Heart Failure and Cardiomyopathies: Clinical and Molecular Aspects in Children

Heart failure is considered the end-stage phenotype of a variety of different basal cardiac defects, determined by several possible cellular regulation mechanisms. Complex and monogenic diseases can be the first manifestation of a developing phenotype leading to final heart failure. Hypertension, myocardial infarction and other forms of atherosclerotic cardiovascular disease can be precursors of heart failure; moreover, different types of cardiomyopathy can evolve to a heart failure phenotype. Recent advances in molecular biology and genetics have allowed for further comprehension of the basis of the development of cardiac diseases. Particularly, genetics of cardiomyopathies, although known since the early 1990s, studies are still in progress as an increasing number of genes (causing or predisposing to the disease) are discovered. Genetic studies in this field are now supported by new technical approaches (such as microarray chips) that increase the output results of the analysis allowing the evaluation of the entire genome in a single experiment and extending the research to new classes of biological molecules such as microRNA. Cellular mechanisms of impaired energetic metabolism, contractile force generation and propagation, ion channel exchanges and mitochondrial functioning are commonly recognized as the principal causes of the development of heart failure. Identifying which genetic cause has led to a specific phenotype is not only important to foresee the prognosis, but also to design a specific pharmacological therapy on the basis of the individual necessity (this approach is known as “pharmacogenetics” or “pharmacogenomics”). Other promising therapeutic innovations are found in stem cell therapy and different classes of cells have been tested for this purpose, but clinical application is, to date, still under investigation.

Keywords: Cardiomyopathies, heart failure, arrhythmogenic right ventricular dysplasia, cardiac remodeling, dilative cardiomyopathy, genetics, hypertrophic cardiomyopathy, pharmacogenetics, restrictive cardiomyopathy, stem cells.