The Surgeon's Approach to Atrial Fibrillation

John M. Mandrola, MD; Richard Whitlock, MD, PhD


October 17, 2022

This transcript has been edited for clarity.

John M. Mandrola, MD: Hi, everyone. This is John Mandrola from | Medscape Cardiology. I'm here in Barcelona at the European Society of Cardiology meeting, and I'm with my friend, professor of surgery at McMaster, Rich Whitlock.

Rich, welcome!

Richard Whitlock, MD, PhD: Thanks, John.


Mandrola: Of course, we're going to talk about the surgical approach to atrial fibrillation. I think it's important to remember that surgeons actually led the way for electrophysiologists, so I'm especially happy to talk to Rich.

Let's start with LAAOS III. You're the principal investigator (PI). Left atrial appendage closure at the time of cardiac surgery showed a significant reduction in stroke. Tell us about that and how that all went down.

Whitlock: That was a multinational collaboration. Many very academically interested individuals participated within that trial to demonstrate that, at a minimum, a patient who comes in for cardiac surgery who has atrial fibrillation, the left appendage should be managed, meaning occluded in some way. There was a 33% stroke reduction over the follow-up of 3.8 years.

In fact, it was a gift that keeps on giving because you've got this divergence of curves for stroke that keep diverging out to 5 years. The number needed to treat by 5 years is around 30 patients. It was a big-impact paper, I would say, that's been accepted well within the community, and I give numerous talks on that.

Now this study has answered the question definitively that management of the left atrial appendage through a surgical epicardial technique reduces the ischemic stroke risk. That had never really been proven.

Mandrola: Patients remained on anticoagulation.

Whitlock: Correct.

Mandrola: This is an important point.

Whitlock: It is. We felt, in designing this trial, that there were enough limitations to anticoagulation that we would still see benefits of left appendage occlusion. In fact, the field of anticoagulation continues to change. There are safer and safer drugs coming out, so really, when we're in there, we don't need to think about that. We just need to take off the appendage because it's beneficial to the patient whether they stay on their anticoagulation or not.

[Those who receive the] most benefit, and the group with the lowest stroke risk, are those patients who have their left atrial appendage occluded, and they stay on their anticoagulation. Surely, in patients who have elevated CHA2DS2-VASc scores, there are other stroke sources beyond the left atrial appendage and beyond atrial fibrillation.

Mandrola: Right. That's a good point because LAAOS III showed, I think for the first time, that the left atrial appendage is important. I was questioning whether left atrial appendage closure as a mechanism to reduce stroke was even valid. I think LAAOS III shows that it is.

Transcatheter Left Atrial Appendage Occlusion

Whitlock: The field was dominated by catheter-based evidence, and really, it was the Watchman device, and they have been doing well in terms of generating evidence. If you look at the patient-level meta-analysis of that, ischemic stroke compared with warfarin, there was a P value of .05 that was favoring warfarin. Hemorrhagic stroke was significantly reduced.

Therefore, the net effect was a noninferiority claim for the Watchman. Again, embolic or ischemic stroke had not been proven to be reduced by left atrial appendage occlusion with an intracardiac device.

Mandrola: Right. Let's talk about that. LAAOS III shows that the appendage is an important source of stroke and closure is important. Why can't we seem to do the same with percutaneous devices?

Whitlock: It's an evolving field. With current technologies, there are some limitations. Leaving something inside the heart, you do have device-related thrombus, there's contact activation of the blood as it touches it until it fully has protein deposition and "endothelialization," which is a misnomer. When you have these devices with residual leak, you have surface area that continues to be exposed for thrombus formation so you can have these late events.

That is different than an epicardial technique where you're not leaving something within the heart. If there was zero effect of the Watchman on ischemic stroke, they probably would not have demonstrated a net clinical benefit noninferiority. There may be some, but I don't think it's as great as an epicardial approach.

Mandrola: What do you say to the people who want to take patients off anticoagulation with epicardial or surgical closure?

Whitlock: Again, this is evidence that we need to establish. Hopefully, within my career — I think I'm still young enough. I have a few trials that we can discuss, but one that I would like to do is a thoracoscopic epicardial closure vs the current best medical practice, and that would be a noninferiority design.

Again, it may be slightly different. We may think about adding in a lower-dose direct-acting oral anticoagulant (DOAC), almost like a COMPASS regimen. We'll bring together experts in the various fields and we'll brainstorm in terms of what the best design is and where we think the greatest safety is for patients. COMPASS showed a reduction in cardiovascular events and strokes just at that lower dose. It probably protects for non-AF strokes by that rivaroxaban 2.5 mg.

