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Atrial Fibrillation: Mechanisms, Therapeutics, and Future Directions

2015/03/16 by Jason Pellman, Farah Sheikh · 1 citation
Medicine · #Atrial Fibrillation Management and Outcomes #Cardiac electrophysiology and arrhythmias #Cardiac Arrhythmias and Treatments

paper · doi:10.1002/cphy.c140047

openalex publication_date 2015/03/16 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/29

Abstract

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 Ca(2+) 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.

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