Syndrome. Cecilia Gonzalez-Corcea is the Director of Pediatric and Congenital Electrophysiology at the Center Hospital, University of St. Justine in Montreal, Canada. And Georgia Sarqueya-Brigada is the Head of Arrhythmias at the San Juan de Dieu Barcelona Children's Hospital. Sorry if I – and my co-chair is Dr. Sammy Viscan. We have encouraged our debaters today to take an alternative approach. So instead of a traditional pro-con rebuttal sequence, they have put together a single presentation where they will debate a series of different patients about provocation testing with Brigada. So I will turn it over to them at this time. Thank you. So in the name of George and myself, I thank the organizers for this possibility to be here with you today. And I want to start by... So I want to start by introducing, in a way, my co-presenter, Georgia, who has a little bit of, we have been doing a parallel paths in our lives. When she was working in Barcelona, I was working in Brussels. And we have both developed this interest in these children that were dying suddenly. And in many ways, in our past and in our lives, we have had children ourselves at the same age. We have been training. We have become directors of our institutions. So for me, it is a pleasure today to be presenting this debate with her. And more than pros and cons, it will be our shared experience of what we have seen with our patients. So Georgia, great to do this with you today. Thank you. So to start with, I want to give a little bit of a background of Brugada syndrome and go back to a common ground for definition. And coming down to the Shanghai scope criteria and the rarity of the type 1 ECG in patients with Brugada syndrome. And the need that, through the Shanghai criteria, we have reached about the requirement of having criteria that go outside the type 1 ECG that can give us a diagnosis of probable or definitive Brugada syndrome. And because this pattern of type 1 ECG that is high risk is also intermittent and has low prevalence, especially in young children or in the young population, we have to use sodium channel blocker drugs to be able to unmask this type 1 ECG. And depending on where we live and where we're located around the world and the availability of the products, we can use either ashmaline, flaconide, prokinamide, rarely plus econide. It's important when we do the provocative test that we are recording ECG continuously and that we move and place some of the electrodes in what we call the high precordial leads above the position of V1 and V2. And the objective of the provocative test is to block the sodium channel that is already dysfunctional and promote this ECG pattern that is called ECG pattern Brugada type 1. And it has certain requirements. There must be a J point elevation of more than 0.2 millivolts with a coped ST elevation and a T wave inversion. And this G point ideally has to be measured in a limb lead and, if unavailable, in a lateral chest lead. So we have here a very clear type 1 pattern. And again, a negative ECG which has some degree of type 1 of J point elevation, but that is not diagnosed with not fulfilling criteria for Brugada syndrome. Apart from that, a positive sodium channel blocker test requires that this type 1 pattern is present in at least one right precordial lead, ideally V1 and V2. And that the leads are either positioned in the standard wave or in the high intercostal space, V2 and V3. So having said this as a base for our talk today, let's set our objectives with decisions we are going to explore into the provocative test indication through a multi-generational family case. And we are asking the audience to vote and participate. And this can be done by raising hands, so please do not be shy. We are going to present a large family. And we are going to move through the different family members and ask you to vote when to do a provocative test. So every story starts with a problem. And I will introduce here our first case in the family, the index case. This is a 15-year-old male that had, at initial presentation, an atrial flutter that progressed then to a chaotic disorganized atrial tachycardia. He had a remarkable past medical history. And he had a positive history of a father with an atrial tachycardia. This is the presenting ECG where we see the flutter waves when there's some degree of heavy conduction in the right side and the left side of the ECG. And following with termination of the tachycardia, we had this ECG with the B1 and B2 position in the usual location. So there's some degree of intraventricular conduction delay, but this is a non-diagnostic ECG, even if AVR looks a little bit weird. Look what happened when the lids were placed in a high lid position. This unmasks, just by changing the location of the lids, this unmasks the clearly diagnostic type 1 ECG pattern. This patient, after this first episode, did well, but presented a couple of weeks later with complete AV block following an allergic episode. So we have the ECG where there is sinus rhythm with AV dissociation and some junctional scape mechanism. So he required temporary pacing. He incidentally recovered the conduction with some high degree AV block and finally recovered conduction completely. Because he had an EP study, he had a flutter ablation, and the HV was normal, we decided not to implant a pacemaker at this point, but we did give him an