Acute hemodynamic effect of ketone bodies in patients with decompensated heart failure

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Background Chronically failing heart increases utilization of ketone bodies as an energy substrate. Purpose This study investigated feasibility, safety and acute hemodynamic effect of exogenous ketosis induced by administration of beta-hydroxybutyrate (OHB) in patients with decompensated heart failure and low cardiac output syndrome. Methods Patients with acutely decompensated heart failure with reduced ejection fraction (HFrEF), who were on inotropic support for at least 24 hours (milrinone 0.5±0.1 ug/kg/min), were given oral solution of OHB (25g of OHB monoester in 65 ml of solution; H.V.M.N Ketone Ester, H.V.M.N, USA) in 3-hour intervals up to a total dose of 75g. Serum concentration of OHB and invasive hemodynamics (Swan-Ganz catheter with continuous thermodilution) were measured repeatedly before and during 24 hours after administration of OHB. The primary endpoint was the maximum change in cardiac index (CI). Results The study included 8 patients with decompensated HFrEF (male/female gender: 6/2; age: 58 ± 6 years; left ventricular ejection fraction: 19 ± 5%; non-ischemic/ischemic cardiomyopathy: 7/1). The baseline OHB concentration was 0.4 ± 0.2 mmol/L (normal range: 0 - 0.6 mmol/L). Mild ketosis (1.8 ± 0.6 mmol/L) was induced in all patients within one hour after administration of OHB. The maximum OHB concentration (2.5 ± 0.8 mmol/L) was reached after a median of 5 hours (IQR, 2 to 7 hours). No complications occurred except of temporary dyspepsia in one patient. Within 3 hours after administration of OHB, the CI increased from the baseline by 39 ± 25% (CI 3.4 ± 0.8 vs. 2.5 ± 0.5 L/min/m2; absolute increase of 1.0 ± 0.6 L/min/m2, p = 0.003). The maximum increase of CI reached 52 ± 20% (1.2 ± 0.4 L/min/m2 from the baseline, p <0.001) and it was observed after a median of 5 hours (IQR 3 to 8 hours). After 24 hours, CI returned to the baseline values (p = 0.4). The increase of CI was nor related to changes in the heart rate (at baseline vs. at the maximum CI: 101 ± 5 vs. 103 ± 6 beats/min, p = 0.5). Conclusion Induction of mild ketosis by administration of OHB on top of established inotropic therapy caused a significant temporary increase in myocardial contractility. This novel therapeutic concept might be a promising adjunction to the inotropic support in patients with decompensated HFrEF.