This session is about infective myocarditis, thinking beyond borders, where we think about some infected disease and myocardial reflections. Dr. Cristiano Pisani from Heart Institute, Sao Paulo, Brazil, that will talk to us about arrhythmias in Chagas disease, what's new. Thank you, Dr. Cristiano. Thank you, everyone. It's a pleasure to be here. And I'm going to talk about Chagas disease. That is an old disease. And when it started to be like 20, 25 years ago, and started cardiology, people say, oh, in the future, Chagas will not exist anymore. But we still see patients with Chagas. We still see even acute infections with Chagas. So I'm going to show something that is new in Chagas disease. I have three topics to talk. I will talk about VT ablation. I will talk about primary prevention in Chagas disease. And I'll talk about radiotherapy in Chagas disease. First, VT ablation. The epicardial access was developed there in our institution. Dr. Mauricio Scannavaca and Dr. Sosa had the idea because it's very common there, Chagas disease. And most of the VTs on the epicardial surface. So there was a need to reach the epicardial space. And then that was developed, the epicardial access. Usually, Chagas disease, they have a small endocardial scar or even like this patient, no endocardial scar. And we can see here the bipolar map. We have some abnormal potentials on the unipolar and then a big scar, epicardial scar. So it's necessary. And my thesis was five years ago that we showed that for all patients, it was a randomized study. And we showed that for Chagas disease, all patients, we must go to epicardial. Because if you go endo only, we will fail in most of the cases. And in this case, the patient that were randomized endo, we went to EPI and the same procedure. Because in four, there was no endocardial scar. And in five, despite ablation, just like I showed before, we have still VT inducibility. But what we have new in VT ablation? We have new data from our database there in court about Chagas disease. It was just presented in the American College of Cardiology as a poster. And like 60% of our VT ablation are in Chagas disease. And these are data. Usually, Chagas disease are younger and even a little higher left ventricle ejection fraction. But what we could see? First, in almost 80% of the Chagas disease, especially since my thesis showed that, I think it's even more, we go epicardial in most of the patients with Chagas disease. But patients with Chagas disease, we have less commonly VT inducible at the end of the procedure. And when we go for the follow-up, the Chagas disease patients are who have the worst follow-up. This is data regarding free from death, heart transplant, or VT recurrence. Most of the Chagas disease have recurrence. It's quite worse compared to the ischemic. And even though ischemic and non-Chagas, they are slightly better compared to Chagas disease patient. This is Andrea Carmo from Belo Horizonte that shows same data, the database of Chagas disease compared to non-Chagas disease. And they have the same result. Chagas disease is quite worse compared to non-Chagas disease patient. And we wrote this editorial for JCE. And the title is, Verticular Tachycardia in Chagas Disease, Our Worst Nightmare. And when we have a Chagas disease with VT ablation is really a problem. We have guidelines, Brazilian guidelines of Chagas disease have just been published. And VT indication are similar to that. But for Chagas, we must prefer the combined endocardial and epicardial approach or like we do first, epicardial and then endocardial approach. Now about primary prevention Chagas disease. There is a very important study that was just published in JAMA, JAMA Cardiology. The main center was there in our institution. It's called the Chagasics Protocol. It was a primary prevention study in Chagas disease. They included patients that has high risk score at least 10 and one episode of non-sustained VT. And those patients were randomized for ICD implantation or just a Milderone. Patients who were in ICD group, they were without Milderone. And patients with Milderone, the other group of patients were with Milderone. The mean injection fraction here was like 30, 37% in both groups. And what we could see is that the all-cause mortality that was the primary endpoint, there was no difference with the ICD compared to a Milderone only. But the sudden cardiac death rate was lower compared to only a Milderone. These are the couple of my curves. The all-cause death, there was some difference at start, but then everything goes equal. And this was the sudden death. Patients that underwent ICD implantation have less cardiac death. And just to show you, the difference was disappeared because patients in the ICD group, they have more deaths related to heart failure. So the ICD in this group, in the mean injection fraction, there was no inclusion, there was not inclusion criteria, the injection fraction, but it was a high C-score. But those patients have died more due to heart failure. So the ICD only changed the way of that in this study. And in the conclusion, there was one big limitation of this study that the rate of events was lower compared from what they expected. And they were planning 1,100 patients, 1,100 patients to be included, but they only included 362 because of the low rate, and it was hard to find those patients. So this is a big limitation. But I felt that even if they completed, the results would be the same and make sense. You put an ICD as a primary prevention, you prevent death from cardiac death, but no heart failure. Because Chagas disease is a disease that has evolution. Even if you do ablation, the patient has no recurrence. Two, three years later, they will continue to go back again, VT, because there is a chronic myocarditis and there's no etiological treatment for Chagas disease. And to finish my presentation, we have some data regarding radiotherapy. We have a protocol that we included 11 patients