internal loop recorder. Following the next three months, we received the pathogenic SN5A variant, and the loop recorder showed us some episodes of wide complex tachycardia. He did record in the meantime intermittent AV block, so we ended by putting him a dual-chamber ICD and treated him with beta blockers for the atrial arrhythmias that he was having intermittently. So we close here the case of our problem, a young boy presenting with atrial arrhythmias, ventricular arrhythmias, a pathogenic mutation, and a type 1 ECG. Clearly, by all the criteria, a Brugada syndrome with phenotypic and genotypic expression. Let's now go to the family. So here we have our family tree. He's the patient zero, the proven. And we learn first, looking when we get the genetic test, and we start looking in depth into the family details, we learn that his grandfather, who had been born in 1945, had had sudden cardiac death during sleep at age 54. This is the only clue that we have up to now. And now we have to start with this detective task that is screening all the family members. And this is when we will jump to discussing the first patient that we will take in charge. This is Paul. It's his father. He was born in 1970. He's asymptomatic, in terms of no syncope. He did have atrial arrhythmias, and is positive for the SCM5A mutation. This is his ECG. So we have a right bundle branch block, but we also have a bifascicular block with a negative QRS in ABF. So in summary, 55-year-old male, CNF5 positive, carrier of the pathogenic family variant, clinical history of atrial arrhythmias, ECG finding with bifascicular block. He's the father of the proven, but he's also the son of somebody that died suddenly. But we don't have an autopsy. We don't have a genetic test. Who would test with a provocative test this individual, Paul? Time to vote. OK, so we are 85 people in this room who have a chance to vote. Sorry, but our chairman are not allowed to vote. So just who would perform a provocative test here? Raise up. 28. OK, so who would not? Who would not do a provocative test? You're not allowed to vote. OK, so 51. So clearly, there is more people thinking that we should, or it's not recommended to perform a provocative test here. So the idea would be, the rationale for that would be that we have a pathogenic mutation in this patient. We have atrial arrhythmias that can go with the syndrome. But we have had no positive ECG type 1 anywhere, right? So how come we put a diagnosis of Brugada syndrome here if we have not seen that pattern anyway? So that's one of the first things that come into our mind when thinking about, when should we perform a provocative test? A sodium channel mutation carrier is not a diagnostic for Brugada syndrome. And to perform a diagnostic of Brugada syndrome, it's clearly needed to have some type 1 Brugada pattern. So even though we are scared to perform that, it's someone who has a not normal ECG, someone who carries a sodium channel mutation, and clearly has a son with Brugada, and a father suspicious of having had something related to Brugada. It's true that sometimes we need to think a little bit different. I'm not suggesting that here there is a right or wrong. But sometimes we are in the middle of nowhere that we need to have clear diagnostic tools in order to say someone that you have Brugada. The good thing is that he has atrial arrhythmias. He hasn't had ventricular arrhythmias, syncope, or something that made us think that he might be in a high risk situation. But anyway, there's nothing that says that clearly he has Brugada. He's a gene carrier of something, but he has not clearly had an ECG with Brugada, right? OK. That is right, Nasir. Now I will come to the other side. There's a minimal risk of performing a provocative test in somebody that has already atrial arrhythmias. We know that they're predictors for bad response for a risk of ventricular fibrillation during the provocative test. And he also has conduction delay. He has a bifascicular block. So there's some risk to perform it. But the most important thing is that even if the test is positive, we don't have data to say if his risk is higher or lower. So it would give us a certain fulfillment for having done something, but we don't really know how that correlates in real life with his individual risk. Absolutely. So I think that we could move forward for the next patient. Whoops. Oh, OK. This was the one. OK. So next patient, it's the brother of our proven case. He's 17 now. And he has been asymptomatic. And in fact, he does not want to be genetically screened because he wants to go to the army. And he does not want to have a genetic test that says he might be carrying something. And he's a little bit, OK, let's say, reluctant to have a further test. But of course, he does not want to die. And we screened him, and we have this ECG that what we see, and I cannot do the pointer, but what we see, there is a slightly prolonged or up to upper normal limit of the PR interval, which is very important. Always check PR intervals. This is a very important thing to do when we are dealing with Brugada. And then we have this incomplete bundle branch block with this, I would say, a slightly elevated ST segment in right precordial leads. So here, we have this guy who we don't know if he's genetically positive. He's absolutely asymptomatic. He has this mild ST segment elevation, but