Heart failure & cardiomyopathies
Myocardial Metabolomics of Human Heart Failure With Preserved Ejection Fraction
Authors' conclusion
Despite marked obesity and diabetes, HFpEF myocardium exhibited lower fatty acid metabolites compared with HFrEF. Ketones and metabolites of the tricarboxylic acid cycle and BCAA were also lower in HFpEF, suggesting insufficient use of alternative fuels.
Study context
- Population
- Patients with heart failure with preserved ejection fraction (HFpEF) or heart failure with reduced ejection fraction (HFrEF) and nonfailing donor controls; plasma and endomyocardial biopsies
- Participants
- 38 / 30 / 20
- Comparison
- HFpEF vs HFrEF vs nonfailing donor controls
- HFpEFn = 38
- HFrEFn = 30
- Controlsn = 20reference
- Outcome
- Myocardial (72) and plasma (69) metabolites: organic acids, amino acids, acylcarnitines
Methodological detailsquantitative targeted metabolomics, integrated with RNA sequencing data, Kruskal-Wallis test with Dunn test, agnostic clustering and machine learning
- Quantitative targeted metabolomics
- Integrated with RNA sequencing data
- Kruskal-Wallis test with Dunn test, agnostic clustering and machine learning
Main finding
As reported in the abstract
- Agnostic clustering of myocardial but not plasma metabolites separated disease groups
- Medium- and long-chain acylcarnitines markedly lower in myocardium from both HF groups vs control; plasma levels no different or higher than control
- Gene expression linked to fatty acid metabolism generally lower in HFpEF vs control
- Myocardial pyruvate higher in HFpEF; TCA cycle intermediates succinate and fumarate lower, as were several genes controlling glucose metabolism
- Non-branched-chain and branched-chain amino acids (BCAA) highest in HFpEF myocardium; downstream BCAA metabolites and genes controlling BCAA metabolism lower
- Ketone levels higher in myocardium and plasma in HFrEF but not HFpEF
- HFpEF metabolomic-derived subgroups differentiated by only a few differences in BCAA metabolites
Further findings
| Outcome | HFpEF | HFrEF |
|---|---|---|
| Obesity and diabetes, HFpEF vs HFrEF | ||
| BMI | 39.8 kg/m² | 26.1 kg/m² |
| Diabetes | 70% | 30% |
- Obesity and diabetes, HFpEF vs HFrEF: both P<0.0001
Original publication
Myocardial Metabolomics of Human Heart Failure With Preserved Ejection Fraction. Circulation. Published 1 March 2023. doi:10.
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