Chapter 3: Evidence for the Use of Early Rhythm Control to Prevent Atrial Fibrillation Progression

This chapter reviews atrial fibrillation (AF) progression and its associated mechanisms, including comorbidities and AF as contributors to atrial myopathy, and atrial myopathy as a contributing factor to AF progression. In addition, the chapter discusses the concept of comorbidities and atrial myopathy as synergistic contributors to adverse outcomes, the notion of "AF begets AF," and the consequences of AF burden if left untreated. Clinical trials evaluating outcomes with antiarrhythmic drugs (AADs) compared with placebo have demonstrated efficacy, but also reveal a possible proarrhythmic and mortality risk if AAD selection is not appropriate and patients are not correctly identified based on risk factors and comorbidities. Data from ATHENA, the first and only trial to demonstrate that an AAD (dronedarone) can reduce cardiovascular (CV) hospitalizations in people with AF, are reviewed, along with studies reporting on the use of catheter ablation versus AADs for AF rhythm control. Finally, recent data showing a reduction in major adverse outcomes if rhythm control is initiated early are summarized, including results from the EAST-AFNET 4 trial, as well as confirmatory results from several large "real-world" trials. Chapter 3 is summarized as follows.