Changes in the atrial transcriptome and atrial fibrillation: susceptibility, persistence, causes, and consequences.

Abstract

Atrial fibrillation (AF) is a common clinical problem, presenting the dual challenges of increasing prevalence and therapeutic complexity.1,2 An improved understanding of the underlying pathophysiology is central to improving management options for the arrhythmia.1,2 As AF persists over time, complications increase and treatment becomes more difficult, and it has been suggested that aggressive early intervention might be valuable in improving outcomes.3 Different AF forms have distinct properties and mechanisms.4 More information is needed about the determinants of the various forms of AF, to improve risk prediction and develop new therapeutic options. Article see p 32 Experimental and clinical studies indicate that different types of AF are characterized by distinct gene expression patterns.5,6 Right atrial samples from patients with valvular heart disease and long-standing clinical AF showed differences in 169 genes relative to patients with valvular heart disease in sinus rhythm, with particularly marked alterations in genes related to gene/protein synthesis, contraction/cytoskeleton, immune/inflammatory response, metabolism, fibrosis, and ion channels.5 One limitation to interpreting observations in patients with long-standing AF is that gene expression differences that predispose to AF cannot be separated from those that result from AF. In a study of ion-channel genomics in AF, a patient sample with sinus rhythm restoration was used to analyze the reversibility of changes, with the presumption that alterations that normalized with sinus rhythm were because of, rather than causes of, AF: all the changes examined proved to be reversible.7 In this issue of Circ Arrhythm Electrophysiol , Deshmukh et al8 present the results of a interesting and elegant analysis of the atrial transcriptome (the global pattern of mRNA expression) in clinical AF. RNA extracted from left atrial samples of 239 patients was subjected to detailed analysis with the use of …