And we are going to begin the session now, and it's my pleasure to introduce Dr. Ashley Chin from Cape Town, South Africa. I think you're going to hear some exciting commentary from him on his presentation today, and it's a privilege for us to listen to such erudite speakers. Thank you. Thanks, Felix, for that introduction. Good afternoon, everyone. All right, so I'm going to kick off the session talking on the burden in Africa, lessons that we learned from the IMOTEP registry. I apologize for my Egyptian colleagues for my pronunciation of IMOTEP, but I'm going to have nothing to disclose. So really the outline for my talk, because of the limited time that I have, I'm going to concentrate on the ARVC, and I'm going to use arrhythmogenic cardiomyopathy interchangeably with the words ARVC, Registry of South Africa, and then briefly speak on a pilot study that we've been involved with called the IMOTEP Registry of Cardiomyopathy from our hospital, Krooderskia, in South Africa, and then briefly also comment on the multicenter pilot study that we conducted in South Africa and Mozambique. So ARVC in South Africa started in around... The first reported cases started in around about 2000. It was a series of about 12 patients that were described. And in 2003, we established the ARVC Registry of South Africa. In 2009, we published the first paper on the clinical features of a survival experience and the profiling of placofilin-2 gene mutations in our cohort. And at the time of the publication, it was around about the seventh largest registry in the world. So just briefly, what did this paper tell us? Well, first of all, I'm not going to have time to go through all of this, but this is our South African cohort of 50 patients, comparing it to the French cohort and a North American cohort. We found that the clinical presentation of ARVC in South Africa was quite similar to other studies across Europe and in North America. It was a disease mainly affecting young men. In South Africa, we have quite a diverse ethnic group, and we can see that ARVC was... Sorry, my point is not showing over here, for whatever reason. But you can see that the ethnicity was really across all ethnic backgrounds, and the list of symptoms were quite characteristic and similar to other cases reported across the world. When we looked at the survival outcomes, the survival at the stage in South Africa, we were just coming through the HIV pandemic at that point, and the life expectancy in South Africa in 2009 was around about... It was between 50 and 55 years. And you can see in the red... Let me show you on the red. Let me just go back there. In the solid line over here, you can see that the mortality was pretty similar to the general population at the time. So ARVC was associated with what we called an early mortality that is no different to the South African general population. But remember, at that time, our life expectancy was between 50 and 55 years. When we looked at the genetics, the main mutations that we were looking for originally in the South African ARVC register was PKP2 mutations, and we found that in 36 patients that genes were taken, we found that the hit rate for PKP2 mutation was around about 25%. We described five novel mutations, and I don't have the time to discuss each one of them, but there was a mutation that had a very common haplotype, and so we reported a founder effect, probably from the European-Dutch ancestry affecting some of our patients, that was common amongst four individuals. And importantly, there was one ACM19.2 that was a compound heterozygote both with a new reported mutation as well as a previously reported mutation that had quite a severe phenotype and had to be transplanted. I think it was around about the age of 18. So that was the original paper that we published. And then in 2014, the Imotep registry was established in South Africa, and really the establishment of this registry was to describe the clinical presentation, the etiology of cardiomyopathies across the intention was to be across multiple African countries but starting in South Africa, so that in 2014, all of the ARVC patients were amalgamated into the Imotep registry in 2014. Some things that we learned about the ARVC data at the time when we were transitioning into Imotep was the large number of patients that were referred to the registry in South Africa that, in fact, didn't have ARVC. So 162 patients were referred. 92 of those were excluded for another cause. And so the important thing, one of the important messages here was beware the mimickers of ARVC. Around about this time also, there was a new diagnostic ARVC published task force criteria which was published in 2010. And when we went back and looked at reclassified patients according to the 2010 criteria compared to the 1994 task force criteria, we found that a certain amount of patients who didn't have sufficient criteria according to the 1994 criteria met major criteria with the 2010 criteria. So, you know, we found it quite useful to reclassify all of our patients using the 2010 criteria. And currently, in about 2019, we had about 70 index cases with ARVC. Some of the mimickers of ARVC that we encountered in this registry was probably the most common was possibly early ARVC but insufficient criteria at the baseline or follow-up. And then there were a number of patients who had an alternative type of cardiomyopathy. Most of our patients had cardiac MRIs at several stages during the registry. And you can see some of the... I've listed some of the cardiomyopathies that patients had instead of ARVC. There were some patients who had idiopathic PVCs as well and some channelopathies. The 70 patients, we