Is AFib ablation the fifth pillar in heart failure care? CASTLE-HTx


Recorded Aug. 28, 2023. This transcript has been edited for clarity.

John M. Mandrola, MD: I’m here at the European Society of Cardiology meeting, and I’m very excited to have two colleagues whom I met at the Western Atrial Fibrillation Symposium (Western AFib) and who presented the CASTLE-HTx study. This is Christian Sohns and Philipp Sommer, and the CASTLE-HTx study is very exciting.

Before I get into that, I really want to introduce the concept of atrial fibrillation in heart failure. I like to say that there are two big populations of patients with atrial fibrillation, and the vast majority can be treated slowly with reassurance and education. There is a group of patients who have heart failure who, when they develop atrial fibrillation, can degenerate rapidly. The CASTLE-HTx study looked at catheter ablation versus medical therapy in patients with advanced heart failure.

Christian, why don’t you tell us the top-line results and what you found.

CASTLE-HTx key findings

Christian Sohns, MD, PhD: Thanks, first of all, for mentioning this special cohort of patients in end-stage heart failure, which is very important. The endpoint of the study was a composite of death from any cause or left ventricular assist device (LVAD) implantation and heart transplantation. These are very hard, strong clinical endpoints, not the rate of rehospitalization or something like that.

Catheter ablation was superior to medical therapy alone in terms of this composite endpoint. That was driven by cardiovascular death and all-cause mortality, which highlights the fact that you should always consider atrial fibrillation ablation in the end-stage heart failure cohort. The findings were driven by the fact that we saw left ventricular reverse remodeling and the reduction of atrial fibrillation in these patients.

Dr. Mandrola: Tell me about how it came about. It was conducted at your center. Who were these patients?

Philipp Sommer, MD: As one of the biggest centers for heart transplantations all over Europe, with roughly 100 transplants per year, we had many patients being referred to our center with the questions of whether those patients are eligible for a heart transplantation. Not all of the patients in our study were listed for a transplant, but all of them were admitted in that end-stage heart failure status to evaluate their eligibility for transplant.

If we look at the baseline data of those patients, they had an ejection fraction of 29%. They had a 6-minute walk test as a functional capacity parameter of around 300 m. Approximately two thirds of them were New York Heart Association class III and IV, which is significantly worse than what we saw in the previous studies dealing with heart failure patients.

I think overall, if you also look at NT-proBNP levels, this is a really sick patient population where some people might doubt if they should admit and refer those patients for an ablation procedure. Therefore, it’s really interesting and fascinating to see the results.

Dr. Mandrola: I did read in the manuscript, and I heard from you, that these were recruited as outpatients. So they were stable outpatients who were referred to the center for consideration of an LVAD or transplant?

Dr. Sohns: The definition of stability is very difficult in these patients because they have hospital stays, they have a history of drug therapy, and they have a history of interventions also behind them – not atrial fibrillation ablation, but others. I think these patients are referred because the referring physicians are done with the case. They can no longer offer any option to the patients other than surgical treatment, assist device, pump implantation, or transplantation.

If you look at the guidelines, they do not comment on atrial fibrillation ablation in this cohort of patients. Also, they have different recommendations between the American societies and the European societies regarding what is end-stage heart failure and how to treat these patients. Therefore, it was a big benefit of CASTLE-HTx that we randomized a cohort of patients with advanced end-stage heart failure.

How can AFib ablation have such big, early effects?

Dr. Mandrola: These are very clinically significant findings, with large effect sizes and very early separation of the Kaplan-Meier curves. How do you explain how dramatic an effect that is, and how early of an effect?

Dr. Sommer: That’s one of the key questions at the end of the day. I think our job basically was to provide the data and to ensure that the data are clean and that it’s all perfectly done. The interpretation of these data is really kind of difficult, although we do not have the 100% perfect and obvious explanation why the curves separated so early. Our view on that is that we are talking about a pretty fragile patient population, so little differences like having a tachyarrhythmia of 110 day in, day out or being in sinus rhythm of 60 can make a huge difference. That’s obviously pretty early.

The one that remains in tachyarrhythmia will deteriorate and will require an LVAD after a couple of months, and the one that you may keep in sinus rhythm, even with reduced atrial fibrillation burden – not zero, but reduced atrial fibrillation burden – and improved LV function, all of a sudden this patient will still remain on a low level of being stable, but he or she will remain stable and will not require any surgical interventions for the next 1.5-2 years. If we can manage to do this, just postponing the natural cause of the disease, I think that is a great benefit for the patient.

Dr. Mandrola: One of the things that comes up in our center is that I look at some of these patients and think, there’s no way I can put this patient under general anesthetic and do all of this. Your ablation procedure wasn’t that extensive, was it?

Dr. Sohns: On the one hand, no. On the other hand, yes. You need to take into consideration that it has been performed by experienced physicians with experience in heart failure treatment and atrial fibrillation in heart transplantation centers, though it›s not sure that we can transfer these results one-to-one to all other centers in the world.

It is very clear that we have almost no major complications in these patients. We were able to do these ablation procedures without general anesthesia. We have 60% of patients who had pulmonary vein isolation only and 40% of patients who have PVI and additional therapy. We have a procedure duration of almost 90 minutes during radiofrequency ablation.

We have different categories. When you talk about the different patient cohorts, we also see different stages of myocardial tissue damage, which will be part of another publication for sure. It is, in part, surprising how normal some of the atria were despite having a volume of 180 mL, but they had no fibrosis. That was very interesting.


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