Conference Takeaways

EHRA 23 – In this short interview, Prof Roland Tilz (University Heart Centre Lübeck, DE) outlines the findings from the POTTER registry.

The POTTER Registry (NCT05273645) gathered data on patients undergoing pulmonary vein isolation (PVI) with a rare complication, atrio-oesophageal fistula (AOF). The registry focuses on the incidence, diagnosis and management of this complication, which affects around 0.016-0.07% of PVI patients. Prof Tilz outlines the patient population, key findings and future prospects of this worldwide, multicenter, retrospective registry.

Questions:

What was the rationale behind the creation of this registry?
What was the patient population and registry design?
What were the key findings?
How should these findings inform and shape practice?
A worldwide survey on incidence, management and prognosis of oesophageal fistula formation following atrial fibrillation catheter ablation: The POTTER-AF study

Recorded on-site at EHRA 2023, Barcelona.

Interviewer: Jonathan McKenna

Editor: Jordan Rance

Transcript

“- Welcome, my name is Professor Roland Tilz. I’m the Director of the Department of Rythmology at the University Hospital in Lubeck. I’m glad to present the results of the International POTTER AF Study.

Rationale

The rationale behind this international registry was to evaluate the incidence, the management, and the outcome of atrial oesophageal fistula formation post AF ablation. Oesophageal fistula formation is a very rare but highly lethal complication following AF ablation.

Patient Population and Registry Design

It is an international retrospective survey. In total, more than 200 centres participated in this study from 35 countries worldwide, so it’s a true worldwide survey. In total, 138 patients were enrolled in this study. In this survey, more than half a million of patients were treated in more than 200 institutions out of 35 countries. Out of this more than half a million patients, 138 patients had an oesophageal fistula formation.

Key Findings

The key finding of these study were the following. Number one, the incidence of esophageal fistula formation post AF ablation is 0.025%. This means 25 out of a hundred thousand patients get an oesophageal fistula. It appears to be a pure RF problem, because 38 out of a hundred thousand patients treated with RF got an oesophageal fistula formation, whereas only 15 out of a million patients treated with cryoablation suffered from an atrial oesophageal fistula. Second, it is very important that you look for these complications and treat them aggressively. You can diagnose the fistula with a CT in over 80% of patients. If you do not treat the patients, the mortality is 80%. If you do not treat the patients, so if you treat them conservatively, the mortality rate is almost 90%. Whereas if you treat the fistula either with surgery or with stenting, their mortality rate is just about 50%. Third, you have to be aware of the complications. If you find it, treat it early. And number four, maybe RF energy is not the right energy to treat patients, because it appears to be a pure RF problem. Cryo energy and pulsed-field ablation energy appear to be much safer with regards to oesophageal fistula formation.

Impact on Practice

So these findings have a huge implication on my daily practice. Number one, awareness is very important, so we have to be aware of this complication. And once the patient is complaining of dysphagia, fever, neurological deficit, after AF ablation you have to do a CT scan to look whether the patient has any evidence of oesophageal injury. Second, you have to treat it aggressively, because if you do wait and treat it conservatively the mortality rate is more than 90%. Treat it early. Third, reconsider your energy of choice. This appears to be a pure RF problem. So other energy sources like cryo, or pulsed field ablation are associated with a much lower incidence.

EHRA 23 – Dr Bruce Wilkoff (Cleveland Clinic, US) joins us on-site to outline the findings of the AdaptResponse randomized study (NCT02205359).

In AdaptResponse, investigators studied the hypothesis that cardiac resynchronization therapy (CRT) devices which utilised AdaptivCRT® (aCRT) algorithm (Medtronic) had better prognosis in patients with normal atrioventricular conduction and left bundle branch block when directly compared with patients who had received standard CRT devices.

Questions:

What was the reasoning behind this study?
What was the patient population and study design?
What are the main findings?
How should these findings be implemented in clinical practice?
What are the next steps?
Recorded on-site at EHRA 2023, Barcelona.

Editor: Mirjam Boros and Jordan Rance

Transcript

“- Hi, my name is Dr. Bruce Wilkoff, I’m the Director of Pacing at the Cleveland Clinic in Cleveland, Ohio, and I was the principal investigator for the AdaptResponse trial.

