Abstract 15256: Treatment With Ketone Ester in Patients With Cardiogenic Shock Improves Cardiac Performance

Introduction: Cardiogenic shock is a life-threatening condition but no medical therapy has been documented to improve outcome. Recent evidence suggests that the ketone body 3-hydroxybutyrate (3-OHB) has favorable hemodynamic effects in patients with stable chronic heart failure. However, the hemodynamic effects of exogenous ketone supplements to patients with cardiogenic shock remains unknown. Hypothesis: In patients hospitalized with cardiogenic shock, acute treatment with a ketone ester has beneficial hemodynamic effects. Methods: In a randomized, double-blind, crossover study, we included 12 patients with cardiogenic shock who were treated with inotropes and/or vasopressors. In random order, patients received an enteral bolus of 500 mg/kg ketone ester (KetoneAid Inc.) and isocaloric, isovolemic placebo containing maltodextrin. Each study period lasted for three hours and was separated by a 3-hour washout period. The primary endpoint was change in cardiac output expressed as area under curve (AUC). Secondary endpoints were recorded at the end of each study period and included mixed venous saturation (SVO 2 ), pulmonary capillary wedge pressure, and echocardiographic measures of contractile function. Results: The ketone ester increased circulating 3-OHB significantly vs. placebo (peak: 3.7±0.5 mmol/L vs. 0.3±0.1 mmol/L, AUC: 6.0±0.9 mmol/L x hour vs. 0.3±0.1 mmol/L x hour, all p<0.001). This was accompanied by an increase in cardiac output (5.1±0.3 L/min vs. 4.4±0.3 L/min, p=0.043; AUC of relative change: 61±22 L vs. 1±18 L, p=0.044), primarily due to a higher stroke volume (53±4 mL vs. 47±4 mL, p=0.048). Ketone ester increased SVO 2 vs. placebo (61±2% vs. 57±3%, p=0.035) whereas heart rate, mean arterial, pulmonary arterial, and pulmonary capillary wedge pressures did not differ between study periods. Ketone ester increased left ventricular ejection fraction (32±3% vs. 28±3%, p=0.005) and global longitudinal strain (-7.3±0.7% vs. -6.5±0.6%, p=0.01) as compared with placebo. Conclusions: Treatment with ketone ester has beneficial hemodynamic effects in patients with cardiogenic shock by increasing cardiac output and left ventricular function.