Influence of Type 2 Diabetes on the Effects of Tirzepatide in Patients With Heart Failure and a Preserved Ejection Fraction With Obesity: A Prespecified Stratification-Based Analysis.

Background: Incretin-based therapies are used to treat type 2 diabetes and obesity, but the presence of diabetes diminishes the magnitude of weight loss produced by these drugs in people with obesity. It is not known whether this attenuated weight change is relevant to the clinical benefits of these drugs in heart failure.

Objectives: The goal of this study was to assess the influence of diabetes on the efficacy and safety of tirzepatide in the SUMMIT trial.

Mechanistic Basis for Differential Effects of Interatrial Shunt Treatment in HFrEF vs HFpEF: The RELIEVE-HF trial.

Background: The RELIEVE-HF trial randomized 508 patients with heart failure (HF) to interatrial shunt-treatment vs placebo-procedure. Randomization was stratified into 2 patient groups with HF with reduced ejection fraction (HFrEF;LVEF≤40%) and HF with preserved EF (HFpEF;LVEF>40%). HF event rates (all-cause death, transplantation/LVAD, HF hospitalization/outpatient worsening) after shunt treatment during 2-year follow-up were directionally opposite: decreased by 51% in HFrEF, increased by 69% in HFpEF.

Natriuretic Peptides, Body Mass Index, and Clinical Outcomes in Heart Failure with Mildly Reduced or Preserved Ejection Fraction.

Background: Natriuretic peptides are the primary biomarkers recommended in heart failure (HF) guidelines to risk stratify patients in clinical practice and serve as key eligibility criteria in contemporary clinical trials. However, threshold levels typically do not account for measures of adiposity, such as body mass index (BMI).

Objective: To evaluate the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) with clinical outcomes in individuals with HF and mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), stratified according to BMI.

Adiposity-Related Anthropometrics and Clinical Outcomes in Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Participant-Level Pooled Analysis of Randomized Clinical Trials.

Background: Obesity is highly prevalent among individuals with heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF) and is associated with increased risk of disability and death.

Objectives: The purpose of this study is to explore the association between different adiposity-related anthropometrics and clinical outcomes in this population.

Methods: In this participant-level pooled analysis of 5 international randomized trials that enrolled adults with HFmrEF/HFpEF, the association between adiposity-related anthropometrics (body mass index [BMI], waist circumference [WC], and waist-to-height ratio [WHtR]) and heart failure (HF) and mortality outcomes was evaluated, overall and by age and sex.

Sacubitril/valsartan and Quality of Life Assessed Using the EuroQol 5-Dimension 3-Level Questionnaire Level Sum Score (EQ-5D-3L-LSS) in Patients with HFrEF and HFmrEF/HFpEF.

Objectives: To investigate the EQ-5D-3L Level Sum Score (LSS) in patients with heart failure (HF) and reduced (HFrEF) and mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and the effect of sacubitril/valsartan on this score using patient-level data from the PARADIGM-HF and PARAGON-HF trials.

Methods: The LSS was calculated by summating the 3 levels (1-3) for each of the 5 domains (minimum sum score=5; maximum sum score=15). Patient characteristics and outcomes were compared across LSS tertiles (T1-T3) at baseline.

Impact of Body Mass Index, Central Adiposity, and Weight Loss on the Benefits of Tirzepatide in HFpEF: The SUMMIT Trial.

Background: The SUMMIT trial showed that the long-acting glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide 1 receptor agonist tirzepatide decreased the risk of cardiovascular death or worsening heart failure (HF) in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). Effects may differ by baseline obesity severity, distribution, or magnitude of weight loss.

Objectives: In this analysis, the authors compared baseline characteristics and effects of tirzepatide on primary and other endpoints according to baseline obesity severity and distribution, and we explored relationships between degree of weight loss achieved and outcomes.

Incidence of Cardiac Arrhythmias Identified by Insertable Cardiac Monitors in Patients With Symptomatic Heart Failure.

Background: Cardiac bradyarrhythmias and tachyarrhythmias in chronic heart failure (CHF) patients are associated with increased morbidity and mortality. Insertable cardiac monitors provide a continuous, ambulatory, accurate monitoring strategy for patients with CHF who are not candidates for cardiac implantable electronic devices.

Objectives: This study aims to assess the occurrence of cardiac arrhythmias (CAs) in patients with CHF across the ejection fraction (EF) spectrum and not indicated for cardiac implantable electronic devices.