he has a strong family history within this family, within this history. So who would perform a provocative test? Or who would suggest to do a provocative test? Please raise your hands. OK. So who would not perform it? OK. This is nice. So half and half, I would say. OK. We are in front of another dilemma here, which will be when we perform a test, it's because we want to think what's going on, on if there is something that's going to change after our result. So if he turns positive, which are going to be our considerations, if he turns negative, what are we going to say? Would we be, how you say, discarded for army? I don't know, because I don't work in this field. And we know that every country has different legislation. For example, you can have a Brugada and be in the army in Spain. Of course, not if you are carrying an ICD. But probably it's different in the United States. So this can be something that we can have a diagnose and then there are going to be certain consequences for his job. There's going to be a diagnose, but there are going to be certain consequences for his life as well. So this is something to have into account that how important it is to have a diagnostic and which are the consequences of that diagnostic. And here we come to the second point, that up to now, we know that the genetic test has a lot of influence in your insurance in the possibility of doing certain kind of jobs, but the provocative test does not. So doing a provocative test may give us a reassurance if he has not type 1 ECG, but we are not certain of what that means without having the genetic to correlate with. So this is a dilemma. And I don't think that we can strongly be pro or con this. In this case, what I would do is discuss with the patient and see what he feels, where he's standing, what are his beliefs, and go on from there. I don't think that this is a right or wrong scenario. Great. So let's... Yeah, so we have then Vincent. Vincent is our case number three. He's the uncle of our proband, of Hugo, and the brother of Paul, Hugo's father. And he's born in 1965. He's completely asymptomatic, and he tests for the test, and he's negative. This is bad. Look at his ECG. Oh, sorry. Right bundle branch block, not very nice. We can even say that there's some QRS fragmentation at right bundle. So let's go to the next one. 16-year-old male, SCN5 negative, asymptomatic. This bundle branch block, the uncle of the proband, and of course, his father also died suddenly during sleep. So who is testing this young man or this patient? Okay, not many. Who would not test? Okay, so here, I think the dilemma is that you are in front of a sodium channel, also mutation negative, and that's why you are reluctant to test, or maybe because he's asymptomatic, and you don't test an ECG, right? So in this point, we start thinking about the polygenicity of Brugada syndrome. This concept that says that, of course, we would love to have one gene, one disease, and one disease, one gene, and our life would be much easier, but I have to say that probably half of the sessions that are being held in this Congress would not exist, right, but polygenicity, and we know it's a very important point in Brugada syndrome, and even though we are very attached to the fact that we have a pathogenic genetic variant there which explains our proband case, we really need to be careful, and sometimes that there might be other factors that present with at least a little bit of controversy and if you have an ECG that you don't like or an ECG that really it's very suspicious to you and you have any type of doubt, even genetics come negative, you may consider performing certain tests, and remember, sometimes labs bring you with a wrong result. It's not a matter of being negative. Maybe you were not negative and the sample was not well taken or the report was bad, so if there's something that does not match in your whole picture, maybe, then you have to rethink, go back, and maybe think, okay, let's think in that case as if I don't have the genetic test and don't just attach to the genetic condition. I will say that I would not test this patient, but I have also to share with you that we have had families in which exactly the same scenario where somebody that suddenly has a SN5A mutation and the first-degree family member that is negative for the mutation has sudden cardiac death, so this has happened and it's sometimes unexplainable, and that would be the only scenario where you could eventually, with this abnormal ECG, consider testing this patient. When we meet Vincent, he tell us that by his father, he learned that before his father was born, there was another brother that died suddenly during sleep as an infant in 1944, so this adds another family member with sudden cardiac death very early as an infant. So then we meet Charles. He's our fourth family member, and he was born in 1980, and he's a transgender man. He was born female, and now he's doing hormonal transition into male, so receiving hormones, testosterone at high doses, and he has had a history when he was 33 of a febrile syncope. He's spending genetics, and we won't have them because insurance with all these health conditions is not accepting to have genetics on him, and he's the son of someone that died during a car accident when he was 44, and he had had repetitive syncope, so there is another branch of this family