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Atrial Fibrillation: Mechanisms, Therapeutics, and Future Directions

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Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, affecting 1% to 2% of the general population. It is characterized by rapid and disorganized atrial activation leading to impaired atrial function, which can be diagnosed on an EKG by lack of a P‐wave and irregular QRS complexes. AF is associated with increased morbidity and mortality and is a risk factor for embolic stroke and worsening heart failure. Current research on AF support and explore the hypothesis that initiation and maintenance of AF require pathophysiological remodeling of the atria, either specifically as in lone AF or secondary to other heart disease as in heart failure‐associated AF. Remodeling in AF can be grouped into three categories that include: (i) electrical remodeling, which includes modulation of L‐type Ca2+ current, various K+ currents and gap junction function; (ii) structural remodeling, which includes changes in tissues properties, size, and ultrastructure; and (iii) autonomic remodeling, including altered sympathovagal activity and hyperinnervation. Electrical, structural, and autonomic remodeling all contribute to creating an AF‐prone substrate which is able to produce AF‐associated electrical phenomena including a rapidly firing focus, complex multiple reentrant circuit or rotors. Although various remodeling events occur in AF, current AF therapies focus on ventricular rate and rhythm control strategies using pharmacotherapy and surgical interventions. Recent progress in the field has started to focus on the underlying substrate that drives and maintains AF (termed upstream therapies); however, much work is needed in this area. Here, we review current knowledge of AF mechanisms, therapies, and new areas of investigation. © 2015 American Physiological Society. Compr Physiol 5:649‐665, 2015.

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Figure 1. Figure 1. Diagram representing the major types of remodeling (electrical, structural, and autonomic) that lead to AF.

Figure 1. Diagram representing the major types of remodeling (electrical, structural, and autonomic) that lead to AF.
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Jason Pellman, Farah Sheikh. Atrial Fibrillation: Mechanisms, Therapeutics, and Future Directions. Compr Physiol 2015, 5: 649-665. doi: 10.1002/cphy.c140047