Survodutide for treatment of obesity: rationale and design of two randomized phase 3 clinical trials (SYNCHRONIZE™-1 and -2).

Objective: The objective of this study was to describe the rationale and design of two multinational phase 3 clinical trials of survodutide, an investigational glucagon and glucagon-like peptide-1 receptor dual agonist for the treatment of obesity with or without type 2 diabetes (T2D; SYNCHRONIZE-1 and -2).

Methods: In these ongoing double-blind trials, participants were randomized to once-weekly subcutaneous injections of survodutide or placebo added to lifestyle modification. Survodutide doses are uptitrated to 3.

Association between growth differentiation factor-15 and adverse outcomes among patients with heart failure: A systematic literature review.

Growth differentiation factor-15 (GDF-15) is an emerging biomarker in several conditions. This SLR, conducted following PRISMA guidelines, examined the association between GDF-15 concentration and range of adverse outcomes in patients with heart failure (HF). Publications were identified from Embase® and Medline® bibliographic databases between January 1, 2014, and August 23, 2022 (congress abstracts: January 1, 2020, to August 23, 2022).

Burden of Heart Failure in Patients With Tricuspid Regurgitation and Effect of Transcatheter Repair on Different Subdimensions of Quality of Life.

Background: Right-sided heart failure (HF) due to severe tricuspid regurgitation (TR) is associated with reduced quality of life (QoL). Here, we analyzed the impact of TR on specific QoL dimensions and the effect of transcatheter tricuspid valve intervention (TTVI) on individual QoL items.

Methods And Results: In this study, we included 174 patients with HF (49% women; median age, 79 years; 97% New York Heart Association ≥3) with baseline QoL assessment undergoing TTVI by transcatheter edge-to-edge-repair at our center between April 2016 and March 2022.

Sodium Zirconium Cyclosilicate in HFrEF and Hyperkalemia: REALIZE-K Design and Baseline Characteristics.

Background: Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced ejection fraction (HFrEF). However, MRAs are often underused because of hyperkalemia concerns.

Objectives: The purpose of this study was to assess whether sodium zirconium cyclosilicate (SZC), a nonabsorbed crystal that traps and rapidly lowers potassium, enables MRA use in patients with HFrEF and prevalent hyperkalemia (or at high risk).

Disparities in prevalence and treatment of diabetes, cardiovascular and chronic kidney diseases - Recommendations from the taskforce of the guideline workshop.

There is a mounting clinical, psychosocial, and socioeconomic burden worldwide as the prevalence of diabetes, cardiovascular disease (CVD), and chronic kidney disease (CKD) continues to rise. Despite the introduction of therapeutic interventions with demonstrated efficacy to prevent the development or progression of these common chronic diseases, many individuals have limited access to these innovations due to their race/ethnicity, and/or socioeconomic status (SES). However, practical guidance to providers and healthcare systems for addressing these disparities is often lacking.

Development and Validation of a Quantitative Coronary CT Angiography Model for Diagnosis of Vessel-Specific Coronary Ischemia.

Background: Noninvasive stress testing is commonly used for detection of coronary ischemia but possesses variable accuracy and may result in excessive health care costs.

Objectives: This study aimed to derive and validate an artificial intelligence-guided quantitative coronary computed tomography angiography (AI-QCT) model for the diagnosis of coronary ischemia that integrates atherosclerosis and vascular morphology measures (AI-QCT) and to evaluate its prognostic utility for major adverse cardiovascular events (MACE).

Methods: A post hoc analysis of the CREDENCE (Computed Tomographic Evaluation of Atherosclerotic Determinants of Myocardial Ischemia) and PACIFIC-1 (Comparison of Coronary Computed Tomography Angiography, Single Photon Emission Computed Tomography [SPECT], Positron Emission Tomography [PET], and Hybrid Imaging for Diagnosis of Ischemic Heart Disease Determined by Fractional Flow Reserve) studies was performed.

Health Status After Transcatheter Tricuspid-Valve Repair in Patients With Severe Tricuspid Regurgitation.

