The Emerging Role of Inflammation and Fibrosis in Atrial Fibrillation and the Potential of Counter Interventions

Michalis Efremidis, Dimitrios Bramos
Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice, affecting approximately 0.% of the population. 1 The prevalence of AF is strongly age-dependent, affecting approximately 1% of persons aged 65 years and 5% of individuals older than 65 years. 2 AF is also associated with an increase in the relative risk of mortality ranging from 1.3 to 2.34, independent of other risk factors as well as an increasing morbidity and adversely affects quality of life.
more » ... ts quality of life. 3-5 Unfortunately, current rhythm control strategies are far from ideal. Data from five comparative studies of a primary rate control vs. rhythm control strategy for patients with a history of AF failed to show a significant superiority of rhythm control. 6-10 In fact, these studies merely emphasized the limited efficacy and high side-effect profile of the currently available anti-arrhythmic drugs. 11 I N f L A m m A t I O N A N D A t r I A L f I b r I L L A t I O N There is now an increasing body of evidence linking inflammation to a broad spectrum of cardiovascular conditions, such as coronary artery disease (CAD), insulin resistance and diabetes mellitus, and hypertension. 12-16 In addition, there is emerging data to support the association between inflammation and AF. 17-18 The pathophysiology of AF is highly complex. It is now recognized that the development of AF leads to functional changes within the atria that perpetuate the arrhythmia ('AF begets AF'), by a process known as electrical remodeling. 1 Structural remodeling of the atria occurs in parallel with the changes of electrical remodeling. The structural changes that define this structural remodeling include left atrial dilatation and increasing atrial fibrosis. 20 Key to this fibrotic process is the deposition of increased amounts of connective tissue between individual cells and with the deposition of large amounts of collagen and fibronectin. 21 Bruins et al. were the first to propose the inflammation-AF hypothesis, following their observations of an increased frequency of AF after coronary artery bypass surgery. They noted that the peak incidence of AF occurred on the second and third post-operative days, which coincided with the peak elevation of CRP levels. 22 Histological evidence to support the association between inflammation and AF has been derived from several sources. 23-27 Results of atrial biopsies taken from patients in AF compared with controls have demonstrated evidence of inflammatory infiltrates and oxidative damage within the atrial tissue. The inflammatory markers that have been most frequently studied are high-sensitivity C reactive protein (hs-CRP) and interleukin (IL)-6. Levels of hs-CRP have been noted to be higher among patients with A tHENs cA rDIOLOGY UPDA tE 2008