with Chagas disease. And all the patients were patients that were no, could not be referred anymore for VT ablation. It was like the last change of the patients. We completed the 11 patients. We are just finishing the follow-up of those 11 patients. And I'm gonna show here some data regarding two of the patients. How we do this? We use all the data we have. We use the VT morphologies induced in the P-study or prior ablation. We use some maps. We're using cardiac MRI processing or other software. CT scan looking for the aneurysm. And we do, usually we do a Zoom planning meeting. Our group, me, Dr. Maurice Canavaca, and the radiotherapy group also. So we decide where we're gonna burn, where we're gonna do the ablation. And then they put on their system. You can see here we have aneurysm. We define here that this was the area. Those are the radiation oncologists. And then put on their system. The physics do the calculation and then the patient go to the lab. Here is the area. This is the patient number five, I think, that was inferior scar. So we decide to apply radiotherapy in this spot. I'm gonna show two cases. The good case first and the bad case after. And then the final data. This was our case number one. This patient was a pretty sick patient. This patient had three or four prior VT ablation. And had a complication, had epicardial access perforation. And in the second procedure, he had liver lesion with need for abdominal surgery. So the patient had two surgeries related to the complication. He was still having VT. So we decide to put this patient, these are the ICD therapies before and after. The day the patient did the treatment, he had VT in the afternoon. But after like six weeks and the prior description of radiotherapy, there's a blanking period because the effect of radiotherapy is not inhibited. This patient goes down the numbers of VT. And after the 50th month, he had no VT anymore. And there was a significant reduction in burden in this patient. And no free from any VT. And after the follow-up, we started doing this in 2023, or 22. This patient, so this patient, actually turn around. This patient have reduced the muterine dose and even a recovery in ejection fraction. You can see here, 40, 23, 30, and 47. We published this case in our Brazilian journal. So this was on the case that we succeeded. But we have failure. And most of the cases were failure. This was patient number six. A patient that, this patient had no prior ablation because she had a very important COVID infection with pulmonary fibrosis. And then she come with VT. And we thought, and we think could not be safe to put this patient for ablation. You can see here, there's an inferior aneurysm that is very typical in Chagas disease. And those were the treatment data was a small area of irradiation. But unfortunately, for, I think was, just like one, two weeks after the, the treatment, she still have VT. And then she come with a slow VT. And she had complications related to the VT treatment. She went necessary to be endotracheal intubation. And then she died in the follow-up. We are just preparing the data regarding necropsy, the pathology of those patients. But I removed it here because of the time. Those are the first data. These are all the seven cases we have the complete follow-up. You can see here that there was a reducing just after the ablation. Then most of the patients have no VT anymore. Sometimes we have some late occurrence. In one case, we repeated ablation. There was no signals where we treated. But seven of the 11 patients died in the follow-up. There was a high mortality. Most were not related to ventricular arrhythmia. Even there was deaths related to non-cardiac cause. But in this population, the rate was high. To conclude, VT ablation. New data showing worse prognosis if an epicardial abscess is used. But it's a highly recommended epicardial abscess primary prevention. Seems to reduce the risk of sudden death. But no all-cause mortality. And ICD changed the way of that. And radiotherapy could be an alternative for refractory patient. Result is not immediate and mortality is high. Thank you for your attention. That was an excellent talk. I think in the interest of time, we'll hold all questions till the end. Okay. I'd like to introduce our next speaker, Dr. Kalambur Narasimhan from AIG Hospital in Hyderabad, India. And he is going to teach us a bit about arrhythmias in tuberculosis myocarditis. Thank you very much. Good morning, friends, ladies and gentlemen. I was tasked to speak about arrhythmias in tuberculosis myocarditis. I'll just tell you, leave behind at the end of this talk, how this is relevant to each and every one of us. How it may change our practice. World is becoming increasingly connected and there is very high prevalence of tuberculosis in certain geographies like parts of Africa, Southeast Asia, and these patients migrate. So wherever you have, for example, even in the US, the immigrant population, wherever there is in Texas, New York, the prevalence of tuberculosis is higher. Secondly, when you follow up patients serially, after a treated for tuberculosis, seven to eight years later, there is occurrence of sarcoid in these patients because they don't clear the tuberculosis antigen. The antigen peptides still present and they trigger a sarcoid-like reaction. So we are all clinicians, let's just start with a case. This is a 42-year-old gentleman presented with palpitations, dizziness, summit VT, was actually referred for VT ablation with no constitutional symptoms. Now early on, we recognized whenever you see a cycle length variation in VT, it suggests that there is an ongoing inflammation. So either you see a pleomorphism of VT or irregular cycle length, we need to investigate this patient further even though your echocardiography and MRI remains normal. So this patient was investigated, baseline evaluation was normal, very strongly positive PPD reaction, PET showed intense uptake, cervical node