Initiating Empagliflozin and Sacubitril/Valsartan Early After Acute Myocardial Infarction: Mechanistic Study
Por:
Martínez-Falguera, D, Aranyó, J, Ferrer-Curriu, G, Teis, A, Revuelta-Lopez, E, Diaz-Güemes, I, Monguió-Tortajada, M, Fadeuilhe, E, Rodríguez-Leor, O, Poblador, F, Montejo, B, Roura, S, Villuendas, R, Sarrias, A, Bazan, V, Jorge, E, Delgado, V, Jimenez-Trinidad, FR, Rigol, M, Martinez-Micaelo, N, Amigó, N, Bayes-Genis, A, Bisbal, F and Gálvez-Montón, C
Publicada:
3 jun 2025
Resumen:
Background Empagliflozin and sacubitril/valsartan are established in heart failure treatment, but their effects after myocardial infarction (MI) are less clear. This study evaluated early empagliflozin initiation, with or without sacubitril/valsartan, on post-MI inflammation, oxidative stress, metabolism, fibrosis, cardiac function, and ventricular tachycardia (VT) risk in a pig model.Methods A total of 24 of 30 pigs survived the MI procedure and were subsequently randomized to receive beta-blocker treatment alone (control-MI), beta-blocker+empagliflozin, or beta-blocker+empagliflozin+sacubitril/valsartan. Immune response, metabolic profile, and cardiac function were monitored. At 30 days after MI, programmed electrical stimulation and high-density mapping were performed and VT inducibility was assessed. Tissue samples were collected for cardiac inflammation, oxidative stress, and metabolic analyses.Results Empagliflozin reduced circulating leukocytes at 2 and 15 days after MI (P=0.010 and P=0.050, respectively) and decreased C-C chemokine receptor 2+ monocytes at 15 days (P=0.049). Nitric oxide bioavailability increased in remote myocardium (P=0.059), along with cardioprotective liver lipids and collagen III in the myocardial scar (P=0.023). No effect on cardiac function or VT inducibility was observed at 30 days. With empagliflozin+sacubitril/valsartan, scar collagen I decreased (P=0.082), left ventricular compliance improved (P=0.029), electrophysiological remodeling improved (reduced border-zone corridors [P=0.006] and deceleration zones [P=0.008]), and VT inducibility decreased (P=0.025).Conclusions In this pig model of nonreperfused MI treated with beta-blocker, early initiation of empagliflozin reduced inflammation, improved nitric oxide bioavailability, increased protective liver lipids, and modified scar composition without affecting cardiac function or VT risk. With empagliflozin+sacubitril/valsartan treatment, scar collagen I and VT inducibility declined and left ventricular remodeling was enhanced.
Filiaciones:
:
Germans Trias i Pujol Res Inst IGTP, ICREC Res Program, Barcelona, Spain
Univ Barcelona UB, Fac Med, Barcelona, Spain
Aranyó, J:
Germans Trias i Pujol Univ Hosp, Heart Inst iCOR, Barcelona, Spain
:
Germans Trias i Pujol Res Inst IGTP, ICREC Res Program, Barcelona, Spain
Germans Trias i Pujol Univ Hosp, Heart Inst iCOR, Barcelona, Spain
Teis, A:
Germans Trias i Pujol Univ Hosp, Heart Inst iCOR, Barcelona, Spain
:
Germans Trias i Pujol Res Inst IGTP, ICREC Res Program, Barcelona, Spain
Germans Trias i Pujol Univ Hosp, Heart Inst iCOR, Barcelona, Spain
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
Diaz-Güemes, I:
Germans Trias i Pujol Res Inst IGTP, ICREC Res Program, Barcelona, Spain
Monguió-Tortajada, M:
Germans Trias i Pujol Res Inst IGTP, ICREC Res Program, Barcelona, Spain
Germans Trias i Pujol Univ Hosp, Heart Inst iCOR, Barcelona, Spain
Univ Lausanne, Dept Immunobiol, Epalinges, Vaud, Switzerland
Fadeuilhe, E:
Germans Trias i Pujol Univ Hosp, Heart Inst iCOR, Barcelona, Spain
:
Germans Trias i Pujol Univ Hosp, Heart Inst iCOR, Barcelona, Spain
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
:
Germans Trias i Pujol Res Inst IGTP, ICREC Res Program, Barcelona, Spain
:
Germans Trias i Pujol Res Inst IGTP, ICREC Res Program, Barcelona, Spain
:
Germans Trias i Pujol Res Inst IGTP, ICREC Res Program, Barcelona, Spain
Germans Trias i Pujol Univ Hosp, Heart Inst iCOR, Barcelona, Spain
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
Univ Vic Cent Univ Catalonia UVic UCC, Fac Med, Vic, Barcelona, Spain
:
Germans Trias i Pujol Univ Hosp, Heart Inst iCOR, Barcelona, Spain
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
Sarrias, A:
Germans Trias i Pujol Univ Hosp, Heart Inst iCOR, Barcelona, Spain
:
Germans Trias i Pujol Univ Hosp, Heart Inst iCOR, Barcelona, Spain
:
Germans Trias i Pujol Res Inst IGTP, ICREC Res Program, Barcelona, Spain
Univ Vic Cent Univ Catalonia UVic UCC, Fac Hlth Sci Manresa, Dept Basic Sci, Barcelona, Spain
:
Germans Trias i Pujol Univ Hosp, Heart Inst iCOR, Barcelona, Spain
Ctr Comparat Med & Bioimaging, Badalona, Spain
Jimenez-Trinidad, FR:
Hosp Clin Barcelona, Inst Clin Cardiovasc ICCV, Barcelona, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona, Spain
Rigol, M:
Hosp Clin Barcelona, Inst Clin Cardiovasc ICCV, Barcelona, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona, Spain
Martinez-Micaelo, N:
Biosfer Teslab, Reus, Tarragona, Spain
Amigó, N:
Biosfer Teslab, Reus, Tarragona, Spain
:
Germans Trias i Pujol Res Inst IGTP, ICREC Res Program, Barcelona, Spain
Germans Trias i Pujol Univ Hosp, Heart Inst iCOR, Barcelona, Spain
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
Autonomous Univ Barcelona, Dept Med, Campus Can Ruti, Barcelona, Spain
:
Germans Trias i Pujol Univ Hosp, Heart Inst iCOR, Barcelona, Spain
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
:
Germans Trias i Pujol Res Inst IGTP, ICREC Res Program, Barcelona, Spain
Germans Trias i Pujol Univ Hosp, Heart Inst iCOR, Barcelona, Spain
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
Green Submitted, gold
|