Melanie Cole, MS (Host): Welcome to the podcast series from the specialists at Penn Medicine. I'm Melanie Cole. And today, our discussion focuses on pulsed field ablation, or PFA. Joining me is Dr. Matthew Bernabei. He's an electrophysiologist and the Section Chief of Electrophysiology and Pacing at Penn Medicine Lancaster General Hospital.

Dr. Bernabei, thank you so much for being with us today. And before we discuss our topic, give us a brief overview of the mechanisms of AFib itself and do we fully understand the origin of AFib?

Matthew Bernabei, MD: Melanie, it's a pleasure to be with you. And it is an important and ever-evolving question. Candidly, I think we're all still a little bit humbled every day by how much we still have to learn about atrial fibrillation. But that being said, we are certainly light years ahead of where we used to be. And it's a story that's actually evolved over a very long period of time, almost at least 70 plus years.

A physician named Gordon Moe back in the '50s and '60s really started to get his arms around this. He was in upstate New York and started describing what at the time was called a multiple wavelet theory, which was basically depending upon a form of re-entry where the electricity kind of gets caught in a loop in the left atrium. And then, this advanced at Washington University in the '70s and '80s and early '90s with a guy named James Cox, who was a CT surgeon, who figured out that by incising the left atrium and then sewing it back together, you could disrupt atrial fibrillation.

But the most pertinent revelation came in the seminal work of two French electrophysiologists, Michel Haïssaguerre and Pierre Jaïs, who in 1998 published in the New England Journal their findings, that atrial fibrillation basically emanated from muscular sleeves around the pulmonary veins. And these pulmonary veins feed back into the left atrium. And if targeted for ablation we often use the term pulmonary vein isolation— as the cornerstone of our AFib ablation strategy, we can definitely impact AFib overall. And that was really speaking to the triggers or drivers of atrial fibrillation, the initiating source, which our French colleagues felt was greater than 90% of the explanation for what triggered or got AFib going.

But it's really been in the subsequent years, in the early 2000s, where we really started to come to understand that the substrate is very important in the perpetuation and maintenance of AFib, hearkening back to what they figured out in the '50s and '60s. So, we often talk about paroxysmal atrial fibrillation, where it's primarily triggered by these pulmonary veins firing predominantly.

One of the most salient aspects of AFib is that it is so heterogeneous. It's so different in everybody, even at a cellular level. A famous saying that you may have heard is AFib begets AFib.

And that idea started circulating in the early 2000s when we realized that the more AFib you have, the more structural changes occur in the antrum of the atrium, often fibrosis, among other things, that then supports and perpetuates AFib moving forward to the point where it tends to become more persistent, and if left unchecked, eventually chronic or permanent.

So, looking across many decades, yes, the pulmonary veins are often implicated as the source or origin of AFib. But that said, there's multiple other elements to this and that's where ablation has really pivoted over many years now to allow some flexibility in targeting not just the pulmonary veins but potentially any other areas, in the left atrium most commonly, that may also benefit from targeted ablation.

Host: Well, thank you for that, Dr. Bernabei, and it is such a prevalent condition. Tell us a little bit about pulsed field ablation or PFA. How does it work? And how is it different from what we've known as traditional radiofrequency ablation and cryotherapy, which have been standards of care in the last bunch of years.

Matthew Bernabei, MD: So, you're indeed right on the money. Radiofrequency ablation really has been the mainstay for decades. Cryotherapy or cryoballoon had some momentum several years ago, because it allowed us to be a little faster and to cover a larger swath of atrium with less applications and less point-by-point ablation, which is the hallmark of radiofrequency ablation.

But I think most of us agree that radiofrequency had iterative evolutionary changes and improvements, but really never seemed to move the needle as far as allowing us to cover a lot more land in a shorter period of time.

And so, one of the, biggest changes here has been in the efficiency afforded by PFA. Data suggests that pulsed-field ablation, does not rely on thermal injury like radiofrequency or cryotherapy. When we're doing an ablation, we're trying to achieve transmurality, which means a lesion through the entirety of that wall. when you're using heat, it's a delicate balancing act, right? Because if you don't use enough heat, you're not getting enough damage through the muscle. If you use too much, you put other structures at risk, whether it's behind or adjacent to what you're ablating.

So, radiofrequency has always had somewhat of a limitation because of that biophysical attribute, same cryotherapy. Pulsed-field ablation is basically using an electrical field to denude and compromise the cell membrane. And its most interesting attribute is that it tends to be cardio-selective, so it's really only affecting cells in the myocardium, as opposed to nerves, for example, or the esophagus. Atrioesophageal fistula is one of the most feared complications of radiofrequency ablation, and even with cryoablation. So, it has proven to be, in short, safer. And that has allowed us, I think, a lot more confidence in applying pulsed-field ablation with greater effect. Safety first and foremost has improved. And that's been a big sea change, I think, for us, and I think probably why PFA is garnering a lot of attention.

Host: So, would you say that that's what appeals most about PFA to electrophysiologists, that it's more comprehensive in its effects, and speak a little bit about patients and the unique benefits for them versus the traditional modalities.

