Dapagliflozin for heart failure according to body mass index: the DELIVER trial.

Aims: Obesity is common and associated with unique phenotypic features in heart failure with preserved ejection fraction (HFpEF). Therefore, understanding the efficacy and safety of new therapies in HFpEF patients with obesity is important. The effects of dapagliflozin were examined according to body mass index (BMI) among patients in the Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure trial.

Neuromodulation devices for heart failure.

Autonomic imbalance with a sympathetic dominance is acknowledged to be a critical determinant of the pathophysiology of chronic heart failure with reduced ejection fraction (HFrEF), regardless of the etiology. Consequently, therapeutic interventions directly targeting the cardiac autonomic nervous system, generally referred to as neuromodulation strategies, have gained increasing interest and have been intensively studied at both the pre-clinical level and the clinical level. This review will focus on device-based neuromodulation in the setting of HFrEF.

Effects of sacubitril/valsartan on glycemia in patients with diabetes and heart failure: the PARAGON-HF and PARADIGM-HF trials.

Background: Compared with enalapril, sacubitril/valsartan lowered HbA1c and reduced new insulin therapy in patients with heart failure with reduced ejection fraction (HFrEF) and diabetes in the PARADIGM-HF trial. We sought to assess the glycemic effects of sacubitril/valsartan in heart failure with preserved ejection fraction (HFpEF) and diabetes, and across the spectrum of left ventricular ejection fraction (LVEF) in heart failure and diabetes.

Methods: We compared the effect of sacubitril/valsartan, relative to valsartan, on HbA1c, new insulin therapy and hypoglycemia in the randomized controlled trial PARAGON-HF, and performed pooled analyses of PARAGON-HF and PARADIGM-HF.

Baroreflex activation therapy with the Barostim™ device in patients with heart failure with reduced ejection fraction: a patient level meta-analysis of randomized controlled trials.

Aims: Heart failure with reduced ejection fraction (HFrEF) remains associated with high morbidity and mortality, poor quality of life (QoL) and significant exercise limitation. Sympatho-vagal imbalance has been shown to predict adverse prognosis and symptoms in HFrEF, yet it has not been specifically targeted by any guideline-recommended device therapy to date. Barostim™, which directly addresses this imbalance, is the first Food and Drug Administration approved neuromodulation technology for HFrEF.

Clinical Outcomes Related to Background Diuretic Use and New Diuretic Initiation in Patients With HFrEF.

Background: Up to 20% of patients in heart failure with reduced ejection fraction (HFrEF) trials are not taking diuretic agents at baseline, but little is known about them.

Objectives: The aim of this study was to examine outcomes in patients with HFrEF not taking diuretic medications and after diuretic medications are started.

Methods: Patient characteristics and outcomes were compared between patients taking or not taking diuretic drugs at baseline in the ATMOSPHERE (Aliskiren Trial of Minimizing Outcomes for Patients With Heart Failure) and PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial) trials combined.

Do CPVT-linked mutations alter RYR2 regulation by cytosolic Ca2+ in cardiomyocytes?

It is controversial whether the cardiac type-2 ryanodine receptor harboring a catecholaminergic polymorphic ventricular tachycardia-associated point mutation is regulated by luminal or cytosolic Ca. This commentary discusses new findings supporting the cytosolic Ca-dependent regulation.

Endovascular ablation of the right greater splanchnic nerve in heart failure with preserved ejection fraction: early results of the REBALANCE-HF trial roll-in cohort.

Aims: In heart failure (HF) with preserved ejection fraction (HFpEF), excessive redistribution of blood volume into the central circulation leads to elevations of intracardiac pressures with exercise limitations. Splanchnic ablation for volume management (SAVM) has been proposed as a therapeutic intervention. Here we present preliminary safety and efficacy data from the initial roll-in cohort of the REBALANCE-HF trial.

Safety and Efficacy of Mesenchymal Stromal Cells and Other Cellular Therapeutics in Rheumatic Diseases in 2022: A Review of What We Know So Far.

Although a number of new immunosuppressive agents and biologics have been approved for treating various autoimmune inflammatory rheumatic diseases, there remains a substantial number of patients who have no clinical response or limited clinical response to these available treatments. Use of cellular therapies is a novel approach for the treatment of autoimmune inflammatory rheumatic diseases, with perhaps enhanced efficacy and less toxicity than current therapies. Autologous hematopoietic stem cell transplants were the first foray into cellular therapies, with proven efficacy in scleroderma and multiple sclerosis.