Obesity and Risk of Kidney Outcomes in Heart Failure With Preserved Ejection Fraction: A Participant-Level Pooled Analysis of 4 Contemporary Trials.

Background: Obesity is prevalent among patients with heart failure with preserved ejection fraction (HFpEF).

Objectives: This study aims to evaluate whether anthropometrics including body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) are associated with kidney outcomes in patients with HFpEF.

Methods: In this participant-level pooled analysis of DELIVER, PARAGON-HF, TOPCAT Americas, and I-PRESERVE, we evaluated the impact of adiposity-related anthropometrics on risk of kidney outcomes (sustained eGFR reduction of ≥50%, end-stage kidney disease, or kidney-related death).

Win ratio analysis of the REVERSE cardiac resynchronization trial.

Background: The novel win ratio statistic has emerged as a promising alternative end point for the comparison of 2 treatment groups on multiple end points simultaneously, but it has not been used for cardiac resynchronization therapy (CRT) trials. REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE; ClinicalTrials.gov identifier: NCT00271154) was the first multicenter, randomized CRT trial in mild heart failure (HF).

Prognostic Significance of Nutritional Scores in Patients With Heart Failure: Insights From the PARAGON-HF Trial.

Background: The Controlling Nutritional Status (CONUT) and Geriatric Nutritional Risk Index (GNRI) are indices that identify individuals at risk of malnutrition. Our study sought to examine the incidence and prognostic implications of abnormal CONUT and/or GNRI in patients with heart failure with preserved ejection fraction.

Methods And Results: The CONUT score and GNRI were serially analyzed in this post hoc analysis of the PARAGON-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Receptor Blockers Global Outcomes in Heart Failure With Preserved Ejection Fraction) trial.

Comprehensive Analysis of the Effects of Sacubitril/Valsartan According to Sex Among Patients With Heart Failure and Reduced Ejection Fraction in PARADIGM-HF.

Background: Women with heart failure (HF) ejection fraction appeared to respond more favorably to sacubitril/valsartan, compared with valsartan, than men in PARAGON-HF (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction), driven by a greater reduction in total (first and recurrent) HF hospitalizations. Sex-specific efficacy and safety of sacubitril/valsartan in PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) remain unreported.

Methods And Results: This post hoc analysis of PARADIGM-HF examined sex-based outcomes in patients with HF and reduced ejection fraction randomized to sacubitril/valsartan or enalapril.

Relationship Between Remote, Ambulatory Pulmonary Artery Pressures, and All-Cause Mortality in Patients With Chronic Heart Failure.

Background: Hemodynamically guided management of patients with chronic heart failure (HF), using a remote, ambulatory pulmonary artery (PA) pressure monitor, has been shown to reduce mortality and morbidity. These improved outcomes were associated with a reduction in PA pressure. However, several pivotal questions remain unanswered: do systolic, diastolic, or mean PA pressures each predict all-cause mortality? Do PA pressures predict mortality across the ejection fraction (EF) spectrum? Do increases or decreases in PA pressure over time predict increases or decreases in mortality?

Methods: Retrospective analyses of data from CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients; n=550), GUIDE-HF (Hemodynamic-GUIDEed management of Heart Failure; n=2358), US PAS (CardioMEMS HF System Post Approval Study; n=1200), and MEMS-HF (CardioMEMS Monitoring Study for Heart Failure; n=234) were performed, including all enrolled patients regardless of treatment assignments (Total N=4342).

Persistent Fibrosis in Heart Failure With a Reduced Ejection Fraction Linked to Phenotypic Differences in Human Cardiac Fibroblast Populations.

Background: Myocardial fibrosis is prevalent in cardiomyopathies that result in heart failure with reduced ejection fraction. Heart failure with reduced ejection fraction treated with a left ventricular assist device (LVAD) yields hemodynamic unloading and may provide partial cardiomyocyte recovery, but contemporary studies reveal no consistent reductions in fibrosis. This study tested the hypothesis that, despite normalization of hemodynamic overload by LVAD, fibrosis and fibroblast activation persist resulting in sustained increases in myocardial stiffness.

Interplay of Chronic Kidney Disease and the Effects of Tirzepatide in Patients With Heart Failure, Preserved Ejection Fraction, and Obesity: The SUMMIT Trial.

Background: Obesity leads to both heart failure with a preserved ejection fraction (HFpEF) and to chronic kidney disease (CKD); CKD may both influence the clinical course of obesity-related HFpEF; and incretin-based drugs may influence renal function.

