Heart failure & cardiomyopathies
Crossover Trial of Exogenous Ketones on Cardiometabolic Endpoints in Heart Failure With Preserved Ejection Fraction
Authors' conclusion
Despite robust ketosis, shifting substrate use away from carbohydrates, and decreasing estimated left ventricular filling pressures, acute KE supplementation did not improve peak VO2 or constant-intensity exercise in HFpEF.
Study context
- Population
- Symptomatic heart failure with preserved ejection fraction (HFpEF)
- Participants
- 20 participants
- Comparison
- Acute ketone ester vs placebo
- Primary endpoint
- Coprimary: peak VO2 during incremental cardiopulmonary exercise testing; time to exhaustion during constant-intensity exercise (75% peak workload)
Methodological detailscrossover, placebo-controlled
- Crossover
- Placebo-controlled
Primary result
As reported in the abstract
| Group | Peak VO2 | Constant-intensity exercise endurance |
|---|---|---|
| Ketone ester (KE) | 10.4 ± 3.6 mL/kg/min | 9.7 ± 7.3 minutes |
| Placebo | 10.5 ± 4.0 mL/kg/min | 8.7 ± 4.4 minutes |
Peak VO2
Ketone ester (KE)10.4 ± 3.6 mL/kg/min
Placebo10.5 ± 4.0 mL/kg/min
Constant-intensity exercise endurance
Ketone ester (KE)9.7 ± 7.3 minutes
Placebo8.7 ± 4.4 minutes
- KE vs Placebo: P = 0.75 — peak VO2
- KE vs Placebo: P = 0.51 — constant-intensity exercise endurance
Further findings
| Outcome | Difference (L/min) (95% CI) | P value | |
|---|---|---|---|
| Resting haemodynamics · At rest — KE vs Placebo · cardiac output | 0.6 (0.3–1.0) | ||
| −0.500.511.5Difference, L/min (linear scale) |
| Outcome | Difference (WU) (95% CI) | P value | |
|---|---|---|---|
| Resting haemodynamics · At rest — KE vs Placebo · total peripheral resistance | −3.2 (−5.2 to −1.2) | ||
| −10−505Difference, WU (linear scale) |
| Outcome | Difference (mL of O2/dL blood) (95% CI) | P value | |
|---|---|---|---|
| Resting haemodynamics · At rest — KE vs Placebo · arteriovenous oxygen content difference | −0.7 (−1.2 to −0.2) | ||
| −1.5−1−0.500.5Difference, mL of O2/dL blood (linear scale) |
| Outcome | Difference (mg/kg/min) | P value |
|---|---|---|
| Plasma glucose appearance rate (6 participants with 6,6-2H2-glucose infusions) · before and during constant-intensity exercise | −0.24 | P < 0.001 |
Resting haemodynamics · At rest
- Heart rate and biventricular systolic function greater with KE; differences mostly disappeared during incremental exercise
Respiratory exchange ratio, NEFA and glucose, estimated LV filling pressures (E/e') · during both exercise protocols
- Lowered with KE
Original publication
Crossover Trial of Exogenous Ketones on Cardiometabolic Endpoints in Heart Failure With Preserved Ejection Fraction. JACC Heart Fail. Published 29 March 2025. doi:10.
Summarised from the published abstract; every number is checked against it