John M. Mandrola


June 26, 2013

Catheter ablation of atrial fibrillation has been an established practice for more than a decade. Worldwide, thousands of procedures have been done, and hundreds of papers published. Given this history and knowledge, one would think the best technique to ablate AF would be agreed on. We should know the best way to ablate AF. But AF is not like other heart-rhythm diseases. AF is special.

That the European Heart Rhythm Society led its late-breaking clinical-trials session at EUROPACE 2013 with the GAP-AF study suggests the electrophysiology community isn't settled on the best technique to ablate AF. 

The central question of GAP-AF says a lot: "Is the complete electrical isolation of pulmonary veins (PVs) superior to incomplete isolation?"

As an AF ablationist who musters all possible forces to completely and durably isolate pulmonary veins, this study's premise came as a shock. How could such epicenters of ablation, in Germany of all places, purposely let patients with incomplete lines leave the laboratory? I've been to Hamburg; gaps in PV lines are not welcome at all.

This was a striking study in many ways. I will tell you about the findings and conclusions later; stick around because you will want to see what actually happened. But first, I think it's important to consider why this study was done.

Rationale for GAP-AF

It gets to the essence of doing good science. The issue of PV isolation (PVI) to treat atrial fibrillation has never been studied in a randomized controlled trial. General opinion in 2013 is that PVs should be completely isolated. The expert consensus statement from Europe says it's so as well. This opinion comes from the observation that 95% of patients with recurrent AF are found to have conduction gaps, and reisolation at these gaps at the repeat procedure increases success rates.

But others in the AF ablation world aren't convinced that complete PV isolation is required. These folks are not necessarily on the fringe. For instance, the Mantra-PAF trial , published in the New England Journal of Medicine in 2012, compared AF ablation to antiarrhythmic drugs. The ablation strategy used in this influential contemporary study did not employ complete PV isolation. And most recently, the work of Dr Sanjiv Narayan, who uses novel mapping techniques to ablate focal impulses or rotors (FIRM), suggests that complete PV isolation may not be required. Early results of the PRECISE trial(presented at HRS 2013)showed high success rates could be achieved without any PV isolation.

Here's one thing you learn after being in medicine for a while. Consensus opinion that is not backed up with strong science is nearly always worthy of skepticism.

So now we can agree that doing the GAP-AF study was well grounded in the scientific method and perhaps not that shocking.

Methods: Patients were randomized to complete PVI (n=117) or incomplete PVI (n=116). In the group with incomplete PVI, the encircling lesion was stopped immediately after PVI to allow reconduction at that site. Patients were then followed with daily ECGs via a heart card (transmitted by phone).

Then . . . all patients, symptomatic or asymptomatic, underwent a second LA procedure to assess PV conduction. (That must have been tough to get through ethics boards.)

The primary end point was time to first recurrence of AF—either symptomatic or two consecutive asymptomatic episodes in 72 hours. The trial was conducted in seven centers in Germany. Patients were enrolled between 2006 and 2010.

Results: Baseline characteristics of the patients were typical of a low-risk population of patients with paroxysmal atrial fibrillation.

At three-month follow-up, sinus rhythm was present in 37.8% of patients with complete isolation and 20.8% with incomplete isolation. The number of days in sinus rhythm was 60 days for the complete group and only 16 days for the incomplete group. Both results were statistically significant. Nearly 90% of all recurrent AF was symptomatic.

At three months, when patients went back to the EP lab, 70% of those in the complete group had gaps vs 89% in the incomplete group. There was considerable overlap between AF recurrence and gaps. In the complete-isolation group, 25% of patients with gaps had no AF, while 17% of those with no gaps had AF. Similarly, in the incomplete-isolation group, 17% of patients with gaps had no AF, while 9% of those with no gaps had recurrent AF.

The overall rates of complications were in line with prior studies, and no differences were noted between the two groups. No strokes or death occurred in either group.

Conclusions: Complete isolation of PVs resulted in significantly more sinus rhythm than incomplete isolation. At EP study after three months, 89% of patients in the incomplete group had developed gaps while 70% of those with complete isolation had gaps.


GAP-AF teaches us a lot. Here are some key points:

The success rate of a single PVI procedure is quite low. These were patients done at major ablation centers in Germany and yet in the complete-isolation group only 38% had sinus rhythm.
Incomplete PVI is an inferior strategy. This makes sense: the presumed mechanism of success for PVI is elimination triggers. If you don't fully isolate the PVs, it stands to reason that failure rates will be higher. Think about it using the atrioventricular nodal reentry tachycardia (AVNRT) model. There are two ways to eliminate AVNRT: one is to eliminate the slow pathway (substrate); the other is to eliminate all premature ventricular contractions (PVCs) and premature atrial contractions (PACs) (triggers). In the PVI strategy, we aren't targeting the substrate (rotors, LA, or something else), so we must completely isolate all triggers (PVs).
It's extremely difficult to achieve durable PVI. At repeat EP study, 70% of those who had complete PV isolation developed gaps. Interestingly, in the incomplete-isolation group, 11% went on to have complete isolation. This implies "maturation" of the lesion with healing—a phenomenon all ablationists have seen.
Finally, we must talk about mechanisms of AF. This is the elephant in the room, isn't it? GAP-AF tempts us to consider the possibility that PVI is not the entire story. Why is there so much overlap between AF episodes and the status of the PVs? Patients with no gaps still have AF, and many patients with gaps remain AF free. Doesn't that tell us that something else is going on? Think back to Dr Carlos Pappone's early work: He wasn't isolating veins, yet he was getting success. We have all seen AF terminate during ablation well before PV isolation occurs. And a more common scenario is when AF persists despite clear PV isolation during RF.

During the "Pioneer of Electrophysiology" lecture in the final session of EUROPACE 2013, Prof Lukas Kappenberger (University Hospital, Lausanne, Switzerland) urged us to better understand AF, saying, "You wouldn't fly an airplane without understanding aeronautics."

This, I believe, is the problem. When we truly understand this disease, then we will be close to mastering therapy. Stay tuned, because I believe we are close.



Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: