Whitney Hamrick (brianmallet74)

Treatment with sacubitril-valsartan reduces mortality and heart failure (HF) events in HF with reduced ejection fraction and may reduce HF hospitalization in women with HF with preserved ejection fraction. EVALUATE-HF randomized 464 participants (109 women) with HF with reduced ejection fraction to sacubitril-valsartan or enalapril for 12 weeks. Documented left ventricular ejection fraction (LVEF) ≤0.40 within the prior 12 months was required, although core laboratory LVEF>0.40 was permitted. Assessments of aortic stiffness (pulse pressure and characteristic impedance, Z ) were performed at baseline and at trough and 4 hours postdose at weeks 4 and 12. In models of change from baseline adjusted for baseline value, treatment with sacubitril-valsartan produced greater overall reductions in mean arterial pressure (treatment group difference, -3.0±0.8 mm Hg, <0.001) and pulse pressure (-3.0±0.8 mm Hg, <0.001). selleck chemicals llc Postdose reductions in Z were greater in the sacubitril-valsartan group (-16±6 dyn 4 and 12 weeks, treatment with sacubitril-valsartan was associated with greater postdose reductions in aortic Zc. In a post hoc analysis, sacubitril-valsartan was associated with sustained reductions in Zc in women with LVEF≥0.40. Registration URL https//; Unique Identifier NCT02874794. New heart failure therapies that safely augment cardiac contractility and output are needed. Previous apelin peptide studies have highlighted the potential for APJ (apelin receptor) agonism to enhance cardiac function in heart failure. However, apelin's short half-life limits its therapeutic utility. Here, we describe the preclinical characterization of a novel, orally bioavailable APJ agonist, BMS-986224. BMS-986224 pharmacology was compared with (Pyr ) apelin-13 using radio ligand binding and signaling pathway assays downstream of APJ (cAMP, phosphorylated ERK [extracellular signal-regulated kinase], bioluminescence resonance energy transfer-based G-protein assays, β-arrestin recruitment, and receptor internalization). Acute effects on cardiac function were studied in anesthetized instrumented rats. Chronic effects of BMS-986224 were assessed echocardiographically in the RHR (renal hypertensive rat) model of cardiac hypertrophy and decreased cardiac output. BMS-986224 was a potent (Kd=0.3 nmol/L) andiated profile from the renin-angiotensin system inhibitor enalapril, supporting further clinical evaluation of BMS-986224 in heart failure. We identify a novel, potent, and orally bioavailable nonpeptidic APJ agonist that closely recapitulates the signaling properties of (Pyr1) apelin-13. We show that oral APJ agonist administration induces a sustained increase in cardiac output in the cardiac disease setting and exhibits a differentiated profile from the renin-angiotensin system inhibitor enalapril, supporting further clinical evaluation of BMS-986224 in heart failure. Empagliflozin reduces the risk of hospitalization for heart failure in patients with type 2 diabetes and cardiovascular disease. We sought to elucidate the effect of empagliflozin as an add-on therapy on decongestion and renal function in patients with type 2 diabetes admitted for acute decompensated heart failure. The study was terminated early due to COVID-19 pandemic. We enrolled 59 consecutive patients with type 2 diabetes admitted for acute decompensated heart failure. Patients were randomly assigned to receive either empagliflozin add-on (n=30) or conventional glucose-lowering therapy (n=29). We performed laboratory tests at baseline and 1, 2, 3, and 7 days after randomization. Percent change in plasma volume between admission and subsequent time points was calculated using the Strauss formula. There were no significant baseline differences in left ventricular ejection fraction and serum NT-proBNP (N-terminal pro-B-ty