also found that when we compared our IMATEP data... So this is the 70 patients now compared to the John Hopkins Dutch Transatlantic Court. I'm not going to go through this, but they were pretty similar in terms of presentation, in terms of symptoms. Remember, all of these were probands that we included in the study. We found South Africa is quite a sporting proud nation, and 20% of our ARVC probands were endurance athletes, which is compatible with the world literature. About 72% of patients had both major repolarization abnormalities, so that would be the T-wave inversion from V1 to V3, as well as left bundle branch block VT. So we found that to be quite high. And about almost a quarter of our patients had a disease-causing mutation for ARVC, so that was 14 out of the 58 patients whose genes were tested. In South Africa, ICDs are not routinely available for all patients, even as a secondary prevention device. In our institution, we would implant an ICD, but a lot of our patients were coming from around South Africa, and there are some centers that don't have access to ICDs. And what we're just trying to show over here is that ICDs improve survival. So in the solid line on the top left, you can see those were patients who received an ICD compared to the hash line who didn't receive an ICD. So, you know, ICDs improve outcomes. In 2015, we then started the single-center pilot study of Emotep. So the rationale for this was to enroll, prospectively, all patients who were referred to our hospital with a diagnosis of cardiomyopathy. So these weren't just arrhythmogenic cardiomyopathies. This was dilated cardiomyopathies, restrictive cardiomyopathies, as well as hypertrophic cardiomyopathies. So between 2015 and 2017, at our hospital, 314 patients were referred. All patients underwent diagnostic testing, which included about 70% of these patients having cardiac MRIs, and that identified about 99 new patients with a diagnosis of cardiomyopathy. And on the top right, I'm going to just show you the breakdown. Most of our patients had an underlying dilated cardiomyopathy. Some patients had hypertrophic cardiomyopathy. We had four of our patients had ARVC, and 9% had restrictive cardiomyopathy. It doesn't project very well, but on the bottom right-hand side, these are the etiologies. About 43% of patients had an alternate, had what we call a secondary cause for the dilated cardiomyopathy, including a large chunk of patients who were referred for peripartum cardiomyopathy. And there were some patients with HIV and some other toxins. 25% of our patients, we thought, had a likely genetic cause based on family history, and 35% had an idiopathic dilated cardiomyopathy. When you look at the presentations at baseline, again, dilated cardiomyopathy was the most common. We had quite a low age compared to international cohorts, so the age of presentation here was about 36 years, and I think it was probably because it was quite a substantial number of women enrolled here with peripartum cardiomyopathy, which probably accounts for that, and then a large chunk of secondary or contributing causes, again, may be skewed by the large number of peripartum cardiomyopathies. These were the events at baseline here, just highlighted in red. So atrial fibrillation was very uncommon in the dilated cardiomyopathy group, occurring in about 5% of patients. VT, all our patients with ARVCs, were referred because of ventricular tachycardia. So that was the initial pilot study. And then between 2016 and 2022, we conducted a multicenter study across four South African sites, including a site from Mozambique, and enrolled 665 cardiomyopathy cases. So this is the data from that study. So this is the multicenter pilot phase, a study that was conducted mainly, most of the chunk of patients came from Cape Town. 75% of patients were still from our center, but three other centers were involved in South Africa and also from Mozambique. And in contrast to the previous study, we enrolled patients who had a preexisting diagnosis with cardiomyopathy as well, so 347 patients had a preexisting diagnosis of cardiomyopathy, and 318 patients were newly diagnosed. So it was a mixed bag of old and new patients. And in a nutshell, I'm just going to present the data here. So similar to the pilot phase at our hospital, we found that, first of all, secondary cardiomyopathies accounted for about 37% of patients. Non-familial causes about 36%, and familial cardiomyopathy about 27%. These are the median age and presentation. Hypertrophic cardiomyopathy, patients being a little bit older than dilated, arrhythmogenic, and restrictive. The disease entity occurred in multiple different ethnic groups. And on the bottom right-hand side here, you can see the pie diagram of the different etiologies. I'm not going to spend time on that, but the majority of patients, again, had a dilated cardiomyopathy, and a large portion of the dilated cardiomyopathies were peripartum cardiomyopathies. I'm just going to just briefly touch on the events at baseline, the arrhythmic events at baseline. So you can see here that dilated cardiomyopathy had about 6% of patients had atrial fibrillation at baseline or an SVT. The restrictive cardiomyopathies, a large proportion of these patients were from Mozambique and had endemocardial fibrosis, and that accounts for why, with advanced cases, why the atrial fibrillation numbers was much higher, 28%. And then ventricular arrhythmias occurring in the arrhythmogenic cardiomyopathy in about 68% of cases. So most of our patients who were presented with arrhythmogenic cardiomyopathy had an underlying ventricular tachycardia. In the last few minutes, I'm just going to just briefly show you some unpublished data from our genetics lab. So these, I'm just concentrating now not on the dilated cardiomyopathies but only on the arrhythmogenic cardiomyopathies. So about 69 of our patients had underlying genotyping and genetic screening looking for desmosomal mutation, phospholambin, and what we call cadherin. And what you can see here, for those patients who were presented with an ARVC phenotype, there were 67 of those. 26 patients had an underlying pathogenic mutation, most commonly PKP2 mutation. If you break down the genotyping in cardiomyopathies, you can see that PKP2 counts for about 30% of our cases with a spread of desmoplacan, cadherin, and then we had one or two patients with filament C and lamin mutations. The data for the dilated cardiomyopathy is still a work in progress. So just finally, then, the key genetic contributions from IMATEP. These are some of the papers from, and this is courtesy of our genetics team here. So we identified an identification of the PKP2 founder effect in South Africa. Just on the bottom right-hand side here, I think that was quite a unique paper looking at, for the first time, the identification of cadherin mutations in arrhythmogenic right ventricular cardiomyopathy occurring in about, I think it was three of our patients in the registry. So probably accounts for a very small percentage, but nevertheless, we found that the cadherin mutation can account for arrhythmogenic right ventricular cardiomyopathy. So the lessons learned from the registry. The IMATEP registry has provided important insights into the etiology, genetics, and treatment of inherited cardiomyopathy from South Africa. We found that ARVC mimickers are frequent. The clinical presentation of ARVC in South Africa is similar to international courts. PKP2 mutations are the most common, and we described some founder effects in South Africa. IMATEP2 is a future study and will aim to collect data from multiple African countries across Africa, up to North Africa, and hopefully this registry can serve as a model for the development of future larger registries across Africa. Thank you very much. APPLAUSE We'll be happy to take some questions from the audience. Let me ask you, Ashley, that was a very nice presentation. Thanks to you. In your reclassification, what imaging modalities did you use? I didn't see that you mentioned any questions about imaging in terms of diagnostics, which may be quite important in this patient subset. And also in your endurance athletes, how did you counsel them from athletic participation after you established such a diagnosis? OK, so some of our patients, from the original study, the 2009 paper, not everybody had MRIs. In fact, I think it was around about 60% of patients had cardiac MRIs to make the diagnosis. Cardiac MRIs are not routinely available across South Africa, and hence that's one of the reasons why. Some of those patients did have follow-up MRIs, and some of the patients were reclassified based on changes in MRI findings. I don't have that particular number with me, but some of the new findings... So the importance of not just accepting one cardiac MRI but serial MRIs over time can help you, you know, re-stratify your patients. So we found that repeat testing would be quite useful. Interestingly enough, in our original paper, I think we over-classified the epsilon wave, and I think around about 2010 or so, there were several papers on the usefulness of the definition of an epsilon wave and what it means, and some of our patients actually were downgraded from definites to borderline based on the change in the epsilon diagnosis. So that we also found quite interesting. All our patients who were... Well, I can't speak for the ones referred across South Africa in part of the registry, but for all our patients, we told them to stop competitive exercise. I know there's been a change now with hypertrophic cardiomyopathy, but most of our patients who had ARVC, these were programs with VT and had ICDs in our institution, we discouraged competitive sport. Just to continue with mild to moderate exercise. Thank you very much, Aisli. The next presenter will be Professor Mavad from Cairo. It's always energizing to listen to Professor Mavad. She is popularly known as the mother of electrophysiology in Africa. We are so privileged to listen to her presentation this afternoon. Thank you. Good afternoon, everybody. It's really my honor to be here. This is a joint session between the African Heart Association and HRS. It's going to be continuously there. The idea of the subject was chosen by our fellow, Dr. Salah Al-Ahwani, who started a research fellowship at Nashville. He made this idea come true. I'm going to present to you the inherited cardiomyopathy diagnosis management utilizing limited resources. This is the team who collected the data with me and did the operations. Two of them are sitting in the hall. I'm going to share with you our experience at HeartBeat Center, which we did a retrospective study obtained from this high tertiary center from January 2015 until March 2023, and we'll compare it to the Imhotep, which is Imhotep, which is a pharaonic name, which is a king. They call it now Akhenaten, after he believed with the prophet Yusuf. Then his name has changed. We had 263 patients, included patients in this study, dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, and restrictive cardiomyopathy. Their median age was 48. We included patients' children from 3 years and more than 18 years. 71 of them were males, and their body mass index, 29, because in Egypt we love to eat. Dilated cardiomyopathy was the common cardiomyopathy in this group and was similar to that in Imhotep study, then followed by hypertrophic cardiomyopathy, then arrhythmogenic cardiomyopathy, and then restrictive cardiomyopathy. Our median age at presentation was a little bit higher, 48 years, compared to 35 years in the Imhotep study, and we were not far away from the European research program where patients tended to be older. The family history was positive in 14% of our study compared to 31 in the Imhotep study. The comorbidities, we recorded it. Hypertension was recorded in 30%, diabetes mellitus in 17%. In the Imhotep, the comorbidities were 31%, HIV virus was there in 13%, and hypertension 10%. HIV virus is not routinely tested in our patients unless it is suspected. The echocardiographic findings showed that the ejection fraction was significantly lower in the dilated cardiomyopathy group. The dilated right side was mainly in the arrhythmogenic cardiomyopathy group. Investigations done, cardiac MRI was done in 12% in our group and Holter in 12%, however, genetic testing in less than 1% because we don't have this facility in our country yet. Sudden cardiac arrest patients presented with it in 1-2%, ischemic stroke, DVT, pulmonary embolism, left ventricular thrombus, but not significantly different. The type of arrhythmia of presentation, which was recorded either in the emergency room on ECG or by Holter monitor or through their devices, was ventricular tachycardia, ventricular fibrillation, mainly ventricular tachycardia in the dilated cardiomyopathy and hypertrophic cardiomyopathy groups. Atrial fibrillation, atrial flutter were also recorded. Comparing our results with the mHOTP study, ventricular arrhythmia was documented in 21%, mainly dilated and hypertrophic, then the arrhythmogenic. Atrial fibrillation, atrial flutter in 22%. In the mHOTP, VT was documented arrhythmia in 67% in those with arrhythmogenic cardiomyopathy. Atrial fibrillation and stroke in 7% and 3.5%. This is the devices in a cluster bar count of the devices implanted for different cardiomyopathy groups. We can see that in cardiomyopathy, CRTDs and CRTPs were implanted, and in the HUCM group, our hypertrophic cardiomyopathy group, we have the other devices. Comparing our results with this registry, 19% received ICD for primary prevention compared to 2.2 in the mHOTP, 14% for secondary prevention compared to 5.3 in the mHOTP, 31% received CRTs compared to 11.3%. Our patients were lucky that we do ablations and complex ablation using 3D mapping in ventricular tachycardia, AF ablation using 3D or cryo, atrial flutter focal ablation, and also his bundle ablation. The challenges encountered in limited resource countries like my country start by the number of population here. The number of population, 1.6 million population, served by 4,000 cardiologists, which is 37 cardiologists per million. We have 120 electrophysiologists, which is 1.1 electrophysiologists per million. Of course, not all of them are capable of 3D mapping. We included those who implant devices and do conventional ablations or received a certification, so they are not talented enough to do the complex procedures. We have 20 centers. 40 of them had 3D mapping. PASCAR made a survey and documented deficiencies in human sources and facilities for arrhythmia. A number of invasive cardiac physicians per population is very low. Even the number of pacemakers implanted is less than one per million. And 50 of the centers don't implant CRTs. In Tunisia, they have the highest number of arrhythmia centers per population, which is 0.8 per million. This is from the PASCAR survey. These are the number of devices implanted. The dark green color, this means that they are implanting high-energy devices. The white color, no implantation. And the light green, the only implant pacemakers, not high-energy devices. The same challenges are there in the EP service. EP service is provided in North Africa and South Africa and little in the West and East Africa. In the Arab Book 2021, Egypt, Algeria, and Morocco provided their data and, unfortunately, all in the first percentile or quantile, which means that not enough number for population. Again, in the ablation category, still Egypt, Algeria, and Morocco in the first percentile. The financial challenges we face come from lack of political will to establish and support hospitals and train workforces and support the equipments. Inadequate maintenance and frequent interruption of electrical current in my beloved African country. Lack of national health insurance, coverage of procedures, and also the high cost of the arrhythmia service. Imaging modalities. Echocardiography is widely available in Egypt with very good training. However, in other African countries like Mozambique, as mentioned in the M-HOTP, ECHO is limited in special referral centers with two machines in the southern, and this is not enough for diagnosis. Regarding cardiac magnetic resonance, we have 20 cardiac magnetic resonance centers serving this 106. Do you think this is enough? This is not enough. In Europe and America, they have 22. They have this higher percentage of machines per population, which is not available in sub-Sahara or in North Africa. Genetic testing. In Egypt, we don't have it yet, except in one or two private labs, which send the results abroad, and it costs a lot of money. Not insured. Zong Etal, in 2021 in Kenya, he said that limited genetic knowledge, lack of practice, guidelines, and equipments, high cost, lack of insurance coverage are all the reasons for genetic testing. How about the surgeons who might need them? The low-income countries, about 0.04 adult cardiac surgeons per million population. In high-income countries, 7.1 per million. And one of the surgeons said that we are like dinosaurs and we are vanishing. Management of cardiomyopathy. I will share with you some of the cases, which were very interesting to show you. This is a male patient, 24 years old. He had family history. His mother and his two sisters died. Suddenly, he presented with syncopal attack, complete heart block. His ECG showed complete heart block, interventricular conduction delay, and he had left ventricular ejection fraction was good, and we implanted for him CRTP. This is his echo picture. We can see the huge dilated right atrium. This is his ECG after implantation of his CRTP, and we tried to convert him to sinus rhythm, but he came back again. And, of course, his anticoagulation. This is a second case. A 39-year-old male presented to the emergency room with syncope and was found to be in ventricular tachycardia, received DC shock. Echo showed asymmetrical septal height, peripheral septum 35. He refused, and he had obstruction. He refused surgery, so we implanted for him dual-chamber ICD. On follow-up, his heart became dilated, and his coronary artery was normal, and he had a VT storm, and he received many shocks, so we took him to the lab. MRI could be done successfully and showed patchy scar. This is his ECG when he came to the clinic, and actually he received a DC shock from his device during this visit. This is why we took him to the lab to do him ablation. We had endocardial and epicardial procedures with our team, who became very, very talented in this, and we were lucky to ablate him or to have successfully ablated his VT using cartoon mapping and very good success. And this is his follow-up. No attacks, no VTs, no even ATP. This is a female patient, 52 years old. Her sister was known to have complete heart block and cardiomyopathy. She presented with ejection fraction, dilated cardiomyopathy, global hypokinesia, and complete heart block. We implanted for her CRTD, and this is her ECG, and she's still following up with antifailure treatment and, of course, follow-up of her device. This is another case who was referred from Libya to us, 15-year-old male boy. He came for ICD implantation. He was in sinus rhythm running all this VT. We did him echo and MRI, and the CMR showed that ejection fraction 35% and was diagnosed as non-compaction. We did him Holter 22% PVCs, so we decided to go and ablate his PVCs. We successfully ablated his PVCs actually in two sessions from the infralateral segment of the left ventricle and on follow-up. He had no PVCs. He had ejection fraction increased to 52%, and he went back to Libya for another follow-up and see if he will receive an ICD for his non-compaction or not. This is an interesting case, a 64-year-old male patient who got palpitation during his daughter's wedding in Ghana, in Hergada. He's very rich, of course. So he waited and went to the emergency room, and he had this VT for which he received ICD. They did him coronary angio, which showed slow flow with normal coronaries. One week after, he got this, another morphology of VT. He received dual ICD, and we did him MRI, and we saw there was a scar in the septum and left ventricle, right ventricle. This is his VT. We took him to the lab, and during VT, he had slow VT, hemodynamically tolerated, and this is a mapping of his VT, and he was ablated in the RVOT, and he was doing great. This is the last case, which I'm going to share with you. She is a doctor. She's a colleague. She's 50 years old with hook-up diagnosed at the age of 38. She was in the swimming team endurance, doing sports until the age of 20. Three years, she presented with ScreenCorp, and she received a dual ICD. You can see her septum was more than 35. She refused any intervention with surgery. She received the dual ICD, and we played with the AV delay in order to pre-excite the ventricle. On follow-up, she got recurrent atrial fibrillation, for which she was going to emergency room to receive a DC shock from her device, and we took him, and her left atrium was hugely dilated. Dr. Rania did this with me, and we ablated her. We did voltage map, and we found scar on the left atrium, and we did good for her. At this, I finished all my cases. I shared with you my experience and my colleagues' experience, and thank you very much for this very nice collaboration. Thank you. Thank you, Professor Mabat. Any questions from the audience? All right. I want to ask you, the patients that were diagnosed with cardiomyopathy that did not get an ICD, I noticed about 19%, and some of your series did not get an ICD. Do you have any follow-up on them, the primary prevention ICD use? Yes. We are not luxurious to implant ICDs for primary prevention according to the insurance and governmental policies. This is why we have this number. We hope that we change the policy of the insurance. Dr. Rania is the chief of one of the insurance hospitals in Egypt. We can. Actually, we risk stratify the patient for any cardiomyopathy we have, and we follow him. These are all my patients from my center, so they are closely followed up, and if we lose follow-up, actually some of them would die, and we get a message from his family that he died. So we follow them. I was just asking because when you look at the data several years ago from the Danish study that high-dose mineralocorticoid antagonists in some of these patients with dilated cardiomyopathy reduce the burden of sudden death, and the primary benefit was actually from reducing arrhythmic sudden death. I just don't know what you do in some of your patients that whether those kind of experiences or therapeutic approach you have utilized. Yes. We intensify medical treatment, and sometimes we have