Atrial shunt device for heart failure with preserved and mildly reduced ejection fraction (REDUCE LAP-HF II): a randomised, multicentre, blinded, sham-controlled trial.

Background: Placement of an interatrial shunt device reduces pulmonary capillary wedge pressure during exercise in patients with heart failure and preserved or mildly reduced ejection fraction. We aimed to investigate whether an interatrial shunt can reduce heart failure events or improve health status in these patients.

Methods: In this randomised, international, blinded, sham-controlled trial performed at 89 health-care centres, we included patients (aged ≥40 years) with symptomatic heart failure, an ejection fraction of at least 40%, and pulmonary capillary wedge pressure during exercise of at least 25 mm Hg while exceeding right atrial pressure by at least 5 mm Hg.

Differences in complications, cardiovascular risk factor, and diabetes management among participants enrolled at veterans affairs (VA) and non-VA medical centers in the glycemia reduction approaches in diabetes: A comparative effectiveness study (GRADE).

Aims: We evaluated differences in participants with type 2 diabetes (T2DM) enrolled in the GRADE study at VA vs non-VA sites, focusing on cardiovascular risk factors and rates of diabetes care target achievements.

Methods: We compared baseline characteristics between participants at VA (n = 1216) and non-VA (n = 3831) sites, stratifying analyses by cardiovascular disease (CVD) history.

Results: VA and non-VA participants had similar diabetes duration (4.

Effect of sacubitril/valsartan on investigator-reported ventricular arrhythmias in PARADIGM-HF.

Aims: Sudden death is a leading cause of mortality in heart failure with reduced ejection fraction (HFrEF). In PARADIGM-HF, sacubitril/valsartan reduced the incidence of sudden death. The purpose of this post hoc study was to analyse the effect of sacubitril/valsartan, compared to enalapril, on the incidence of ventricular arrhythmias.

Diabetes and pre-diabetes in patients with heart failure and preserved ejection fraction.

Aim: There is an association between heart failure with preserved ejection fraction (HFpEF) and insulin resistance, but less is known about the diabetic continuum, and in particular about pre-diabetes, in HFpEF. We examined characteristics and outcomes of participants with diabetes or pre-diabetes in PARAGON-HF.

Methods And Results: Patients aged ≥50 years with left ventricular ejection fraction ≥45%, structural heart disease and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) were eligible.

P068 Racial and Socioeconomic Disparities in Acute Care Utilization in a National Cohort of Veterans With IBD.

Background: Hospitalizations for Black patients with inflammatory bowel disease (IBD) have increased in recent decades though our understanding of disease behavior in Black patients remains limited and concerns related to healthcare equity persist. Existing data are largely drawn from small case series at IBD referral centers or national registries lacking granular longitudinal outpatient data. Our aim was to determine whether there are racial or socioeconomic disparities in acute care utilization as measured by hospitalizations and emergency department (ED) visits within a large national cohort of IBD patients.

Pathophysiology and Pathogenesis of Marfan Syndrome.

Marfan syndrome (MFS) is a systemic connective tissue disorder that is inherited in an autosomal dominant pattern with variable penetrance. While clinically this disease manifests in many different ways, the most life-threatening manifestations are related to cardiovascular complications including mitral valve prolapse, aortic insufficiency, dilatation of the aortic root, and aortic dissection. In the past 30 years, research efforts have not only identified the genetic locus responsible but have begun to elucidate the molecular pathogenesis underlying this disorder, allowing for the development of seemingly rational therapeutic strategies for treating affected individuals.

Connective Tissue Disorders and Cardiovascular Complications: The Indomitable Role of Transforming Growth Factor-β Signaling.

Marfan Syndrome (MFS) and Loeys-Dietz Syndrome (LDS) represent heritable connective tissue disorders that segregate with a similar pattern of cardiovascular defects (thoracic aortic aneurysm, mitral valve prolapse/regurgitation, and aortic dilatation with regurgitation). This pattern of cardiovascular defects appears to be expressed along a spectrum of severity in many heritable connective tissue disorders and raises suspicion of a relationship between the normal development of connective tissues and the cardiovascular system. With overwhelming evidence of the involvement of aberrant Transforming Growth Factor-beta (TGF-β) signaling in MFS and LDS, this signaling pathway may represent the common link in the relationship between connective tissue disorders and their associated cardiovascular complications.

Sacubitril-valsartan as a treatment for apparent resistant hypertension in patients with heart failure and preserved ejection fraction.

