Should Exogenous Ketone Body Supplementation Be Considered in Patients Hospitalized for Acute Heart Failure? Rationale and Design of the KETO-AHF Trial.

Background: Acute heart failure (AHF) is associated with high mortality rates, and contemporary medical treatments provide limited benefits in survival. Emerging evidence suggests that exogenous ketone bodies may have beneficial cardiovascular effects in patients with heart failure. The KETO-AHF (KETOne Supplements in Patients Hospitalized for Acute Heart Failure) trial is designed to assess the clinical benefits of initiating ketone supplementation with 1,3-butanediol compared with placebo in patients hospitalized for AHF with reduced ejection fraction.

Methods: KETO-AHF is a multicenter, randomized, double-blind, placebo-controlled trial investigating the effects of 1,3-butanediol (33 g 3 times daily) in patients hospitalized for AHF. Patients with symptoms and signs of AHF requiring intravenous loop diuretics and/or vasoactive treatment, elevated natriuretic peptides, and a left ventricular ejection fraction ≤ 35%, whether de novo or known heart failure, will be enrolled within 5 days of hospital admission. Participants will be randomized 1:1 to receive either 1,3-butanediol or placebo for a 30-day treatment period. The study aims to enroll 125 patients in each group. The primary endpoint is a hierarchical composite of all-cause mortality, heart failure rehospitalization, 6-minute walk test improvement, and reduction in NT-proBNP levels at 30 days.

Conclusion: The KETO-AHF trial will provide insights into the effects of supplementation with the ketone body 1,3-butanediol in patients hospitalized for AHF.