Hi, this is Eric Prystowski, welcome to another segment of EP on EP. It's a delight for me to have back on our show, Dr. Silvia Piori, who's a professor of cardiology at the University of Pavia. So welcome back. Thank you. So the last time we were together, we talked about the long QT syndrome, and today I'm going to ask you a very simple question, which is, in Bugata, how do we decide who gets an ICD? Very simple, right? Very simple, sounds simple, maybe not so simple. So the ICD definitely, let's start from the clear-cut things, it goes in the patients who have survived a cardiac arrest, secondary prevention. The other thing that we know is that the patients with a spontaneous type 1 pattern will also have a syncopal episode in their history, and a syncopal episode, of course, that sounds likely a rhythmic syncopal event, then is a group that is constantly, most of the study, very higher risk than the one without the syncope, so they also have a class 1 indication for the ICD. So let me just stop you briefly, only because in the long QT, I'm sorry, in the hypertrophs, it's been suggested that the syncope was beyond 6 months, it has less of a significance. Is there any time factor for the syncope in Bugata? No, there is nothing that has emerged so far in that direction. Then the question becomes, what about the patients who have a spontaneous pattern, and they don't have the syncope yet, at least. So what do we do in this subgroup? This subgroup is always called a medium risk group, meaning that the lower risk is the group of patients who have the pattern only induced by the drug. So when the pattern is induced by the drug, they are lower risk, and you can be confident in not treating them and keeping them observed, just to monitor if they develop spontaneously, maybe during fever or so, the spontaneous pattern that upgrades them in the risk category. So the real question is what to do when you have a spontaneous pattern and no syncope. You leave the patients alone, you give them quinidine, or you put an ICD. Or you could do an EP study. Right. If you want to consider the ICD, if the patient is ready to take an EP study knowing that if he's inducible he will get an ICD, that is something that you need to wonder if you want to do. Okay, so let's talk about the EP study for a moment. If it's positive, if it's negative, if it's doubles or triples, can you just tell us a little more on that? Yeah, I think that this can use data from a recent study that really demonstrated in a clear-cut way the fact that adding a third premature stimulus doesn't add anything to the predictive value. So if you do your study and you use two premature extra stimuli, you can identify patients that have twice the risk of having a cardiac event at follow-up, and this is good. I think that what is more challenging, though, is the fact that if the patient is not inducible, as physicians we would be inclined to tell the patients, you are not inducible so you can relax, you are a lower-risk patient. This is not correct, we shouldn't tell the patients, because actually data show that the patients that are not inducible do not have a reduced hazard ratio of events. This means that probably the response to programmed electrical stimulation that we label the patient as non-inducible at day zero, maybe three years later has changed, and then the patient has event. So it becomes very difficult also to give an implication of what is the value of programmed electrical stimulation over time when it's negative, and how long you can reassure the patient. And this has to do with the fact that Brugada changes, and patients may be not spontaneous now, spontaneous later on, and probably this means that the substance is changing. So this is a really important point, and I have to tell you, it goes back to some earlier studies I was involved in, like the MUST trial, and at the same time the MADIT was ongoing, and we wondered about should we repeat the test, because the whole trial is based on the initial study, and we know people's disease progressed, right? So you had a negative EPS on day zero, but that doesn't necessarily mean it will be negative two years from now. So are you, I don't mean you're suggesting, but should one take these sort of data to be, you should do it every other year or something, EP study, if you're EP study inclined? Yeah, well, what I think is that several gray area remain around the EP study. We know that even repeated in two days, you know, one day we do it, then we wait, and then we repeat it on the third day, the result may be different. So that is very scared. That's not very good. Our data that we published 10 years ago, but they still, you know, remain very clear in my mind as a question mark. And then really we could repeat it, but how much, how long, what is distance, and what is feasible, and what the patient can take also, because the EP study from the patient side is something that is quite invasive. So I wouldn't say that every two years is realistic to propose to a person 20, 30 years of age that feels unhealthy because he's never had symptoms. We could say now every two years you need to do an EP study, and there is no evidence. So maybe we should explore whether repeating it five years might be better. Even if, you know, with an experience of over 3,000 cases of Brugada followed in our database, we have had patients that came to the visit, everything seemed normal, and then one month later from non-spontaneous pattern, they had a cardiac arrest. So how fast the transition could be, you know, and how the substrate is actually deeply influenced by stochastic factors, that means, you know, environmental factors, or just development of the disease that we still do not understand what is the cause of the disease. So here's the problem for a clinician, though. You're a wonderful scientist, and I know that you also treat patients, so