Trial Background

The background to the AdaptResponse trial is that we have CRT that can be delivered both with adaptive response or with biventricular stimulation. And it was our intent to study whether we could improve that outcome by using adaptive mechanisms.

Study Design and Patient Population

So the patients involved in the AdaptResponse trial were designed to be highly responsive to CRT therapy. We took patients with adjudicated left bundle branch block and function class two or three heart failure. These are patients that are expected to respond well to CRT trial. And then we took those patients and we randomised them between the adaptive algorithm and standard CRT therapy. This is by far the largest trial of CRT pacing. It is larger than all the other prior studies combined and has a longer follow up than all the other trials as well. So this is a very large trial and a very prolonged follow up.

Key Findings

The key findings were that adaptive pacing produced the very best outcomes we’ve ever seen in a heart failure population, followed for longer than any other trial, and provided for the best survival and the lowest mortality. Unfortunately, even after eight years from the first randomization to the last follow up, we failed to produce an 18% reduction in the outcome, but we did find 11% reduction, which was not statistically significant. But we were able to take those patients that had adaptive mechanisms and that were very highly LV paced and have found that those patients did 24% better than the patients with traditional CRT pacing.

Impact of Findings on Patient Care

Well, the first thing that we should think about when we interpret this data is that this is the population that CRT was intended to work for, and it works really well. And when applied to this population, we got the very best outcomes. So whatever competitive therapies there are, this is the therapy that should be benchmarked against. This is long-term follow up. We had a median follow up of 59 months and we had very excellent results. So this is the therapy for these patients, and competitive therapies are going to need to benchmark against this kind of therapy. In addition, we know that patients with left bundle branch block, which are the prime source of patients for CRT, really do need to get CRT. There are a lot of other therapies out there, but for left bundle branch block patients, this therapy is unmatched.

Next Steps

Well, the next steps is we have to delve more deeply into this very rich database. One of the really interesting parts of this study is that we had 43% women randomised in this trial, by far the largest number of women. So we have various demographics that are very broadly based. It’s worldwide, we’re talking about 27 countries, over 270 centres, 3,617 patients that were enrolled in the longest follow up. So we’re very excited to delve really closely into this data. I think one of the things that we’re going to really be interested in looking at is this percent adaptive pacing, I think that’s a really interesting finding and that we’re going to have to really sneak into that a little bit further.”

EHRA 2023 — Join us as we dive into the latest research with investigator, Dr Vivek Reddy (Mount Sinai Hospital, New York, NY, US). He discusses the findings from the MANIFEST-PF registry, adding insights to the evolving landscape of pulsed-field ablation.

The trial studied the use of the Pentaspline PFA Catheter in patients with paroxysmal or persistent atrial fibrillation in order to understand how the device is being used in clinical practice and its outcomes. 24 centers were involved in the trial, with 1500 patients participating.

Questions:

What is the current evidence on the use of the pentaspline PFA catheter?
Please describe the study design of MANIFEST-PF.
Please provide an overview of the cohort enrolled in MANIFEST-PF.
What are the key findings from MANIFEST-PF?
What are some of the unknowns around PFA? What are the promises of this technology?
What are the planned next steps or future directions based on the findings from MANIFEST-PF?
Recorded on-site at EHRA 2023, Barcelona.

Editor: Mirjam Boros and Jordan Rance

Transcript

“- I’m Vivek Reddy from Mount Sinai Hospital in New York City, and I’m going to be speaking on the Manifest-PF Registry one year results.