Background: In the TRILUMINATE Pivotal (Trial to Evaluate Cardiovascular Outcomes in Patients Treated with the Tricuspid Valve Repair System Pivotal), tricuspid transcatheter edge-to-edge repair (T-TEER) reduced tricuspid regurgitation (TR) and improved health status compared with medical therapy alone with no benefit on heart failure hospitalizations or survival.

Objectives: The purpose of this study was to better understand the health status benefits of T-TEER within the TRILUMINATE Pivotal trial.

Methods: TRILUMINATE randomized patients with severe TR to T-TEER (n = 175) or medical therapy (n = 175).

Data from network meta-analyses can inform clinical practice guidelines and decision-making in diabetes management: perspectives of the taskforce of the guideline workshop.

In recent years, several novel agents have become available to treat individuals with type 2 diabetes (T2D), such as sodium-glucose cotransporter-2 inhibitors (SGLT-2i), tirzepatide, which is a dual glucose-dependent insulinotropic polypeptide receptor agonist (GIP RA)/glucagon-like peptide-1 receptor agonist (GLP-1 RA), and finerenone, a non-steroidal mineralocorticoid receptor antagonist (MRA) that confers significant renal and cardiovascular benefits in individuals with (CKD). New medications have the potential to improve the lives of individuals with diabetes. However, clinicians are challenged to understand the benefits and potential risks associated with these new and emerging treatment options.

Bioprosthetic Valve Remodeling in Nonfracturable Surgical Valves: Impact on THV Expansion and Hydrodynamic Performance.

Background: There are limited data on the effect of bioprosthetic valve remodeling (BVR) on transcatheter heart valve (THV) expansion and function following valve-in-valve (VIV) transcatheter aortic valve replacement (TAVR) in a nonfracturable surgical heart valve (SHV).

Objectives: This study sought to assess the impact of BVR of nonfracturable SHVs on THVs after VIV implantation.

Methods: VIV TAVR was performed using 23-mm SAPIEN3 (S3, Edwards Lifesciences) or 23/26-mm Evolut Pro (Medtronic) THVs implanted in 21/23-mm Trifecta (Abbott Structural Heart) and 21/23-mm Hancock (Medtronic) SHVs with BVR performed with a noncompliant TRUE balloon (Bard Peripheral Vascular Inc).

Remote Patient Monitoring for Patients with Heart Failure: Sex- and Race-based Disparities and Opportunities.

Remote patient monitoring (RPM), within the larger context of telehealth expansion, has been established as an effective and safe means of care for patients with heart failure (HF) during the recent pandemic. Of the demographic groups, female patients and black patients are underenrolled relative to disease distribution in clinical trials and are under-referred for RPM, including remote haemodynamic monitoring, cardiac implantable electronic devices (CIEDs), wearables and telehealth interventions. The sex- and race-based disparities are multifactorial: stringent clinical trial inclusion criteria, distrust of the medical establishment, poor access to healthcare, socioeconomic inequities, and lack of diversity in clinical trial leadership.

Timing of bioprosthetic valve fracture in transcatheter valve-in-valve intervention: impact on valve durability and leaflet integrity.

Background: Bioprosthetic valve fracture (BVF) can be used to improve transcatheter heart valve (THV) haemodynamics following a valve-in-valve (ViV) intervention. However, whether BVF should be performed before or after THV deployment and the implications on durability are unknown.  Aims: We sought to assess the impact of BVF timing on long-term THV durability.

Effect of Dapagliflozin on Health Status in Patients With Preserved or Mildly Reduced Ejection Fraction.

Background: Patients with heart failure with mildly reduced ejection fraction (HFmrEF) and heart failure with preserved ejection fraction (HFpEF) experience a high burden of symptoms, physical limitations, and poor quality of life; improving health status is a key goal of management.

Objectives: In a prespecified analysis of the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial, we examine effects of dapagliflozin on health status using the Kansas City Cardiomyopathy Questionnaire (KCCQ).

Methods: The DELIVER trial randomized patients with symptomatic HFmrEF/HFpEF to dapagliflozin 10 mg or placebo.

