Heart failure & cardiomyopathiesMechanistic study
Mechanical Unloading is Accompanied by Reverse Metabolic Remodelling in the Failing Heart: Identification of a Novel Citraconate-Mediated Pathway
- Mechanistic study
Authors' conclusion
We report, for the first time, the in-vivo biochemical effects of LVAD unloading in the human heart. Our data identify citraconate as a potentially important regulator of the TCA cycle in the failing heart.
Study context
- Population
- Patients with end-stage heart failure with reduced ejection fraction (HFrEF) with or without left ventricular assist device (LVAD) support, and healthy volunteers
- Participants
- 13 / 20 / 18
- Comparison
- LVAD-supported HFrEF vs HFrEF vs healthy volunteers
- Healthy volunteersn = 13reference
- HFrEFn = 20
- LVADn = 18
- Outcome
- Myocardial biochemical effect of LVAD support (targeted metabolomics and lipidomics on transcardiac blood samples)
Main finding
As reported in the abstract
- Myocardial uptake of purine, nucleotide and tricarboxylic acid (TCA) cycle intermediates depressed in HFrEF, with recovery in LVAD
- Glucose uptake suppressed in HFrEF but restored in LVAD
- Metabolite changes suggestive of impaired fatty acid oxidation in HFrEF but not in LVAD
- Citraconate significantly released by HFrEF hearts vs controls; increased citraconate in HFrEF myocardium but not in LVAD
- Citraconate increased SDH activity in cardiomyoblasts; its isomer itaconate suppressed SDH activity
- SDH activity maintained in HFrEF myocardium but diminished in LVAD myocardium
Original publication
Mechanical Unloading is Accompanied by Reverse Metabolic Remodelling in the Failing Heart: Identification of a Novel Citraconate-Mediated Pathway. Eur J Heart Fail. Published 4 June 2025. doi:10.1002/ejhf.3704
Summarised from the published abstract; every number is checked against it