Evidence on the Pentaspline Catheter

Well, if you look at the current data with the Pentaspline Catheter, we’re really looking at the first in human trials that were performed about two plus years ago, and there, the data was quite good. We have excellent durability data and excellent one year outcome data. With the paroxysmal population, in which it was tested, the outcomes were about 83% success at one year. With persistent patients, we do have some data, but really, in a very small number of patients. So now fast forward to two, three years later, now the Pentaspline PFA Catheter has approval. It has CE mark approval here in Europe and is now being used in clinical practice. So the purpose of the Manifest-PF Registry was to try to understand how it’s being used in practice and what are the outcomes in practice. We had previously had a Manifest-PF survey. We published that about a year ago. That was really a centre level survey that was really focused on safety events and acute procedural success. We had no data on long term procedural success, and we didn’t have patient level data. So we went back to the first 24 centres that started doing pulsed field ablation. We asked for information on the first group of patients that they treated after the device was approved in 2021. And overall, it was 24 centres, everybody participated, so 100% participation. We included just over 1,500 patients, who underwent first time ablation for either paroxysmal or persistent Afib. It was about 2/3 paroxysmal, 1/3 persistent, so a lot of patients, lot of centres, a lot of operators.

MANIFEST-PF Study Design

The Manifest-PF Registry was designed as a retrospective analysis of, at many centres, prospectively collected cohort of patients. It was a patient level analysis, so we had individual patient level data, and we wanted to understand the one year outcomes in clinical practice. So, and the primary endpoint for our study was looking at freedom from any atrial arrhythmia recurrence with a three month blanking period. So, one year time horizon. We had a secondary outcome of freedom from arrhythmia or also freedom from taking an anti-arrhythmic drug or undergoing a redo ablation procedure. That was our secondary endpoint. So, we got the information from all of the centres, and then we combined the data and then just recently presented the data.

Overview of Cohort Enrolled in MANIFEST-PF

If we look at the patient population enrolled in Manifest-PF, it was about 2/3 of the patients were paroxysmal Afib, 1/3 were persistent, very few long-standing persistent patients. Sort of, I think, the kind of patients that are typically treated in clinical practice. About 40% of the patients were receiving a class one or a class three anti-arrhythmic drug before entering the trial. The remaining were receiving beta blockers or calcium channel blockers. The ejection fraction was largely preserved in this population with relatively few heart failure patients. So, let’s talk about the key findings in MANIFEST.

Key Findings from MANIFEST-PF

So the patients were followed for a median of 367 days, so about a one year follow up, and what we saw for the primary endpoint, freedom from atrial arrhythmia recurrence, in the full cohort, was a success rate of 78%. If we separate it by AF subtypes, the success rate was 82% in the paroxysmal population and 71% in the persistent population. If we look at the secondary endpoint of freedom from arrhythmia or redo procedure or anti-arrhythmic drug, the success rate dropped a little bit in the cohort to about 72-73%. We also did some analyses to try to understand what predicted success versus failure in terms of centres. We did analysis, looking at centres that did a lot of procedures versus few procedures, and basically, there was no difference in outcomes, and one thing that says is that using this catheter, people have pretty good outcomes pretty much the first time they used it. Now, I should note, these are 24 experienced centres, so these are not novice centres, but the point is, with an experienced centre, introducing this catheter for literally the first time that they’ve ever used it, they’re having good outcomes. On the safety side, what we saw was, just as we saw in the previous survey, there were no esophageal complications, no evidence of PV stenosis, and happened in literally one in 1,000 patients, actually less than one in 1,000. And we saw no other unusual side effects, so overall safety continued to look good.

Unknowns around PFA and Promises of this Technology

When we think about what’s unknown about PFA, I think that Manifest really helped in trying to understand what is the efficacy in sort of clinical practice. I think that’s very important. But there are other questions on the efficacy side. For example, what if we have an implantable loop recorder, and we are looking at short bursts or asymptomatic Afib, that may not otherwise be detected in clinical practice, will that track just as we see, for example, with thermal ablation? My guess is yes, but we don’t have that data, and we need to assess that. On the safety side, look, this is over 1,000 patients, over 1,500 patients, and the safety looks excellent. Of course, I’ll feel even more comfortable after 10,000 patients, to continue to see, number one, that these sort of complications that we’re looking for continue to be either not happening or extremely rare. And number two, there’s always the possibility of the unknown unknown, the complication we’ve never even thought about that may potentially occur after 10,000 patients. Again, it seems less likely, but it’s something that we need to continue to watch for.

