The Role of the Atrial Neural Network In Atrial Fibrillation: The Metastatic Progression Hypothesis

With the advent of catheter ablation of atrial fibrillation (AF) there has been acceleration in our understanding of the mechanisms underlying the etiology of this common clinical arrhythmia. In this regard, the role of the intrinsic cardiac autonomic nervous system in the initiation and maintenance of AF began to receive attention in numerous experimental and clinical investigations. Up to now, the focus has been on the large ganglionated plexi (GP) which are located in the posterior left atrium mainly at the pulmonary vein-atrial junctions. As long term outcomes have been reported and single procedures have indicated diminished success rates particularly for persistent/long standing persistent AF, emphasis has begun to shift away from the pulmonary vein isolation (PVI) alone as well as GP ablation with or without PVI. An understanding of the atrial substrate represented by the extensions of the intrinsic cardiac autonomic system constituting the atrial neural network is beginning to evolve. In this review, the contribution of the intrinsic cardiac autonomic nervous system to the etiology of AF is addressed, particularly in regard to the greater prevalence of AF in the elderly. In addition, we emphasize the involvement of the atrial neural network in the "metastatic" progression of paroxysmal to persistent and long standing persistent forms of AF.