Effect of empagliflozin on total myocardial infarction events by type and additional coronary outcomes: insights from the randomized EMPA-REG OUTCOME trial.

Background: The effect of empagliflozin, a sodium-glucose-co-transporter-2 inhibitor, on risk for myocardial infarction has not been fully characterized.

Methods: This study comprised prespecified and post-hoc analyses of the EMPA-REG OUTCOME trial in which 7020 people with type 2 diabetes (T2D) and cardiovascular disease [mostly atherosclerotic (ASCVD)] were randomized to empagliflozin or placebo and followed for a median 3.1 years.

Vascular Disease Burden, Outcomes and Benefits with Empagliflozin in Heart Failure: Insights From the EMPEROR-Reduced Trial.

Background: The presence of ischemic heart disease impacts prognosis in patients affected by heart failure and reduced ejection fraction (HFrEF). It is not well known how the extent of vascular disease impacts prognoses and responses to therapy in this setting.

Methods: In this post hoc analysis of the EMPEROR-Reduced trial, outcomes and the effects of empagliflozin, were assessed in study participants according to the extent (none vs mono vs poly [≥ 2] vascular bed) of vascular disease.

"Click and mortar" opportunities for digitization and consumerism in trials.

Background: Digitization (using novel digital tools and strategies) and consumerism (taking a consumer-oriented approach) are increasingly commonplace in clinical trials, but the implications of these changes are not well described.

Methods: We assembled a group of trial experts from academia, industry, non-profit, and government to discuss implications of this changing trial landscape and provide guidance.

Results: Digitization and consumerism can increase the volume and diversity of trial participants and expedite recruitment.

Lessons From COVID-19 for Pandemic Preparedness: Proceedings From a Multistakeholder Think Tank.

While the coronavirus disease 2019 (COVID-19) pandemic continues to present global challenges, sufficient time has passed to reflect on lessons learned and use those insights to inform policy and approaches to prepare for the next pandemic. In May 2022, the Duke Clinical Research Institute convened a think tank with thought leaders from academia, clinical practice, the pharmaceutical industry, patient advocacy, the National Institutes of Health, the US Food and Drug Administration, and the Centers for Disease Control and Prevention to share, firsthand, expert knowledge of the insights gained from the COVID-19 pandemic and how this acquired knowledge can help inform the next pandemic response. The think tank focused on pandemic preparedness, therapeutics, vaccines, and challenges related to clinical trial design and scale-up during the early phase of a pandemic.

Health status across major subgroups of patients with heart failure and preserved ejection fraction.

Aims: There are limited data on health status and changes in it over time across major subgroups of patients with heart failure and preserved ejection fraction (HFpEF), including ejection fraction spectrum, age, sex, region, body mass index (BMI), and comorbidities including diabetes, chronic kidney disease (CKD), anaemia, and atrial fibrillation/flutter.

Methods And Results: In the EMPEROR-Preserved trial, the Kansas City Cardiomyopathy Questionnaire (KCCQ) was assessed at baseline, 12, 32 and 52 weeks. Determinants of baseline KCCQ score and change over time, and the impact of empagliflozin on KCCQ scores were studied in specified subgroups.

Impact of Empagliflozin in Heart Failure With Reduced Ejection Fraction in Patients With Ischemic Versus Nonischemic Cause.

Background Outcomes and treatment effects of therapy may vary according to the cause of heart failure (HF). Methods and Results In this post hoc analysis of the EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction) trial, the effect of empagliflozin on cardiovascular and renal outcomes was assessed according to the cause of HF. The cause of HF was investigator reported and stratified as ischemic or nonischemic.

Comparative effectiveness of Empagliflozin in reducing the burden of recurrent cardiovascular hospitalizations among older adults with diabetes in routine clinical care.

Background: The effect of sodium glucose cotransporter 2 inhibitors (SGLT2i) on the total (first and recurrent) burden of cardiovascular (CV) hospitalizations, including hospitalization for heart failure, myocardial infarction, and stroke, is poorly understood.

Objective: To assess the effect of empagliflozin, an SGLT2i, on total CV hospitalizations among older adults with T2D.

Methods: Using data from Medicare fee-for-service (08/2014-09/2017), we identified 1:1 propensity score-matched cohorts of patients with T2D initiating empagliflozin versus sitagliptin or empagliflozin versus glucagon-like peptide-1 receptor agonists (GLP-1RA), balancing >140 baseline covariates.

