{"id":"b49add0c9b39","type":"article","url":"https://hartvaat.nl/2024/05/07/orale-ketonester-bij-hfref-gerandomiseerde-trial/","title":"Orale ketonester bij HFrEF: gerandomiseerde trial","title_en":"Cardiovascular Effects of Oral Ketone Ester Treatment in Patients With Heart Failure With Reduced Ejection Fraction: A Randomized, Controlled, Double-Blind Trial.","category":"hartfalen","category_label":"Hartfalen","professions":["cardioloog"],"tags":["dapa-hf","emperor-trials","soul-trial","step-hfpef","summit-trial"],"journal":"Circulation","doi":"10.1161/CIRCULATIONAHA.123.067971","source_url":"https://doi.org/10.1161/CIRCULATIONAHA.123.067971","authors":["Kristoffer Berg-Hansen","Nigopan Gopalasingam","Kristian Hylleberg Christensen","Bertil Ladefoged","Mads Jønsson Andersen","Steen Hvitfeldt Poulsen","Barry A Borlaug","Roni Nielsen","Niels Møller","Henrik Wiggers"],"significance":6,"published":"2024-05-07","source_date":"2024-05-07","image":"","kennis":["https://hartvaat.nl/kennis/hartfalen/wat-is-hartfalen/","https://hartvaat.nl/kennis/hartfalen/ivabradine-bij-hartfalen/"],"congress":"","summary_en":"This randomized trial of oral ketone ester therapy in HFrEF showed that exogenous ketone supplementation increases cardiac output, exploring metabolic modulation as a novel heart failure treatment approach.","created":"2026-07-03T10:30:55Z","updated":"2026-07-03T13:29:58Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"Gerandomiseerde trial onderzocht het cardiovasculaire effect van orale ketonestertherapie bij HFrEF. Het middel verhoogde het ketonenniveau en verbeterde de cardiac output, wat ketonmetabolisme als therapeutisch doel bij hartfalen ondersteunt.","abstract_original":"BACKGROUND: Heart failure triggers a shift in myocardial metabolic substrate utilization, favoring the ketone body 3-hydroxybutyrate as energy source. We hypothesized that 14-day treatment with ketone ester (KE) would improve resting and exercise hemodynamics and exercise capacity in patients with heart failure with reduced ejection fraction. METHODS: In a randomized, double-blind cross-over study, nondiabetic patients with heart failure with reduced ejection fraction received 14-day KE and 14-day isocaloric non-KE comparator regimens of 4 daily doses separated by a 14-day washout period. After each treatment period, participants underwent right heart catheterization, echocardiography, and blood sampling at plasma trough levels and after dosing. Participants underwent an exercise hemodynamic assessment after a second dosing. The primary end point was resting cardiac output (CO). Secondary end points included resting and exercise pulmonary capillary wedge pressure and peak exercise CO and metabolic equivalents. RESULTS: We included 24 patients with heart failure with reduced ejection fraction (17 men; 65±9 years of age; all White). Resting CO at trough levels was higher after KE compared with isocaloric comparator (5.2±1.1 L/min versus 5.0±1.1 L/min; difference, 0.3 L/min [95% CI, 0.1-0.5), and pulmonary capillary wedge pressure was lower (8±3 mm Hg versus 11±3 mm Hg; difference, -2 mm Hg [95% CI, -4 to -1]). These changes were amplified after KE dosing. Across all exercise intensities, KE treatment was associated with lower mean exercise pulmonary capillary wedge pressure (-3 mm Hg [95% CI, -5 to -1] ) and higher mean CO (0.5 L/min [95% CI, 0.1-0.8]), significantly different at low to moderate steady-state exercise but not at peak. Metabolic equivalents remained similar between treatments. In exploratory analyses, KE treatment was associated with 18% lower NT-proBNP (N-terminal pro-B-type natriuretic peptide; difference, -98 ng/L [95% CI, -185 to -23]), higher left ventricular ejection fraction (37±5 versus 34±5%; P=0.01), and lower left atrial and ventricular volumes. CONCLUSIONS: KE treatment for 14 days was associated with higher CO at rest and lower filling pressures, cardiac volumes, and NT-proBNP levels compared with isocaloric comparator. These changes persisted during exercise and were achieved on top of optimal medical therapy. Sustained modulation of circulating ketone bodies is a potential treatment principle in patients with heart failure with reduced ejection fraction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05161650."}