Aims: Patients with heart failure and preserved ejection fraction (HFpEF) frequently have difficult-to-control hypertension. We examined the effect of neprilysin inhibition on 'apparent resistant hypertension' in patients with HFpEF in the PARAGON-HF trial, which compared the effect of sacubitril-valsartan with valsartan.

Methods And Results: In this post hoc analysis, patients were categorized according to systolic blood pressure at the end of the valsartan run-in (n = 4795).

Integrating High-Sensitivity Troponin T and Sacubitril/Valsartan Treatment in HFpEF: The PARAGON-HF Trial.

Objectives: This study examined the relationship among high-sensitivity troponin-T (hs-TnT), outcomes, and treatment with sacubitril/valsartan in patients with heart failure (HF) and preserved ejection fraction (HFpEF).

Background: hs-TnT is a marker of myocardial injury in HF.

Methods: The PARAGON-HF trial randomized 4,796 patients with HFpEF to sacubitril/valsartan or valsartan.

Phase III/IV, Randomized, Fifty-Two-Week Study of the Efficacy and Safety of Belimumab in Patients of Black African Ancestry With Systemic Lupus Erythematosus.

Objective: Enrollment of patients of Black African ancestry with systemic lupus erythematosus (SLE) in phase II and phase III of the belimumab trials was not reflective of the racial distribution observed in the lupus population. This study was undertaken to assess the efficacy and safety of intravenous (IV) belimumab plus standard therapy in patients of self-identified Black race.

Methods: EMBRACE (GSK Study BEL115471; ClinicalTrials.

Development and external validation of prognostic models to predict sudden and pump-failure death in patients with HFrEF from PARADIGM-HF and ATMOSPHERE.

Background: Sudden death (SD) and pump failure death (PFD) are the two leading causes of death in patients with heart failure and reduced ejection fraction (HFrEF).

Objective: Identifying patients at higher risk for mode-specific death would allow better targeting of individual patients for relevant device and other therapies.

Methods: We developed models in 7156 patients with HFrEF from the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial, using Fine-Gray regressions counting other deaths as competing risks.

Diagnostic criteria for apathy in neurocognitive disorders.

Introduction: Apathy is common in neurocognitive disorders (NCD) but NCD-specific diagnostic criteria are needed.

Methods: The International Society for CNS Clinical Trials Methodology Apathy Work Group convened an expert group and sought input from academia, health-care, industry, and regulatory bodies. A modified Delphi methodology was followed, and included an extensive literature review, two surveys, and two meetings at international conferences, culminating in a consensus meeting in 2019.

Global Differences in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Trial.

Background: Heart failure with preserved ejection fraction (HFpEF) is a global public health problem with important regional differences. We investigated these differences in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF), the largest and most inclusive global HFpEF trial.

Methods: We studied differences in clinical characteristics, outcomes, and treatment effects of sacubitril/valsartan in 4796 patients with HFpEF from the PARAGON-HF trial, grouped according to geographic region.

Cardiac and Noncardiac Disease Burden and Treatment Effect of Sacubitril/Valsartan: Insights From a Combined PARAGON-HF and PARADIGM-HF Analysis.

Background: The net clinical benefit of cardiac disease-modifying drugs might be influenced by the interaction of different domains of disease burden. We assessed the relative contribution of cardiac, comorbid, and demographic factors in heart failure (HF) and how their interplay might influence HF prognosis and efficacy of sacubitril/valsartan across the spectrum of left ventricular ejection fraction.

Methods: We combined data from 2 global trials that evaluated the efficacy of sacubitril/valsartan compared with a renin-angiotensin antagonist in symptomatic HF patients (PARADIGM-HF [Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure; n=8399] and PARAGON-HF [Prospective Comparison of Angiotensin-Converting Enzyme Inhibitor With Angiotensin Receptors Blockers Global Outcomes in Heart Failure With Preserved Ejection Fraction; n=4796]).

Serum potassium and outcomes in heart failure with preserved ejection fraction: a post-hoc analysis of the PARAGON-HF trial.

Aims: The relationship between serum potassium concentration and outcomes in patients with heart failure and preserved ejection fraction (HFpEF) is not well-established. The aim of this study was to explore the association between serum potassium and clinical outcomes in the PARAGON-HF trial in which 4822 patients with HFpEF were randomised to treatment with sacubitril/valsartan or valsartan.

Methods And Results: The relationship between serum potassium concentrations and the primary study composite outcome of total (first and recurrent) heart failure hospitalisations and cardiovascular death was analysed.