some charity hospitals like Aswan Heart Center and Ines Heart Center. We can send this patient to them if we cannot get the sponsor from the government or sometimes we get donation from one another and implant. When we reach the point that the patient should receive an ICD or CRTD, we do all our best. Alfie is here. He is the coordinator of all these communications. Okay. All right. If no other questions, thank you very much. Okay. I think we're going to play the video now for the next speaker. Should I make it? Ruben. Ruben, yeah. I think it's a— Sorry, the third speaker could not make it. It's sent pre-recorded. Dr. Ruben got his Ph.D. in the States from, recently he is from Tanzania. It is recorded. I saw it. I saw it, I saw it. Okay, hat. Mesh. Okay, Dr. Rubin was going to talk about epidemiology in Sub-Saharan Africa with etiology, diagnostic criteria, and management. Cardiomyopathy is a myocardial disorder in which the heart muscle is structurally and functionally abnormal in absence of coronary artery disease, hypertension, valvular disease, and congenital heart disease sufficient to explain the myocardial abnormality. Infective cardiomyopathy is a disease in which the structural or functional heart disorder are observed as a result of presence of a past infectious disease of various infection agents. Etiology of infective cardiomyopathy viruses, which are RNA, Coxsackie virus, HIV virus, and DNA virus, CMV virus. Bacteria like myobacteria, TB, spirochetes, leptospira, fungi like candida, protozoa, tryptozoa, macrosi, parasites, E. coli, granulosis, rickettsia, lycoxia, labuneti. The prevalence of dilated cardiomyopathy is ranging from 10% to 17% in most Sub-Saharan countries, most common at the third or fourth decade of life, twice as much in males as compared to females. Infective cardiomyopathy in Africa shows striking regional variabilities. In Nigeria, Toxoplasmosis, Coxsackie B virus play a role. Kenya, history shows evidence of viral myocarditis but no serological evidence. In Cameroon, 27% showed evidence of tryptosoma. In Africa, the presence of positive HIV test, non-viral myocarditis may be dominant. This is the number of viral genome detected. We can go to the next one. Yes, this is infectious disease diagnosis by tuberculosis. As you can see, this is a biopsy, and this is the X-ray of the chest and the heart in this tuberculosis infection. A specific single etiology of endomyocardial fibrosis has not been established. Suggested potential causes, parasites like Helminthus parasites, protozoa, Toxoplasmosis. As you can see in this echo, and this is the right side failure. This is very common in Africa. You see this picture a lot. Neglected tropical cardiomyopathies like Chagas disease, and this is tested by serological testing. Diagnosis of infective cardiomyopathies starts by ECG, non-specific abnormalities, presence of AV block or bundle branch block, atrial or ventricular arrhythmias. ECG is sensitive in 47%, and this is specific but not real diagnostic. Echocardiography, when you find unexplained left ventricle and right ventricle structure functional abnormalities, with systolic and diastolic dysfunction, and with or without ventricular dilatation. Then you think of arrhythmogenic cardiomyopathy. Cardiac MRI assessment of lead gadolinium is helpful in making diagnosis of infective cardiomyopathy. Infective cardiomyopathy, lead gadolinium T1, irreversible myocardial injury, scarring, and fibrosis are hyper-echo compared to normal cell. In infective cardiomyopathy, scarring occurs in the intramuscular or subepicardial. A differential from ischemia occurs as it occurs only subendocardial. CMR should be done before endomyocardial fibrosis in hemodynamically stable patient. Endomyocardial biopsy plays an important role in the diagnosis. It is not performed at all because of lack of technical possibilities and expertise. Important to perform endomyocardial biopsy in every patient with suspected infective cardiomyopathy. This is a gold standard. We wish we can do it in all African countries. Endomyocardial biopsy should be done early. Eight to 10 specimens in order to go to the lab with sufficient data. Immunohistopathology, histochemistry, and viral genome, and PCR should be performed at the time of the specimen. Treatment in the course of infective cardiomyopathy. Cardiomyocytes can be damaged by direct action of the virus, antiviral immune response, or autoimmune response. Cardiomyocytes can be regenerated. The focus is improving at the tissue. They are not affected. Response depends on the cause, severity, and irreversibility of the changes. Regardless of the cause, optimal heart failure treatment is the key to help these patients. So for treatment, we have heart failure treatment, treatment of rhythm disturbance, transplantation, and specific underlying etiology antithrombosomal treatment. Antiviral treatment should be early in the course of disease before irreversible changes occur. And also use of interferon B can eliminate adenovirus and enterovirus from the cardiomyocytes and improve heart function. Immunosuppression using steroids or steroids combined with azathioprine or cyclosporine A. Performing endomyocardial biopsy before starting immunosuppression is very important. Also, it is only important for autoimmune infective cardiomyopathy. High doses intravenous immunoglobulin. No consensus exists on the benefit of high dose intravenous immunoglobulin in the treatment of infective cardiomyopathy. Immunosuppression. The aim of immunosuppression is elimination of antibodies against cardiac proteins. There are some studies that confirm the efficacy of immunosuppression in dilated cardiomyopathy. Thank