P3193The ketone body 3-hydroxybutyrate increases cardiac output without affecting myocardial external efficiency

Abstract

Background: Myocardial utilization of the ketone body 3‐hydroxybutyrate (3‐ OHB) is increased in patients with heart failure and reduced ejection fraction (HFrEF). 3‐OHB fuels myocardial ATP production during fasting and metabolic stress, but the mechanoenergetic effects of this metabolic shift are unknown. Purpose: To investigate the effects of short‐term 3‐OHB infusion on left ventricular (LV) external stroke work (EW), myocardial oxygen consumption (MVO2), and myocardial external efficiency (MEE) in stable HFrEF patients and age‐matched control subjects. Methods: HFrEF patients and healthy age‐matched control subjects underwent 11‐C‐acetate positron emission tomography (11‐C‐acetate‐PET). All participants received 3‐OHB (0.18 g/kg/h) or saline (placebo) at an equivalent volume for 3 hours in a randomized single‐blinded cross‐over design. I) LV mechanical external work was calculated as EW = stroke volume (SV) x heart rate (HR) x mean arterial pressure (MAP), II) oxidative phosphorylation rate as MVO2, and III) mechanoenergetic coupling as MEE (%) = EW/MVO2 x LV mass. EW, MVO2 and MEE were all derived non‐invasively based on 11‐C‐acetate‐PET. Results: We studied 10 HFrEF patients (LVEF 37±3%, NYHA 2‐3, age 62±14 years) and 10 control subjects. Compared to placebo, 3‐OHB infusion increased circulating 3‐OHB levels from 0.2 [IQR:0.1‐0.6]mM to 3.5 [IQR:3.1‐3.6]mM. (p<0.001, figure 1A) with no difference between groups (p=0.82). Cardiac output increased approximately 40% due to an increase in SV and HR with a minor decrease in MAP (table). Accordingly, EW and MVO2 increased with an associated increment in myocardial blood flow (p<0.001). MEE was lower in HFrEF patients than in control subjects, but 3‐OHB infusion had no effect on MEE (figure 1B). (Table presented) (Figure presented) Conclusion: 3‐OHB demonstrates beneficial hemodynamic effects without deteriorating myocardial external efficiency. These findings suggest that 3‐OHB may be valuable in the treatment of patients with HFrEF.