Hi, this is Eric Prostowski. Welcome to another episode of EP on EP. With me today is one of the most celebrated electrophysiologists in our field, and he's done wonderful work, Professor Michel Hassegger, who is the chief of electrophysiology at the University of Bordeaux, and also the director of the Lyric Institute for Cardiac Electrophysiology. Welcome to the show, Michel. Welcome, Eric. Thank you for your meeting. So I will have to start out on a personal note. There is an award that's in my name, the Lectureship Award, and you won this year, and I want to tell you how proud I am that you got an award with my name on it. Thank you. Thank you for this honor. Yes. So today we're going to talk about ventricular fibrillation in humans, and you've done some pioneering work in that area. So why don't we talk initially about VF in humans and some of your observations? When we had discovered the role of pulmonary veins in actual fibrillation, we also did the same job in ventricular fibrillation in patients who had multiple episodes of VF. And we looked at the ectopic, isolated and the ectopic-initiating VF, and then when we mapped them, we found that most of the triggers of ventricular fibrillation in humans were associated with Purkinje activity. We assumed that this tissue, representing only 2% of the myocardial mass, it's a very small part, is particularly aggressive in terms of trigger initiation. And beside the Purkinje system, we also have some ectopics coming from the RVOT or LVOT. Now this is interesting because there is a group of patients who died simply because they have a Purkinje excitability, despite everything else, all the myocardium being normal. They died because they have a one millimeter of tissue which is excitable. And this is a significant issue in idiopathic VF. I suppose it's something like 20% of these patients. And there is also a group of patients with myocardial disease, particularly post-myocardial infarction, where most of the VF storm occurring two weeks after, or post-angioplasty or post-surgery, have a storm of VF, and 95% are due to Purkinje excitability. In that case, the life of the patient is of course in danger, and ablation can be a solution. Also quinidine, as shown by this screen, can also work in this particularly Purkinje ectopic with short couple interval. So you've published on this, and I've read your work on this. Let's talk a little bit about how you go after a patient like that. For example, if they are in the midst of having it, you take us what you do. You take them to the lab, and what are you, mapping and ablation. Can you walk us through that? Yeah. This is an important issue, because the ectopics are elusive, transient. We make a lot of effort before going to the lab to document on 12-lead ECG the morphology of this ectopy. Most of the time, it's not a single ectopy, it's multiple ectopy. We have to take time. We say to the nurse, please take a kilometer of papers to have it. This is the mean. We have sometimes all this file, but within the file, we have the 12-lead of 5 or 10 ectopics. And it's sufficient to know where to go with the catheter. So let me stop you there. Do you key on the initiating beat? In other words, the first beat, that's the morphology that you're going after? Yes. Okay. And when you say multiple sources, Michel, let's take an idiopathic, and then we'll talk about post-MI. In an idiopathic, is it diverse areas of the heart, or is it multiple sources usually with one or two fascicles? Yeah, it's one or two fascicles, yeah. Okay. In fact, we said multiple ectopics because when you look carefully, you see some subtle changes, but they come from the same cluster, say, posterior fascicle, anterior fascicle, or moderator band on the right side. Okay, but your experience has been you don't necessarily see moderator band on the right side, plus the anterior fascicle, the posterior. They're sort of localized in an area. So this is a tough question, but normal heart, why? Why the anterior fascicle versus the posterior? What have you found out? Because I know you've been looking at genetics. We have not advanced on that. We have not advanced clinically in experimental. We don't know why this patient, I suppose they have something abnormal in the Purkinje. In terms of genetics, we found three, four, five different genes. They are all different, but they are all involved in the calcium handling. It is a triggered activity, but maybe many different factors can converge to the calcium handling to do that. But we didn't find a specific gene abnormality. So let's take now, you take them to the lab, you've identified these areas. Now you're in the lab. Let's take it two ways. You start to see ectopy. I assume you'll target that for ablation. Yes? Yes. Okay. And will you just put like one lesion there or do you cover an area? Yeah, this