Genetic aspects of heart failure

Heart failure is a major health problem and is associated with a high mortality and morbidity. Recently, the role of the genetic background in the onset and the development of the disease has been evidenced in both heart failure with and without systolic dysfunction and in familial and non-familial forms of this condition. Preliminary studies suggest that the I/D polymorphism of the Angiotensin Converting Enzyme gene influence the development of left ventricular hypertrophy, a major determinant of heart failure. Familial hypertrophic cardiomyopathy (FHC) is a highly heterogenous autosomal dominant disease. Seven genes have been identified which all encode proteins of the sarcomere or proteins involved in the regulation of contraction. More than one hundred mutations have been evidenced. Modifier genes such as the I/D polymorphism seem to play a role in the expression of the disease. Susceptibility genes have been searched for in sporadic forms of dilated cardiomyopathy and conflicting results have been published with regard to the I/D polymorphism. Finally, familial forms of dilated cardiomyopathy (FDC) are frequent. Various modes of inheritance and phenotypes have been reported and this condition appears genetically highly heterogenous. It has been postulated that the molecular defect involved in FDC is an abnormality in the transmission of contractile force. The analysis of genetic factors that predispose to heart failure looks promising: it should allow better understanding of the underlying mechanisms that promote the progression of the disease, to identify subjects at risk of the disease who would benefit from early medical management and promote the development of pharmacogenetics.