosis. However, they may be influenced by the presence of non-cardiac comorbidities (e.g.

Empagliflozin and serum potassium in heart failure: an analysis from EMPEROR-Pooled.

Aims: Hyperkalaemia frequently leads to interruption and discontinuation of neurohormonal antagonists, which may worsen heart failure prognosis. Some studies suggested that sodium-glucose cotransporter 2 inhibitors reduce hyperkalaemia, an effect that may have important clinical implications. This analysis evaluates the effect of empagliflozin on the occurrence of hyper- and hypokalaemia in HF.

Association of combined fractional excretion of phosphate and FGF23 with heart failure and cardiovascular events in moderate and advanced renal disease.

Background: High levels of FGF23 associate with adverse events in CKD. The urinary fractional excretion of phosphate (FePi) might modify this association, although data are limited in moderate and advanced CKD. We investigated the association of combined FePi and serum FGF23 with incident heart failure, cardiovascular events and mortality in patients with CKD stages 2-4.

Outcomes with empagliflozin in heart failure with preserved ejection fraction using DELIVER-like endpoint definitions.

Aims: To report data from EMPEROR-Preserved according to prespecified endpoints of DELIVER.

Methods And Results: In order to assess the impact of DELIVER-like definition on EMPEROR-Preserved outcomes, the following differences were reconciled: (1) the primary outcome in DELIVER added urgent heart failure (HF) visits to cardiovascular death or HF hospitalizations; (2) the EMPEROR-Preserved trial did not require documentation of physical findings or laboratory tests for confirming a HF hospitalization and it included events of 12-24 h if intensification of treatment was not only oral diuretics; (3) DELIVER excluded undetermined causes of deaths from the primary endpoint; (4) the composite renal endpoint in DELIVER included a sustained ≥50% decline in estimated glomerular filtration rate and incorporated renal death; and (5) DELIVER will assess outcomes in the overall population and in patients with ejection fraction (EF) <60% separately. Using the endpoint definitions from DELIVER, the primary outcome overall occurred in 13.

Myogenic Underactive Bladder and Heart Failure Resemblance: A Novel Role for SGLT2 Inhibition?

The heart and bladder share physiological biomechanical determinants of contraction. Heart failure (HF) and myogenic underactive bladder (mUAB) also share similarities in their pathophysiology. In both cases there is muscle injury that is directly linked to disease stage.

Clinical Prediction Models for Heart Failure Hospitalization in Type 2 Diabetes: A Systematic Review and Meta-Analysis.

Background Clinical prediction models have been developed for hospitalization for heart failure in type 2 diabetes. However, a systematic evaluation of these models' performance, applicability, and clinical impact is absent. Methods and Results We searched Embase, MEDLINE, Web of Science, Google Scholar, and Tufts' clinical prediction registry through February 2021.

Sympathovagal imbalance in early ischemic stroke is linked to impaired cerebral autoregulation and increased infarct volumes.

Background And Purpose: Autonomic dysfunction is associated with worse outcome of ischemic stroke patients by mechanisms that are not fully understood. There is evidence of autonomic influence in cerebrovascular control but this has not been studied in acute stroke. Therefore, we examined the relationship between heart rate variability (HRV) and baroreflex sensitivity (BRS) in dynamic cerebral autoregulation in the early hours post ischemia, and its impact in clinical and radiological outcome.

Effects of Empagliflozin on Symptoms, Physical Limitations, and Quality of Life in Patients Hospitalized for Acute Heart Failure: Results From the EMPULSE Trial.

Background: Patients hospitalized for acute heart failure experience poor health status, including a high burden of symptoms and physical limitations, and poor quality of life. SGLT2 (sodium-glucose cotransporter 2) inhibitors improve health status in chronic heart failure, but their effect on these outcomes in acute heart failure is not well characterized. We investigated the effects of the SGLT2 inhibitor empagliflozin on symptoms, physical limitations, and quality of life, using the Kansas City Cardiomyopathy Questionnaire (KCCQ) in the EMPULSE trial (Empagliflozin in Patients Hospitalized With Acute Heart Failure Who Have Been Stabilized).

Cardiac remodelling - Part 1: From cells and tissues to circulating biomarkers. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology.

Cardiac remodelling refers to changes in left ventricular structure and function over time, with a progressive deterioration that may lead to heart failure (HF) development (adverse remodelling) or vice versa a recovery (reverse remodelling) in response to HF treatment. Adverse remodelling predicts a worse outcome, whilst reverse remodelling predicts a better prognosis. The geometry, systolic and diastolic function and electric activity of the left ventricle are affected, as well as the left atrium and on the long term even right heart chambers.