Heart failure is associated with accumulation of long chain acylcarnitines in children suffering from cardiomyopathy

Abstract

Heart failure in adults is characterized by a reduction in beta oxidation of long-chain fatty acids in favor of carbohydrate metabolism. Thus, the reduction of beta oxidation leads to a decrease in energy production and an accumulation of toxic derivatives such as LC acylcarnitines. This lipidomic disturbance has been shown to impair cardiac function, and is called cardiolipotoxicity. No data are available concerning lipid homeostasis modification in heart failure in children. We compared acylcarnitines profiles performed in our centre from 2015 to 2021 in children explored for a non-metabolic dilated cardiomyopathy (DCM) and in control children. Sixteen children aged from 3 months to 15 years old referred to our centre for DCM were included. Eight of them had clinical symptoms of heart failure and elevated NT pro BNP (DCM-HF), while the 8 others had no symptoms of HF and normal NT pro BNP (DCM-N). Sums of total acylcarnitines, as well as sum of long chain, medium chain or short chain acylcarnitines were enhanced in DCM-HF children compared to the control population, and also compared to DCM-N children ( Figure 1 ). C16OH-Car/C16-Car, and C14:1-Car/C12:1-Car ratio were significantly higher in DCM-HF group than in DCM-N group or control group, suggesting a downregulation of specific enzymes of long chain fatty acids beta oxidation. Our results support a reduction of fatty acid oxidation in children with DCM-HF. This metabolic modification needs to be further investigated in a larger scale study. Such lipidomic alteration could worsen heart function and may suggest considering a metabolic treatment of heart failure in children.