Abstract
Empagliflozin and sacubitril/valsartan reduce cardiovascular mortality and heart failure hospitalization rates, but the effect of early initiation of these drugs following myocardial infarction (MI) remains unknown.
Twenty-four pigs with MI were randomized to receive treatment with beta blockers (BB) (Control, n=8), empagliflozin + BB (Empa, n=8), or empagliflozin + sacubitril/valsartan + BB (Empa + Sac/Val, n=8). Cardiac function was assessed via MRI, systemic immune response via flow cytometry, and metabolic profile via nuclear magnetic resonance spectroscopy over time. At follow-up, arrhythmogenic properties, myocardial fibrosis, and vascularization were evaluated.
Empagliflozin treatment reduced acute systemic inflammation, decreasing the number of circulating leukocytes 2 days post-MI (P=0.010) and CCR2+ monocytes 15 days post-MI (P=0.049), increased hepatic lipid content with a cardioprotective profile, and raised type III collagen content in the myocardial scar (P=0.023), however did not modify the arrhythmogenic properties and cardiac function parameters. Empa + Sac/Val treatment increased the number of circulating monocytes at 30 days (P=0.003), predominantly CCR2–, boosted triglyceride metabolism, lowered collagen I content in the scar (P=0.082), decreased ventricular tachycardia inducibility (P=0.025), and improved cardiac function (iLVEDV P=0.029; LVSV P=0.044).
Empagliflozin modulates systemic inflammation, myocardial scar collagen composition, and increases cardioprotective lipid content in the liver. The combination treatment of empagliflozin and sacubitril/valsartan modulates triglyceride metabolism, reduces collagen I in the myocardial scar, decreases arrhythmias, and improves cardiac function.