Objectives: This analysis had dual objectives: 1) to evaluate the influence of CKD on the clinical responses to tirzepatide in patients with obesity-related HFpEF; and 2) to investigate the complexity of tirzepatide-related changes in renal function. For both objectives, we focused on discrepancies between creatinine-based and cystatin C-based estimates of the estimated glomerular filtration rate (eGFR).

Effects of Sacubitril/Valsartan According to Natriuretic Peptide Levels in Patients Enrolled in PARADIGM-HF and PARAGON-HF.

Background: Recent trials of new heart failure (HF) treatments suggest the effect of therapy may vary by N-terminal pro-B type natriuretic peptide (NT-proBNP) level.

Objectives: The authors examined the efficacy of sacubitril/valsartan according to NT-proBNP levels in patients with reduced, mildly reduced, and preserved left ventricular ejection fraction (LVEF) enrolled in PARADIGM-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Converting-Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial) and PARAGON-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Receptor Blockers Global Outcomes in HF with Preserved Ejection Fraction).

Methods: Individual patient data from PARADIGM-HF and PARAGON-HF were pooled and participants were divided into categories defined by quintiles of NT-proBNP level.

Impact of Multimorbidity on Mortality in Heart Failure With Mildly Reduced and Preserved Ejection Fraction.

Background: How different combinations of comorbidities influence risk at the patient level and population level in patients with heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction is unknown. We aimed to investigate the prevalence of different combinations of cardiovascular and noncardiovascular comorbidities (ie, multimorbidity) and associated risk of death at the patient level and population level.

Methods: Using patient-level data from the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) and PARAGON-HF trial (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction), we investigated the 5 most common cardiovascular and noncardiovascular comorbidities and the resultant 45 comorbidity pairs.

Mouse model of post-traumatic stress disorder negatively impacts cardiac homeostasis.

Post-traumatic stress disorder (PTSD) is a disabling psychological disorder characterized by chronic symptoms of intrusiveness, avoidance, and hyperarousal after a traumatic event. Retrospective studies have indicated PTSD increases the risk for cardiovascular disease (CVD) including arrhythmia, hypertension, and myocardial infarction. The goal of this study was to: 1) use a murine model of cued fear conditioning (inescapable foot shock, IFS) to develop a scoring method to distinguish a PTSD-like phenotype, and 2) use this model system to characterize the cardiac phenotype and function in mice with extreme PTSD-like behaviors.

Continuous risk monitoring and management of heart failure: Rationale and design of the ALLEVIATE-HF trial.

Aims: Early identification and management of worsening heart failure (HF) is necessary to prevent disease progression and hospitalizations. The ALLEVIATE-HF (Algorithm Using LINQ Sensors for Evaluation and Treatment of Heart Failure) trial is a prospective, randomized, controlled, double-blind, multicentre trial that aims to assess the safety and efficacy of using the Reveal LINQ™ insertable cardiac monitor (ICM) in patients with HF to continuously monitor and evaluate HF risk status and guide timely interventions.

Methods: The ICM algorithm uses parameters derived from electrocardiogram (atrial fibrillation [AF], ventricular rate during AF, heart rate variability, and night heart rate), three-axis accelerometer (patient activity duration), and subcutaneous bioimpedance (fluid volume, respiration rate).

Clinical Characteristics and Outcomes of Patients With Heart Failure With Preserved Ejection Fraction and With Reduced Ejection Fraction According to the Prognostic Nutritional Index: Findings From PARADIGM-HF and PARAGON-HF.

Background: The importance of nutritional status is underappreciated in patients with heart failure (HF). This study aimed to describe the range of the prognostic nutrition index (PNI), and the clinical characteristics and outcomes according to PNI, in patients with HF with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). The primary outcome was the composite of HF hospitalization or cardiovascular death.

Incidence of atrial fibrillation in patients with an insertable cardiac monitor and symptomatic heart failure.

Aims: We aim to evaluate the incidence of atrial fibrillation (AF) in a large real-world cohort of patients implanted with an insertable cardiac monitor (ICM) who had a clinical history of symptomatic heart failure (HF) with reduced or preserved left ventricular ejection fraction (LVEF).

Methods: Patients with an ICM and a history of HF events were identified from the Optum® de-identified Electronic Health Record dataset merged with an ICM device dataset collected during 2007-2021. All ICM-detected AF episodes that were available with ≥30-s of ECG at onset were adjudicated using artificial intelligence (AI model).