Patients With Bicuspid Aortic Stenosis Demonstrate Adverse Left Ventricular Remodeling and Impaired Cardiac Function Before Surgery With Increased Risk of Postoperative Heart Failure.

Background: Differences in adverse cardiac remodeling between patients who have bicuspid (BAV) and tricuspid aortic valve (TAV) with severe isolated aortic stenosis (AS) and its prognostic impact after surgical aortic valve replacement remains unclear. We sought to investigate differences in preoperative diastolic and systolic function in patients with BAV and TAV who have severe isolated AS and the incidence of postoperative heart failure hospitalization and mortality.

Methods: Two hundred seventy-one patients with BAV (n=152) or TAV (n=119) and severe isolated AS without coronary artery disease or other valvular heart disease, scheduled for surgical aortic valve replacement, were prospectively included.

Prognostic Implications of N-Terminal Pro-B-Type Natriuretic Peptide and High-Sensitivity Cardiac Troponin T in EMPEROR-Preserved.

Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) are associated with disease severity and outcomes among patients with heart failure (HF) with preserved ejection fraction.

Objectives: The authors evaluated associations between both biomarkers and clinical outcomes in the EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction) trial.

Methods: Of 5,988 study participants, 5,986 (99.

Acute Decompensated Heart Failure in the Setting of Acute Coronary Syndrome.

Acute coronary syndrome (ACS) is frequently complicated by evidence of heart failure (HF). Those at highest risk for acute decompensated HF in the setting of ACS (ACS-HF) are older, female, and have preexisting heart disease, type 2 diabetes mellitus, hypertension, and/or kidney disease. The presence of ACS-HF is strongly associated with higher mortality and more frequent readmissions, especially for HF.

Empagliflozin in patients with type 2 diabetes mellitus and chronic obstructive pulmonary disease.

Aims: Type 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD) often co-exist, yielding increased risk of cardiovascular (CV) complications including heart failure (HF). We assessed risk of cardiorenal outcomes, mortality and safety in patients with versus without COPD in the EMPA-REG OUTCOME trial.

Methods: Patients (n = 7,020) with T2DM and CV disease (CVD) were treated with empagliflozin (10 mg or 25 mg) or placebo.

Empagliflozin, Health Status, and Quality of Life in Patients With Heart Failure and Preserved Ejection Fraction: The EMPEROR-Preserved Trial.

Background: Patients with heart failure with preserved ejection fraction have significant impairment in health-related quality of life. In the EMPEROR-Preserved trial (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction), we evaluated the efficacy of empagliflozin on health-related quality of life in patients with heart failure with preserved ejection fraction and whether the clinical benefit observed with empagliflozin varies according to baseline health status.

Methods: Health-related quality of life was measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and 12, 32, and 52 weeks.

Empagliflozin in Heart Failure With Predicted Preserved Versus Reduced Ejection Fraction: Data From the EMPA-REG OUTCOME Trial.

Background: In the EMPA-REG OUTCOME trial, ejection fraction (EF) data were not collected. In the subpopulation with heart failure (HF), we applied a new predictive model for EF to determine the effects of empagliflozin in HF with predicted reduced (HFrEF) vs preserved (HFpEF) EF vs no HF.

Methods And Results: We applied a validated EF predictive model based on patient baseline characteristics and treatments to categorize patients with HF as being likely to have HF with mid-range EF (HFmrEF)/HFrEF (EF <50%) or HFpEF (EF ≥50%).

Cardiovascular Events, Acute Hospitalizations, and Mortality in Patients With Type 2 Diabetes Mellitus Who Initiate Empagliflozin Versus Liraglutide: A Comparative Effectiveness Study.

Background In cardiovascular outcome trials, the sodium glucose cotransporter 2 inhibitor empagliflozin and glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide caused similar reductions in major adverse cardiac events (MACE). We compared clinical outcomes in routine clinical care. Methods and Results EMPLACE (Cardiovascular and Renal Outcomes, and Mortality in Danish Patients with Type 2 Diabetes Who Initiate Empagliflozin Versus GLP-1RA: A Danish Nationwide Comparative Effectiveness Study) is an ongoing nationwide population-based comparative effectiveness cohort study in Denmark.

Empagliflozin and health-related quality of life outcomes in patients with heart failure with reduced ejection fraction: the EMPEROR-Reduced trial.

Aims: In this secondary analysis of the EMPEROR-Reduced trial, we sought to evaluate whether the benefits of empagliflozin varied by baseline health status and how empagliflozin impacted patient-reported outcomes in patients with heart failure with reduced ejection fraction.

