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Ablation for persistent atrial fibrillation – the new core-to-boundary strategy

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The mechanisms sustaining persistent atrial fibrillation (perAF) are still a hot topic in electrophysiology and cardiology in general. Recent randomized trials demonstrate that pulmonary vein isolation (PVI) alone achieves outcomes similar to those of more extensive ablation strategies in treating perAF.1 However, the perAF outcomes remain suboptimal compared to those for paroxysmal atrial fibrillation (AF). This is generating ongoing research interest to better understand which trigger sites outside the pulmonary veins should be ablated. A new study2 compared an individualized core-to-boundary ablation approach, guided by non-contact charge-density mapping (CDM), to an empirical pulmonary vein isolation (PVI) plus posterior wall electrical isolation (PWI) strategy. The incidence of acute perAF termination by ablation was significantly higher in the core-to-boundary group compared to the control group: 73% vs 10% (p<0.001). The outcomes of the two patient groups were compared two years after treatment, without anti-arrhythmic drug usage during that time.


During the STAR AF II trial, linear lesions in the left atrium and focal ablation to eliminate atrial signals that show complex activity, were compared with a PVI-only approach for treating perAF. The results showed no reduction in the rate of recurrent AF when either linear ablation, or when complex fractionated electrograms were ablated, in addition to PVI. But, as the authors point out, after completing their study design, other supplemental targets were reported to be effective adjuvant ablation strategies, among them the identification of non-pulmonary-vein triggers and rotational activity within the atria.3

To examine whether an individualized core-to-boundary approach guided by charge-density mapping could improve the outcomes for perAF, researchers conducted a prospective observational study using this approach at the Royal Brompton Hospital in London and the John Radcliffe Hospital in Oxford. This unique study saw researchers use non-contact charge-density mapping (CDM) with iterative mapping capability to help them identify patient-specific areas of interest outside the pulmonary veins.

Dr. Tom Wong, Consultant Electrophysiologist at the Royal Brompton & Harefield Hospitals and one of the study’s two joint senior authors, describes it as a follow-up to the UNCOVER AF Trial.4 That trial showed how global charge density mapping can be used to guide individualized ablations. However, the clinical outcome of this novel approach, compared to conventional ablation strategies, was not yet known. That’s why the two teams, from London and Oxford, decided to conduct a prospective study with 40 patients experiencing de novo perAF (duration 10 ± 5 months).

The Acutus CDM system was used to identify key cores in the study group. If the sites were near the ostium of the PVs, they were incorporated into the lesion of the PVI. Afterwards, the chamber was remapped to identify further targets for ablation. Those sites were then joined up with the nearest anatomical (nonconducting) boundary, such as the pulmonary vein encirclements or the mitral valve annulus. The research team named this approach the “core-to-boundary ablation” strategy, Dr. Wong explains.

The core-to-boundary approach in detail

For the individualized strategy, researchers used CDM to identify targeted conduction pattern cores (CPCs). Following the initial propagation mapping of perAF, they then performed circumferential PVI to incorporate CPCs identified within 1 cm of the pulmonary vein (PV) ostia. After PVI, CDM of perAF was repeated to confirm the treatment effects and identify possible new or altered CPC sites.

The remaining CPCs were ablated according to the core-to-boundary strategy, with core ablation lesions that were then “anchored” to the nearest non-conducting boundary, such as the PVI lesion set or the mitral annulus. The map–ablate–remap steps were repeated until AF termination or CPC depletion.

If AF persisted after CPC depletion was confirmed in the left atrium (LA), then researchers mapped the right atrium (RA). In the RA, the CDM-guided ablation strategy was at the discretion of the operator, with either the same C-to-B strategy or core-only strategy, if the target site was in the vicinity of the intrinsic conduction system or phrenic nerve. The incidence of acute perAF termination by ablation was significantly different between the study’s ablation strategies and control groups (73% vs 10%; p<0.001). This matches the results from a systematic review and meta-analysis that showed a correlation between acute termination of perAF by AF “driver” ablation and long-term outcomes.5

In cases where AF converted to atrial tachycardia (AT), physicians mapped the tachycardia and ablated accordingly. If AF persisted after all CPCs were eliminated, a synchronized cardioversion was performed to restore sinus rhythm (SR). Physicians confirmed bidirectional block at the PVs and across the linear ablation lines with either differential electrical stimulation maneuvers and/or CDM.

