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.