is an important question. In fact, when you see a VF starting, the first bit is the triggers, but the second bit is a bit different. The third bit is different. It suggests we have a movement, a progressive movement around. And we use the term of pruning the tree because we suppose it's then moving into the loop of the distal arborization. And if we cut it, we minimize the number of focal activity, but we also minimize the chance of having loop and polymorphic VT and VF. And this works well. I will say typically when we have one spot, we will deliver six, seven applications around just to consolidate by pruning the tree. Right. I do understand pruning the tree. That's a great saying. So now let's take the patient that you've covered the morphology, but now you're in the lab and nothing's happening, okay? The next morning or something. Do you pace and try to mimic? What's your strategy then? Yeah, but this is risky. We do the maximum to avoid to come in the lab without any things, without any identified target. We do all the job before. And the nurse knows that very well. But let's say that patient is having a lot of that at night, but then the next morning you're ready to go to the lab and it's quiet. During the night, we will have the documentation. Right. So let's say you have the documentation, but when you get into the lab, they're quiet. Yeah, but with the documentation, we have the 12 lead with pace mapping, we can identify. So you'll pace map. Yeah. That's what I meant. So you'll pace map and identify those areas. What's your success been pace mapping versus when they're actually in the throes of having ectopy? Have you noticed a difference in success? I would say probably very close because the method is when you have a pace map, say 1.5 centimeters square, we will do multiple application. It's a bit what we do even when we have a spontaneous ectopy. We just do around some additional application. So to use your term, do you do a little more pruning when you have nothing to guide you? Yeah, this is possible. Yeah. In some cases, we are dying without anything. Yeah. What is crucial is to ablate the distal arborization. I mean, the local Purkinje should be less than 10 milliseconds of the ventricle to be sure you are at the distal. If you ablate where you have a time of 15 milliseconds, you will change, you will burn the fascicle and you will modify arborization and activation. So have you found just in your lab and experience that you can give an agent like epinephrine or isopraternal that can bring them out or does that not work? We do that. We do. It depends how is a patient in clinics, but we can use some types of this. Sometimes work. Yeah. It's sometimes. Yeah. I'm so sorry. Go ahead. Yeah. Sometimes it works. But again, the best is to have the documentation before. Yeah. So you really try very hard, even if it's a couple of days of monitoring to make sure you have the sites. Absolutely. You can. That's valuable. Okay. So let's go to the post-MI model. That's always been fascinating to me. There's a lot of people who've looked at that. Any thoughts on why? Why one person? If you looked at, like, just give us a handle, like, there could be a hundred people with no problem. Then you'll have a person who has it. Is there anything you found in your research? No. It's the same question that you had before in idiopathic VF. Why this patient? Right. We do not know. Now, we know that in post-myocardial infarction, the Purkinje is a bit protected by office ischemia, but because it's subendocardial, we suppose that. But it's a bit damaged by some ischemia, and it can react by making some ectopic activity. Okay. So let me summarize, if I can. By the way, your work has been brilliant in this area, but no surprise. That's been your career, and you've helped us. You're becoming the fibrillation king. So is that a VIF? Now VF. But basically, we don't have a good handle, when I say we, the field from what you've worked on of exactly why in a particular patient, post-tumor or even normal heart, it's happening. The key is to make sure you identify the sources, the ectopy that starts it. You'll get them in the lab. At that point, you'll prune your tree. You'll know the source, and then you'll make sure you hit around the source. What would you tell us is your overall success rate, do you think? I would say 85%. 85%? Oh, yeah. Now, when we have a patient with polymorphic from both ventricles, we will try quinidine. This is a suggestion of Sammy Viskin, and I think it's better to try quinidine at least to see before we do that, when we have complex case like that. Yeah, it's 85%. Your work is great. Thank you so much for joining us on the show. It's always great to see you, Michel. Thank you.

ventricular fibrillation

Purkinje activity

genetic factors

calcium handling

mapping and ablating