Increased acylcarnitines in infant heart failure indicate fatty acid oxidation inhibition: towards therapeutic options?

ESC Heart Fail. 2023 Oct;10(5):3114-3122.doi: 10.1002/ehf2.14449. Epub 2023 Aug 23.

Jean Issa 1 2 Pierre Lodewyckx 1 2 Hélène Blasco 2 3 Isabelle Benz-de-Bretagne 3 François Labarthe 2 4 5 Bruno Lefort 1 2 5 6 <

PMID: 37614055 PMCID: PMC10567663  DOI: 10.1002/ehf2.14449



Aims: Heart failure in adults is characterized by reduction of long-chain fatty acid oxidation in favour of carbohydrate metabolism. This adaptive phenomenon becomes maladaptive because energy conversion decreases and lipid toxic derivatives known to impair cardiac function are accumulating. No data are available concerning metabolic modification in heart failure in children.

Methods and results: In order to evaluate the fatty acid oxidation in children suffering from heart failure, acylcarnitine profiles on dried blood spots were obtained from children under 16 years old with dilated cardiomyopathy and clinical heart failure (DCM-HF) and control children. Nine children were included in the DCM-HF group and eight in the control group. Acylcarnitine profiles revealed a significant 3.1-fold increase of total acylcarnitines (sum of C3 to C18 acylcarnitine species) in DCM-HF children compared with controls. This result persisted considering the sum of long-chain acylcarnitines (sum of C14 to C18 species), medium-chain acylcarnitines (sum of C8 to C12 species), and short-chain acylcarnitines (sum of C3 to C6 species), respectively, 2.0-, 2.6-, and 1.9-fold increase compared with the control group. A significant linear correlation was found between left ventricular dilatation or ejection fraction and acylcarnitines accumulation. Finally, acylcarnitine ratio C16OH/C16 and C18OH/C18 enhanced in the DCM-HF group, suggesting a diminution of the long-chain hydroxyl acyl-CoA dehydrogenase activity.

Conclusions: Our results suggest down-regulation of fatty acid oxidation in children with heart failure. Such lipidomic alteration could worsen heart function and may suggest considering a metabolic treatment of heart failure in children.

Keywords: Acylcarnitines; Children; Dilated cardiomyopathy; Fatty acid beta-oxidation; Heart failure.

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