Effects of Tirzepatide on the Clinical Trajectory of Patients with Heart Failure, a Preserved Ejection Fraction, and Obesity.

Background: Patients with heart failure, a preserved ejection fraction (HFpEF), and obesity have significant disability and suffer frequent exacerbations of heart failure. We hypothesized that tirzepatide, a long-acting agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, would improve a comprehensive suite of clinical endpoints, including measures of health status, functional capacity, quality of life, exercise tolerance, patient well-being, and medication burden in these patients.

Methods: 731 patients in class II-IV heart failure, ejection fraction ≥50%, and body mass index ≥30 kg/m were randomized(double-blind) to tirzepatide(titrated up to 15mg subcutaneously weekly)(n=364) or placebo(n=367), added to background therapy for a median of 104 weeks (Q1=66, Q3=126 weeks).

Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity.

Background: Obesity increases the risk of heart failure with preserved ejection fraction. Tirzepatide, a long-acting agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, causes considerable weight loss, but data are lacking with respect to its effects on cardiovascular outcomes.

Methods: In this international, double-blind, randomized, placebo-controlled trial, we randomly assigned, in a 1:1 ratio, 731 patients with heart failure, an ejection fraction of at least 50%, and a body-mass index (the weight in kilograms divided by the square of the height in meters) of at least 30 to receive tirzepatide (up to 15 mg subcutaneously once per week) or placebo for at least 52 weeks.

Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial.

Patients with obesity-related heart failure with preserved ejection fraction (HFpEF) display circulatory volume expansion and pressure overload contributing to cardiovascular-kidney end-organ damage. In the SUMMIT trial, patients with HFpEF and obesity were randomized to the long-acting glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonist tirzepatide (n = 364, 200 women) or placebo (n = 367, 193 women). As reported separately, tirzepatide decreased cardiovascular death or worsening heart failure.

Proposed Mechanisms and Associations of COVID-19 with Cardiometabolic Risk Factors.

Cardiovascular disease (CVD) and cardiometabolic risk (CMR) are highly prevalent globally. The interplay between CVD/CMR and COVID-19 morbidity and mortality has been intensely studied over the last three years and has yielded some important discoveries and warnings for public health. Despite many advances in cardiovascular medicine, CVD continues to be the global leading cause of death.

Experiences of Spanish-Speaking Families with a Remote Neurodevelopmental Assessment.

U.S. Hispanic families with limited English proficiency experience barriers to autism diagnosis, such as lack of Spanish-speaking providers and assessments.

A novel controlled metabolic accelerator for the treatment of obesity-related heart failure with preserved ejection fraction: Rationale and design of the Phase 2a HuMAIN trial.

Aims: Compared with those without obesity, patients with obesity-related heart failure with preserved ejection fraction (HFpEF) have worse symptoms, haemodynamics, and outcomes. Current weight loss strategies (diet, drug, and surgical) work through decreased energy intake rather than increased expenditure and cause significant loss of skeletal muscle mass in addition to adipose tissue. This may have adverse implications for patients with HFpEF, who already have reduced skeletal muscle mass and function and high rates of physical frailty.

Recommendations for patient-centered emergency care.

Introduction: Patient-centred care is more than just an aspiration, it represents a fundamental shift in the way healthcare must be delivered. Patient-centred emergency care is important for improving the patient and clinician experience and is essential for optimizing health outcomes. Creating a patient-centred emergency department emphasizes the importance of the patient's experience, preferences, and values.

A fortune cookie problem: A test for nominal data whether two samples are from the same population of equally likely elements.

This article considers a way to test the hypothesis that two collections of objects are from the same uniform distribution of such objects. The exact -value is calculated based on the distribution for the observed overlaps. In addition, an interval estimate of the number of distinct objects, when all objects are equally likely, is indicated.

Atrial Shunt Device Effects on Cardiac Structure and Function in Heart Failure With Preserved Ejection Fraction: The REDUCE LAP-HF II Randomized Clinical Trial.

Importance: Although the results of A Study to Evaluate the Corvia Medical Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure (REDUCE LAP-HF II) trial were neutral overall, atrial shunt therapy demonstrated potential efficacy in responders (no latent pulmonary vascular disease and no cardiac rhythm management device). Post hoc analyses were conducted to evaluate the effect of shunt vs sham stratified by responder status.

Objective: To evaluate the effect of atrial shunt vs sham control on cardiac structure/function in the overall study and stratified by responder status.

Endovascular Ablation of the Right Greater Splanchnic Nerve in Heart Failure With Preserved Ejection Fraction: Rationale, Design and Lead-in Phase Results of the REBALANCE-HF Trial.