biopsy. We strongly recommend histopathology from the adjacent node. Mycobacterial cultures were positive and therefore we started this patient on antituberculous therapies, ICD was implanted, and antiarrhythmic therapies were instituted. But lo and behold, despite doing everything, after about two months, patients developed incessant VT and we took up for ablation, endo and epi ablation in the posterolateral wall, this is a common reason, either in the septum or in the posterolateral wall, endo and epi ablation is successfully, we thought we successfully ablated, but the frequent recurrences which settled down after a period of about three months. Now this kind of helped us to go back and look at our data and this was very well reported in neurotuberculosis. When they start antituberculous therapy, there is an exacerbation of seizure activity in these patients. So there is a paradoxical worsening of arrhythmias when you start ATT because of the bactericidal effects, there is an increased immune response and therefore we learned not to ablate these patients but to start them on steroids upfront when there is myocardial tuberculosis. Now as a clinician, you need to understand what is the spectrum of the patient you are seeing. You have a very sick patient with miliary tuberculosis, emaciated, that is a patient with diffused tuberculous involvement of the myocardium, there you don't start steroids. On the other hand, if you have nodular tuberculosis, lymph node tuberculosis, you need to start them on steroids. So it can present as sinus tachycardia, VT, atrial flutter fibrillation, complete AV block and several of the antituberculous therapy like bedaquiline and some of the quinolones can cause QT prolongation and there are a series of patients where autopsy series have shown sudden cardiac death and then myocardial tuberculoma has been recognized thereafter. So this is a large series published in Tuberculosis Journal, autopsy series showing that several patients had granuloma in the myocardium, either in the septum or in the lateral wall but most of them were not diagnosed antemortem in these patients, they were diagnosed postmortem. So we published a series of about 18 patients and there, most of them were culture positive. The only clue is that they have mediastinal adenopathy. Whenever you have a patient with VT and mediastinal adenopathy on CT scan, you need to think of granulomatous disease and one of them is tuberculosis and these patients are generally post-bacillary tuberculosis and therefore, invariably, they have an exaggerated skin response, MANTU response is strongly positive. This is, of course, I'm sorry, this is a combined series of both sarcoid and TB, but with appropriate either anti-cubicless therapy, there is a remarkable reduction in the VT events, but it takes about six to eight weeks. Don't rush in for an ablation in this phase, even if it's incessant, you're tied over with sympathectomy and steroid therapy in the initial phase. Now, as a clinician, we need to be sensitized. This patient actually came from cardiac surgery unit, a patient who was about to be taken up for a mitral valve surgery with a small mass on the mitral valve. He presented with the Venkebach, and therefore, we were asked to put a pacemaker before the procedure. And as you can see, this patient had significant mitral regurgitation. I don't know, for some reason, this doesn't play. He was slated for excision of the mass, as well as pacemaker implantation and a mitral valve replacement. But we diagnosed this patient, again, had a lymph node which was casiating, and tuberculosis, the mass disappeared, the MR disappeared, AV block disappeared. This patient went home without any additional therapy other than anticubiclus therapy. So it doesn't look very attractive not to do a procedure, but the patient comes to us for getting well. You don't need to necessarily offer, this patient was eternally grateful. In fact, donated something to the hospital at the end of this because he was saved by the end of surgery and a mitral valve replacement. This is another person who was referred for AFib ablation, recurrent AFib, and has got abdominal distension, who came primarily to the liver unit and then came back to us. He was started on anticoagulants, did respond, started on amiodarone, had liver enzyme elevation, and then came back to us. On further evaluation, all that gave away the clue was, we couldn't see the upper end, there's all the features of constrictor pericarditis. You can see a septal bounce, exaggerated response, and there is hepatic flow reversal. Everything suggests that he had a constriction. He needed to go for surgery, and he was sent for this. We published a large series of about 15 patients with, this you can see an intense uptake of FDG in the myocardium, atrial myocardium. They can present with atrial flutter and fibrillation. We published a series of granulomatous myocarditis. Three of the 15 had tuberculosis because of which they had recurrent atrial flutter and fibrillation. The importance of diagnosing this disease is it's not semantic. Because even if the CHAD score is zero, the risk of stroke is very high in the subset of patients because inflammatory process in the atrial myocardium is highly thrombogenic, and therefore despite CHAD score being zero, when you have a person with atrial myocarditis, we offer them anticoagulation and prefer not to take them up for ablation till the inflammatory process is settled. Now this is a series of 23 cases, varied presentations of tuberculosis. We have had patients with severe heart failure, refractory heart failure, where antituberculous therapy, the heart failure results is taken off transplant list. We have also had on autopsy, tubercles of the myocardium. One of the interesting series which came out from the German group was they took up this patient with refractory ventricular tachycardia to the OR, epicardial mapping was done, they found a nodule on the