you very much. And thank you, Ruben. Wow. Extra thank you to Professor Marvin. Just right on the spot. He did it. Thank you very much. The next speaker is Professor Tandre who will talk to us about creating ARVC ablation program and also developing a registry. Thank you. Thank you for watching. I'd like to thank Mervat Sala for having me here. So switching the gears here, I'm going to talk about how do you build a new inherited cardiomyopathy, a new rhythmic cardiomyopathy program. Now why am I giving this talk other than Sala is currently at Vanderbilt with us? I was also a part of the best ARVC ACM program in this country, Hopkins ARVC program. I was actually, in fact, the first fellow in that program. Sort of a vision of Dr. Hawkins, Hugh Hawkins, who actually built the program ground up. It takes a lot of time. It's 25 years since the program's been started and how successful that program is. It's hard to see that far in the future when you really start a program. You have four patients in all. And when you start it, and you forget to see what it can become. And basically, I'm trying to give you a synopsis of what do you need in place to put this together. Now why have a program in the first place? And the genetics people on the cloud will really love it. This is a 37-year-old patient with structural heart disease, sudden death survivor, has a mutation in desmoplacan. He's got two children and he's concerned about what do I need to do for these children? But that's not the real question. The bigger question is, what is the extent of penetration in this family itself? And especially in a place like US, these people may be seeing you in Nashville or Hopkins. And the other families in California, you don't really understand that identifying a patient gives you a sneak peek into the entire family. And that is very important because the events happen in a similar frequency within the same generation to identifying. And that is the whole purpose of having that bigger picture, stepping back from the patient. And that can only happen if you have the resources in place. Because in a very busy practice, you're just seeing one patient at a time. And it's often very easy to forget what's behind the patient. Not only that, the same mutation can have different patterns of expression in the disease. I think when we started the program, we were looking at very specific phenotype. We're looking at ARVC, you wanted right ventricular disease. If you had left ventricular involvement, you didn't even belong to the program. You got kicked out automatically, right? But then over a period of time, you then compare notes. And you have desmoplacan patients can have both RV and LV involvement. Some patients present with RV chromopathy. Some patients present with the LV chromopathy. Lamin is a totally different picture. So having that outlook of saying that same thing can present in different ways sort of gives you the perspective. Now, I think the nomenclature has slowly changed. Now we're talking about arrhythmic chromopathy, ACM. I think that sort of makes sense, especially looking at it from an EP perspective. It is the arrhythmia that brings them to our notice. It's not heart failure, it's just the arrhythmia. And the arrhythmia is disproportionate to the amount of cardiomyopathy they have. There's often a familiar or inherited pattern, not always, but if you look at it closely, it is. There is an electrical component for the disease and there's a structural component. There's often an underlying genetic mutation, but you've seen that even in Africa, placophilin seems to dominate the picture. But a significant proportion of patients do not have an identifiable mutation. Maybe we'll find that down the road. Histologically, there's fibrous replacement of the myocardium. It's different from ion channelopathies where you don't have anything like that. And there's a progressive clinical course. Now, the purpose of having a program is having an accurate and early diagnosis, as the earlier speaker alluded to. You can have a lot of referrals to what they think is ARVC and it turns out to be that they have something else. They don't have ARVC, so it's really important to have a structure in place. You can say whether you have the disease or not, or you're indeterminate, and we need to follow you. It's very important for family screening. It's important for a multidisciplinary approach. You need other specialties, heart failure, sometimes cardiac surgery involved, so you really need a group team effort. It's important to step back and identify patterns in disease, right? If you just see one patient at a time, it's difficult, but if you have a group of people, you can always identify patterns to test new treatment, especially gene therapies on the, just around the corner. They're really looking for specific groups of patients who meet criteria. You want placophilin, early disease, no heart failure, have one episode of VT, have an ICD. Only if you have a registry, you can pick out ten patients and say, yes, I can find these people, so it's very important. And collaboration is key for discovery. Now, this is the Vanderbilt Arrhythmic Carmapathy Program, which I just recently started, and just putting all these together. What do you really need for an ACM program? I'm going to put that right on top, because I don't want to be excluded from this group. I need the electrophysiologist in there. It's important, because they present with arrhythmias, right? You also need somebody interested in heart failure. Now, there's a lot of pushback. An athlete who's really great comes with arrhythmia, and you send him to a heart failure specialist, he gives