Abstract and Introduction
Abstract
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and its prevalence is increasing with the ageing of the population. Presently available treatment options are far from optimal and new insights into underlying mechanisms are needed to improve therapy. A variety of recent lines of research are converging to reveal important and relatively underappreciated multidimensional roles of cellular Ca content, distribution, and handling in AF pathophysiology. The objective of the present paper is to review the participation of changes in cell Ca and related processes in the mechanisms that lead to AF initiation and maintenance, and to consider the relevance of new knowledge in this area to therapeutic innovation. We first review the involvement of Ca-related functions in the principal arrhythmia mechanisms underlying AF: focal ectopic activity due to afterdepolarizations and re-entrant mechanisms. The detailed molecular pathophysiology of focal ectopic and re-entrant activity is then discussed in relationship to the participation of cell Ca changes and related Ca-handling and Ca-sensitive signalling systems. We then go on to consider the participation of Ca-related functions in electrical and structural remodelling processes leading to the AF substrate. Finally, we consider the implications for development of new arrhythmia management approaches and future research and development.
Introduction
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and its evolving management is the subject of active consideration in Europe and North America. Consideration of presently available therapeutic options indicates many important unanswered questions about underlying mechanisms, resolution of which is needed to improve AF management. Several recent lines of research have converged to reveal an important and underappreciated role of Ca in AF pathophysiology. The objective of the present paper is to review the participation of changes in cell Ca and related processes in the mechanisms leading to AF initiation and maintenance, and to consider their relevance to the development of new treatment approaches.