epicardium, and when they excised the tuberculoma, patient's VT stopped. But he had disseminated sepsis the following day and died. Nevertheless, it can be one of the presenting manifestation of tuberculoma. So to this audience, what do I say? If you have a patient where unlike a normal monomorphic VT where beat to beat to beat, it's constant, if you have a irregularity in cycle length or pleomorphism of the morphology, please consider underlying inflammation. It can be as simple as sarcoid in several series where TB is not endemic, but highly prevalent areas you need to consider tuberculosis. In patients with immunosuppression, we have seen aspergillus and syphilis gamma presenting this kind of presentation. And if a person has idiopathic VT who's referred for ablation, if there is a patient with a bundle branch block or fascicular block, you need to consider a granulomatous myocarditis. If there is QRS fragmentation in any of the leads, consider granulomatous myocarditis. Don't take them up directly to the table without imaging. If the QRS amplitude is very low, myocardial edema attenuates the bipolar voltages. So if you have an inferior limb lead voltages getting attenuated, that suggests there is some degree of myocardial edema, you need to consider granulomatous myocarditis and therefore investigate these patients further. So in summary, Chairman, ladies and gentlemen, tubercular myocarditis is rare. However, it can present as AV conduction disease, atrial arrhythmias and ventricular arrhythmias. It can also lead to sudden cardiac death if unrecognized. If treated early, these patients respond very well to anticubiclus therapy. In our experience, about 20 to 30% of these patients have an exacerbation of their arrhythmia when anticubiclus therapy is initiated. And this paradoxical worsening of the arrhythmia can be mitigated by a small dose of immunosuppressive therapy when you start the patients on steroids. Thank you very much for the patient listening. Thank you. Thank you, the next speaker is Dr. Thank you. Good morning, everyone. And thanks for this opportunity to come here and give this talk. So I'll be talking about atrial and ventricular arrhythmias in COVID myocarditis. And we'll be discussing the epidemiology, the mechanism of COVID-19 myocarditis, the mechanisms of arrhythmias, the different atrial and ventricular arrhythmias, the incidents, outcomes, and their management, the risk of sudden cardiac arrest and long-term risk of arrhythmia in this population. So as of today, this morning, according to the WHO data for COVID infection, there have been 777 million cases of COVID confirmed with over 7 million deaths around the globe. 13.64 billion vaccine doses have been administered. So when we look at the CDC data in US population, the incidence of COVID myocarditis was 150 per 100,000 from COVID infection versus nine in 100,000 in non-COVID infection. So COVID infection increased the risk of myocarditis by more than 15 fold. Myocarditis has also been reported with COVID vaccine. However, the incidence was very low in different studies, varying from one to 10 per million. They were noted to be higher in males, in younger, less than 40 years population, with the use of mRNA vaccine and the second dose of vaccine. So the problem with COVID myocarditis and literature review on this is the incidence is unclear as definitions vary. Most of the COVID myocarditis was diagnosed on clinical grounds with symptoms, increased cardiac biomarkers, EKG changes, and not based on confirmatory diagnosis of myocarditis. The diagnosis based on imaging alone should be avoided because it's never been validated. There are different EKG changes with ST elevation, PR depression, new bundle branch block, bradyarrhythmias, QT prolongation, pseudo-infarct pattern, PVC polymorphic VT. So just a heterogeneous presentation. Autopsy data has in some instances shown the coronavirus to cardiac infection. Endomyocardial biopsy may also show positive RNA by RT-PCR and viral particles by electron microscopy. Blood tests are pretty nonspecific, increased lactate, CRP, ESR, procalcitonin, increased troponin and BNP. And of course, cardiac MRI showing late gadolinium enhancement, increased T2 signal and hypokinesia. So in this view of the two MRI in a patient who had COVID, elevated troponin, we found that the ventricular function was pretty much preserved. There was some septal dyskinesis. And go to the next slide. And on T2-weighted imaging, what we saw was increased myocardial edema involving the septum. And there was also late gadolinium enhancement showing patchy mid-myocardial enhancement again, suggestive of myocarditis. So what are the different mechanisms of myocarditis? So the SARS-CoV-2 binds to the cardiomyocytes using the angiotensin converting enzyme two receptor. And then it is processed by the antigen-presenting cell, activates the native T cell, causing significant T cell-mediated toxicity and cytokine storm. So the potential mechanisms of arrhythmogenesis in COVID-19 include not only direct infection and direct injury from the variants, but also a result of inflammatory response from the systemic infection, as well as patients with systemic illnesses having hypoxemia, acidosis, hemodynamic instability, which predispose to arrhythmias. And finally, by causing autonomic aberration, causing different arrhythmias from perturbation of sympathetic and parasympathetic tone. So in this initial survey of over 600 respondents around the globe during the initial phase of COVID, atrial fibrillation was reported in by 21% responders, flutter in 5%, and then sustained VT in 3.6%, non-sustained VT in 6%, polymorphic VT in 3.5%, and cardiac arrest, including VT, VF in 5%, and PA arrest in about 5%. Now, this was another meta-analysis of 28 studies in having 12,499 patients who had COVID-19. There was a 10.3% prevalence of arrhythmia, 6.2% SVT, 2.5% VT, 1.8% bradyarrhythmia. In critically ill patients who were in the ICU, the relative