Video

AF Symposium 25: MANIFEST-REDO: Re-Do Procedures After PFA for AF

Published: 21 Jan 2025

  • Views:

    Views Icon 387
  • Likes:

    Heart Icon 0
Average (ratings)
No ratings
Your rating
View Transcript Download Transcript

AF Symposium 25 - The MANIFEST-REDO sub-study suggests repeat ablation procedures due to clinical recurrence of atrial fibrillation (AF) can be performed safely and with an acceptable success rate.

Prof Daniel Scherr (Medical University, Graz, AT) joins us onsite at AF Symposium 25 to discuss the insights from MANIFEST-REDO, investigating repeated ablation following pulmonary vein isolation (PVI) with a pentaspline catheter (Farawave; Boston Scientific Inc). Patients with AF, persistent AF, or atrial tachycardia (AT) across 22 European centres were enrolled from the MANIFEST cohort, a trial assessing the safety and efficacy of pulsed field ablation (PFA) of AF. The primary effectiveness endpoint was freedom from documented AF or AT.

Findings showed that PFA with the pentaspline catheter achieved the primary effectiveness endpoint in over half of the patients; however, PV reconnections were not uncommon. MANIFEST-REDO also revealed that if additional imaging was used in the first procedure, as opposed to fluoroscopy alone, PVI durability was increased significantly.

Interview Questions:
1. Could you remind us of the reasoning behind MANIFEST-REDO?
2. Could you tell us about the study design and patient population?
3. What were the key findings?
4. How do the MANIFEST-REDO findings shed new light on the findings from MANIFEST-PF?
5. How should these findings impact clinical practice?
6. What further research is needed?

Recorded on-site at AF Symposium in Boston, 2025.

Editors: Yazmin Sadik, Jordan Rance
Videographers: Oliver Miles, David Ben-Harosh
Interviewer: David Ramsey
Support: This is an independent interview produced by Arrhythmia Academy.

Transcript

I'm Daniel Scherr, Professor of Electrophysiology at the Medical University of Graz, Austria, and it's a pleasure to be here.

Could you remind us of the reasoning behind MANIFEST-REDO?

Well, thank you for inviting me. Well, first of all, I have to say I'm speaking here on behalf of all MANIFEST investigators. That's 22 centres, 48 investigators all over Europe. The study PI is Vivek Reddy from Mount Sinai Hospital, New York. And really the reasoning behind is that we are already hitting 200,000 PFA, approximately 200,000 PFA procedures worldwide. And really, the pentaspline catheter has been leading the way. It's the most used catheter, and it's certainly been part of most PFA studies.

The MANIFEST consortium was put together three years ago, investigating in 100,050 patients not only the safety aspects of PFA ablation in AFib but also the efficacy aspects of it. And we've been publishing quite successfully.

Now we know that PFA works, but also recurrences of atrial fibrillation happen, and repeat ablations for atrial fibrillation are necessary. And the outcomes, efficacy outcomes and safety outcomes of those repeat ablations in patients who previously had an AFib ablation with PFA are largely unknown. The second thing that makes our study relevant is the fact that really the aspect of PVI durability, which is important in AFib ablation to sustain sinus rhythm, hasn't been thoroughly investigated with PFA, especially in the repeat ablation patient population.

Now, I would like to highlight two smaller studies. The EU-PORIA registry. Nice paper, 140 patients. And they really showed that in a repeat ablation population— so those were patients that previously had an ablation for atrial fibrillation using the pentaspline catheter, using PFA— those patients came back for clinical failures and they were remapped and reablated. And in these procedures, it was found that only 70% of all veins were isolated at the start of the procedure, and only 38% of all patients had durably isolated veins at the start of the procedure. And a similar finding was found by [indistinct] and colleagues in a smaller registry.

So you can look at it in a way that we are trying to assess in the repeat ablation population, patients that have previously undergone a PFA ablation, the incidence and maybe predictors of pulmonary vein isolation and pulmonary vein reconnection.

Could you tell us about the study design and patient population?

It's the largest, at least to my knowledge, PFA repeat ablation population that's been investigated so far. It's out of the MANIFEST cohort: 427 patients in 22 European centres that underwent repeat ablation for an atrial fibrillation or atrial tachycardia recurrence after a previous PFA ablation with the pentaspline catheter. Now, those procedures took place nine months after the initial ablation procedure. And I think the findings were quite interesting.

What were the key findings?

I'd like to highlight, I'll probably skip the procedural part as I think we've published this and the paper on our findings is as of yesterday already available online in Europace. But I'd like to highlight maybe two findings and maybe we could discuss this.

So I'm going to start with the first one, and that is really pulmonary vein isolation durability. So again, those 427 patients came back to the lab and were mapped. They all had a previous PFA ablation with the pentaspline catheter, and they had a clinical failure for AFib and ATach. So when they were mapped, it was found that only 45% of those patients had four durably isolated veins. And on the pulmonary vein level, 71% overall of all pulmonary veins were isolated. The reconnections were evenly distributed among the main four pulmonary veins— so left superior, right superior, and so on. That's interesting.

