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Since the clinical use of digitalis as the first pharmacological therapy for atrial fibrillation (AF) 235 years ago in 1785, antiarrhythmic drug therapy has advanced considerably and become a cornerstone of AF clinical management. Yet, a preventive or curative panacea for sustained AF does not exist despite the rise of AF global prevalence to epidemiological proportions. While multiple elevated risk factors for AF have been established, the natural history and etiology of AF remain incompletely understood. In the present article, the first section selectively highlights some disappointing shortcomings and current efforts in antiarrhythmic drug therapy to uncover reasons why AF is such a clinical challenge. The second section discusses some modern takes on the natural history of AF as a relentless, progressive fibro-inflammatory “atriomyopathy.” The final section emphasizes the need to redefine therapeutic strategies on par with new insights of AF pathophysiology.

Revisiting Antiarrhythmic Drug Therapy for Atrial Fibrillation: Reviewing Lessons Learned and Redefining Therapeutic Paradigms