risk for VT was 10.5, for SVT was 10.1. And then we also saw QTC prolongation, and there was an increased incidence of arrhythmias in non-survivors, hospitalized patients. In the multicenter COVID rhythm registry, which my colleague, Dr. Gopinathan Nair, presented at HRS 2023, amongst over 6,000 patients, 46% had an incident arrhythmia, of which atrial fibrillation was the commonest, new-onset AFib occurring in 22%, VT in 17%, 19% had a second incident arrhythmia during the same hospitalization. And what they found was the incident VT and second incident arrhythmia were associated with a higher risk of mortality. So in this paper at Mount Sinai by Dr. Vivek Reddy and group, they looked at atrial fibrillation in the setting of COVID-19 and compared it to atrial fibrillation in the setting of influenza. What they found was they had a 10% AFib occurrence with COVID and 4% were new when they looked at the automated electronic record. The increased risk of new AFib was confirmed by increased inflammatory markers, increased myocardial injury, and increased intubation, vasopressor use, and increased use of steroid. However, even though the increase, there was an increase in mortality with incident AFib and flutter compared to those who did not have AFib flutter. The relative risk was similar in both the influenza group as well as COVID-19 group. Similar results were seen in the AHA COVID-19 cardiovascular disease registry where over 31,000 patients with COVID hospitalized from 120 US institutions. The incidence of AFib was, new-onset AFib was 5.4%. And again, there was an increased risk of mortality with AFib versus those who did not have AFib. However, when they did multivariable adjustment for comorbidities, the new-onset AFib did not confer additional mortality risk. So that suggests that this is likely a marker for adverse clinical factors and not an independent cause of mortality. So how do we manage these patients? In addition to optimizing hemodynamic status, rate rhythm controls, stroke prevention, it's important to address the triggers and take care of them. And these patients should also be monitored for long-term AFib recurrence. How about ventricular arrhythmia in these patients with COVID myocarditis? The prevalence has been reported from 0.1 to 8%, depending on what study and what population you look at. The incidence was higher when they're in patients with elevated troponin and in critically ill patients. Ventricular arrhythmias were associated with a higher risk of mortality. And then there was an increased risk of VT storm in patients with ischemic heart disease, cardiac sarcoidosis, and Brugada syndrome. And then with QT-prolonging drugs used for treatment of COVID, polymorphic VT and Torsades were also seen. So how do we treat these patients? The best treatment is treating the COVID infection with antimicrobials, anti-inflammatory disease, and then using guidelines for antiarrhythmic treatment, VT ablation, and left stellate ganglion blockade if nothing else is working. The incidence of sudden cardiac arrest in a worldwide survey was 4.8% for VT-VF and 5.6% for PEA and acystery. COVID rhythm registry showed an incidence of 4.5%. Out-of-hospital cardiac arrest increased by 200% during early part of pandemic compared to before pandemic. And larger proportion of these happened at home with decreased bystander CPR compared to pre-pandemic era. So there was a, depending on different studies, 38 to 120% increase in incidence of cardiac arrest, higher mortality, higher rate of out-of-hospital cardiac arrest, lower rate of bystander CPR and defibrillation, 27% reduction in shockable rhythm, longer delays to intervention, 35% reduced survival to hospital admission, and 48% reduced survival to discharge. In the AHA COVID cardiovascular registry, the in-hospital cardiac arrest was 5.9%, mainly in the ICU patients with a predominance of non-shockable rhythm. The predictors for in-hospital cardiac arrest were older age, black race, Hispanic ethnicity, and survival to discharge was 6.9%. Now, when these patients with COVID were followed for 12 months, there was almost a two-fold increased risk of different arrhythmias, including AFib, sinus tach, sinus bradycardia, ventricular arrhythmias, and atrial flutter. Now, we also have to be careful about the drug interactions, especially ritonavir, which is a component of baclovid, and this kind of is a strong cytochrome 3-4-A inhibitor. So to summarize, development of atrial and ventricular arrhythmias in COVID-19 is multifactorial. Clinically stable and ambulatory COVID-19 positive individuals are at less risk for arrhythmias compared to those with severe infections. There's a higher incidence of ventricular arrhythmia and sudden cardiac death in COVID-19 patients, and prompt treatment of COVID-19 is the key to favorable outcomes. Management of arrhythmias and autonomic dysfunction should be based on current guidelines. Continued long-term arrhythmia surveillance is prudent in any patients who has COVID infection. Patients who are being treated for COVID-19 need monitoring for QT prolongation and drug-drug interaction, and there is no consistent evidence to demonstrate an increased risk of arrhythmia or sudden death attributable to COVID-19 vaccines. Thank you for your attention. Thank you, Dr. Khabra for that excellent review. Our final speaker for this session is Dr. Ashley Chin. Dr. Chin comes to us from the Groote Sjoerd Hospital in South Africa, and he will be talking about arrhythmias and endomyocardial fibrosis. So, good morning, everyone. Mr. Chair, thanks very much for the introduction. All right, so I've been asked to give a talk on endomyocardial fibrosis, because we see a few cases in South Africa now and again. I've got no disclosures related to this talk. So, endomyocardial fibrosis is one of those neglected diseases of the world. And what is neglected? It's a disease that predominantly affects sort of low- and middle-income countries. It's not been