Next Steps Based on MANIFEST-PF Findings

Now, following up the Manifest-PF Registry, there are a couple of analyses that we’ve already had planned. It is interesting, for example, to try to think about how different populations fare with pulsed field ablation. For example, there’s been some data that women, for example, may not do as well with catheter ablation of atrial fibrillation as men do. There’s other data suggesting that may not be the case. I think it’s very important for us to understand how different genders. I think it’s very important for us to understand what the effect of pulsed field is on different genders, so that’s an analysis that we’re planning. We’re also planning on looking at the redo patients and trying to better understand why failures occur. And then following up MANIFEST, we are thinking about a different analysis, more based on a safety analysis, at even larger numbers of patients, but again, this is in the planning stages.”

EHRA 23 – We are joined onsite by Prof Carlo Pappone (IRCCS Policlinico San Donato, IT) who outlines the key findings of the BRUGADA Randomized trial.

In a randomized controlled trial, 150 patients with Brugada syndrome were enrolled in to develop an evidence-based treatment for the condition. Patients were randomized in a 2:1 fashion to receive either catheter ablation treatment with an ICD, or an ICD alone to evaluate the effectiveness of epicardial ablation in reducing rates of sudden cardiac death.

Questions:

What is the reasoning behind this study?
What are the unmet needs in the treatment of Brugada Syndrome?
What was the study design and patient population?
What are the key findings?
What could be the impact of these results on clinical practice?
What further research is needed?
Recorded at EHRA 2023, Barcelona.

Editor: Jordan Rance

Transcript

“- Good morning, I am Professor Carlo Pappone, Italy. I am the Chief of Department of Cardiovascular Disease at San Donato University Hospital. The topic we are going to discuss today is Brugada syndrome therapy.

Reasoning Behind the Study

The main reason of this study was the demonstration that the ablation can eliminate the substrate of Brugada syndrome. In the past this condition was considered just an electrical disease based on the genetic predisposition. Very recently, our group demonstrated that this condition is associated with the substrate localised in the pericardial cavity. The only solution for this patient is the ICD implant. So these patients at high risk are designated to keep for the rest of their life the ICD implanted limiting their normal life. The project of this study is to find an alternative therapeutic option excluding the ICD as a therapeutic approach.

Study Design and Patient Population

We randomised the patient with ICD implant and ablation and patients only with ICD implant. All the population had a previous cardiac arrest one time or more time. And we recruited the patient and randomised in two to one. So we have much more people in the ablation group than in the ICD group. And actually the results are showing that the superiority of the ablation is very clear and the patient with the ICD continue to have a lot of complication due to the lead infection, rupture dislodgement. So the ablation can become in the future the real solution for the treatment of this condition.

Key Findings

The key finding after the discovery of the substrate of this disease in the pericardial space with the 3D mapping system, we do the mapping of the substrate. We target the substrate and eliminated the abnormal electrical activity on this substrate using radiofrequency with a very simple catheter. The duration of the procedure is about one hour and the day after the patient is at home. This is the first demonstration that is possible to do the ablation in cardio genetic disease. In the past was considered an impossible target.

Impact on Clinical Practice

Most of these patients otherwise designated to die for the sudden death. In the future we’ll have the opportunity to be completely cured with the elimination of the substrate responsible for sudden death. Actually, we found that in the same pericardial cavity our localised other important cardio genetic disease like long QT syndrome, early repolarisation and right ventricular dysplasia. So we are very close to the final solution of cardio genetic disease associated with sudden death. And this is the first demonstration that the ablation can prolong the life of the patient.

EHRA 23 – Dr Marco Bergonti (Istituto Cardiocentro Ticino, CH) to discuss the key takeaways from the ANTWOORD II Trial.

In this study, 605 heart failure patients undergoing atrial fibrillation ablation were enrolled to receive an ANTWERP Score, which aimed to predict LVEF recovery. 70% of patients were categorised as ‘responders’, patients identified as those who could benefit the most from AF ablation.

Results suggest that responders to the study achieved 10 times fewer deaths and heart transplantations, 10 times fewer heart failure hospitalisations and 8 times more positive left ventricular remodeling.

