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EP on EP Episode 100!: The Future of Arrhythmia Th ...
EP on EP Episode 100!: The Future of Arrhythmia Th ...
EP on EP Episode 100!: The Future of Arrhythmia Therapy
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Video Transcription
Hi, this is Eric Prostowski and welcome to another segment of EP on EP. This isn't just another segment. This is actually my 100th segment and because of that, I invited two incredibly distinguished electrophysiologists in our field and both very good friends of mine for years. I did the first one in the early part of 2008. So with me today are Dr. Silvia Priori, who's the Director of Molecular Cardiology at the University of Pavia and Dr. Douglas Packer, who is a lot of things, but I think I can sum it up by saying clinical electrophysiologist, translational electrophysiologist and a man about the world. So what we're going to do for this special segment is nothing to do with now. What I'd like our two guests to talk about is maybe EP 10 plus years from now. What is it going to look like for all of us? So I'm going to start with Silvia. So Silvia, I'll just give you an example and let you take off. So I have a patient who comes to me with long QT, maybe symptoms, okay, let's give him symptoms to make it easier for you. Am I going to be able to send him to my friendly geneticist and have them lose their syndrome because of some genetic modification? Where are we at with that, genetic cures of syndromes? Yes, we are finally advancing after about 10 years in which the field has been making small steps one after the other. So now there is a broad community of electrophysiologists and clinicians who take care of patients with genetic diseases that have figured out how we can fix the consequences of mutations. So 20 years ago, we were still looking at the patients and measuring the ACG and thinking that that was all the story. Then the genetic came in, but it took a good 15 years up to the point that we are now where knowing the mutation, we can fix the consequences of that mutation. So a mutation can reduce the function of a protein and we can add that protein by expressing the gene that produces that protein and normalizing the situation. On the other side, if instead of being non-functioning, it's functioning too much, we can turn it off and modulate it with RNA. So we really have the tools and the strategies for achieving this result. So your patients in 10 years will get genetic testing. After genetic testing, a genetic strategy will be proposed most likely. So you say it so easily, but my guess is there's a lot more to this than meets the eye, as we say, right? So there has to be some downsides, some worries things? Yeah, definitely there is still a development that we'll have to go ahead before we can really say every single person can get his personalized gene therapy. For example, delivery. Right now, the idea is to use viruses that are not able to replicate because they have been adapted to carry the genetic molecules that will cure the patients or fix the problem of the patient. Those viruses can still do some issue. They can activate immune reactions, for example. In the patient? In the patients. And that is something that we are trying now to work to calm or to use other alternatives like lipid particles that's being used for the vaccine. And I have to say that it's interesting, but the COVID pandemic, that has been a terrible thing that we don't want to see again, but has pushed a lot the gene therapy because after all, the vaccine is an RNA therapy. We have done this trial with millions of persons that now set the stage for this therapy being safe. Well, before I get to Doug, I want to ask you one more thing, because I've read your work on CPVT and I know you've actually gotten into, I think, an animal model, right? So why aren't we treating humans at this point? I mean, is it because of the worry part? Well, we have to treat humans because the mice are engineered to have the same mutations of the humans. And so they serve as a model. Now there are also genetically modified pigs that have the advantage to allow to test the gene therapy in an animal that has the same body size and heart size and in heart that is very similar to the human one. And so I think that that will be another tool to facilitate the translation from animal studies to human studies. So is it fair to say, since we're talking 10 years from now, that this may be a reality in 10 years, do you think? Yeah, I think that the first trial will start probably in a couple of years. You know, the trial for testing and finding the discovery, identifying the problems. But in 10 years, probably we will be more advanced than now and patients will get better treatment. I think it's very exciting stuff. And of course, you're a world leader in this area and we so much appreciate all the work you've done in this area. So now we're going to go from the sublime to Dr. Packer. So Dr. Packer, guess what topic I want you to discuss. It has to do with protons and it has to do with ablation and it all started back in college. So tell us kind of how you came on this idea and really, will we in 10 years be doing a lot of ablations without ever putting catheters in patients? So walk us through that. Eric, the answer is we do it now. The question is how well do we do it now and how well we do it in 10 years from now. So where you started with this is, you know, my undergraduate degree was in chemistry and physical chemistry, so we did a lot with quantum mechanics. And with quantum mechanics, what we really wanted to know is we wanted to know whether or not you could do something with cells. One cell to the other, phosphorylation or something that was triggered or fluorescence or phosphorescence or anything like that. So that was the concept. Now, so sometimes I'm slow, Eric. And it took a little while. Well, can I interrupt you a second? While you were doing that, I was drinking beer in college. So you're not too slow, just to let you know. While you were drinking beer in college, I was drinking Sprite. That's true. And I was drinking Sprite with lime, and so maybe it's a little bit different, but it took me a little bit while. But six