the subject of systematic research, and the epidemiology and natural history is very poorly understood. And I would argue on that list of neglected diseases, probably endomyocardial fibrosis would be one of the, one at the bottom of the pile, so to speak, in terms of research and in terms of clinical research. So, the epidemiology of endomyocardial fibrosis is quite a fascinating one. It was discovered about, first reported in Uganda more than 75 years ago. You can see it's, these are the endemic areas of the world where endomyocardial fibrosis has been reported. Interestingly, this disease occurs in tropics and in areas where, even within a country, it occurs in certain sort of clusters. You can see that Mozambique is quite a hotspot in Africa, whereas South Africa, interestingly, we don't see a lot of cases. The only population-based study that I know of endomyocardial fibrosis is the one that was published way back in, I think, 2008 from a Mozambique group that did echocardiography in a random sample in northern Mozambique. And what they did is they sampled over about 1,000 patients with echocardiography in different age groups. And the interesting thing was that there was a very high prevalence rate of endomyocardial fibrosis. In fact, the overall prevalence rate was around about 20%, with the hotspot being in sort of young men, although it affects both sexes. Interestingly, over time, this is the incidence rates from a Ugandan institute. Remember, Uganda is one of the hotspots of the world in terms of endomyocardial fibrosis. And they plotted the incidence rates from 2007 here to 2020. And you can see that there is a marked reduction in the new incidence rates of endomyocardial fibrosis. So we don't have a lot of data, but it does look like in some areas, and I think there have been reports from India as well, that endomyocardial fibrosis is decreasing, probably with the increase in socioeconomic status. The etiology of endomyocardial fibrosis is very sketchy at the moment. And it really, there are multiple, multiple theories as to why someone develops this. The most commonly held theory is that a patient has an underlying genetic susceptibility, although there have been no genes that have been directly implicated so far. Coupled with that, you have malnutrition, low socioeconomic status. And then you need an insult from, usually what we think the most commonly held theory is that you have a parasitic infection. In some areas of the world, this is cystosomiasis, particularly in the Ugandan Lake Victoria area. But that cannot be the universal explanation because cystosomiasis is not commonly found in other areas of the world where this is reported. Malaria has been implicated in some worm infestations. What then happens is that there's an inflammatory response, there's a theory that there may be some autoimmunity, and then patients develop this myocarditis and fibrofatty fibrosis under the endomyocardium. So on the left-hand side here, you can see the risk factors. We think there's a genetic susceptibility, a parasitic infection, coupled with poor economic status and malnutrition. And this results in what they think is an acute phase reaction. In South Africa, we still see cases of TB, myopericarditis, acute rheumatic fever. It sounds like the myocarditis pattern is a similar sort of presentation. What we do see, however, is the chronic phase. And this is when patients present. They present often with heart failure symptoms. They present with ascites, pleural effusions, signs of both right and left heart failure, and ventricular and supraventricular arrhythmias. And this is the phase where most of the patients get present. So briefly, the clinical presentation. Patients can present with both left and right heart failure. There's been an RV predominant clinical presentation that's been described, as well as an LV predominant clinical presentation. What happens is you have this severe, restrictive, what looks like cardiomyopathy with massively dilated atria, often associated with thrombi in both the atria and the ventricles. And then the key finding is that often these ventricles, ventricular sizes are small. There's apical, what they call retraction, and also thrombotic obliteration of both apices. Some of the ECG abnormalities that's been described. This was an editorial that was written in 2011. And it was more, I think, an opinion piece. Couldn't really track the original studies. But it seems like first degree AV block and right bundle branch block is relatively common. They described this QR pattern in V1, possibly as a result of pulmonary hypertension, a right-sided right ventricular hypertrophy, and then some both right atrial and left atrial enlargement. Interestingly, there have been reports of T-wave inversion in the lateral leads, mimicking sort of an apical hypertrophic cardiomyopathy ECG. This is one of the few natural history studies, or natural studies that have been reported. This was from the 1980s from an Indian group. And they reported the clinical course of endomyocardial fibrosis in about 145 patients. You can see here on the left-hand side the clinical profile of 145 patients. And I'm just sort of highlighting in red the arrhythmic manifestations of 145 patients. 