Rotational Drivers in AF: Are Multiple Studies Circling Similar Mechanisms?

Introduction

There is an urgent need to define the mechanisms that sustain AF, as ablation at anatomical and empiric targets has not improved outcomes over pulmonary vein isolation (PVI) alone ^1–4 . Rotational drivers are promising mechanistic targets which are highly topical, yet for which data continue to accumulate. Scientifically, rotational drivers maintain AF using the gold standard of optical mapping ⁵, across most species including human atria. Clinically several studies of rotor ablation show promising results ⁶, although divergent data ⁷ have to be reconciled. Since AF mechanisms may vary with mapping technique, novel mapping studies in this space are welcome.

The Present Study

In this issue of the Journal, Calvo et al⁸ studied patients with long standing persistent AF using a novel technique (Cartofinder), and identified sites of rotational activity. These sites fluctuated yet remained spatially stable over time and, when ablated, the impact on local and remote tissue was consistent with elimination of mechanistic drivers. The authors found stable sites of rotational activity (defined as >3 cycles, observed mean 9.2±2.2) in both right and left atria, stabilized in ‘attractor’ regions over time. Clinically, driver sites were bisected after PVI using ablation lesions of 3.5cm length taking an average of 9 mins. Ablation altered AF dynamics locally and remotely, with elimination of frequency gradients consistent with eliminating a rapid driver. Termination of AF to sinus rhythm was also seen in cases by rotor domain ablation, but not by PVI. Clinical outcomes were excellent for patients with longstanding persistent AF, with 70% in sinus rhythm at 12 months.

The authors should be congratulated on this work. Cartofinder is a novel mapping approach, yet utilizes phase and activation analyses ⁹ which appear similar to existing systems ^10,11. Elimination of frequency gradients is a novel endpoint indicating loss of rapid regional activity, and is an intriguing electrophysiology endpoint¹² compared to prior endpoints such as prolonged AF cycle length. However, frequency gradients are confounded by spatio-temporal instability ¹³ and the study is limited by lack of detailed mapping of intra-atrial frequency (only appendages were used). Finally, the study was small, with only 13 patients (men, average age 53 years, 30% prior ablation) which limits its generalizability. Because remapping of AF after ablation was not done, it is unproven if ablation directly abolished rotational circuits.

Same Mechanisms, Different Names?

This study adds to an apparent convergence in AF mapping results by diverse methods (table). Why, then, is there controversy in the field of AF mapping? We attribute this to 3 main factors: i) lack of a consistent nomenclature, ii) absence of randomized trials showing clinical benefit of driver ablation, and iii) unappreciated differences between mapping methods.

Firstly, in terms of definitions, rotor, rotational activity, localized re-entrant driver, phase singularity and repetitive activation patterns have all been used to describe clinical phenomena that in many respects are qualitatively similar^5,14,15. The table shows that, for instance, whether an AF driver is stable with temporal fluctuations, or ‘transient’ but remaining in constrained regions over time may be semantic. Other features, such as spatial location (2/3 in left atrium) and acute impact of ablation are also qualitatively similar between studies.

A second reason for controversy is the important question of whether mapped sites physiologically important, i.e. mechanistic AF drivers? Ultimately, this will be addressed only by randomized clinical trials compared to traditional PVI, which are ongoing.

A third reason for conflicting data is that some mapping methods are clearly more sensitive for AF drivers than others. Traditional AF maps are based on marking electrogram onset, which can be difficult in complex or fractionated signals, and often show partial rotations. In recent reports, traditional maps showed partial rotations precisely where other methods (e.g. phase) reveal stable rotational circuits and where ablation terminated persistent AF ¹⁴. One future approach to reconcile AF mapping is compare methods with complementary strengths, for instance phase mapping (sensitive for rotations) with traditional mapping (specific¹⁴). Recent efforts are making AF mapping software and data freely available online ¹⁶.

Future Directions in Defining AF Drivers

Better mapping tools are needed. Current basket may have sufficient resolution to resolve drivers^17,18, yet should be improved. One approach to minimize unmapped regions is to deploy baskets in multiple positions to fill in under-sampled areas. Similar criticisms can be applied to body surface mapping, which may not map the septum and PV antra. The optimal ablation approach for drivers is also undefined. Studies with dense lesions have better results ¹⁹ than those with sparse lesions ²⁰, and some authors suggest that connection to a boundary is vital^21,22. Finally, the clinical endpoint remains unclear. Is it required to abolish drivers on remapping, or is the current approach to abolish frequency gradients sufficient? Such studies are clearly needed.

Conclusions

Calvo et al should be congratulated for adding novel data to a growing convergence in the literature that localized circuits may drive human AF. The authors use an emerging clinical mapping system, and demonstrate the efficacy of ablation using the novel endpoint of abolition of dominant frequency gradients. Despite these recurring motifs, randomized studies of ablation outcomes and further definition of differences between comparative mapping approaches are urgently needed to advance the field.

Table.

Summary of mapping studies showing similar properties of AF drivers. Current study*

Mapping Technique	AF type	No.	Atrial Location	Driver Dynamics	Impact of Ablation: Acute	Impact of Ablation: Chronic
FIRM Narayan 2012, Miller 2017, Spitzer 2016, Sommer 2016, Wilber	Paroxymsal, persistent and long standing persistent	3–4	LA 2/3 RA 1/3 PV 40%	Stable with precession for >10 mins	Term in 20–30% (2/3 to sinus)	Improves over PVI
Endocardial phase Alhusseini 2017 (used basket data, Kuklik 2017 method)	Paroxymsal, persistent and long standing persistent	3–4	LA 2/3 RA 1/3 PV 40%	More meander than FIRM	“Similar to FIRM”	“Similar to FIRM”
ECGI Haissaguerre 2014, Knecht 2017	Persistent	4–5	LA 2/3 RA 1/3 PV 40%	“Unstable” in same regions 24h (stable?)	Term in 40–70% (1/5 to sinus)	Improves over PVI
CartoFinder Daoud 2015 Schilling 2017	Paroxysmal and persistent	3–4	LA 2/3 RA 1/3 PV 40%	Stable with precession for >10 mins	Term in 20–30% (2/3 to sinus)	–
EGM Dispersion Seitz, 2017	Paroxysmal and persistent	4–6	LA 4/5 RA 1/5 PV 80%	No remaps	Term in >90%	Improves outcome
Dominant Frequency Atienza 2014	Paroxysmal and persistent	2–5	LA 4/5 RA 1/5 PV>70%	No Remaps	Term 30–40%	Equal to PVI
Body Surface DF Rodrigo 2017	Computer modeling	3	PV>70%	Greater Precession	N/A	N/A
CartoFinder Calvo 2017*	Long standing persistent AF	1.8	LA 2/3 RA 1/3 PV 21%	“Highly repetitive & recurrent rotational activity”	Term 15% (all to sinus)	70% freedom from AF after 12 months