Objective: Splanchnic vasoconstriction augments transfer of blood volume from the abdomen into the thorax, which may increase filling pressures and hemodynamic congestion in patients with noncompliant hearts. Therapeutic interruption of splanchnic nerve activity holds promise to reduce hemodynamic congestion in patients with heart failure with preserved ejection fraction (HFpEF). Here we describe (1) the rationale and design of the first sham-controlled, randomized clinical trial of splanchnic nerve ablation for HFpEF and (2) the 12-month results of the lead-in (open-label) trial's participants.

Systems-Based Practice in Graduate Medical Education: Evolving Toward an Ideal Future State.

Systems-based practice (SBP) was first introduced as a core competency in graduate medical education (GME) in 2002 by the Accreditation Council for Graduate Medical Education as part of the Outcomes Project. While inclusion of SBP content in GME has become increasingly common, there have also been well-documented stumbling blocks, including perceptions that SBP has eroded the amount of curricular time available for more medically focused competencies, is not relevant for some practice contexts, and is not introduced early enough in training. As a result, SBP learning experiences often feel disconnected from medical trainees' practical reality.

Source, co-occurrence, and prognostic value of PTEN mutations or loss in colorectal cancer.

Somatic PTEN mutations are common and have driver function in some cancer types. However, in colorectal cancers (CRCs), somatic PTEN-inactivating mutations occur at a low frequency (~8-9%), and whether these mutations are actively selected and promote tumor aggressiveness has been controversial. Analysis of genomic data from ~53,000 CRCs indicates that hotspot mutation patterns in PTEN partially reflect DNA-dependent selection pressures, but also suggests a strong selection pressure based on protein function.

Obesity in heart failure with preserved ejection fraction: Insights from the REDUCE LAP-HF II trial.

Aims: Obesity is causally related to the development of heart failure with preserved ejection fraction (HFpEF) but complicates the diagnosis and treatment of this disorder. We aimed to determine the relationship between severity of obesity and clinical, echocardiographic and haemodynamic parameters in a large cohort of patients with documented HFpEF.

Methods And Results: The REDUCE LAP-HF II trial randomized 626 patients with ejection fraction ≥40% and exercise pulmonary capillary wedge pressure (PCWP) ≥25 mmHg to atrial shunt or sham procedure.

Perspectives of Healthcare Providers to Inform the Design of an AI-Enhanced Social Robot in the Pediatric Emergency Department.

Children commonly experience pain and distress in healthcare settings related to medical procedures such as blood tests and intravenous insertions (IVIs). Inadequately addressed pain and distress can result in both short- and long-term negative consequences. The use of socially assistive robotics (SARs) to reduce procedure-related distress and pain in children's healthcare settings has shown promise; however, the current options lack autonomous adaptability.

Exploring the needs of children and caregivers to inform design of an artificial intelligence-enhanced social robot in the pediatric emergency department.

Background & Objective: Socially assistive robots (SARs) are a promising tool to manage children's pain and distress related to medical procedures, but current options lack autonomous adaptability. The aim of this study was to understand children's and caregivers' perceptions surrounding the use of an artificial intelligence (AI)-enhanced SAR to provide personalized procedural support to children during intravenous insertion (IVI) to inform the design of such a system following a user-centric approach.

Methods: This study presents a descriptive qualitative needs assessment of children and caregivers.

Phase II Randomized Trial of Carboplatin, Pemetrexed, and Bevacizumab With and Without Atezolizumab in Stage IV Nonsquamous Non-Small-Cell Lung Cancer Patients Who Harbor a Sensitizing EGFR Mutation or Have Never Smoked.

Introduction: Patients with non-small-cell lung cancer (NSCLC) who have never smoked or have tumors with mutations in EGFR generally derive minimal benefit from single-agent PD-1/PD-L1 checkpoint inhibitors. Prior data indicate that adding PD-L1 inhibition to anti-VEGF and cytotoxic chemotherapy may be a promising approach to overcoming immunotherapy resistance in these patients, however prospective validation is needed. This trial in progress (NCT03786692) is evaluating patients with stage IV NSCLC who have never smoked or who have tumors with sensitizing EGFR alterations to determine if a 4-drug combination of atezolizumab, carboplatin, pemetrexed, and bevacizumab can improve outcomes compared to carboplatin, pemetrexed and bevacizumab without atezolizumab.

Update on Atrial Shunt Therapy for Treatment of Heart Failure.

Heart failure with preserved ejection fraction is associated with elevated left atrial pressure during exercise. Sodium-glucose cotransporter-2 inhibitors have demonstrated the evidence of benefit in heart failure with preserved ejection fraction, but even with this treatment, heart failure hospitalizations remain high, and improvements in quality of life scores are modest. Thus, there is growing interest in nonpharmacological methods of limiting the rise in left atrial pressure during exertion.