with a very kind of important information there that gives us a little bit more information in the overall family. So this is Charles ECG. We see this right bundle branch block. We see that the PR is not prolonged here, and there is no ST segment elevation, but it's true that there are certain in AVR there might be something like a little bit of a slurry thing there. So in this case, 45-year-old transgender man with an unknown genetic context with one febrile syncope, and with this ECG and this family history that we already know, who would perform a provocative test? Okay. Who would not perform a provocative test? Okay. Okay, so I think this is something that adds more information to what we know about brugada, which is fever, first of all. Whatever happens with fever in a brugada context family, that it's something that scares us like times three or four, right? And second thing is hormonal status. So if we are receiving overload of a hormone called testosterone that we know, and we have seen over the years that have a good impact on sodium channel and the performing of a sodium channel, there is something that we should take into account and how this would affect. And second and most important for Charles is can I keep taking it? I am safe taking it. I'm 44, so I would say that, or 45, I'm just about to leave this kind of high risk period, but you know, you are 40 something, 40 something man, brugada, hormones, this is like the hot moment, right? Should I keep taking that medication which can put me in risk? So this is another point of information that to take into account. So let's now move to the next patient that we have. This is Ben, and this is something that sometimes we see. He was born, he's Charles' brother. Again, we don't know if this branch of the family has the variant or not, through the father that has repetitive syncope, born in 1983, he has leukemia. He's going through treatment with leukemia and has a drug-induced type 1 ECG. The oncologist comes to see us. We cannot see the type 1 ECG. We don't know if it's real or not, but this is his ECG immediately after finishing his chemotherapy. So we don't, the oncologist is asking us, can we continue with the therapy or not? Is there any risk to give them medications that could potentially block the channel? And there's no time to wait for the genetic test. He needs the treatment. So who would test Ben, 48, 42 years old, mutation unknown, asymptomatic, but apparently with a type 1 ECG, but a very abnormal ECG? Who would test this patient to tell the oncologist proceed, move forward? There's no type 1 ECG. You can give whatever drug you want. Who would not test? Okay. What if we have a positive genetic test? I mean, what are the chances that a leukemia kills you if you don't receive treatment compared to the chances of having a brugada and receiving something that makes your ECG look uglier? Right. So that's a question that sometimes arrives that with a patient with brugada or maybe brugada or confirmed brugada, that suddenly someone wants to put an antipsychotic drug, antidepressant drug, because has a psychotic event and they are very worried about the brugada. I'm very worried about the psychotic event. So sometimes we just need to give medication, which is in the list of those things that we should not give, should not give, but we have to balance which are the risks. And here, even though we could discuss if this patient needs a provocative test to rule out if he's really brugada or not, is it going to change anything? Are we going to stop or just delay the administration of chemotherapy for his leukemia just because we want to have a diagnostic? Is it going to change anything? So sometimes we really need to focus which are the real risks for our patients. And that makes us... And we are going to be the ones saying, yeah, you can give this medication. Well, yes, probably it enlarges the QRS, but so what? Right? Sami, would you test this patient? No. She has not tested any patient. That's why I'm asking him. Because we need to have this also. So I think that there's common sense and agreement in this. Now let's look at the children, Sergio, of the family. OK, so she's Olivia, and she's 12. She's asymptomatic, and she has been... The genetic test came positive on her. OK, so this is the ECG from Olivia. And the question is 13-year-old, adolescence, genetic positive, asymptomatic. ECG is, I would say, normal. Who would perform a provocative test now? OK, who would perform a provocative test in three or four years? OK. Who would not perform a provocative test at all? OK. So here comes the clear case, and I think that's nice, that, first of all, thinking about performing a provocative test before poverty in an asymptomatic patient, really, there's no... Or at least this would be one of the situations I would never perform a provocative test. And I do a lot of provocative tests, OK? So I had to defend the cons about provocative tests, and I struggled with that, because I was like... I called her and said, I don't know how I'm going to do the cons on provocative tests, but this is one situation. In a pre-adolescent girl with... Forget about genetics. With a family history of brugada, normally ECG, asymptomatic, there's no point in that. Whatever it comes, even if it's negative, I'm going to repeat after poverty. So why performing it before poverty, OK? Second