Dapagliflozin in heart failure with improved ejection fraction: a prespecified analysis of the DELIVER trial.

With modern treatments for heart failure with reduced ejection fraction (EF), indicative of impaired cardiac systolic function, patients may exhibit an increase in EF. Limited data are available regarding the clinical management of this growing population, categorized as heart failure with improved EF (HFimpEF), which has a high event rate and has been excluded from virtually all prior heart failure outcomes trials. In a prespecified analysis of the DELIVER trial ( NCT03619213 ), of a total of 6,263 participants with symptomatic heart failure and a left ventricular EF >40%, 1,151 (18%) had HFimpEF, defined as patients whose EF improved from ≤40% to >40%.

Effects of once-weekly semaglutide 2.4 mg on C-reactive protein in adults with overweight or obesity (STEP 1, 2, and 3): Exploratory analyses of three randomised, double-blind, placebo-controlled, phase 3 trials.

Background: Inflammation is a key driver of atherosclerotic cardiovascular disease. C-reactive protein (CRP), an established biomarker of inflammation, is commonly elevated in people with overweight/obesity.

Methods: STEP 1, 2, and 3 were 68-week, placebo-controlled trials of semaglutide for weight management in participants with overweight/obesity, with (STEP 2) or without (STEP 1 and 3) type 2 diabetes.

Efficacy and safety of dapagliflozin in patients with heart failure with mildly reduced or preserved ejection fraction by baseline glycaemic status (DELIVER): a subgroup analysis from an international, multicentre, double-blind, randomised, placebo-controlled trial.

Background: Type 2 diabetes and prediabetes are risk factors for heart failure and adverse heart failure outcomes. The Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure (DELIVER) trial showed that dapagliflozin was associated with a reduction in the primary outcome of worsening heart failure or cardiovascular mortality in patients with heart failure with mildly reduced or preserved ejection fraction. We aimed to assess the efficacy and safety of oral dapagliflozin in these patients by their baseline glycaemia categories.

Semaglutide improves cardiometabolic risk factors in adults with overweight or obesity: STEP 1 and 4 exploratory analyses.

Aims: Evaluate the effects of once-weekly subcutaneous semaglutide 2.4 mg on cardiometabolic risk factors in people with overweight/obesity without diabetes in the STEP 1 and 4 trials.

Materials And Methods: STEP 1 and 4 were phase III, 68-week, placebo-controlled trials of once-weekly semaglutide 2.

Predicting stroke in heart failure and reduced ejection fraction without atrial fibrillation.

Aims: Patients with heart failure with reduced ejection fraction (HFrEF) are at significant risk of stroke. Anticoagulation reduces this risk in patients with and without atrial fibrillation (AF), but the risk-to-benefit balance in the latter group, overall, is not favourable. Identification of patients with HFrEF, without AF, at the highest risk of stroke may allow targeted and safer use of prophylactic anticoagulant therapy.

Iron Deficiency in Heart Failure and Effect of Dapagliflozin: Findings From DAPA-HF.

Background: Iron deficiency is common in heart failure and associated with worse outcomes. We examined the prevalence and consequences of iron deficiency in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure) and the effect of dapagliflozin on markers of iron metabolism. We also analyzed the effect of dapagliflozin on outcomes, according to iron status at baseline.

Pragmatic diagnostic and therapeutic algorithms to optimize new potassium binder use in cardiorenal disease.

Background: Pivotal randomized trials demonstrating efficacy, safety and good tolerance, of two new potassium binders (patiromer and sodium zirconium cyclosilicate) led to their recent approval. A major hurdle to the implementation of these potassium-binders is understanding how to integrate them safely and effectively into the long-term management of cardiovascular and kidney disease patients using renin angiotensin aldosterone system inhibitors (RAASi), the latter being prone to induce hyperkalaemia.

Methods: A multidisciplinary academic panel including nephrologists and cardiologists was convened to develop consensus therapeutic algorithm(s) aimed at optimizing the use of the two novel potassium binders (patiromer and sodium zirconium cyclosilicate) in stable adults who require treatment with RAASi and experience(d) hyperkalaemia in a non-emergent setting.