Methods And Results: Health status was assessed by the Kansas City Cardiomyopathy Questionnaires-clinical summary score (KCCQ-CSS). The influence of baseline KCCQ-CSS (analyzed by tertiles) on the effect of empagliflozin on major outcomes was examined using Cox proportional hazards models.

Implementation of sacubitril/valsartan in Sweden: clinical characteristics, titration patterns, and determinants.

Aims: The aim of this study is to study the introduction of sacubitril/valsartan (sac/val) in Sweden with regards to regional differences, clinical characteristics, titration patterns, and determinants of use and discontinuation.

Methods And Results: A national cohort of heart failure was defined from the Swedish Prescribed Drug Register and National Patient Register. A subcohort with additional data from the Swedish Heart Failure Registry (SwedeHF) was also studied.

Diagnostic Accuracy of [C]PIB Positron Emission Tomography for Detection of Cardiac Amyloidosis.

Objectives: This dual-site study evaluated the diagnostic accuracy of the method.

Background: Pittsburgh compound ([C]PIB) positron emission tomography (PIB-PET) has shown promise as a specific and noninvasive method for the diagnosis of cardiac amyloidosis (CA).

Methods: The study had 2 parts.

Comorbidities and cause-specific outcomes in heart failure across the ejection fraction spectrum: A blueprint for clinical trial design.

Background: Comorbidities may differently affect treatment response and cause-specific outcomes in heart failure (HF) with preserved (HFpEF) vs. mid-range/mildly-reduced (HFmrEF) vs. reduced (HFrEF) ejection fraction (EF), complicating trial design.

Relationship between hypoglycaemia, cardiovascular outcomes, and empagliflozin treatment in the EMPA-REG OUTCOME® trial.

Aims: Hypoglycaemia, in patients with Type 2 diabetes (T2D) is associated with an increased risk for cardiovascular (CV) events. In EMPA-REG OUTCOME, the sodium-glucose co-transporter-2 inhibitor empagliflozin reduced the risk of CV death by 38% and heart failure hospitalization (HHF) by 35%, while decreasing glycated haemoglobin (HbA1c) without increasing hypoglycaemia. We investigated CV outcomes in patients with hypoglycaemia during the trial and the impact of hypoglycaemia on the treatment effect of empagliflozin.

[Bicuspid aortic valve - a common congenital cardiac malformation associated with serious complications].

Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, affecting 1-2% of the general population. BAV is associated with an increased morbidity and mortality related to diseases of the aortic valve (aortic stenosis and aortic regurgitation) and the thoracic aorta (aortic aneurysm and aortic dissection). These conditions can often be treated surgically to prevent adverse events and reduce mortality.

Sex-Based Differences in Heart Failure Across the Ejection Fraction Spectrum: Phenotyping, and Prognostic and Therapeutic Implications.

Objectives: This study assessed sex-related differences in a large cohort of unselected patients with heart failure (HF) across the ejection fraction (EF) spectrum.

Background: Females are under-represented in randomized clinical trials. Potential sex-related differences in HF may question the generalizability of trials.

Prevalence and Prognostic Implications of Longitudinal Ejection Fraction Change in Heart Failure.

Objectives: This study sought to evaluate the incidence, the predictors, and the associations with outcomes of changes in ejection fraction (EF) in heart failure (HF) patients.

Background: EF determines therapy in HF, but information is scarce about incidence, determinants, and prognostic implications of EF change over time.

Methods: Patients with ≥2 EF measurements were made in the Swedish Heart Failure Registry were categorized as heart failure with preserved ejection fraction (HFpEF) (EF ≥50%), heart failure with midrange ejection fraction (HFmrEF) (EF 40% to 49%), or heart failure with reduced ejection fraction (HFrEF) (EF <40%).

Quantification of C-PIB kinetics in cardiac amyloidosis.

Background: The purpose of this work was to determine the optimal tracer kinetic model of C-PIB and to validate the use of the simplified methods retention index (RI) and standardized uptake value (SUV) for quantification of cardiac C-PIB uptake in amyloidosis.

Methods And Results: Single-tissue, reversible and irreversible two-tissue models were fitted to data from seven cardiac amyloidosis patients who underwent C-PIB PET scans and arterial blood sampling for measurement of blood radioactivity and metabolites. The irreversible two-tissue model (2Tirr) best described cardiac C-PIB uptake.