The Matter of Matrix: Recurrence of Atrial Fibrillation after a Surgical Maze Procedure

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Its prevalence is increasing as the population ages. Among the various mechanisms putatively responsible for the development of AF, structural atrial remodeling appears to be an important element. In 2004, Xu et al. [1] studied the structure of atrial extracellular matrix (ECM) in explanted hearts from patients with end-stage heart failure. He showed that, in the atrium, the selective downregulation of tissue inhibitors of metalloproteinases (TIMP-2) along with upregulation of metalloproteinases (MMP-2) and collagen type I volume fraction (CVF-1) are associated with the development of sustained AF. Several other studies have demonstrated alterations in MMP and TIMP expression in patients with AF [2,3,4].In addition, abnormal levels of serum MMP and subnormal levels of TIMP seem to predict the outcome of rhythm control therapy for AF. Thus, an abnormal serum MMP-2 level predicted AF recurrence in 102 patients after pharmacological or electrical cardioversion [5]. Similar results were found more recently with elevated MMP-9 and low TIMP-4 [6]. Furthermore, abnormal serum MMP-2 levels predicted AF recurrence in 50 patients who underwent catheter ablation for drug-resistant AF [7]. Interpretation of some of these studies is limited by the fact that tissue assessment of MMP and TIMP were not performed and inferences were drawn only from plasma measurements. In a recent issue of Cardiology, Wang et al. [8] provide evidence that increased left atrial tissue expression of MMP-2 is associated with recurrence of AF in patients undergoing mitral valve replacement and surgical AF ablation. The assessment of recurrent AF was not robust yet the early postoperative period was censored to avoid influence of surgery itself on AF recurrence. In addition to the expression of ECM proteins, the size of the left atrium predicted the recurrence of AF in this study. This is consistent with the earlier finding that the extent of atrial scars assessed with MRI is associated with success of ablative therapy for AF [9]. This further supports the notion that there is a threshold of left atrial damage/remodeling beyond which rhythm maintenance strategies are unlikely to provide sustained success. The gap between the pathogenesis of AF and evidence of structural atrial remodeling appears to be narrowing. Thus, atrial remodeling, whether measured macroscopically by echocardiography through left atrial size or at the cellular level by measuring the expression of ECM proteins, has predicted AF recurrence. Certainly, the expression of the ECM markers is a very promising path to understanding the pathophysiology of AF. Indeed, it may help identify patients who will benefit from ablative therapy.