discussion here would be, would this patient ever need a provocative test by being genetically positive? And this is, once again, the thing that comes on the table. Like, would we perform provocative tests in a genetically positive, asymptomatic, normally ECG patient at some point in life, OK? We also have to consider, in a way, the gender, no? Being a female, we know that she may not have the same transition and hormonal risk during adolescence. So I think that there's overall agreement. Let's go to Olivia's sister, and this is our last case to discuss today. This is Lucy. She was born in 2016. She had syncope recently, but she's SN5A negative. This is her ECG. So it's a normal child ECG with a T-wave inversion in LITV1 and a funny transition with a bimodal T-wave in V2. But overall, a normal ECG for her age. So 8-year-old girl, SN5A negative. She presented with severe breath-conditioning spells, some with seizures when she was an infant, but they lasted longer than usual. She had these breath-conditioning spells until she was 6 years old, and she has now a normal ECG, but she had a syncope coming out of a hot shower last week. Who would test this patient? Who would not test her? So the thing is how... OK, let's do it more difficult. Fibrile syncope. OK, forget about the hot shower. You know, we all think basil bagel, right? She has fever, and she has syncope. Full recovery, but she has fever and clear syncope. It's not like the seizing thing of your fever going up. It's like clear syncope. Who would test this patient? I would test, for example, myself. Once again, I am not going on corns, but I would test her. Once again, are we trusting the genetics? Again, are we putting all the money on the genetics here? We have had febrile syncope in context of brugada in this family. And of course, the patient has a normal ECG, but it's a febrile syncope anyway. So, with family history of brugada. So, would we consider, in my center, we would perform provocative test? At least to say, okay, it might come negative, but at least I have discarded this option. And the risk of Ashmelin test performed in good hands is almost zero. We have performed many and had no problem so far. And it's clearly a febrile syncope. So, now, would I doubt with this type of syncope, vasovagal syncope? I probably would not perform in this type of syncope. So, the interrogation about how the syncope was is clearly clear syncope. How important is to go deeply into this interrogation and to really know the details of the clinical condition that has happened. Very good. Are there any comments up to now? Or can we move forward and share with you what have the recent HRS consensus statement have brought up a couple of months ago about provocative tests for both adults and children? Okay. So, we have this problem, just to sum up, on this family. We have the family screening after a problem with a definite Brouhada syndrome. And there are certain, I would say, recommendations that are being explored. Like, you start with genetics. Is this clearly a genetic background? If yes, we will follow that genetic because we think it's an important factor. But there are certain points of discussion here. For example, if we... Do you see the arrow? No. Okay. So, if we go to the left branch, so if this patient, with the new patient, it explores a sodium channel negative, so not a carrier of the genetic condition, and has a symptomatic with normal ECG, there is a reassurance and discharge following what has been published. So, we have had a lot of discussion. I am part of that document. And we have had a lot of discussion about how should we discharge a child, you know, that has the whole life in front of them. So, personally, and this is a personal opinion, know what is said in the article personally, discharging someone forever, when you have 80 years above you, saying... I would definitely reassure, but it would be really difficult for me to discharge certain patients without having at least one ECG with fever, which for me is very reassuring, a normal ECG with fever. And maybe I would suggest, okay, let's do an ECG in five years, let's say, or two, three, five years. Okay, that's one point. So, just to follow the order, I have to... Okay, just a disclosure, I have to say who put order in this presentation is Tethylia. She did an extraordinary work. And to make sense, to try to explore with these cases every single situation, complicated situation that we would see. So, of course, if we have no genetic background in that family, we will follow what ECG says. And we would, of course, be in the situation that if we have a type 1, a spontaneous type 1 brouhada pattern, there's no need to perform a provocative test. We already have the diagnostic. There's no need sometimes people ask you, oh, but you don't have it all the time. Yeah, I don't care. I had one, right? And that's important. So, have that in mind that there's no indication on doing a provocative test if you already have a diagnostic. Provocative test is to unmask something, right? So, if we don't have the type 1, that provocative test would be advised. So, in the cases that we have genetic pathogenic or likely pathogenic variant, in case our patient is negative for that variant, what the document suggests is what I said. I say if everything's normal, symptomatic, normal ECG, reassure. I would reassure and we will see. And, of