32% had atrial fibrillation, not surprisingly with the remodeled atria. Some patients had ventricular PVCs, but these were quite uncommon, 3%. And some patients had heart block, but this was also quite uncommon, 3% to 4%. When they looked at the cause of death in the 66 patients that were followed up over time, they found that the most common cause of death was that of congestive heart failure. But I just wanted to highlight here the terminal arrhythmias, which was responsible for about 9%. So some patients presumably had sudden deaths, presumably from ventricular tachyarrhythmia. And again, there were a large percentage of patients that were unknown. And it's speculative, but I think some of these patients died from sudden death, and that counted for about 31% of cases. So sudden death may occur. So to me, the differential diagnosis when I see these patients in the clinic, in fact, in South Africa, I would think, first of all, being a TB hotspot of the world, I would, if I saw this clinical presentation, I would be thinking of constrictive pericarditis. But there are a whole host here on the left-hand side of diseases that can mimic endomyocardial fibrosis. So let me show you a case that we saw a couple of years ago now. This was a patient that presented to us with monomorphic ventricular tachycardia. It was a 27-year-old black African gentleman from KwaZulu-Natal, which is found on the east coast of South Africa. He wasn't actually from Mozambique, but resided in South Africa. And he presented in quite bad right heart failure, as well as also a monomorphic ventricular tachycardia. And you can see over here, this is the left bundle branch black light morphology with the superior axis. And this was his echocardiogram on the top left-hand side here. You can see that his function looked relatively preserved. He had massively dilated atria. You can see a thrombus, sort of the arrow there, in the right atrium. There was also a thrombus in the right ventricle with severe mitral regurgitation. On the top right, you can see a ventriculogram of his right ventricle. You can see how dilated it is with poor ventricular function with very poor function. And this was his baseline ECG. You can see the sort of QR pattern that I previously mentioned, the T-wave inversion. And initially, in fact, because we weren't an EMF endemic area, in fact, our first working diagnosis with this patient was that possibly did he have arrhythmogenic right ventricular cardiomyopathy. In fact, he had three major and one minor criteria. So by all accounts, this would meet major criteria for arrhythmogenic right ventricular cardiomyopathy. He came to us because we're a transplant center in South Africa. And this gentleman had recurrent VT, which eventually managed to settle on quite high doses of amiodarone. But he was quite marked in right heart failure and was admitted to our hospital for quite an extended period. And our decision at that point was to actually put him forward for heart transplantation because of both of his heart failure and his VT. Unfortunately, he had quite a large amount of HLA antibodies and a lot of donor incompatibility testing. And in fact, he remained in the hospital close to a year before we received a heart transplant. He was transplanted in 2014. Now interestingly, at the time of explant, remember our working diagnosis here was possibly arrhythmogenic right ventricular cardiomyopathy. We were quite surprised when the pathologist called us up because the explanted heart, in fact, didn't show features of ARVC. And in fact, showed quite marked endomyocardial thickening. You can see the sort of white plaques, dense white fibrous tissue that's quite obviously seen here in the right ventricle as well as also extending into the atrium. And the explanted heart microscopy findings also didn't show typical features of ARVD. There was no fibrosis within the aggregates of myotocin. So the explanted heart pathology report was this was endomyocardial fibrosis without eosinophilia with an obliterative cardiomyopathy. So this patient, in fact, had endomyocardial fibrosis, which was a sporadic case. But in fact, he presented with predominantly right ventricular involvement and intractable VT. Going back into the literature, there have been case reports of exactly this sort of presentation that has been published. So endomyocardial fibrosis, although VT is said to be uncommon, I think is an important cause for sudden death in these patients. So just finally, I'd just like to show you a subdative that we've collected in a registry called the Imotep Registry in South Africa. This is a prospective registry that enrolled about 665 cardiomyopathy cases. So this was all types of cardiomyopathy cases from South Africa, from multiple centers, as well as from Mozambique. And Mozambique was the area, again, a hotspot for EMF. And in fact, we had one case from South Africa and 30 cases from Mozambique. And these were some of the baseline characteristics of the 30-odd patients. It occurred in both children, as well as in adults and in adolescents. The mean age was 24 years of age. It was predominantly females, mostly black African people. They presented mostly with heart failure, so class 2 and class 3 symptoms. Some patients had a family history of sudden death of cardiomyopathy, although that was uncommon. And most patients had preserved ejection fractions. Intracardiac thrombi were seen in a large percentage of patients. They were seen in about 34% of cases. Both atria were predominantly involved with some thrombi in the left ventricle. They predominantly were advanced cases who presented with heart failure. And I'd just like to point out here that atrial arrhythmias was almost a universal finding. It occurred in about 70% of cases. So most of these patients, in fact, had presented with atrial fibrillation at baseline. Ventricular arrhythmias, that's the one case that we contributed from the one that I've just shown you. A lot of these patients were on heart failure medication. When we looked at the ECGs, again, the atrial fibrillation was the most common atrial arrhythmia. There was a patient with atrial flutter. Because most of them were in AF, we couldn't, you know, there was one patient who had first degree AB block. Only four patients were in sinus rhythm. And you can see here, a lot of the patients had underlying distal conduction system disease in the terms of incomplete or complete right bundle branch block. So, in summary, Mr. Chairman, I'd just like to, I presented endomyocardial fibrosis, which is one of those neglected diseases. It's still highly prevalent, I think, in Africa, although we do think the incidence is falling. Arrhythmias are a common