you'll appreciate where I'm coming from as a clinician. So I see a patient in the office who's totally asymptomatic, someone does an ECG for whatever reason, and it looks like Brugada, they get sent to me. Zero history of anything, 52 years old, whatever, male, of course. What do you tell them? So I'll be frank with you. After I've reviewed all the literature, including your wonderful studies, I don't do much. I mean, except tell them to avoid certain things, like beavers and all the common things. But I don't know that I'm doing the right thing. I guess I could do an EP study, but if it's negative, it hasn't helped me. If it's positive, I guess you could say, okay, put the ICD in. I get that. But I also know that it's not always reproducible, and what about next year? And then I understand there's some maybe use for quinidine, but I'm still trying to figure this out. So what's the latest on quinidine? The latest on quinidine is that it's pretty clear that the high dose that has been used so far in most of the studies has led to 37, 38, to 50% of patients having to discontinue the treatment for side effects. So we have tried a lower dose, half of the dose, 450 milligram as an average dose of hydroquinidine, and we have demonstrated in a study that just came out in Circulation EP that these patients had a reduction of events as compared to the cost. Were these people who had previous events? This patient, of course, when you do a study, you need to do it in patients who had previous events. Otherwise, you cannot say it's useful, or you need to follow them for 10 years before you can say that. So these are people who had an event and you treated half quinidine, half not, it was randomized, and the group with quinidine had less effects. So basically, I think that we are going in a direction that could be, but is not in the guidelines yet, that non-spontaneous pattern induced only with flecainide or ashmaline, you do nothing. You observe when they develop the spontaneous. The spontaneous may get the quinidine, and the spontaneous plus syncope may get the ICD. That middle statement, that the spontaneous without syncope benefits of quinidine, is something that we are currently testing. So I need to rethink what I'm doing. We need to come back in a few years and see what's going on. It's interesting because for a while, I bought into the whole EPS, you know, I mean from the Bugata papers and stuff, and then I started seeing other data come along and it sort of forced me in the other direction. And even in my own group of 15 electrophysiologists, there is differences of how to approach it, which I think is fair based on what you're telling us today. It is fair. I think that the fact that it seems also in this more recent study that there is an increase in the risk in the one inducible, you know, it's okay. You may want to go in that direction, but still, you know, the one that are non-inducible, maybe instead of saying you're non-inducible, you don't need to do anything, maybe there would benefit of the quinidine. So two quick things before we finish up. One is age of presentation. So are you a little more aggressive if it's, say, it's a younger patient, or does it really age of presentation not matter? I don't think that we have enough numbers to say the age role, because in the pediatric population, pediatric adolescent, young adults, it's very rare that they have manifestation and cardiac arrest. It occurs, but it's rare, and so the numbers are not adequate to say whether early manifestation means worse outcome over follow-up, so we need to wait a little bit on that. Well, this has been a wonderful discussion, as always. So I'm going to give you one last thing you're going to tell me. My 52-year-old patient now comes to you, because he has just an ECG done. What would you do? I understand all the stuff you said, but what would say to me? Yes, a Brugada pattern, of course. That's it. Brugada pattern, nothing else. Came to see me a couple months ago, but I wasn't there that day, so Sylvia Piori took care of my... I gave you the money, of course. What would you do? What would you... Really, I mean, I understand there's no one thing to do. What would you do? Yeah. I explain the fact that having a Brugada pattern is not a disease. I explain to my patient that having a Brugada pattern is a risk factor for predisposition to cardiac arrest. And a predisposition, you can think of it as a predisposition to cardiac arrest. I explain to my patient that having a Brugada pattern is not a disease. I explain to my patient that having a Brugada pattern is a risk factor for predisposition to cardiac arrest. I explain to my patient that having a Brugada pattern is a risk factor for predisposition to cardiac arrest. And a predisposition, you can handle by doing nothing or by taking some measure. Gotcha. Taking some measures can be taking quinidine, doing a programmed electrical stimulation and see if you need a defibrillator. If you are inducible, in that case, you may still need to be protected with quinidine. And then discuss with the patient the pro and cons, the probability that the study becomes positive if he has a physician who does two or three premature beats. And then we try to go in the direction of which is the threshold of tolerance of risk of dying suddenly of the individual patient. Some people don't want the defibrillator, absolutely they refuse it. Some people don't want the study, some people don't want the drugs. So where we don't have data or where the data seems to be either this option or that option, I think I discuss this with the patient and try to get to the solution that is more suitable to the individual patient. I like your approach. Thank you. So as always, it's wonderful having you on the show.

implantable cardioverter-defibrillator

Brugada syndrome

decision-making process

cardiac arrest

spontaneous pattern