Abstract
Mechanism (s) responsible for the cardiac benefits of SGLT2 inhibitors remain unknown. Aim: To examine the effect of increased ketone concentration (with infusion of beta-hydroxybutyrate [BOHB]) on left ventricular (LV) function and myocardial glucose uptake (MGU) Methods: Two groups (12 per group) of T2DM with HFrEF (<45%) were studied. Group I (Age=60; BMI=32 kg/m2; A1c = 7.7%) received randomly a 6-hr BOHB infusion (Prime =1.5 mg/kg.min, then 0.75 mg/kg.min) or 6-hr HCO3 infusion (control) . Group II (Age=57; BMI=32 kg/m2; A1c=7%) received a 3-hr BOHB infusion at a higher rate. A cardiac MRI was performed before and after each infusion. Additionally, Group I underwent a PET study with 18FDG Results: Groups I and II achieved plasma ketone levels of 1.2 and 2.6 mmol/L respectively. In both groups, the BOHB infusion significantly (P<0.05) increased CO, stroke volume (SV) , and ejection fraction (EF) ; the increase in EF was greater in Group II vs. Group I (<0.001) (Figure 1) . NaHCO3 infusion had no effect on CO, SV, or EF. Myocardial glucose uptake was not altered by BOHB Conclusion: In patients with T2DM and HFrEF, increased plasma ketones significantly increases LV function and may be dose-dependent. These findings support the hypothesis that plasma ketones can provide an additional fuel for the heart, without interfering myocardial glucose metabolism and may be used therapeutically to improve cardiac function in HFrEF. Disclosure C.Solis-herrera: Speaker's Bureau; Novo Nordisk. Y.Qin: None. H.Honka: None. A.Moody: None. G.D.Clarke: None. C.L.Triplitt: Consultant; Bayer AG, Speaker's Bureau; Eli Lilly and Company, Novo Nordisk. E.Cersosimo: Research Support; AstraZeneca. R.A.Defronzo: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Intarcia Therapeutics, Inc., Novo Nordisk, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Speaker's Bureau; AstraZeneca. Funding Merck and Co and The Max and Minnie Tomerlin Voelcker Foundation and
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