Cardiovascular Effects of Oral Ketone Ester Treatment in Patients With Heart Failure With Reduced Ejection Fraction: A Randomized, Controlled, Double-Blind Trial

In a randomized, double-blind crossover study, 24 patients with heart failure with reduced ejection fraction (mean age 65) received 14 days of ketone ester (KE) and 14 days of an isocaloric comparator, in 4 daily doses with a 14-day washout. The primary end point was resting cardiac output. At trough levels, resting cardiac output was higher with KE (5.2 versus 5.0 L/min) and pulmonary capillary wedge pressure was lower (8 versus 11 mm Hg). During exercise, KE was associated with lower wedge pressure and higher cardiac output at low to moderate steady-state exercise but not at peak, and metabolic equivalents were similar. In exploratory analyses, NT-proBNP was 18 percent lower and left ventricular ejection fraction was higher (37 versus 34 percent, P = 0.01).