Current Perspectives of Electrical Remodeling and Its Therapeutic Implications

Abstract

Electrical remodeling involves alterations in the electrophysiologic milieu of myocardium in various disease states, such as ventricular hypertrophy, heart failure, atrial tachyarrhythmias, myocardial ischemia, and infarction that are associated with cardiac arrhythmias. Although research in this area dates back to early part of the 19th century, we still lack the exact knowledge of ionic remodeling, the role of various genes and channel proteins, and their relevance for the newer antiarrhythmic therapies. Structural remodeling may also have an impact on the electrical remodeling process, although differences in both structural and electrical remodeling are associated with different disease states. Various electrophysiologic, cellular, and structural alterations, including anisotropic conduction, increased intracellular calcium levels, and gap junction remodeling predispose to increased dispersion of action potential duration and refractoriness. This constitutes a favorable substrate for early and late afterdepolarizations and reentrant arrhythmias. Studying the role of ionic remodeling in the initiation and propagation of cardiac arrhythmias has significant relevance for developing newer antiarrhythmic therapies, for identifying patients at risk of developing fatal arrhythmias, and for implementing effective preventive measures. Further research is required to understand the specific effects of individual ion channel remodeling, to understand the signal transduction mechanisms, and to address whether detrimental effects of electrical remodeling can be altered.