course, for any abnormality you see on the ECG and any type of symptoms which would imply palpitations, dizziness, syncope, of course, we will doubt about that genetics or we will think that probably there is something added there and we would value the fact of doing the provocative test. And for those patients with positive sodium channel carriers, what should we do? So, sodium channel is not routinely recommended, but that routinely, it took like seven votes, seven rounds of voting. So, how should we do that? There, for me, for example, once again, this is a personal opinion, it reassures me a lot the fact of even you are a sodium channel carrier, I'm giving you the worst I could give and nothing happens. This is something that, okay, relax if you need to take fluoxetine, you know, because if Ashmalin does nothing on your ECG, just, okay, you can take fluoxetine easily, don't worry, okay. So, this is something that, for me, gives me a lot of, I would say, prognostic or style and helps me with taking decisions and reassuring for good situations, okay. So, there are, you want to continue? I can cover this slide. So, here we have a summary of the last recommendations that came out recently in Europace. This was a working group including representatives from PACES, HRS, Asian Pacific, Heart Rhythm Society, and LARS, and we, as Shorsha mentioned, there has been a lot of controversy. Leah, who is now in the audience, was also there, and Shekel Feld, Elijah Berg. So, there has been a lot of controversy, but in a way, we presented this information acknowledging that every circumstance, every family needs to be considered as individual basis, and these are recommendations given by the experts, but most of them are not really based up by strong data to support this, okay. So, in the end, what we agreed upon is that if we have a suspected Rugada syndrome, we can consider a sodium channel blocking test in the context of at least one of the following situation, a cardiac arrest or syncope, a family history of Rugada syndrome, a family history of sudden unexplained death, or a type 2, type 3 non-diagnostic Rugada ECG pattern with other features and or one of the above, and this last sentence had a lot of discussions, because we consider that having just a type 2 or type 3 ECG by itself without any of the other conditions was not enough to propose a sodium channel blocking test. So, if these conditions are not fulfilled, do not perform the test, advise the panel. If they do, if they are fulfilled, then we go through patient counseling. We discuss with the patients the pros and cons before taking the consent for the test, and what we consider as a group as the advantages for performing the test is that it excludes Rugada syndrome in the presence of a negative test, especially when using more powerful inhibitors of the channel like Ashmalin, and there's also here all the grades that come with using flaconide over kinamide with an increased percentage of false negative. So, the second advantage is to help avoid the diagnostic ambiguity. Many, many families saying, we don't know if we have Rugada syndrome. There has been this diagnosis, but it's yet unclear in our family. It also guides the extended family screening. It plays somebody with a clear diagnosis and helps also put in their place the other members of the family. It informs on the safety of the sodium channel blocker when we're using chemotherapy or other drugs or also seizure medication or antipsychotics, and it informs of the need to take care to suppress fever and to be aggressive in fever, mostly in our population of many of us that are children. What are the disadvantages? It has a limited specificity, the Ashmalin most of all because it's the most powerful, and it has a limited sensitivity, and a positive test can generate anxiety and an unnecessary intervention despite favorable prognosis in asymptomatic patients, and it has a potential of a negative impact on insurability, but we have discussed also here in future jobs, and also in the possibility of pursuing sports or a career in sports or in professions that could be at higher risk in the presence of syncope. Finally, the procedural risk, especially for patients with a pathogenic SCM-5 variant, may be a disadvantage. Again, in the right hands, with appropriate equipment, with a backup of an intensive care, and a pump of isoprotenol by our side, I think that this last risk is minimized. So finally, reframing the debate, we have to know that the drug challenge is not perfect. It's a tool to be used with clinical judgment, and it's an important decision. Not all family members need testing, and that's very important, and testing may need repetition based on age or phenotype. So if we, for whatever reason, had to perform the test before poverty, remember that with a negative test before poverty, we should consider if we have to repeat it after poverty. And finally, it's important that when talking about children, we have to say that it's a safety situation, but we have not specific protocols. Of course, there should be done and interpreted by a specialized pediatric electrophysiologist, and of course there are certain conditions in your home or hospital that should be indicated, as Cecilia said. Of course, we can perform them easily. We don't need to do them under any type of sedation or anesthesia. Just playing with them