Controversies About Atrial Fibrillation Mechanisms
Aiming for Order in Chaos and Whether it Matters
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Major electrophysiological mechanisms underlying atrial fibrillation were described around 100 years ago, but important recent improvements in biophysical theory, mapping of cardiac electric activity, and noninvasive imaging have generated significant new and controversial ideas. Here, we discuss these ideas, the evidence on which they are based, their significance for arrhythmia research and therapy, and the common underlying molecular mechanisms that may allow for therapeutic improvements even without definitive resolution of the electric processes that maintain atrial fibrillation.
Atrial fibrillation (AF) is an extremely common clinical problem, with major public health implications and increasing prevalence.1 Drug therapy is widely used but has limited effectiveness and is plagued by adverse effects.2 Ablation approaches have developed rapidly over the past 20 years but continue to experience failures, recurrences, and complications. There is therefore a major need for innovative treatment strategies, and there exists a widely held (and historically justified) notion that a better understanding of underlying mechanisms is needed to improve AF management options.2 Although key basic concepts of AF pathophysiology have been available for >100 years,3 recent work has questioned the specifics of some of these longstanding ideas. There are widespread, ongoing disagreements about the interpretation of various studies and the principal mechanisms underlying AF. The objectives of this article are (1) to review briefly recent developments in mechanistic thinking about AF, their basis, and the differences among them, (2) to consider to what extent these differences really have practical consequences for therapeutic innovation, and (3) to consider approaches to improving AF therapy that might be effective whether or not we can resolve the underlying mechanism(s) maintaining the arrhythmia.
Principal Concepts of AF Mechanisms
The classical ideas about the mechanisms underlying AF that held sway for almost a century3 are shown in Figure (A). They consist of (1) a primary role for …