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Empagliflozin Ameliorates Adverse Left Ventricular Remodeling in Nondiabetic Heart Failure by Enhancing Myocardial Energetics

Santos-Gallego, Carlos G. ; Requena-Ibanez, Juan Antonio ; San Antonio, Rodolfo ; Ishikawa, Kiyotake ; Watanabe, Shin ; Picatoste, Belen ; Flores, Eduardo ; Garcia-Ropero, Alvaro ; Sanz, Javier ; Hajjar, Roger J. ; Fuster, Valentin ; Badimon, Juan J.

Journal of the American College of Cardiology, 2019-04, Vol.73 (15), p.1931-1944 [Periódico revisado por pares]

United States: Elsevier Inc

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Empagliflozin Ameliorates Adverse Left Ventricular Remodeling in Nondiabetic Heart Failure by Enhancing Myocardial Energetics
Autor: Santos-Gallego, Carlos G. ; Requena-Ibanez, Juan Antonio ; San Antonio, Rodolfo ; Ishikawa, Kiyotake ; Watanabe, Shin ; Picatoste, Belen ; Flores, Eduardo ; Garcia-Ropero, Alvaro ; Sanz, Javier ; Hajjar, Roger J. ; Fuster, Valentin ; Badimon, Juan J.
Assuntos: Adenosine triphosphate ; Amino acids ; Analysis of Variance ; animal models ; Animals ; Benzhydryl Compounds - pharmacology ; Blood pressure ; cardiac remodeling ; Cardiology ; Chain branching ; Congestive heart failure ; Coronary artery ; Diabetes ; Diabetes Mellitus ; Diabetes mellitus (non-insulin dependent) ; Disease Models, Animal ; Echocardiography ; Echocardiography, Three-Dimensional - methods ; Enzymes ; Fatty acids ; Glucose ; Glucose metabolism ; Glucosides - pharmacology ; Glycolysis ; Heart ; Heart failure ; Heart Failure - diagnostic imaging ; Heart Failure - drug therapy ; Heart Function Tests - drug effects ; Hemoglobin ; Infarction ; Investigations ; Ischemia ; Ketones ; Magnetic resonance imaging ; Metabolism ; Metabolites ; myocardial metabolism ; Occlusion ; Production methods ; Random Allocation ; Reference Values ; SGLT2 inhibition ; Sodium-Glucose Transporter 2 Inhibitors - pharmacology ; Statistics, Nonparametric ; Stroke Volume - drug effects ; Stroke Volume - physiology ; Swine ; Switches ; Treatment Outcome ; Uric acid ; Utilization ; Variance analysis ; Veins & arteries ; Ventricle ; Ventricular Function, Left - drug effects ; Ventricular Function, Left - physiology ; Ventricular Remodeling - drug effects
É parte de: Journal of the American College of Cardiology, 2019-04, Vol.73 (15), p.1931-1944
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SourceType-Scholarly Journals-1
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Descrição: Empagliflozin cardiac benefits in the EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial cannot be explained exclusively by its antihyperglycemic activity. The hypothesis was that empagliflozin’s cardiac benefits are mediated by switching myocardial fuel metabolism away from glucose toward ketone bodies (KB), which improves myocardial energy production. Heart failure was induced in nondiabetic pigs (n = 14) by 2-h balloon occlusion of the proximal left anterior descending artery. Animals were randomized to empagliflozin or placebo for 2 months. Animals were evaluated with cardiac magnetic resonance imaging and 3-dimensional echocardiography. Myocardial metabolite consumption was analyzed by simultaneous blood sampling from coronary artery and coronary sinus. Myocardial samples were obtained for molecular evaluation. Nonmyocardial infarction animals served as comparison. Despite similar initial ischemic myocardial injury in both groups, the empagliflozin group showed amelioration of adverse remodeling at 2 months (lower left ventricular [LV] mass, reduced LV dilatation, less LV sphericity) versus the control group. LV systolic function (LV ejection fraction and echocardiography-derived strains) was improved, as was neurohormonal activation. Compared with nonmyocardial infarction, control animals increased myocardial glucose consumption mainly through anaerobic glycolysis while reducing utilization of free fatty acid (FFA) and branched-chain amino acid (BCAA). Empagliflozin-treated pigs did not consume glucose (reduction in myocardial glucose uptake, and glucose-related enzymes) but instead switched toward utilization of KB, FFA, and BCAA (increased myocardial uptake of these 3 metabolites, and enhanced expression/activity of the enzymes implicated in the metabolism of KB/FFA/BCAA). Empagliflozin increased myocardial ATP content and enhanced myocardial work efficiency. Empagliflozin ameliorates adverse cardiac remodeling and heart failure in a nondiabetic porcine model. Empagliflozin switches myocardial fuel utilization away from glucose toward KB, FFA, and BCAA, thereby improving myocardial energetics, enhancing LV systolic function, and ameliorating adverse LV remodeling. [Display omitted]
Editor: United States: Elsevier Inc
Idioma: Inglês

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Empagliflozin Ameliorates Adverse Left Ventricular Remodeling in Nondiabetic Heart Failure by Enhancing Myocardial Energetics

Santos-Gallego, Carlos G. ; Requena-Ibanez, Juan Antonio ; San Antonio, Rodolfo ; Ishikawa, Kiyotake ; Watanabe, Shin ; Picatoste, Belen ; Flores, Eduardo ; Garcia-Ropero, Alvaro ; Sanz, Javier ; Hajjar, Roger J. ; Fuster, Valentin ; Badimon, Juan J.

United States: Elsevier Inc

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