and putting some YouTube videos is enough, and having the parents with them, it's easy. It makes life very easy for everybody. And of course, that symptoms in children are very important. So febrile syncope and febrile seizures are part of it. And finally, if everything is normal, wait after poverty to do whatever you need to do, and negative test before poverty should be repeated. Finally, of course, the importance of fever. Thank you. These are pictures from our hospitals, and I really appreciate everyone who's here. For me, as a Barcelona team follower, being here, doing this presentation, while Barca and Madrid are playing right now the final cup for the King's Trophy, it's very important. I haven't looked at the score yet. I don't want to see it because I'm very nervous. But I have to say that none of my... We're good? Okay. So it was important, and I'm very thankful that so many people was here. Probably you are not soccer followers. Otherwise, you won't be here. There is a big amount of people somewhere hidden looking at the match somewhere in the Congress. Thank you very much. Okay, we do have time for questions. There's a microphone over here if anybody wants to step up. There are a number to the e-question format, so I will start with these. So the first one, plus-minus provocative testing, SCN5A, EKG, symptoms, nothing diagnosis, Bregada syndrome. You're confusing me more. Real world, what do we do? Thank you. So I think that overall what we intended to do was not to confuse you, but to give you the complexity of the spectrum of families and patients that we are seeing. Overall, I think that to keep it in mind is the consensus that we have just shared with you. If you have a patient that has a clear SCN5 mutation and is asymptomatic, you're safe if you don't perform the provocative test, but regarding the clinical circumstances, you may consider it if there is any syncope or if there is any clinical scenario that leads you to perform the test. In the case of patients who are SCN5 negative, if they are, or if the family doesn't have, remember that most of the family, I would say 70% of the family, in 70% of the family, we don't identify a gene that is causative of disease. So this family was in a part easy because we had the gene and we didn't want to give a scenario that was too complex, but in real life, most of the families have the type 1 ECG in the proband, and we don't have a genetic test to rely upon and to test the family members. In these cases, we have to individually understand the scenario, the ECG, and the symptoms of each, and the age and sex of each individual patient, and make a target therapeutic and diagnostic plan. That could be an option. So the question for the ones who could not listen if if we would put an ICD to Charles which is the transgender in order for him to follow the to follow the treatment, the transgender or the transition treatment. Well, you would, from my point of view, and you would consider it if you have a definitive definitive diagnosed of brouhada which we don't have because we consider that it was positive, the provocative test. If it's yes, his collapse with febrile seizure, he's positive, yes, I would consider implanting an ICD, which would probably would be a long discussion, I assume. Is there any other question? There's there's several on the on the list here. Do brouhada syndrome patients who have positive provocative tests have a higher risk of sudden cardiac arrest than those who are negative? Well, for me a patient who has negative provocative tests has no brouhada syndrome. So of course patients with positive provocative tests have more risk because they have the brouhada syndrome compared to those who have negative provocative tests who don't have brouhada syndrome. So, yes. Next one. Would bifascicular block in the uncle be a contraindication for ajmaline? Not for me. I mean, of course, we have to be careful and you don't put ajmaline or at least this is our protocol. We don't put ajmaline and forget about it and see the final result. We give it in a continuous pump. In children we do in 10 minutes because sometimes we have jumps, very sudden jumps on the result. So everything is negative until minute three and suddenly minute four is super positive. So we would like to give it in 10 minutes and in continuous infusion, no boluses of every minute. So I think that it can be done with some unknown degree of higher risk. But what I have seen that is the worst marker for risk of ventricular arrhythmias during the provocative test is PR prolongation. Usually what happens is we start the ajmaline infusion and because there's some degree of sinus nodule function, they go into bradycardia and then the cases that I have seen that have developed ventricular fibrillation start with after the polarizations and then trigger the arrhythmias. So we have to be very, very careful, mostly with young individuals that have PR prolongation, atrial arrhythmias or sinus node dysfunction. Sometimes you can turn into having an AV block. But remember, ajmaline has a half-life of five minutes. If whatever happens, it's going to be five minutes long. Okay, so this is very important. Actually, the only... There is no ajmaline in Spain. We need to import it from Germany. So it was very difficult a while ago to get that. So we were using flecainide and actually we had a complication with