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The pathogenesis of cardiomyopathies is complex and a simple approach cannot describe the whole picture. Different etiologies are reported in pediatric age and heart failure onset can lead to poor prognosis in term of need of heart transplantation and ventricular assist device implantation. Based on hypothesis that heart failure development is related to heart inability to meet metabolic demands of the body, our study will focus to evaluate cardiac metabolism as one of the most critical factors and the accompanying changes of metabolic and echocardiographic profiles at different stages of heart failure. The heart is a unique organ working continuously as a pump supplying blood to the body. To meet this requirement, the myocardium utilizes fatty acids to generate 70-90% of the adenosine triphospate, with the rest being produced by oxidation of glucose, lactate, ketone bodies, aminoacids. Utilization of fatty acids is reduced in the failing heart and there is a metabolic shift to generation of adenosine triphospate from glucose. In patients with advanced cardiomyopathies, the heart is unable to utilize either metabolite and thus "runs out of fuel". It is reported that the adenosine triphospate level is approximately 30% lower in failing human hearts compared with non-failing hearts. In addition to this premise about the metabolic profile of the failing heart, recent advances in the field of metabolomics have indicated that several metabolites and/or metabolic pathways have a role in heart failure. Metabolism of lipids, glycolysis, fructolysis, aminoacids, and ketone oxidation have been found to be altered in non-ischemic cardiomyopathy in adult population. Also in adult heart failure patients some metabolic profiles resulted pronounced perturbated. Taking advantage of the high throughput, metabolomics is a platform for identifying metabolic signatures in children at each stages of heart failure (from pre clinical heart failure to end stage forms). We also will determine whether metabolomic analysis provides sensitive evaluation of heart failure in terms of remodelling at different stages and in disease regression after therapeutic interventions. Study desing is conceived in two parts. The first part is retrospective and we will analyze all echocardiograms in all children affected by cardiomyopathies. The second part is a cross sectional study in which will evaluate untargeted metabolomics in children at any stage of heart failure (A,B, C, D) and in control group. We will evaluate the clinical applicability and significance of plasma metabolomic analysis in the diagnosis and prognosis of heart failure in pediatric ages.
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Patients with Cardiomyopathies
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