Genetic aspects of heart failure

Heart failure is a major health problem and is associated with a high morta lity and morbidity. Recently, the role of the genetic background in the ons et and the development of the disease has been evidenced in both heart fail ure with and without systolic dysfunction and in familial and non-familial forms of this condition. Preliminary studies suggest that the I/D polymorph ism of the Angiotensin Converting Enzyme gene influence the development of left ventricular hypertrophy, a major determinant of heart failure. Familia l hypertrophic cardiomyopathy (FHC) is a highly heterogenous autosomal domi nant 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. Susc eptibility genes have been searched for in sporadic forms of dilated cardio myopathy 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 an d this condition appears genetically highly heterogenous. It has been postu lated that the molecular defect involved in FDC is an abnormality in the tr ansmission of contractile force. The analysis of genetic factors that predi spose to heart failure looks promising: it should allow better understandin g of the underlying mechanisms that promote the progression of the disease, to identify subjects at risk of the disease who would benefit from early m edical management and promote the development of pharmacogenetics. (C) 1999 Published by European Society of Cardiology. AU rights reserved.