Significantly improved outcomes with a core-to-boundary approach

The clinical outcomes of the 40 patients who received the individualized ablation strategy were then compared to a propensity score-matched control group of 80 patients. The control group received empiric anatomical ablations, isolating the PV and the posterior wall. At 24 months, the group receiving individualized ablations guided by CDM had a significantly higher success rate concerning freedom from AF and atrial tachycardia (AT), when compared to the control group: 68% vs. 46% (p=0.043).

The authors identified three key conduction patterns that might be important in the maintenance of perAF, and therefore worth targeting in an individualized ablation approach. The first are local irregular activated areas, where activation decelerates and re-accelerates or changes direction. The second type are sites with localized rotational activation (LRA) that pivots around one discrete area. The third activation pattern is a centrifugal activation from a focal point (FCA).

  • Confirmation is key for core-to-boundary ablations: Confirm the elimination of LRA/LIA by re-mapping and closing linear gaps and narrow channels that may emerge between targets with ablation.

The right atrium (RA) is, according to Dr. Wong, an underrecognized chamber for perAF and might be important for maintaining it. In a portion of the patients (n=4) where they were not able to terminate AF after ablating lesions/all the conduction pattern cores in the left atrium, physicians also mapped and ablated the RA. In two of those patients, they were able to convert AF to sinus rhythm. This indicates that for a portion of patients, the RA is important for maintenance of AF.

Study outcomes at a glance

  • In 29 of 40 patients (73%) in the core-to-boundary arm versus 10 of 80 patients (10%) in the propensity score-matched control arm, perAF was successfully terminated during the procedure (P<0.001), either after CDM-guided PVI alone (8 of 40 patients, 20%), or after core-to-boundary ablation (21 of the 40 patients, 53%). At 24 months, 68% of patients with the CDM-guided core-to-boundary ablation approach still showed freedom from AT/AF vs. 46% of the patients that had shown AF termination in the control group (p=0.043).
  • A majority of CPCs (77%) identified in the pre-PVI maps were still present after PVI (see graph). This indicates that pre- as well as post-PVI mapping are vital to identifying remaining ablation targets.
  • On average, an additional 2.2 ± 0.6 CPCs were ablated following PVI. Given the frequency of CPCs present after PVI on the anterior wall, septal wall and roof, an empiric PVI + PWI ablation strategy would have missed these potentially important sites (see graph).
  • The number of CPCs that had to be ablated before AF termination correlated with the duration of perAF.


  1. Verma A et al. Approaches to Catheter Ablation for Persistent Atrial Fibrillation. N Engl J Med 2015; 372:1812-1822.
  2. Shi R et al. Individualized ablation strategy to treat persistent atrial fibrillation: Core-to-boundary approach guided by charge-density mapping. Heart Rhythm. 2021;S1547-5271(21)00136-3.
  3. Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial Part II (STAR AF II); Verma A et al. Approaches to Catheter Ablation for Persistent Atrial Fibrillation. N Engl J Med 2015; 372:1812-1822.
  4. Willems S, Verma A, Betts TR, et al. Targeting Nonpulmonary Vein Sources in Persistent Atrial Fibrillation Identified by Noncontact Charge Density Mapping: UNCOVER AF Trial. Circ Arrhythm Electrophysiol. 2019;12(7):e007233.
  5. Baykaner T, Rogers AJ, Meckler GL, et al. Clinical Implications of Ablation of Drivers for Atrial Fibrillation: A Systematic Review and Meta-Analysis. Circ Arrhythm Electrophysiol. 2018;11(5):e006119.