Questions:

Can you provide a brief overview of the ANTWOORD I trial and explain the research question that ANTWOORD II aims to address?
Could you elaborate on the ANTWERP scoring system and how it is used in the study?
Can you describe the study design, entry criteria, and patient population in detail?
What were the main findings of the study and what conclusions can be drawn from them?
What are the clinical implications of the study?
What are some limitations of the study that should be considered?
What are the next steps?
Recorded from EHRA 2023, Barcelona.

Interviewer: Jonathan McKenna

Editor: Jordan Rance

Transcript

“- My name is Marco Bergonti, I’m working now at Cardiocentro Instituto Ticino in Lugano, and we are here today to discuss our study about the possibility to predict left ventricular function recovery after AF ablation in patients with heart failure. It’s called the ANTWOORD II Study.

ANTWOORD I Overview and ANTWOORD II Aims

So for more than two decades now, many different randomised controlled trials have tried to understand what is the best treatment strategy for patients with heart failure and atrial fibrillation. We try to understand whether rhythm control is better than rate control and ablation is better than medication. But actually, the result of this trial has been conflicting and indeed, there is no clear recommendation from the guidelines on who deserves an ablation. So we try to change a bit the paradigm. We didn’t want to find a treatment that was good for everybody. What we wanted to do was to understand which patients will benefit from AF ablation, and which patients will not benefit from AF ablation, and may benefit from something else. So what we did in the ANTWOORD I study was to identify predictors of left ventricular ejection fraction recovery in this subset of patients and with this predictor, we built a score for individualised assessment.

The ANTWERP Scoring System and How it is Used in the Study

So the ANTWOORD score was built based on the ANTWOORD I where we analysed in a logistic regression analysis and cross-validation the predictors of left ventricular ejection fraction recovery. We were able to find four different categories for different baseline characteristics which were then used to build the score. We want to highlight that it’s a negative score so the higher the point, the lower the possibility of recovery. And specifically, the variable included are the dimension of the left atrium so severe atrial dilation and paroxysmal AF, and this have a point of one, and on the other side we have two points for the presence of known aetiology and for the presence of wide QRS. So overall, putting together these four simple variables we are able to predict, or at least this was the hypothesis of the ANTWOORD I we are able to predict if a patient was going to recuperate its ejection fraction after the ablation, and this was the question that we wanted to confirm with the ANTWOORD II.

Study Design, Entry Criteria and Patient Population

The question that we wanted to answer was is the ANTWOORD score developed in the ANTWOORD I effective in an external validation study? So in order to answer this question, we designed the ANTWOORD II. The way that we thought was to select the same entry criteria, so we selected again the patients with heart failure and impaired ejection fraction, so less than 50% and atrial fibrillation, which were referred for AF ablation, and these patients were followed over one year. So the entry criteria was the presence of AFib and LV dysfunction. These patients all underwent AFib ablation and then after one year, we were able to collect the echographic follow-up, and see who were the responders.

Main Findings

So based on this entry criteria, we were able to identify eight centres in Europe who were providing the patients and overall we were able to collect 605 patients. The follow-up was available for each one of these patients, and at the end of the follow-up, 70% was classified as responders. Then, when we applied the score to our patient population, we saw that indeed the patient with a low score had a very high probability of left ventricular function recovery, while patients with high score had a low probability of recovery. So overall, the general idea of the score was confirmed and indeed, when the score was applied to the general population the predictive value was very good, with a area under the curve of 0.86 and a p-value of less than 0.001.

Clinical Implications

So I think that our study has two important clinical implications. The first clinical implication is the possibility to better discuss the procedure with the patient, so the clinician can really talk with the patient and explain what is our expectation, what is your probability of recovery, and on the other side it’s on a clinical science, clinical research level because if we have a score we are more able to standardise the inclusion criteria to homogenise the population, and to avoid the conflicted finding that we have had so far.

Limitations of the Study

Of course, our study has some limitation. I think the most important limitation is the inclusion of only patients referred for AF ablation. So these are already kind of selected patients with positive characteristics, and ideally what we should do in the future is to apply and redo the same study, but in the overall population of patients with heart failure and AFib and to guide the referral, maybe based even on the score. That’s the first thing, and the second thing, the second important limitation is that we don’t have that many data on heart failure medication that the patient were taking, and, of course, this has an important role in determining the prognosis of this patient, so this should also be a better study in the future.

