Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans. Although AF prevalence is lower in Asian populations ( 1%) than in Caucasians, the absolute numbers of patients in Asia suggest that the overall disease burden attributable to AF may eclipse that found in Western countries [1]. To combat this surging regional AF epidemic, new strategies resting on a more detailed understanding of the AF pathophysiology will be needed. A fundamental challenge in the field is that arrhythmia dynamics during AF remain unclear, despite over a century of research [2]. AF has been hypothesised to involve a combination of local drivers, including re-entrant circuits known as rotors and focal sources, or due to multiple simultaneous re-entrant wavelets, with a related postulated role for endo-epicardial wavefront dissociation [3]. It is clear that AF arises in the context of electrophysiological and structural remodelling occurring in the context of clinical risk factors including aging, heart failure, valvular heart disease, sinus node disease, hypertension, obesity and obstructive sleep apnoea. These factors are known to modulate local conduction velocity, refractoriness and heterogeneity to create the critical substrate for AF arrhythmogenesis. Recently, increasing attention has been paid to the role of detailed muscular architecture of the atrium in providing the substrate for AF re-entrant circuits. The complex interlacing myoarchitecture of the atrium, whose detailed structure was first outlined by Papez [4], may provide a functional substrate for AF, even in the absence of disease. Specific attention has been focused on the histoanatomy of the pulmonary vein (PV)–posterior left atrium (LA) junction. Klos et al. identified source–sink mismatch at the PV–LA junction as a possible mechanism for wavebreak at the onset of AF in the sheep heart [5]. Simulation studies have further delineated the 3-dimensional nature of myofiber orientation as a critical player. In humans, the PV–LA junction and posterior LA have similarly been determined as locations for conduction delay and block, providing an intrinsic histologically pre-determined substrate for re-entry [6]. It is in this context, that the recent study of Matsuyama et al. sheds further light on the relationships between histoanatomy and atrial arrhythmogenesis [7]. This investigation used high-density optical mapping to study atrial flutter/atrial fibrillation in isolated rat hearts [7]. Atrial arrhythmia was induced in 15 of 19 hearts tested by programmed stimulation from the right atrium [7]. Atrial arrhythmia in this model was predominantly initiated by a common re-entrant mechanism, with conduction slowing and block at the left atrial roof, with rapid antegrade conduction along the coronary sinus, providing the basis for a re-entry on the posterior wall of the LA. For the first time, these findings were correlated with the intrinsic histology of the regions [7]. Myocyte density was reduced and fibrosis increased on the roof and posterior LA compared to the CS [7]. Myocytes in the LA roof had a broader distribution of cut lengths than in the CS, with more lateralised expression on
Read full abstract
Oct 1, 2016
Anil Madan Potdar + 3
Open Access
