Clinical research in cardiology : official journal of the German Cardiac Society · 2026
Continuously elevated plasma ketone bodies are linked to adverse outcomes in patients with heart failure.
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Palm Constantin L, Scholte Niels T B, Lu Lirong, Kamar Sabrina Abou, Bakker Barbara M, Voorrips Suzanne N, Mahmoud Belend, Connelly Margery A, Suthahar Navin, de Boer Rudolf A, Umans Victor A, Akkerhuis K Martijn, Hillege Hans, Boersma Eric, Kardys Isabella, Westenbrink B Daan
Аннотация
BACKGROUND: Elevated plasma ketone bodies (KBs) are linked to poor outcomes in heart failure (HF), yet the prognostic value of repeated KB measurements is uncertain.
OBJECTIVE: To study temporal changes in plasma KBs in HF patients in relation to prognosis.
METHODS: Plasma KBs were measured by nuclear magnetic resonance spectroscopy in 467 patients from the TRIUMPH study. Blood was obtained up to seven times during 1-year follow-up after HF hospitalization. Associations between serial KB measurements and the endpoint of death and HF rehospitalization were investigated by joint modeling. Similar analyses were conducted in the Bio-SHiFT study, including 397 chronic HF patients with up to 10 repeated blood samples during a median follow-up of 2.1 years. The endpoint in Bio-SHiFT was a composite of cardiovascular death, HF hospitalization, left ventricular device implantation and heart transplantation.
RESULTS: In TRIUMPH, median age was 74 years, 37% of patients were female and 82% were in NYHA class III/IV. Estimated KBs were continuously higher in the 185 (40%) patients reaching the combined endpoint. Hazard ratios (HR) (95% confidence interval [CI]) for the endpoint per doubling of total KBs (TKBs), acetone, and β-hydroxybutyrate were 2.10 (1.27-3.71), 1.62 (1.08-2.44) and 1.62 (1.22-2.23), respectively, at any time during follow-up after adjustment for clinical characteristics and NT-proBNP at baseline. In Bio-SHiFT, median age was 64 years, 28.5% of patients were female, and 124 (31.2%) patients reached the primary endpoint. KBs were higher in patients reaching the endpoint. The HR per doubling of TKB was 5.36 (95% CI 2.18-14.0) and 4.24 (31.4-5.95) for acetone.
CONCLUSION: Serially measured KB levels were associated with adverse events in two independent HF cohorts. Patients with adverse events displayed consistently higher KBs, potentially reflecting ongoing metabolic stress.
OBJECTIVE: To study temporal changes in plasma KBs in HF patients in relation to prognosis.
METHODS: Plasma KBs were measured by nuclear magnetic resonance spectroscopy in 467 patients from the TRIUMPH study. Blood was obtained up to seven times during 1-year follow-up after HF hospitalization. Associations between serial KB measurements and the endpoint of death and HF rehospitalization were investigated by joint modeling. Similar analyses were conducted in the Bio-SHiFT study, including 397 chronic HF patients with up to 10 repeated blood samples during a median follow-up of 2.1 years. The endpoint in Bio-SHiFT was a composite of cardiovascular death, HF hospitalization, left ventricular device implantation and heart transplantation.
RESULTS: In TRIUMPH, median age was 74 years, 37% of patients were female and 82% were in NYHA class III/IV. Estimated KBs were continuously higher in the 185 (40%) patients reaching the combined endpoint. Hazard ratios (HR) (95% confidence interval [CI]) for the endpoint per doubling of total KBs (TKBs), acetone, and β-hydroxybutyrate were 2.10 (1.27-3.71), 1.62 (1.08-2.44) and 1.62 (1.22-2.23), respectively, at any time during follow-up after adjustment for clinical characteristics and NT-proBNP at baseline. In Bio-SHiFT, median age was 64 years, 28.5% of patients were female, and 124 (31.2%) patients reached the primary endpoint. KBs were higher in patients reaching the endpoint. The HR per doubling of TKB was 5.36 (95% CI 2.18-14.0) and 4.24 (31.4-5.95) for acetone.
CONCLUSION: Serially measured KB levels were associated with adverse events in two independent HF cohorts. Patients with adverse events displayed consistently higher KBs, potentially reflecting ongoing metabolic stress.