Mandrola: Before we go on something else, what do you think about the idea of appendage closure at the time of surgery in patients without atrial fibrillation?

Whitlock: Again, the evidence is not there. In fact, if you look at the current evidence, the Mayo Clinic put out a database study that suggested that the only thing they saw was an increase in postoperative atrial fibrillation that may or may not be harmful to the patients.

This is a trial that we are undertaking that we hope to start recruitment in October of this year. It'll be 6500 patients. Not every patient comes from heart surgery. We have defined a group of patients that we know have risk factors for development of atrial fibrillation and risk factors for stroke. The heart rhythm societies have consensus documents out, so we now have data to support what the patient profile is for risk for these events. That's in atrial cardiomyopathy.

Surgical Ablation

Mandrola: Let's move to the second area that surgeons are involved in with atrial fibrillation, and that's surgical ablation. It's a bit of a Wild West out there because we have Dr Cox, who led the way with the specific surgery, but now there are seemingly all these different approaches.

Whitlock: It's interesting to think back to Dr Cox's long-term paper, where he showed a stroke reduction relative to what was expected based on CHA2DS2 score. Now, one must take into consideration that the Cox-Maze IV procedure included left atrial appendage management. It's my sense, and I think Dr Cox would be supportive of this, that the dominant source of stroke control is by managing the left atrial appendage. As things shifted to catheter-based, the left atrial appendage was left behind, and everybody was focused on rhythm control.

As you know, rhythm control, whether it's through drug or catheter-based procedures, really has never been shown to reduce stroke. For surgeons, again, the heavy ablators really believe in performing that full Maze at left and right atrium and taking off the appendages. Again, I think management of the left atrial appendage is incredibly important, but there is question out there as to what the extent of the ablation should be based on other risks.

Those risks include, as shown in our meta-analysis, that when you do that by atrial ablation, you increase the pacemaker risk compared with just doing the left side of the lesion. You may lose some efficacy by just doing left-sided lesion set in terms of reduction of burden of AF. Whether that reduction is worth it based on avoiding that pacemaker risk, we've yet to establish.

Mandrola: Right. I read the 2018 EP Europace meta-analysis. Basically, I think you said that all of the evidence is pretty low quality.

Whitlock: Yes. Again, as a surgical field, we're hoping to change that now. We'll be starting a 2000-patient trial (SAFE) that follows the track of CASTLE-AF and RAFT-AF, suggesting that there may not be a large stroke benefit by altering the rhythm or getting into sinus rhythm, but it looks like we affect progression of heart failure. The focus of that trial will be on heart failure outcomes and death.

We will be randomizing 2000 patients. Again, surgery offers the opportunity to do this with a sham control and in a blinded fashion. Hopefully, it will contribute to the literature significantly. That will be left-sided ablation set vs no ablation set. Everybody gets the left atrial appendage managed.

Partnered with that, I'm in discussions with Pat McCarthy out of Chicago, where they're looking at randomizing  patients (being a heavy-ablating center) to left-side lesion set vs biatrial lesion set. They will be able to answer that question around efficacy of left atrial ablation alone vs biatrial ablation and impact on pacemakers. I think that those two trials partnering together are going to yield some excellent information.

Mandrola: This is great because we're going to get data on surgical ablation even though it's been going on for 20 years — I guess it's better late than never — but I'm really glad to hear that there is going to be evidence.

Whitlock: Yes. As you know, there was the CAPLA trial presented here, that I'm sure is going to be a bit of surprise to many surgeons and electrophysiologists. Adding the posterior wall lesion did not change outcomes or burden of AF in persistent AF.

We need to read that paper carefully to see what the success rate of the lesion set in the posterior wall was, but still, as you say, it's the Wild West out there.

We need to homogenize the procedure to some degree to get surgeons to really buy in and for uptake of this procedure because right now, we have plateaued in uptake. For all comers, it's around 30%-33%. For CABG and AVR patients, it's down at 10%-15% use of ablation if they have atrial fibrillation.

Whether that's right and we shouldn't be doing this or whether we're missing big opportunity to stop progression of heart failure, we've yet to prove.

Mandrola: We need the data. Thanks so much for coming on. It's really great to talk to and see you.

Whitlock: John, it's great to see you.

Mandrola: Excellent.

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