Welcome to the episode of The LEAD, I'm Prash Sanders from the Digital Education Committee at the Heart Rhythm Society. I'm joined today by Dr. Jason Andrade from Vancouver and Dr. Melanie Gunawodner from Germany. We're going to discuss a paper that's just been presented at the ERA meeting. This is the single-shot champion study that was simultaneously published in the New England Journal of Medicine. Jason, could you present the paper for us? Sure, happy to. So this was a randomized non-inferiority trial that was performed in two centers in Switzerland. They took patients with symptomatic paroxysmal atrial fibrillation and randomly assigned them in a one-to-one ratio to undergo pulse field ablation or cryo-balloon ablation. All patients received an implantable cardiac monitor to detect recurrences. Their primary endpoint was freedom from atrial tachyarrhythmia between days 91 and 365. It was designed as a non-inferiority trial with a 20% margin. The operators randomized 105 patients to each group. At one year, they observed that the recurrence of atrial tachyarrhythmia occurred in 37% assigned to pulse field and over 50% assigned to cryo-balloon ablation. The absolute difference was 13.6 percentage points, which was a P of 0.046 for superiority for pulse field ablation. Safety endpoints were observed in one patient assigned to pulse field ablation and two patients assigned to cryo-balloon ablation. Important secondary endpoints included measures of quality of life and atrial fibrillation burden. The authors observed no difference in time spent in atrial fibrillation between the two groups with a burden of 1.4% with pulse field ablation and 1.9% with cryo-balloon ablation. In terms of healthcare utilization outcomes, there was no difference in hospitalization or emergency department visits, no difference in electrical cardioversion, and a trend towards more repeat ablations in the pulse field group compared to the cryo-balloon group. Antaryrhythmic drug usage was no difference between the arms of the trial and quality of life metrics on the EQ5D with similar improvements in both groups. Thanks, Jason. Melanie, what do you see as the limitations that this study has and is there anything else you wanted to add? Thank you very much. So first of all, I think one of the limitations obviously is that it has been performed in only two centers that were very experienced. So it is questionable how generalizable those results will be for others to repeat it. The next thing is that there might have been an underperformance for the cryo-balloon in the study, because when you look into the procedural detail, you can find that 20% of the patients in the cryo group had a left common pulmonary vein versus 6.7% of the patients in the PF arm. And we know that it is hard to ablate a common ostium with the cryo-balloon. Next, I think that when we are looking at the reablation number, as Jason Andrade just mentioned, there were 16 reablations in the PF arm, which could have maybe added to the reduced AF burden in that cohort, right? Because we do more to gain sinus rhythm. And lastly, we have to look at the endpoint that was freedom from atrial tachyarrhythmias. And this is rather binary. We're looking at occurrence of recurrence, yes or no, but when we look at the burden that was the same in both groups over the follow-up. So we wonder if this is really clinically meaningful to find the same time spent in AF in both patient cohorts. Samia, I'm going to tease you out. So do you think that this has done away with cryo-ablation now? Do you think there's adequate evidence here to say cryo-balloon is not first line for paroxysmal AF ablation? What are your thoughts? Well, as always, this is one study, and then we have all the others that also made it into the guidelines and actually changed recommendations in the guidelines. For example, from Jason Andrade or Osama Wasny, that also looked at first line ablation and have been published in the same journal, and they showed that it was effective as a first line ablation compared to antiarrhythmic drugs, right? So there we have already data that has been repetitively shown that there was a good benefit of the cryo-balloon, and this is one study we're looking at. Jason, you've been a great advocate of moving away from the 30-second time to first event analysis, which was used in this trial, and they also used loop recorders here, so they did have some AF burden data. What do you think is the ideal that they should have used in this trial? So when we think about the endpoints of trials, I think we have to conceptualize it from the picture of the patient, from what we're trying to answer in terms of the technology evaluation, as well as the picture from the healthcare system, like healthcare utilization. So in this case, the trial is designed as a technology comparison. What we want to know really is one technology better than the other. If we want to know that truth, we have to have a way to detect arrhythmia recurrences that has high fidelity, so loop recorders is absolutely the right choice here because we're not going to under-detect recurrences, and so you could argue that when you're using non-invasive monitors like what was used in the previous ADVENT trial, you're at risk of missing recurrences, you're at risk of a type 2 error or assuming there's no difference when actually there is one. By having the loop recorders, I think they're absolutely sure that there is a difference, so we know that less recurrences happen with PFA, I don't think that's debatable. Where it becomes important to extrapolate from there is the other endpoint, so looking at burden, looking at anti-arrhythmic drug use, looking at reablation, none of those seem to point towards there being superiority, let's say, of PFA, and so now we're getting into the nuance of did we over-detect meaningless arrhythmias at a rate of about 14% because they weren't actionable, it didn't lead to more prescriptions of anti-arrhythmic drugs, it didn't lead to lower quality of life, and so this is, I think, a very clear example of the problems we have with trial endpoints by relying on binary recurrences because it assumes that every binary recurrence is the same and very clearly this trial is telling us that it is not. We need to have something more quantifiable there to give us the big picture. I agree. Look, I've had the feeling that the investigators downplayed symptoms as a potential role, and they used the accrued measure of symptoms rather than AF symptoms, and then the other thing that bothered me is by using the loop recorder, they had actually more than double the rate of reablation within 12 months compared to ADVIC, and so I presume that was driven by knowing about arrhythmias early from the loop recorders, but what are your thoughts there? I mean, I don't think we know at this point what was the thing that led to the higher rates of reablation. I mean, I would say a reasonable hypothesis is the recurrences that happened potentially were more symptomatic and drove a need for intervention, and that may have led to more reablations, and so even though there were less numerical recurrences, perhaps they were qualitatively worse recurrences than what we're seeing. It may be just knowing in terms of the detection of arrhythmias were higher, but you could have made the argument that the same thing should have happened in the cryo group as well, and so if you had a much higher rate of recurrence in cryo, proportionately you should have seen the same number of reablations if the recurrences were qualitatively the same. Loop recorders offer an ability to really dig into the data to gain understanding, and I think that secondary analyses here to try and get to the nuance of what was observed will be very helpful. In clinical practice, we don't necessarily implant loop recorders for all of our ablations because asymptomatic recurrences of short duration that are not actionable, we don't necessarily need to know about those. Symptomatic recurrences, recurrences that lead to emergency room visits or healthcare utilization, those are actionable, those are things that we would respond to, and I think the message here is very similar to ADVENT in that there was no difference in terms of that type of recurrence. And I think it's totally fair to say that we really need the details because we know there were eight rehospitalizations to the emergency department due to arrhythmia recurrence in the cryoarm, so this means those were highly symptomatic patients, and in a complete cohort there were ten reablations, were those exactly those eight patients, right? So I'm totally agreeing with what you were saying, which kind of arrhythmia received a reablation in this study? So this is a great study that's been presented, it confirms the data that we've had from the ADVENT trial that really shows that we have good technologies for ablating atrial fibrillation. Thank you for joining us on this episode of The Lead.

pulse field ablation

cryo-balloon ablation

paroxysmal atrial fibrillation

atrial tachyarrhythmia

Single-Shot Champion Study