Matthew Bernabei, MD: So, it's a great question, when you look at the patient population, The evolutionary changes in ablation technology have come with data suggesting, mortality benefit, like the CASTLE-HTx trial recently, or EAST-AFNET, some endpoints suggesting that we probably should be even more aggressive in more patients with ablation than we would have thought about previously.

While the technology is allowing you to be more efficient and to do the procedure in a more safe manner, at the same time, a body of patients that we should be considering for ablation continues to expand.. So for example, there was a time not that many years ago when we thought patients over 75 years of age, maybe 80, that the effects of the atrial had affected or impacted the left atrium to such a degree that it was an insurmountable problem; and therefore, we abandoned rhythm control options, in this case, ablation.

That has really moved the needle. And, it's causing us to reflect and come back to these patients. Where we're thinking, well, the procedure's safer and it doesn't hurt to take shot at this at least once with this new modality.

I think you will see "the indication of ablation" continuing to evolve, if not just because the data has suggested that we should probably be more aggressive even in patients that were heading towards left ventricular assist devices and really end-stage heart failure, which was the patient population in  CASTLE-HTx

Also when the tools that enable you to do this prove safer and more efficient, the bar gets lower; and therefore, a larger swath of population and demographic of patients can be considered.

Host: Dr. Bernabei, as you're expanding the patient population that's suited for AFib ablation, what's the patient experience like? Are there any perceptible differences for the patient with regard to the procedural experience compared with traditional RFA? Tell us about that.

Matthew Bernabei, MD: Anecdotally, in our experience. I think radiofrequency, specifically in heat, one of the more common things we would hear or see was some pericarditis or inflammation after the ablation, some chest discomfort. We don't seem to get that with pulsed-field.

Otherwise, the experience in and of itself, I think, is almost identical by and large. I mean, there are some subtle changes. For example, when you're doing a procedure that is so much more efficient and really is a procedural time much shorter by comparison, little things that maybe we don't think about all the time, can prove important.

For example, some institutions when they did radiofrequency were using Foley catheters because the procedures tended to be a little bit longer. And now that you have a much shorter procedure, you don't really need worry about Foleys and urinary issues just anecdotally. one of the more common "complications" in days of old was a UTI.

But by and large, I think the experience for patients is pretty close. If it had a traditional ablation previously, I think it's going to be probably somewhat similar in that we still go through the femoral veins. Patients are often supine and bedrest for at least one to two hours afterwards, or more at some institutions, but by and large, similar.

Host: Doctor, I'd like you to speak to other surgeons for a minute as far as the learning curve since it's relatively new on the scene. Give us any technical considerations. You've mentioned a few, but just expand a bit. Is it done as outpatient? Are there learning curves involved? Tell us just a little bit about the procedure itself for other surgeons.

Matthew Bernabei, MD: Fair question. So, learning curve on this type of device, I think most would find to be extraordinarily user-friendly  Radio frequency and point-by-point ablation tend to require and demand more experience and a greater evolved skill set.

There's a couple of companies now in this space, but the most commonly used is FARAPULSE by Boston Scientific, which we happen to use. And, you know, it depends on your prior experience. For example, I did use a cryoballoon earlier in my career as well as radiofrequency, and having that optionality was always I thought a plus. But having some experience with a cryoballoon, did translate into my comfort with this system. So, I think it depends on your experience and maybe training and biases in practice. But I think most would agree that this energy source or modality is very easily picked up and adopted.

And yes, to answer your other question, for us, it has always been, an outpatient procedure.

As far as the experience goes, I often joke with our patients that it feels like getting on a plane for a short flight in the air, it takes longer to get on the plane and off the plane than you're actually in the air. In this case, the anesthesia often proves to be the rate-limiting step for us. It takes, you know, half an hour to an hour to get asleep, half an hour to wake up, but the actual work itself is anywhere from 20 to 30 or 40 minutes on average.

Host: That's a great analogy, Dr. Bernabei. And as we get ready to wrap up, I'd like you to speak about key messages that you would like other referring physicians to know about PFA at Penn Medicine, what you're doing there, and why this is so important now.

Matthew Bernabei, MD: I think the conversation, but also the decision-making has evolved and changed. And what I mean by that is there was a time in my early career where ablation was really considered a secondary therapy. It started with anti-arrhythmic drugs and medications. And then if that wasn't working or there was a side effect, then we would pivot and consider ablation.

We're at the point now where ablation is really, I think, rapidly becoming, the primary treatment option. And the population of patients that I talked about earlier has expanded exponentially. And so, I guess I would just encourage our colleagues when they're seeing patients with AFib to consult us, pick up the phone. My colleagues across the Penn Medicine system are more than happy to expound on AFib because this is all we do every day, all day. It's something we think about all day and are quite passionate about and spend a lot of time trying to help patients navigate.

So, I think, bottom line, yes, we're becoming more and more aggressive and more and more bullish on ablation. So, any questions or thoughts, please reach out and we're happy to see these patients and try to figure out what the next best step is.

Host: Thank you so much for joining us and sharing your incredible expertise today. To refer your patient to Dr. Bernabei at Penn Medicine, please call our 24/7 provider-only line at 877-937-PENN, or you can submit your referral via our secure online referral form by visiting our website at pennmedicine.org/referyourpatient. That concludes this episode from the specialists at Penn Medicine. I'm Melanie Cole.