Home » Articles » Atrial Fibrillation Structural Substrates: Aetiology, Identification And Implications Atrial Fibrillation Structural Substrates: Aetiology, Identification And Implications Ahmed M Al-Kaisey Ramanathan Parameswaran Jonathan M Kalman Login or register to view PDF. Order reprints Abstract Atrial remodelling in AF underlines the electrical, structural and mechanical changes in the atria of patients with AF. Several risk factors for AF contribute to the development of the atrial substrate, with some evidence that atrial remodelling reversal is possible with targeted intervention. In this article, the authors review the electrophysiological changes that characterise the atrial substrate in patients with AF risk factors. They also discuss the pitfalls of mapping the atrial substrate and the implications for developing tailored ablation strategies to improve outcomes in patients with AF. Keywords AF, atrial substrate, atrial remodelling, reverse remodelling, low-voltage area, electroanatomic mapping Disclosure RP is supported by a National Health and Medical Research Council (NHMRC) research scholarship. JMK is supported by a NHMRC practitioner fellowship, and has received research and fellowship support from Biosense Webster, St Jude Medical and Medtronic. AMAK has no conflicts of interests to declare. Correspondence Jonathan M Kalman, Department of Cardiology, Royal Melbourne Hospital, Grattan St, Parkville, VIC 3050, Australia. E: [email protected] Received date 22 April 2020 Accepted date 20 July 2020 Citation Arrhythmia & Electrophysiology Review 2020; epub ahead of press. DOI http://sci-hub.tw/10.15420/aer.2020.19 Open access This work is open access under the CC-BY-NC 4.0 License which allows users to copy, redistribute and make derivative works for non-commercial purposes, provided the original work is cited correctly. AF is the most common sustained cardiac rhythm disorder and is associated with increased morbidity and mortality. Since the first description of AF initiation by triggers from pulmonary veins sleeves, pulmonary vein isolation (PVI) has become the standard ablation strategy in patients with AF.1 However, freedom from the arrhythmia, particularly in non-paroxysmal AF, remains suboptimal, and it is now clear that, in these patients, AF is maintained by an atrial substrate beyond the pulmonary veins. Although electrical remodelling may be reversible with termination of the arrhythmia, the development of atrial substrate due to fibrosis contributes to the progression of the AF phenotype from paroxysmal to persistent AF, leading to an arrhythmia that is more refractory to intervention.2 It is clear from animal and human studies that prolonged AF can cause this structural change. Moreover, it is also apparent that a range of risk factors associated with AF, including age, obesity, heart failure (HF), valvular heart disease, hypertension (HT), sleep apnoea and alcohol intake, may also progress atrial remodelling. The rise in the prevalence of cardiovascular risk factors (particularly driven by ageing populations and the obesity epidemic) has been associated with an increase in the prevalence of AF and AF-related hospitalisations.3 In this review, we focus on insights from electrophysiological mapping studies in cohorts with AF risk factors. We discuss substrate mapping and its implications for AF management and outcomes, and also focus on potential pitfalls. The Second Factor: Structural Remodelling is Required for AF Maintenance Early studies of animal models have demonstrated that AF promotes acute electrical remodelling, which in turn leads to further AF, thereby introducing the seminal concept that ‘AF begets AF’.4–6 In response to either induced AF or rapid atrial pacing, a reduction in the atrial effective refractory period (ERP) occurs with an increase in the spatial heterogeneity of ERP and loss of normal ERP rate adaptation, all resulting in progressively longer durations of AF. In this model, termination of the arrhythmia results in remodelling reversal, suggesting that sinus rhythm may beget sinus rhythm. However, human studies of early intervention to re-establish sinus rhythm do not fully support this concept; the re-establishment of sinus rhythm has not been found to prevent the progression of AF in the majority of patients.7,8 Ongoing work has indicated that, beyond acute electrical remodelling, structural remodelling also occurs and is not necessarily fully reversible. This so-called second factor has been shown to occur as a result of longer durations of AF. However, the multiple conditions associated with AF also appear to promote significant structural remodelling. Abnormal Atrial Substrates and Structural Remodelling in Conditions Predisposing to AF It is well known that certain cardiac conditions and risk factors (i.e. age, obesity, HT, HF, structural heart disease, sleep apnoea and alcohol intake) are associated with AF, likely through both different and interacting mechanisms. In the next section, we review the evidence describing the nature of atrial structural remodelling in these conditions, even prior to the development of AF (Figure 1). The Role of Atrial Stretch The impact of acute atrial stretch on electrical remodelling has been studied in animal models and in humans. Despite variability in the reported effect on atrial ERP, evidence from these studies consistently demonstrates conduction slowing, conduction block and increased frequency of AF.9–11 In studies of atrial stretch related to loss of atrioventricular (AV) synchrony, Sparks et al. demonstrated evidence of both electrical and mechanical remodelling.12,13 Although refractoriness showed a variable increase, there was conduction slowing, sinus node impairment and a decrease in parameters of atrial contractile function. These changes developed over 3 months and were fully reversible with the return of AV synchrony.
