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.