or seven years ago, then we looked, and I had some interactions with a couple of different companies and interactions with the people at CERN in Geneva. And the issue was there were protons, and there were helium particles, and there were carbon particles. And so my concept was that you could take one of those particles and you could use the particle to deliver through a gantry. And so what you do is you send it through a synchrotron, and then you send it through a linear accelerator, and then you guide it, you steer it, and you send it into the body. So we started working about, again, six or seven years ago, to do that in animals. And the thing that we found is we could actually ablate atrial tissue, pulmonary veins, ventricular tachycardia. We could induce ventricular tachycardia with myocardial infarctions. And then with that, you could actually deliver the therapy, a particle, one or two millimeters in terms of focus, into that area and eliminate the VT. So that's what we've been working on. But your question's a little bit different. What are we going to be doing in 10 years? Correct. And how do you identify the site in 10 years? What we have to do is we have to get better at identifying exactly where the site is. And you have to do that with looking specifically about the contour of the heart. Where's the LV? Where's the endocardium? Where's the epicardium? And then you have to be able to look at infarction, fibrosis. Let's say you've got a non-ischemic VT, and it's mid-myocardial. You have to find that. You have to identify where that is vis-a-vis the contour of the heart. And then we do simulations. And when we do simulations, we do deliveries based on specific treatment planning. So those are the things that have to happen to a much, much better degree than what we're doing right now. So that when we do that, we know exactly where we're going. We're delivering it into an area that is problematic. And you're not delivering it into an organ at risk. Because see, if you take any large lesion ablation capability, needle electrons, or if you were going to do something like PFA, and you delivered it, let's say your ejection fraction is 10%. You have to be worried about the organs at risk or the residual myocardium at risk. So if you're shooting, and you've already got a 10% ejection fraction, and you hit any area that's residual, you could take somebody and put them into a heart failure that you can't get them out of, 10% going to 5%. So that's something that we have to do. And we have to do better. And we have to be able to do that not only there, but we have to be able to do that in the left atrium. We've done that to some degree, but we have to do that to deal with it as far as atrial fibrillation. We have to deal with it from the standpoint that you've only got so much tissue. And if you fry it too much, then that's not good. But these are, and I don't mean to say this in a, it's going to come out a little wrong, but these are technical issues. And I don't mean to play down technical issues, but my experience in over 40 years in the field is working with really smart people, engineers, developing different things, that you get to a certain point where you take off. So yes, there'll be, in other words, you've spent all this time getting there. My guess is the journey for you in this quest is going to be a lot different in the next eight to 10 years because you're going to figure those things out. And one of my favorite shows has always been Star Trek. And there's this wonderful scene you see sometimes, right? Bones goes in there and the patient's in a enclosed thing and he does some zapping thing and the patient's suddenly well. I think that could be our field 10 years from now. I have no doubt that you'll overcome the technical issues. Yeah. You have to learn difficult things about cells and how they interact before you can get to the point where you can actually deal with a contracting myocardium. You got 10 years, I'm going to give it to you. Well, and we'll come back here in 10 years. And when we do that, then we'll have the same kind of conversation at the end of that conversation. We'll see if we did it or not. So before I end, Sylvia, he opened an interesting point. Your area has really been in the arrhythmic syndromes, but do you think we'll get to a point where you can regenerate cardiac tissue, a patient's had an MI? Are we going to be real far away from that or what do you think? Well, cardiac regeneration has had some obstacle in the development because it has been shown that even if the heart is not replicating, if you really make cardiac cells to go back and becoming more immature to the point that that cell can divide, then you may get tumors, proliferation. Oh, right. So it's that being at the boundaries between how much you have to differentiate the cell. But gene therapy and regenerative medicine are really going in parallel. Yeah. I think this whole thing's very exciting and I want you to work really hard on it before I get there because I'm older than the two of you and I expect you to be there for me in 10 years when I need this, or I hope at least 10 years. This has been a wonderful discussion. I can't thank the both of you more for being on this with me. You're both good friends of mine for years and you've both done so much for the field. So thank you. Thank you very much, both of you. Thank you.
Video Summary
In the 100th segment of EP on EP, Dr. Prostowski discusses the future of electrophysiology with Dr. Silvia Priori and Dr. Douglas Packer. Silvia talks about the progress in genetic cures for syndromes by fixing mutations. However, delivery of the therapy, like using adapted viruses, still poses challenges due to potential immune reactions. Doug discusses using protons for ablations without catheters, targeting specific areas in the heart to avoid damage. He emphasizes the need to improve precision in identifying treatment sites and avoiding harming healthy tissue. Both agree on the exciting advancements in gene therapy and regenerative medicine, foreseeing a promising future in the field.
Keywords
electrophysiology
genetic cures
adapted viruses
proton ablations
regenerative medicine
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