John Mandrola


September 11, 2015

In the practice of medicine, especially catheter ablation of atrial fibrillation, history has proven it wise to be careful about what we believe. Belief is a strong word. It means an acceptance that something is true.

Now let's consider the BELIEF trial, which was presented at the European Society of Cardiology 2015 Congress during a hot-line session.[1] Being selected as a hot-line presentation is important because it gives a study visibility, ensures media coverage, and enhances credibility among impressionable young doctors.

Marlene Busko, reporting for heartwire from Medscape, covered the details of BELIEF in this news story. My short summary is as follows:

Dr Luigi Di Biase (Montefiore-Albert Einstein Center for Heart & Vascular Care, New York, and Texas Cardiac Arrhythmia Institute at St David's Medical Center, Austin) and colleagues performed a randomized clinical trial of two ablation strategies in patients with long-standing persistent AF.

Their aim was to assess whether empiric isolation of the left atrial appendage (LAA) in addition to standard ablation would improve freedom from AF. BELIEF was a multicenter trial in which 173 patients were assigned to either standard ablation plus LAA ablation (n=85) or standard ablation alone (n=88). During repeat ablation, which was done in 62 patients (n=27 in LAA group; n=35 no-LAA group), LAA isolation was performed in all patients. Outcomes were assessed at 24 months.

The two groups were evenly matched. These were primarily male patients with mean body-mass index (BMI) of approximately 33 kg/m2—a point I will revisit at the end of this post. Mean procedure time averaged around 3 hours, and each group had more than an hour of fluoroscopy.

At 12-month follow-up, freedom from AF after a single procedure was reported in 48 patients (56%) in the LAA-isolation group and 25 (28%) in standard-ablation group. At 24 months and an average of 1.3 procedures, freedom from AF was reported in 65 patients (76%) in the LAA-isolation group and 49 (56%) in the standard-ablation group. Both these differences reached statistical significance.

At 6-month follow-up, researchers reported transesophageal echocardiogram (TEE) results in the 93 patients who had LAA isolation. Preserved LAA contractile function was noted in 45 (48%) patients, while 48 (52%) had impaired function. There were no stroke or transient ischemic attack (TIA) events in the LAA-isolation group, while four (4.5%) patients in the standard-ablation group had stroke (a difference that was not statistically significant). One patient in each group had pericardial effusion.


Trial discussant Dr Gerhard Hindricks (Leipzig Heart Center, Germany) began by congratulating the research team for performing and completing a randomized trial. He noted the difficulty of treating patients with long-standing persistent AF as well as the lack of data in this area. He then spent the next 10 minutes questioning the background, methodology, and results of this trial. It was a cordial but robust rebuke. The last bullet point on his final slide declared that LAA isolation should not be recommended as an integral part of the ablation strategy in patients with long-standing persistent AF. He said more studies are necessary before such recommendation.

I agree. This trial scares me. It comes from a well-known research group that has great influence in the electrophysiology community. The European Society of Cardiology increased this influence by selecting the trial for a hot-line session.

As a community of doctors committed to the care of patients with atrial fibrillation, we must be mindful not to make the treatment of the disease worse than the disease itself.

I have five issues with this trial.

First is the notion that the LAA appendage is a frequent non-pulmonary-vein trigger of atrial fibrillation. No one debates that the LAA can be a source of triggering; what is debated is the frequency. I've been ablating AF for more than a decade, and I don't see the LAA come into play that often. I would suggest that if you put a circular catheter in the left atrial appendage in the presence of high-dose isoproterenol, you might see catheter-induced ectopy a lot.

The second problem is the extent of the ablation. This research group already advocates for complete ablation of the posterior left atrial wall as part of the pulmonary-vein–isolation process.[2] Then they recommend ablation of all non-PV triggers—a process that often entails more ablation. The point is that their "standard" ablation is extensive. Now add LAA isolation. Isolating the highly variable appendage means burning superiorly along the roof, anteriorly and inferiorly. I've done it; it's hard. When you combine the extensive lesions required for LAA isolation to the already-extensive lesions of standard ablation, there is very little of the left atrium left untouched by human-made scar. I can't help using a fishing analogy: if you drain the stream; you catch fish.

What makes such an aggressive strategy seem dubious is the STAR AF II trial.[3] This randomized controlled trial, published last year in the New England Journal of Medicine, definitively showed that in patients with persistent AF, PV isolation alone was superior to PV isolation with additional ablation. To many experts, STAR AF II came as a surprise; the prevailing idea at the time was that patients with persistent AF required more ablation. Yet STAR AF II confirmed a less-is-more approach to ablating persistent AF.

The third problem I have with LAA isolation is that if it works the LAA no longer contracts. Stasis of blood in the appendage means lifelong anticoagulation or yet another aggressive risky procedure—percutaneous LAA closure. You might counter this concern by saying these are sick patients who will likely require anticoagulation anyway. You would be wrong. More than half the cohort in BELIEF had CHADS2 scores of 0 to 1. Although there were no strokes in the LAA-isolation group (n=85), one worries that if LAA isolation became accepted, strokes would increase. In the hot-line discussion, Dr Hindricks presented data[4] from the group of Dr Karl Heinz Kuck (Hamburg, Germany), in which they looked at 50 patients who had LAA isolation. Kuck's group found LAA thrombus in 21%, and three patients had a stroke.

The fourth problem with BELIEF is that we now have a better approach to patients with persistent atrial fibrillation. Dr Prash Sanders and his colleagues from Adelaide, Australia, have changed the minds of most electrophysiologists when it comes to the antiarrhythmic benefits of risk-factor management, including weight loss. In the ARREST-AF[5] and CARDIOFIT[6] trial, overweight patients with cardiometabolic risk factors—like those in BELIEF—garnered significant benefit from an intensive physician-led risk-factor management clinic. AF patients who lost weight and gained fitness enjoyed more freedom from AF whether or not they had ablation. Most of these patients had good outcomes without having their entire left atrium ablated.

The fifth problem I have with this trial is its cost implications. In the US, ablation costs tens of thousands of dollars per procedure. Many patients with advanced AF undergo multiple procedures. Long-term follow-up shows disappointing results. Ablation alone does nothing to reduce the need for anticoagulation or treat the associated life-limiting diseases seen in typical patients with persistent AF, such as diabetes, obesity, and hypertension. In a world of scarce resources and severe inequality of care, it is nuts for electrophysiologists to continue thinking that the answer to AF lies only with a catheter.

I'm not an ablation nihilist. The procedure can be useful, life-changing even. Yet there are rules. One is that you can't undo lesions. Patients who have extensive ablation of the left atrium, including low-risk patients with CHADS scores of 0 to 1, live the rest of their lives with human-made scar and possibly a noncontractile appendage. That is a lot. And it's on us—the doctors, whose ultimate rule is to do no harm.

If you want something to believe in, believe in seeing advanced AF as a symptom of widespread disease—one that requires much more than a catheter to fix.



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