Introduction

The worldwide prevalence of atrial fibrillation (AF) continues to follow an upward trajectory, mirroring evolving population demographics and the growing burden of comorbidities known to increase the risk of developing AF. Epidemiological studies indicate that between 20-30% of individuals with AF have the paroxysmal form; in most cases it is either persistent or permanent (1). Single procedure success rates following pulmonary vein isolation (PVI) utilizing contemporary techniques for catheter ablation in paroxysmal AF (PAF) approach 80% at 12 months (2). Outcomes following PVI in persistent AF (PsAF) are far more modest, with often more than 50% of patients experiencing recurrence within a year (3).
The trigger-substrate model of arrhythmogenesis consists of an initiating arrhythmogenic trigger, often an ectopic beat, encountering a tissue substrate with electrophysiological properties conducive to sustaining the arrhythmia (4). PVI, aimed at eliminating such ectopic triggers, is now established as a fundamental component of invasive therapies for rhythm control (5). However targeting pulmonary vein triggers has not proven to be effective in PsAF and shifted focus to adjunctive targets aimed at altering the arrhythmogenic substrate. To date, substrate modification approaches have included linear ablation lesions, aimed at compartmentalizing and debulking the atrial tissue, rendering it less able to accommodate re-entry (6–8). Attempts have also been made to target critical areas involved in promoting re-entry and/or harboring potential drivers for AF. Such an approach has included the ablation of complex fractionated atrial electrograms (CFAEs), presumed to be sites of slow conduction, thus providing pivot points for re-entrant waves (9). Focal impulse and rotor modulation mapping has been suggested to identify drivers for AF (10). While all of these approaches have shown encouraging results in initial trials, their early promise has never borne out when implemented on a larger scale (11,12).
There is growing interest in substrate modification targeting areas of low voltage (LVAs) identified during electro-anatomical mapping (EAM). Such LVAs represent areas of pathological fibrosis that have a pivotal role in promoting re-entry and perpetuating AF, a construct adapted from learnings through ablation of ventricular arrhythmia. Indeed progressive fibrotic infiltration of the atrial myocardium has been noted in animal models (13,14) and human studies of AF (15,16), and suggested to correlate with AF recurrence following ablation (17). However there is no consensus on methods to delineate de novo fibrotic tissue or how to differentiate electrical inert bystander tissue from that involved in maintaining AF. In the present review, we summarise the current experience in LVA-guided substrate modification, and then discuss the components of the arrhythmogenic substrate in AF and techniques for assessing this in the clinical setting.