Progressive Conduction Diseases

Progressive cardiac conduction disease (PCCD), a source of considerable morbidity, comprises a heterogeneous group of conditions resulting from genetic predisposition, environmental modifiers, and other physiologic determinants, including aging. The genetic factors include numerous mutations and variants within the cardiac sodium channel gene, SCN5A. The electrocardiographic phenotype has variable penetrance and is associated with appearances ranging from an isolated conduction disorder to an association with tachyarrhythmias and clinically significant cardiomyopathy. A heterozygotic Scn5a mouse model provides evidence that PCCD may lead to cardiac remodeling consistent with clinical observations in addition to slowing of intracardiac conduction. PCCD has also been associated with the altered expression of genes encoding other proteins involved in impulse propagation, including those responsible for Ca^2+- activated ion channels and cytoskeletal components, both in the presence or absence of structural abnormalities.