Atrial Remodeling: Evolving Concepts

The term "Electrophysiological remodeling" defines the changes of atrial electrophysiologic properties taking place in atrial myocites during atrial fibrillation and/or following periods of sustained atrial fibrillation (AF). Early research was prompted by clinical observations: many patients were seen to get through increasingly frequent and longer paroxisms of AF to persistent AF, until chronic AF eventually ensued, without significant changes of underlying heart disease. Indeed, clinical electrophysiology investigations reported peculiar differences between AF patients and patients without atrial arrhythmias. It was felt that the electrophysiologic milieu was the cause of AF 1,2, until a change of perspective occurred in the early 90's, thanks to experimental research. In his pioneering work, Wijffels kept goats fibrillating by an implanted device, while measuring atrial refractoriness and its rate adaptation as spontaneous restoration of sinus rhythm occurred. He found that, after several self terminating short bouts of AF, the arrhythmia became considerably longer until a duration of days or weeks was reached. The electrophysiologic companionship of AF pattern transformation consisted of significant shortening of atrial fibrillation cycle, which was paralleled by shortening of atrial ERP and loss of ERP adaptation to heart rate: either flat (no change with shortening cycle length) or inverted (paradoxical shorter ERP at longer cycle length) ERP relationships to cycle length were observed. This findings had been already observed in AF patients1,2; the novelty was that AF itself was the cause of these abnormal electrophysiologic properties, which could in turn promote further recurrences of AF, and arrhythmia persistence in some cases. By the light of this observations, AF may be seen as self-maintaining by creating a functional electrophysiologic substratum, despite the coexistence of only minor structural heart disease or occasional triggers. This principle has been summarised by Maurits Allessie in the aphorism "AF begets AF". Following this observations, several studies have addressed the issue of the mechanisms by which atrial electrophysiologic remodeling occurs in different settings: basic electrophysiology, experimental electrophysiology, and clinical electrophysiology. It is nowadays believed that, beyond structural heart disease, changes of the atrial electrophysiologic substratum are responsible for AF recurrence and/or perpetuation. The aim of this review will be to assess the extent at which atrial remodeling occurs in the experimental animal and in humans, and its relevance to clinical practice.