And also I think, although only univariately associated, one interesting finding also was that if the operator had used in the first procedure some sort of imaging, CT imaging, ICE imaging, rotational angiography or electron atomic mapping, as opposed to having done the procedure only with fluoroscopy. So the use of some sort of imaging increased the PVI durability rate significantly. This is a univariate finding, so you have to be cautious. But certainly as it changed my clinical practice. Remember, this is Europe, not all centers, not all countries are using ICE. But from now on, I think it's mandatory to, if you use the pentaspline catheter to use some sort of imaging or electron atomic mapping in your procedure.

Now another finding, and I'll stop there for the first part, is PVI durability, which is natural and which we've seen in the past with other thermal energies, is the fact that paroxysmal, the distribution was different in terms of PV reconnection between paroxysmal and persistent AF patients.

But may I add one more interesting thing to put that finding into perspective, and that is you can look at the glass of half full or half empty. So one would say, well, that's this great new catheter and only 45% of patients have four durably isolated veins. Well, guess what? At least in my knowledge, in a clinical failure population, a clinical repeat ablation population, that's about the highest number, at least that I'm aware of, that's ever been reported for any energy form of PVI durability rate in repeat ablation population.

If you look back to seminal studies like FIRE AND ICE or CIRCA-DOSE investigating RF ablation in AF or investigating cryoballoon ablation in AF, what you will find when you look at their repeat ablation papers, PVI durability rates in the repeat ablation population, they were significantly lower. I think in CIRCA-DOSE, it was like 10% on the patient level as opposed to 45% in our study. And I think on the pulmonary vein level, it was something between 45% and 60% in those study, as opposed to 70% in our study. So, yes, also with the pentaspline cast, also with PFA, we can do better in terms of PVI durability, but it's already a great start for a new technology.

How do the MANIFEST-REDO findings shed new light on the findings from MANIFEST-PF?

Let me certainly not shed light on the findings from MANIFEST-REDO because it's the original MANIFEST-REDO study. But certainly add to the findings of MANIFEST. And another clinical finding, it's all about the patient. So on the clinical side, what MANIFEST-REDO also is telling us, besides those interesting findings on PVI durability, what can a patient expect in terms of success rate if he undergoes a repeat ablation after having previously undergone a PFA ablation?

And the findings are quite encouraging. So in MANIFEST-REDO, overall, 65% of all patients achieved sinus rhythm with their second procedure, 65% not of the overall cohort, but just of the previous kind of failure cohort that went for repeat ablation. I think that's an encouraging finding. And in those 65%, you see the obvious, that people that came back with the recurrent arrhythmia being paroxysmal AF or atrial tachycardia, doing better than those patients who came back with persistent AF. And again, persistent AF being the recurrent arrhythmia being a predictor of worse outcome as opposed to paroxysmol AF.

How should these findings impact clinical practice?

These findings should, in my view, impact clinical practice in three ways. For me, it's been an encouraging finding with regard to PFA and AFib ablation in general and specifically to the pentaspline catheter. So, you know, we certainly cannot cure all of these patients, but overall, the patients are doing really well. There is a high efficacy rate and there's a good safety profile.

Number two, finding number two for me is a patient who comes back with a recurrent, symptomatic arrhythmia after having previously undergone an AFib ablation with PFA with the pentasline catheter should be encouraged to undergo a second ablation because the outcome is fairly good.

And finding number three is that with all these encouraging findings and with the pentaspine catheter in this repeatablation population showing us fairly high PVI durability rates, 45% on the patient level, 71% on the pulmonary level, there is still room for improvement in terms of PVI durability.

So what can we do? Remember that MANIFEST, that MANIFEST-REDO covers the very early experience. Those were patients done in 2021, 2022. So we have learned quite a bit on how to handle PFA, on how to handle the pentaspline catheter to give additional applications on the anterior side of the right pulmonary veins, olive applications, carina applications. So I think we have improved already.

And a second thing that I'm really looking forward to is kind of the second generation catheters that are truly 3D integrated, single-shot PFA devices, and the pentaspine catheter will be one of those, that's going to improve success rates and PVI durability rates. I'm sure, it's just hypothesis, but I'm pretty sure about that.

And finding number three is really for your daily practice. When you treat the patient with AFib with PFA with the pentaspine catheter, in whatever setting you are, in whatever part of the world you are, use some sort of additional imaging or mapping, whether it's ICE, whether it's electroanatomic mapping, whether it's a pre- procedural CT or whether it's rotational angiography.

What further research is needed?

Well certainly it's exciting times, right, for our patients. You know, industry especially has really been driving progress over the last couple of years. The procedures have, and that's the most important thing, a reasonable safety profile and have shown high efficacy and also high lab efficiency. Remember that those days when our AFib procedures took a couple of hours, they're only 10, 15 years past. So now you can do a PVI isolation in the symptomatic patients in 30 minutes at best with these new technologies.

Additional research is needed. Efficacy is encouraging. Safety always can be better but is encouraging. But we can do better in terms of PVI durability, we can do better in terms of success rates.

So I'm really looking forward to all the findings of this meeting and of all the research ongoing with these new platforms. And again, I want to highlight and stress the fact that PVI durability is key and we have to improve on that. And with 3D integration and ICE and all these things, we're working on that.

Comments

You must be to comment. If you are not registered, you can register here.