Next Steps

For what concerns the next step, I think there is a great need to understand how to treat non-responders because we had 70% responders, and in these patients AF ablation works perfectly, these patients are good. The problem is the 30% of non-responders. In this patient we saw a 10 times higher mortality, 10 times higher hospitalisation, and we know that AFib ablation is not really working at least in the way that we are doing it now. So the real question is should we get better with ablation, or ablation is not the strategy, and I think that what’s needed most is a trial among non-responders that should compare different treatment strategies for these patients, hopefully finding a solution.”

EHRA 2023 — Dr Juan Caro Codón (La Paz University Hospital, Madrid, ES) discusses the findings from the TEMPO-HCM study investigating extended ECG monitoring in hypertrophic cardiomyopathy (HCM) patients.

This was a prospective, observational, multicenter trial that included patients with a diagnosis of hypertrophic cardiomyopathy. Investigators compared the rate of clinically relevant arrhythmias within 30 days vs their first 24 hours with an ECG.

Questions:

What is the significance of this study and what are the barriers in treating HCM patients?
Study design, patient cohort, and outcome measures?
Current findings of the study?
How should these findings influence practice and guidelines?
What are the next steps?
Filmed on-site at EHRA 2023, Barcelona.

Editor: Jordan Rance

Transcript

“- Good morning. My name is Juan Caro Codón. I’m a consultant from Hospital Universitario La Paz and we are going to discuss extended ECG monitoring in patients with hypertrophic cardiomyopathy.

Importance of the Study

Well, the TEMPO-HCM study is in fact a call for new research regarding extended ECG in this group of patients because what we have learned from this study is that non-sustained VTs are absolutely prevalent among these population and this raises questions regarding its true ability to discriminate high risk from low-risk patients regarding sudden cardiac death. And we also think that it’s very important because there is a signal here that perhaps is an useful technique to screen for atrial fibrillation in these patients.

Study Design, Patient Cohort and Outcome Measures

We are conducting a prospective observational multicenter registry including patients with diagnosis of hypertrophic cardiomyopathy and we aim for a low-risk score. So we are excluding patients with an already implanted ICD and what we do is to use a dedicated device for ECG monitoring for 30 days and we compare the rate of clinically relevant arrhythmias during 30 days versus the first 24 hours. And what we have found is that the detected incidence of significant arrhythmias is much higher with extended ECG monitoring than with 24 hours monitoring.

Findings to Date

The findings is that there are absolutely more arrhythmias using extended ECG monitoring, and that difference was highly significant, and it was mainly driven by the certainly high prevalence of non-sustained VTs in the low-risk patients with hypertrophic cardiomyopathy during extended ECG monitoring.

Influence of Findings on Practice and Guidelines

I think that we should start considering extended ECG monitoring in patients with hypertrophic cardiomyopathy in order to adequately screen for atrial fibrillation and that we should be very careful when some patients show us in their device some episode of non-sustained VT, we should be very careful to adopt clinical With that information, we should encourage research in this area.

Next Steps

The next obvious steps are to include more patients in our registry. We are trying to aim for a large cohort and we are expecting to continue the follow-up and to report clinical outcomes from these patients, which I think, they will be very, very interesting.”

EHRA 2023 — Investigator, Prof Nicolas Doll (Schuechtermann-Klinik, DE) joins us to discuss the take-home messages from the international prospective randomised multi-centre CEASE-AF study (NCT02695277).

In a randomized controlled trial, 146 patients were enrolled to compare the safety, efficacy, and quality of life outcomes of a combined epicardial surgical plus endocardial catheter technique with a standard endocardial catheter ablation technique for patients with persistent or long-standing persistent atrial fibrillation (AF). The study aims to provide evidence for the effectiveness of a combined surgical and catheter ablation approach as a standalone therapy for AF, contributing to the existing body of research on AF treatment options.

Questions:

1. Unmet needs in persistent and longstanding persistent AF patients?
2. CEASE-AF study and experimental procedure overview?
3. Eligibility criteria and study population of CEASE-AF trial?
4. Key findings of CEASE-AF study?
5. Take-home messages from CEASE-AF findings?
6. Next steps based on CEASE-AF results?