manifestation, specifically for endomyocardial fibrosis, occurring in 80% of the cases that we had in our registry. I think that funding for research of EMF should be prioritized. We've seen quite advancements in research finances for rheumatic heart disease and tuberculosis, and I think some work has to be put in endomyocardial fibrosis, and as well as an increase in healthcare spending for the better treatment of these patients. So, thank you very much for your attention. Thank you. Thank you, that was another excellent presentation. With our remaining minutes, we'd like to open it up to questions. We did have a question come through the app, and so if you have questions, you can either come up to the podium, or use the app. We also have some questions, too, if there's time. And so, I think, Dr. Forgata, do you want to go ahead and present the first question that was on the forum? From the app, for Dr. Pisani, could target treatment for Chagas disease have any role in patients' inflammatory symptoms? Inflammation in the T, ongoing inflammation. Could you repeat the etiological treatment? Yeah. Yeah, actually, there is a etiological treatment that is benzonidazole, was tested on benefit trial, but usually, there's no benefit of the use of the drug, because Chagas usually, despite we have some acute, there are some, it's a chronic disease, but some acute decompensations, but usually, there's no role for the etiological treatment, even immunosuppression. In some cases, we did, when we get the apicardial puncture, we sent to pathology to look for the protozoan, but it was not possible, we could not find, so probably, we deal with the complications, not the acute infection. A question for Dr. Narasimhan, you had mentioned the increased frequency of VT after the initiation of antidepressant treatment, and how corticosteroids are part of that treatment strategy. You'd also mentioned something about sympathectomy, because you wanna wait and not treat in the acute setting. Can you provide us with a little more information about when do you consider sympathectomy, and how often are you performing that in these patients? So, if you have a person where you initiate therapy with beta blockers and imidrone, the VT completely settles down on monitoring everything is okay, then we don't do anything further. So, a large majority of them can be conservatively managed, because they have a device, but a subset, a small percentage of patients take a long time to settle down. They have recurrent VT in the hospital, despite the etiological therapy being initiated, steroids being initiated. We don't take them up for ablation, but we temporize the acute phase by doing a sympathectomy. So that you buy some time, and despite that three months down the line, four months down the line, the patient has a VT, we do a PET scan at that stage. If PET shows the inflammation is completely gone, and the VT is persistent, then we take it for ablation. Okay, you know, that's on that topic of time course. A question for Dr. Cabra, you know, for the acute COVID infection, you know, what is the general timeframe to development of COVID myocarditis? You know, as someone who's looked a little bit at long COVID, you know, there's a quiescent phase. Before that happens, is there anything like that for the COVID myocarditis, or this is all just in the acute setting? So, most of it is in the acute setting. And I think the main challenge is, like how do you, what is the best way to diagnose it? So, we rely on cardiac MRI, and sometimes PET scan, and sometimes they don't show anything, and still, like clinically, patient has signs of myocarditis. So, it's typically, fibrosis, which can trigger future arrhythmias, but those are mostly not because of acute myocarditis. Thank you. Any questions from the audience? I'll ask for Dr. Chin. You showed previously a slide showing a decrease of the incidence of endomyocardial fibrosis in Uganda experience. And there's a trend worldwide? Or what do you think it's about? Yeah, I think there's definitely been a trend in Uganda. They reported that. And also in India, there have been reports that the incidence is falling. Nobody knows exactly why. So one of the major etiologies is an unidentified trigger that's associated with poverty and malnutrition and protein malnutrition is one of the major theories. And it's probably speculative that with that, with the improvement in diet. So I think it's quite multifactorial, but definitely over, you know, at least in two areas of the world it has been decreasing. You know, and I wanted to reiterate something that you mentioned, Dr. Chen, in your talk that I think can be applied to, you know, all of these presentations today is that this concept of the neglected disease and the fact that increased research and healthcare spending is crucial to help combat some of these. I think all of us can attest to that. In the last minute, I guess, just for the group, if anyone wants to comment, you know, AFib was one of the common threads in all of these different myocarditis processes. So in terms of anticoagulation, I know that Dr. Kalambord mentioned definitive treatment with anticoagulation irrespective of CHADS-2-S score. Is that the same for some of the other processes as well, for the other speakers? For CHADS, they don't have too much atrial fibrillation, but they have the apical aneurysm. Sometimes when they have the apical aneurysm and the thrombus, we do anticoagulation. But without thrombus, we do not do prophylactic anticoagulation. Okay, and with that, I think Dr. Fregata and I would like to thank certainly our presenters and the audience for coming. We hope that we carry this excitement forward for the rest of the meeting, and I hope everyone has a great rest of their HRS. Thank you.

Infective Myocarditis

Chagas Disease

Arrhythmias

Ventricular Tachycardia

Epicardial Access

Tuberculosis Myocarditis

COVID-19 Impact

Endomyocardial Fibrosis

Heart Failure

Global Health