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Access this article Similar content being viewed by others Data availability Not applicable Abbreviations ACC: Acetyl-CoA carboxylase ACE2: Angiotensin converting enzyme-2 ACS: Acute coronary syndrome ACEI: Angiotensin-converting enzyme inhibitors AKT: Protein kinase B AMP: 5-Adenosine monophosphate AMPK: 5-Adenosine monophosphate-activated protein kinase Ang II: Angiotensin II ANP: Atrial natriuretic peptide APN: Serum lipocalin ARB: Angiotensin II receptor blockers AS: Atherosclerosis ASCVD: Atherosclerotic cardiovascular disease AT: Angiotensin II type ATP: Adenosine triphosphate AT1R: Angiotensin II type I receptor BHB: -Hydroxybutyrate BMI: Body mass index BNP: Brain natriuretic peptide CaMKII: Calmodulin-dependent kinase II cAMP: Cyclic adenosine monophosphate CCR2: CC chemokine receptor 2 cGMP: Cyclic guanosine monophosphate CI: Chronotropic incompetence CI: Confidence interval CIMT: Carotid intima-media thickness CKD: Chronic kidney disease CPT-1: Carnitine palmitoyltransferase1 CRP: C-reactive protein cTGF: Connective tissue growth factor CV: Cardiovascular CVD: Cardiovascular disease CVOTs: Cardiovascular outcomes DGAT1: Diacylglycerol O-acyltransferase 1 EAT: Epicardial adipose tissue ECM: Extracellular matrix eNOS: Endothelial nitric oxide synthase Epac-1: CAMP-activated exchange protein-1 ERK: Extracellular signal-regulated kinase FFA: Free fatty acid GLP-1: Glucagon-like peptide-1 GLP-1 R: Glucagon-like peptide-1 receptors GLP-1 RAs: Glucagon-like peptide-1 receptor agonists GLS: Global longitudinal strain HF: Heart failure HFmrEF: Heart failure with mid-range ejection fraction HFpEF: Heart failure with preserved ejection fraction HFrEF: Heart failure with reduced ejection fraction HO-1: Heme oxygenase-1 HR: Hazard ratio hsCRP: Hypersensitive C-reactive protein ICAM-1: Intercellular adhesion molecule-1 IGT: Impaired glucose tolerance IL-1: Interleukin-1 KCCQ-CSS: Kansas City Cardiomyopathy Questionnaire Clinical Summary Score KBs: Ketone bodies LV: Left ventricle LVEF: Left ventricular ejection fraction LVH: Left ventricular hypertrophy MACE: Major adverse cardiovascular event MCP-1: Monocyte chemoattractant protein-1 MDA: Malondialdehyde MI: Myocardial infarction miR21: MicroRNA-21 MMPs: Matrix metalloproteinases mTOR: Rapamycin MRA: Mineralocorticoid receptor antagonists MRI: Magnetic resonance imaging 6MWD: 6-Minute walk distance NA: Not available NF-B: Nuclear factor-B NHE3: Sodium-hydrogen exchanger isoform 3 NLRP3: NOD-like receptor thermal protein domain associated protein 3 NOX: NADPH oxidase NO: Nitric oxide NPs: Natriuretic peptides Nrf-2: Nuclear factor erythroid 2-related factor 2 NT-proBNP: N-terminal pro-B-type natriuretic peptide NYHA: New York Heart Association ox-LDL: Oxidized low-density lipoprotein P: Probability PFK-1: Phosphofructokinase-1 PGC-1: PPAR- coactivator 1 PI3K: Phosphatidylinositol-3-kinase PKG: Protein kinase G PPAR: Peroxisome proliferator-activated receptor p70S6K: TRPV1-ribosomal protein 70 S6 kinase PTEN: Phosphatase and tensin homolog PVD: Polyvascular disease RAAS: Renin-angiotensin-aldosterone system RCTs: Randomized controlled trials ROS: Reactive oxygen species RyR2: Ryanodine receptor 2 Sc: Subcutaneous SERCA2a: Sarcoplasmic reticulum calcium ATPase 2a sGC: Soluble guanylate cyclase SGLT2i: Sodium-glucose cotransporter-2 inhibitors SH: Spontaneous hypertension SOD: Superoxide dismutase T2DM: Type 2 diabetes mellitus TNF-: Tumor necrosis factor- TXNIP: Thioredoxin interacting protein ULK1: UNC-51-like kinase 1 VAT: Visceral adipose tissue VCAM-1: Vascular cell adhesion molecule-1 Vs: Versus References McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bhm M, Burri H, Butler J, elutkien J, Chioncel O et al (2023) 2023 Focused update of the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure

CJC-1295 with DAC modification may show slightly improved stability due to its larger molecular structure