COMMENTARY

AF Ablation Latest: Whom to Treat and How Early to Intervene

Thomas M. Munger, MD; Peter A. Noseworthy, MD

Disclosures

May 12, 2021

Editorial Collaboration

Medscape &

This transcript has been edited for clarity.

Thomas M. Munger, MD: Hello. I'm Tom Munger, electrophysiologist and heart rhythm services chair at Mayo Clinic in Rochester, Minnesota, where my colleague, Dr Peter Noseworthy, also serves as an electrophysiologist. We're here to discuss the role of ablation in atrial fibrillation (AF).

AF is a very common arrhythmia that we deal with each day. It will affect over a quarter of the population ≥ 45 years of age and has been increasing in frequency dramatically over the past several decades.

Several recent trials have dealt with the topic of ablation in AF. Peter, I'd like to begin by asking you about CABANA, a large randomized trial completed here by Douglas Packer, for which you served as a co-author.

Peter A. Noseworthy, MD: It's nice to be with you today, Tom, and there's a ton to talk about. It's a very exciting time in electrophysiology. I think we have more trials over the past couple of years than we've had for the decade before, which has given us a lot to talk and think about.

The most awaited study in cardiac electrophysiology was indeed the CABANA trial. For a long time, we've been looking at surrogate endpoints like symptom control and burden, focused on that 30-second threshold at which we diagnose AF. Conversely, CABANA was the first study powered to look at hard clinical endpoints.

Many of us thought we might be able to demonstrate an improvement in stroke, mortality, major bleeding, and cardiac arrest with ablation. However, as has been well discussed with this trial, there was much crossover and even some patients in the ablation arm that didn't undergo ablation. These issues kept the effects that we observed from being sufficiently robust, and it was therefore considered a neutral trial. It left most of us thinking about the role for catheter ablation along the same terms of symptom control and reduction in AF burden.

Ablation for Patients With Heart Failure

Munger: There was a suggestion from the subgroup analysis that it might be of benefit for heart failure patients by intention-to-treat, that ablation had benefits. Can you comment on that relationship to heart failure?

Noseworthy: I think CABANA will be the gift that keeps giving, and we're going to see many subgroup studies from this valuable data. Just recently, we did finally see the results of the heart failure subgroup, which drew on data from nearly 800 patients in the trial and showed a benefit in terms of the trial's primary endpoint.

We always have to take these post-hoc and subgroup analyses with a grain of salt. But it's at least something that I think is emerging and is consistent with the overall literature, that perhaps we have to be more aggressive in managing AF in patients with concomitant heart failure.

Munger: Prior to CABANA, there was the CASTLE-AF trial. How do these results compare and contrast?

Noseworthy: That was another very dramatic trial in our field and one of the first to demonstrate a mortality benefit with catheter ablation.

We think those patients were very different from the heart failure subgroup of CABANA. In CASTLE-AF, they all had cardiac devices and it was a study of systolic heart failure. We don't have echo data on the entirety of patients from CABANA, but it looks like most had heart failure with preserved ejection fraction.

Together, I think these two studies support ablation in the heart failure population, regardless of whether it's preserved systolic function or whether there's reduced systolic function.

Rate vs Rhythm Control

Munger: Going back 20 years to early in my career, there was the large AFFIRM trial, in which over 4000 patients were randomized to receive either rate control or rhythm control. That was a neutral study that didn't show a benefit for mortality or stroke at early maintenance of sinus rhythm vs the rate control strategy. I think that's driven a lot of the thinking over the past couple of decades that we'll treat these patients, try to rate-control them, and then if there are problems, move to a rhythm strategy. Have there been any studies that change the thinking around early intervention?

Noseworthy: In some ways, there has been this competing narrative over the past several decades. One camp says it's all about stroke prevention and rate control, and rhythm control has a minimal role only for symptom control. Then for the other camp, the concept is that AF begets AF, and we need to interrupt that vicious cycle. I think that most of us fall into one of those two camps.

This was recently readdressed in the EAST trial. Much like the AFFIRM trial, it was an examination of rhythm vs rate control, but it differed by occurring very early in the course of the disease. In fact, many patients were enrolled after their first episode. This was not an ablation trial, per se. Less than 10% of patients in EAST underwent ablation, and many were treated with flecainide and some with amiodarone. But it did demonstrate an improvement in hard cardiovascular endpoints with early rhythm control. I think this caused many of us to reassess the notion that had been established after AFFIRM, and it is generally supportive of early rhythm control.

