99-LB: Myocardial Blood Flow in Association with Baseline Ejection Fraction after Elevation in Plasma Ketones in Patients with T2DM and Heart Failure

Background: SGLT2 inhibitors have been shown to provide CV benefits in HFpEF and HFrEF patients with and without diabetes. The underlying mechanisms continue being explored.

Objective: To examine the effect of hyperketonemia on myocardial blood flow (MBF) in patients with HF and T2DM.

Methods: Subjects with T2DM and HF (EF <50%) received a 6-hr BOHB infusion or a HCO3 infusion (control). A cardiac MRI and a PET study with 18FDG and 15O water were performed before and after the infusion.

Results: Twelve Subjects were studied (Age=60; BMI=32 kg/m2; A1c = 7.7%). Plasma ketone levels reached 1.6±0.2mmol/L. MBF significantly increased in six subjects (“responders” 1.05±0.13 to 1.38±0.17, p = 0.003) and decrease in six subjects (“non-responders” 1.44±0.07 to 0.95±0.08, p = 0.007). With multivariable analysis, only baseline EF was shown to significantly correlate with the increase in MBF.

Conclusion: These findings suggest that patients with a higher baseline EF might be more responsive to ketones and be able to increase MBF as an additional mechanism of CV improvement. These novel results shed new light on the potential effect of ketones in different populations of patients with HF and needs to be further explored.