Recorded at EHRA 2023, Barcelona.

ACC.23/WCC – Principal Investigator, Dr Atul Verma (McGill University Health Centre, CA) joins us on-site at ACC’s 2023 Scientific Sessions to outline the findings of the PULSED-AF Trial (Medtronic Cardiac Rhythm and Heart Failure) (NCT04198701).

In this prospective, multicenter study, 421 patients with persistent atrial fibrillation (AF) were treated with the Medtronic PulseSelect Pulsed Field Ablation (PFA) System to study the safety and effectiveness of this device.

Questions:

1. What is the background of this trial?
2. What are benefits of this novel technology?
3. Can you tell us about the study design, eligibility criteria and outcome measures?
4. What are the findings presented at ACC?
5. What are the potential implications of this data on practice and further research?
6. What are the next steps?

For more content from ACC.23/WCC and the Late-breaker Discussion series head to Late-Breaking Science Video Collection.

Recorded on-site at ACC 2023, New Orleans.

Editor: Mirjam Boros

Video production: Oliver Miles, Dan Brent, Mike Knight

Transcript

“- I’m Atul Verma and I’m a cardiologist and cardiac electrophysiologist at McGill University Health Centre in Montreal, Canada.

What is the background of this trial?

This trial is one of the first large global trials evaluating the effectiveness and safety of pulsed field ablation for catheter ablation of atrial fibrillation. Pulsed field ablation is a new technique compared to old techniques for ablation. So in the past when we were ablating tissue, we either had to burn it with radiofrequency or freeze it with cryotherapy, so it was always thermal. Pulsed field ablation is non-thermal, so by exposing the tissue to very high-intensity but very short frequency electrical pulses, we can cause hyperpermeabilisation of the cell membrane and then the cells eventually die.

What are the benefits of this novel technology?

In the past when we were using thermal ablation and we still do, it worked very well for ablating cardiac tissue but there was also a risk of damaging collateral tissues like the phrenic nerve, the oesophagus, and this could result in some very serious complications. With pulsed field ablation. The pre-clinical data in animals has shown that the oesophagus, phrenic nerve, pulmonary veins are very resistant to this type of energy source. So that means, the chance of us causing pulmonary vein stenosis, esophageal damage or phrenic nerve damage is almost zero.

Can you tell us about the study design, eligibility criteria and outcome measures?

This was a dual-cohort prospective clinical trial where we had two cohorts of patients. One was a paroxysmal AF cohort of 150 patients and the other was a persistent AF cohort with 150 patients. In terms of eligibility criteria, all of the patients had to be resistant to antiarrhythmic drugs, so none of the patients were allowed to enter the trial unless they had previously failed antiarrhythmic drugs and all of them had to be undergoing their first ablation procedure for atrial fibrillation. The key findings of the study, first of all from an efficacy point of view, is that the success rates of ablation in both the paroxysmal and the persistent cohorts seemed to be very consistent with the success rates of thermal ablation.

What are the findings presented at ACC?

So, we beat the benchmarks that were established by the clinical trial and found about a 66% success rate in the paroxysmal AF population and a 55% success rate in the persistent AF population. And this was using very rigorous monitoring. So, not only did the patients have intermittent holter monitoring, but they also had transtelephonic monitoring where they had to send us a transmission every week and every time they had symptoms. So, we had more than 12,000 recordings from the patients over the course of this trial. If we look at strictly using a primary efficacy point of freedom from atrial fibrillation, because there were actually multiple ways by which the patients could fail in this trial, then the success rates were more like 70% in the paroxysmal group and 62% in the persistent group. From a safety point of view, this was very, very safe technology. The overall complication rate was less than 1%. It’s one of the smallest complication rates ever reported in a large global catheter ablation trial for atrial fibrillation. And the procedure times were also remarkably short. One of the other advantages of pulsed field ablation is it can be delivered in a very short period of time. And so, the average procedure time was about 60 minutes and this included a 20-minute waiting period. So if you eliminate the waiting period, we’re talking about procedure times much less than an hour.

What are the potential implications of this data on practice and further research?