Munger: Patients in the EAST trial were around 70 years of age, on average, which would be typical of many that we treat. One caveat would be that many of those patients didn't have remarkable symptoms, and the other would be that up to half had it as their first episode of AF. Are there any questions or concerns that arise from that? Are these the type of patients typically encountered in practice?

Noseworthy: I think it is representative of the patients that clinicians probably see every day in their practice. Sometimes in electrophysiology we see people who are sort of at the end of the road, who have been managed for years and years. Those would not be the typical EAST patient.

The question about the relationship between symptom burden and hard clinical endpoints is an interesting one. Studies demonstrate that people who present either without symptoms or with atypical symptoms have a higher rate of cardiovascular endpoints, which makes sense if you think about an older patient with more comorbidities competing for their attention. Sometimes AF is caught incidentally in that group, among whom we worry about the risk of incident cryptogenic stroke. Medicare studies have demonstrated that the mortality in that group is even higher than the stroke risk.

Therefore, recognizing AF in that population, treating it early, even if they're minimally symptomatic, may help move the needle in terms of hard clinical endpoints.

Munger: I agree with you. I feel that just putting patients on a rate-control drug and sending them out into the wild blue yonder is not productive, because if they have atypical, minimal, or no symptoms, then they can show up in your clinic 2 years later with heart failure. We must remember to regularly follow up with these patients because they can get out of hand, so to speak, with other things like heart failure if you are not watching them.

Noseworthy: That's a good point. Smart people can disagree on the role of early intervention and rate vs rhythm control, and we can all look at the same data from different approaches. But I agree with your point of following patients closely and intervening when it becomes justified. Certainly, I still treat many patients with a rate-control strategy, but we will see how that evolves over the coming years.

Latest Data on Early Ablation

Munger: You noted that only approximately 10% of patients in the EAST trial underwent ablation. Are there other trials that are increasing our understanding of the role of early ablation?

Noseworthy: This year saw the arrival of two new trials, EARLY-AF and STOP AF, both of which looked at early cryoablation for paroxysmal AF.

These were smaller studies which were not powered for the same hard cardiovascular endpoints that we saw in CABANA and EAST. They either monitored for AF with a loop recorder or a relatively rigorous protocol of serial ECGs, Holter monitoring, and so on. Both studies demonstrated a consistent result that catheter ablation was superior to antiarrhythmic drugs for the maintenance of sinus rhythm at 1 year.

Munger: With trials like EAST, we don't know yet the persistence of beneficial effects with early rhythm maintenance. I am reminded of Jeanne Poole's recent paper on the long-term outcomes from the SCD-HeFT trial. That's a defibrillator trial looking at primary prevention in heart failure patients. Early results from this trial indicated that patients with both ischemic and nonischemic heart failure benefited. However, this latest analysis with more than a decade of follow-up found that the defibrillator's beneficial effects only stuck in the ischemic group as opposed to the nonischemic group. So I think we have to keep in mind that longer-term follow-up will be beneficial in the AF group of patients.

Another key consideration when discussing ablation and AF is lifestyle modification. Can you speak to that as well?

Noseworthy: You and I both do ablations, and it is easy for us to focus on that as our lane. We have to think of AF as a common final result of many comorbidities that are all interrelated. Unless we can address those in a holistic and comprehensive way, we are not doing our patients much benefit.

Just like there is nice literature around the intervention for lifestyles around the time of myocardial infarction, we can think about an AF ablation or presenting for AF care as a sentinel event for a patient to reassess lifestyle interventions, and go down that laundry list of things that are addressable and modifiable. It will pay dividends — not only for the AF but also for their life in general, in terms of hypertension, diabetes, obesity, sleep apnea, energy level, and all of this. Our patients will do much better if we take a comprehensive approach.

Munger: Peter, I think those are all terrific points that you made about lifestyle intervention being akin to post–myocardial infarction care or the patients who have coronary disease. They are all applicable to AF as well.

I want to thank Dr Noseworthy for these very important insights that he has given us about ablation and AF. I want to thank you all for joining us on theheart.org | Medscape Cardiology.

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