flecainide with an electromechanical dissociation. And that lasts a lot. I mean, you really do massage for a long time until this flecainide stops doing the effect. So that was, I would say, the positive thing of this complication, is that that was the final shout from our group to say, okay, we need ajmaline. So we are allowed and now we have easily ajmaline in the hospital. And since then, which it was eight years ago, we have always performed the test with ajmaline. So whatever happens is going to be five minutes. And this is very important. And this is why it's so useful to ajmaline compared to flecainide, just because bad things are going to be shorter. You may have just answered the next question, which is, if you don't have access to ajmaline, do you prefer flecainide or procainamide for provocative testing? Well, I will get this. I think that the procainamide, even if it's a little bit less specific in the result, gives us the possibility of titrating the dose IV and to have a short effect, which you don't have with flecainide. The flecainide, once you develop the type 1 ECC, usually it lasts for hours. And usually you have to admit the patient. I think the ECC is completely normal. So in Canada, we don't have ajmaline and we do use procainamide. The next question, I believe, is referring to Paul and it is, will a positive provocative test change your management in the father? Well, so Paul is the one who's asymptomatic but has atrial arrhythmias. And for me, it won't change because atrial arrhythmias are atrial arrhythmias. I would say, okay, probably I won't give flecainide to treat those atrial arrhythmias and anyway, with a sodium channel positive genetic test, I would not give flecainide. But, you know, it's one of the treatments you may use. So out of this family, I would suggest that you do an ECG to your patients whenever you give flecainide because you may have surprises to find out that they developed a brugada pattern after you started flecainide for an atrial fibrillation. So this is also important to have in mind. So it will not change my decision-making in this patient because he's genetically positive and it won't change. How was the EKG of the transgender patient when they were a female and was there a change? Do you have a pre-hormone EKG? We don't. I'm sorry, but we don't. I'm not sure which EKG this question refers to, but it's about diagnosing the type 1 pattern and the importance of the beta angle. And the EKG that the questioner is referring to appeared to have an acute angle. So does the beta angle play into your diagnosis on a type 1? I wonder which ECG it refers to, but of course, I am very... You know, sometimes the ECGs, we see them and we say we don't like it, you know. Can you just move back the presentation for the ECG? Yeah, the first ECG, not the very, very, very first, but the second or third slide. So the one that when replacing and putting the electrodes in an upper position, we had clearly a diagnostic pattern. Okay, so that's even before I think. Anyway, so this is the other thing. Just put your electrodes in upper precordial leads. This is very important. It is very easy. And whatever, if you check a patient for whatever, think of a syncope and fever it's in between, just do it systematically and you will get a lot of information here. Just can you go the previous one? Look, and of course, just the previous one. Yeah. Yeah, okay. So this is his basal ECG. This is not a normal ECG. Even though the ST segment in right precordial leads, it's not elevated, like it's not the one that we would say, okay, this smells like brugada. I have to say that ABR, it's very ugly. ABL, it's very ugly. And PR is normal, but overall this ECG, it's awful. Like, I love it. But it's, I mean, even there is nothing clear here, this is not a normal ECG, okay? And but how much it changes just by putting those precordial leads. Normally I do first, second, and third. I do normal ECG and then I do a first, second, and third intercostal space. So V1, V2, V3, V4, V5, V6. Okay, so I have explored the whole precordium and we have the most of the information. So this is not a normal ECG. So that ECG with something related to fever or palpitations or something, this claims you to do something here, right? So this is the feelings that we have with the ECGs. And I'm sorry, but I don't calculate the angle. I don't know how to do it. It just is very It's not reliable. No, no, no, no, no, I might be, but for me it's like, it's a matter of looking at an ECG and feeling that this is ECG, I don't like it. Sometimes it's like, exactly why? I don't know, but I don't like it. So I'm sorry, I'm like this. But I think this is what you have to integrate. That if something does not match, if you don't like something, if it's not clear that this is normal, just be persistent, find something. Okay, that's the real idea of that. I think this brings us to the end of our time. There are still a number of questions. If anybody had a really critical question, please feel free to approach our speakers. But I'd like to thank the two of you for your wonderful presentation and for everybody for joining us today. Thank you.

Brugada syndrome

pediatric electrophysiology

congenital electrophysiology

provocative testing

ECG pattern

sodium channel blockers

family case studies

genetic screening

clinical judgment

guidelines recommendations