Well, I think that everyone in the EP community is very excited about pulsed field ablation. Many think that it will completely replace thermal ablation. I’m not sure it’ll happen right away, but I think over the next five years, that is going to happen. Keep in mind that thermal ablation has been around for 25 years and this is the first generation of a pulsed field ablation system. And so, obviously, there’s going to be a lot of refinement that happens over the next five to 10 years and I hope this will lead to even better success rates than what we’re seeing today.

What are the next steps?

So you know, this study I worked on with Medtronic for their pulseselect system. They are developing a number of other pulsed field technologies. So, I think that’s going to be very exciting to see how that all fits together. And I think as a whole, the field is going to really try and see how flexible pulsed field can be by delivering it off of different types of catheters. So, it’s going to be a very, very exciting time.

AHA 22 – Dr Jonathan Piccini (Duke University Medical Center, Durham, US) joins us to discuss the findings of the NOVA Phase II trial (NCT03779841).

NOVA Phase II is a multicenter, randomized, dose-ranging study that aims to find the efficacy and safety of botulinum toxin type A (AGN-151607) (AbbVie) in preventing post-operative atrial fibrillation (POAF) in patients undergoing open-chest cardiac surgery.

The study showed that of botulinum toxin type A (AGN-151607) in patients undergoing cardiac surgery does not seem to reduce the rate of postoperative atrial fibrillation overall.

Questions:

1. What is the reasoning behind this trial?
2. What is the mechanism of action of botulinium Type A?
3. What was the study design and patient population?
4. What are the key results?
5. What are your take-home messages for clinicians?
6. What further research is needed?

Access our full AHA 22 Scientific Coverage here.

Recorded remotely from Durham, 2022.

Interviewer: Jordan Rance, Mirjam Boros
Video Specialist: Tom Green

AHA 22 – CardioNerds Fellow, Dr Saahil A Jumkhawala (Rutgers New Jersey Medical School, US) joins us in this collaboration between the @CardioNerds and Radcliffe Cardiology to interview Prof Hiroyuki Daida (Juntendo Graduate School of Medicine, JP) investigator of the RESPECT EPA trial.

This randomized phase 4 trial looked at Japanese participants to assess whether long-term use of icosapent ethyl 1800 mg daily in addition to statin therapy would be more effective in preventing cardiovascular events in patients with hypercholesterolemia compared to station therapy alone.

Access our full AHA 22 Scientific Coverage here.

Recorded remotely from Tokyo & New Jersey, 2022.

Editor: Mirjam Boros, Jordan Rance
Video Specialist: Oliver Miles

AHA 22 – Dr Kate Wilcox, CardioNerds Academic Fellow (Medical College of Wisconsin, US) joins us in this collaboration between the @CardioNerds and Radcliffe Cardiology to interview Dr Jason Andrade (Vancouver General/Montreal Heart Institute, CA), investigator of the late-breaking PROGRESSIVE-AF trial (NCT05514860).

The aim of PROGRESSIVE-AF is to assess if the initial treatment choice, cryoballoon-based PVI or anti-arrhythmic drug therapy influences AF disease progression, as measured by continuous cardiac monitoring.

The trial showed that first-line ablation was associated with a significantly lower progression to persistent atrial fibrillation when compared to initial anti-arrhythmic drug therapy.

Access our full AHA 22 Scientific Coverage here.

Recorded remotely from Montreal and Wisconsin.

Editor: Mirjam Boros
Video Specialist: Oliver Miles

AHA 22: Dr Paul Wang (Cardiac Arrhythmia Service at Palo Alto, Stanford, CA, US) joins us remotely to discuss the findings of the ENHANCE-AF trial, originally presented at the American Heart Association’s 2022 Scientific Sessions.

ENHANCE AF aimed to evaluate whether a shared-decision-making pathway tool would reduce the risk of stroke as a result of atrial fibrillation when compared to standard care. Over 1000 patients were involved in the trial.

Questions:

What was the reasoning behind this study?
What was the patient population and study design?
What were the key findings?
Based on these findings, how should this study impact practice?
What further study is still needed?

Recorded Remotely from Stanford, 2022.
Interviewer: Jordan Rance
Videography: Dan Brent