Human atrial fibrillation substrate: towards a specific fibrotic atrial cardiomyopathy

Abstract

The atrial structure/substrate of patients with atrial fibrillation (AF) and clinically similar characteristics can present very differently, and also the 'phenotype' (i.e. paroxysmal, persistent, and long standing persistent) of the arrhythmia cannot comprehensively explain these differences. It was unclear why some patients stay in paroxysmal AF for decades, whereas other patients with the same characteristics progress to persistent AF within a few months. In this review, evidence is described that AF patients without apparent structural heart disease have a chronic fibrotic bi-atrial substrate. There is also evidence from intraoperatively obtained specimen analysis, post-mortem autopsy findings, electroanatomic mapping studies, and delayed enhancement-MRI investigations that a higher mean value of fibrosis is detected in patients with persistent vs. paroxysmal AF but that the variability in the extend of fibrosis is always very high with part of paroxysmal AF patients having massive fibrosis and part of persistent AF patients showing mild fibrosis. In addition, patients undergoing ablation very early after the first AF episodes show already significant fibrosis. These data do not support a causal relationship that AF (significantly) produces fibrosis in the sense of 'AF begets AF' instead of being a consequence of the fibrotic process. In patients with mitral stenosis, evidence for reverse atrial remodelling after commissurotomy was reported, however, in patients with 'lone' AF, the atrial substrate progressed after successful AF elimination indicating towards the independent/progressive disease process of an underlying structural atrial disease called fibrotic atrial cardiomyopathy. Other 'conventional wisdoms' also need to be re-considered including the aetiological role of age and arterial hypertension for human structural atrial remodelling.

Keywords: Atrial fibrillation; Cardiomyopathy; Fibrosis; Pathophysiology; Substrate.