you a pushback. It's like, I don't have heart failure. I don't want to go to a heart failure specialist. You may have to rename that as heart function improvement specialist or whatever. It's important, because there is always this patient don't want to go see heart failure people, but it's important to have them as a part of the group. Pediatric EP, a lot of patients present early in their course of disease. Cardiogenetics, folks who can make sense of the genetic mutation and help you understand if it's important or not. You need cardiac surgery. I think we are presented with patients who have refractory arrhythmias. They do help us with sympathectomies and so on. But again, transplantation is definitely on the cards. Patients who present early in teenage years with VT are more likely to be in that phase by the time they reach the third or fourth decade of life. You need a genetic counselor. It's very important to have them as a part of the picture. They end up being one of the most important points of contact for the entire program. You need a program coordinator who makes sense of the whole thing, keeps these patients constantly engaged, coming back to the program. We also need research coordinators. We need post-doctoral fellows who can take up and put these data together, make sense of it, and publish. We need a psychologist. This is something that we've been working on to see how do you deal with these patients not only who have physical needs because of all their arrhythmia, but also have a lot of mental health issues because of being diagnosed with this condition when they're peak of their health and also have heart failure. You need patients to start with. This is something that I grappled with when we started this program at Vanderbilt. First of all, you come there, you don't know where to start, right? You basically, you know that there are patients who have ACM in this cohort. Lots of different people are following them. How do you group them all together? So you basically do a medical record search to see who are being followed. And then once you establish a program, rope them all in into one center. You have to look in cardiomyopathy clinics, patients who present to heart failure to see who all fall under arrhythmic cardiomyopathy. Patients who directly come to the EP lab with VT, that's an easy cohort for us to find and put in. And then you look at family screening, who among those patients have been screened with family. And of course, some patients are just referred saying, hey, this looks like ARVC to me on the imaging, what do you think? But then you look at a patient who was not referred for that in the first place. And that happens to a lesser extent. So you put all these people together. Just off the bat, just coming in to start a new program within three months, I was able to identify 170 patients who would fit the criteria of ACM. And put them all together in one group. Again, it's very important for an ACM program to have access to excellent echocardiography and cardiac MRI, right? I know this is one of the biggest things that are resource-strapped place where in Africa we wanna put things together. But it is important to have accurate imaging to be able to classify these people. Not only that, you need trained CMR readers. You need people who know what they're talking about when they look at CMR and trying to find out what is delayed enhancement? What constitutes a patent for non-ascending chromopathy? How not to over-diagnose this disease, right? That can easily happen when you start to lower your criteria. And you need some sort of a monitoring, some remote monitoring that you can actually do, ability to do halters, ability to do extended periods of monitoring, seven days, 14 day monitoring. And exercise testing, you frequently do that for patients with exercise-induced arrhythmias. And also to clear people when you have done a successful ablation, you really want to know what they can do and what are the limits and whatever. It's less on the order, but definitely useful. Now, the intersection of ACM and artificial physiology is a rapidly evolving field. I think our knowledge of ablation as ACM is improving, some of the substrates still are quite difficult. Titan and lamin tend to be difficult arrhythmic substrates. But as novel mutations are being identified, we're understanding what disease patterns, what arrhythmias they lead to. And we do know to an extent that once you know the genotype, you kind of understand what the phenotype is gonna look like based on what the genotype is. If you have a lamin, I'm always looking for septal VTs, titans, periodic VTs, and so on. So you really understand how a genotype predicts a phenotype, which in turn predicts the arrhythmia. So constantly updating yourself with what's happening out in the genetic field and how it affects the structure. Understanding the new diagnostic criteria. Now, the next set of diagnostic criteria is being worked on. What is ARVC, what's ALVC, and what are these different criteria? So I know this is still a work in progress on when would you diagnose a left ventricle chromopathy. It's very easy when you have the genetic mutation or when you have somebody presenting with arrhythmias, but that's not always the case. Also understand what are the indications of primary prevention ICDs. It's very simple to say that if you meet task force criteria, you need a device. That will mean a lot of patients who have a family history of it or somebody in the family getting diagnosed with ARVC. Now, you already have two points. And all you need is some T wave inversion and a few PVCs, and you have to say, well, you need a device. It's not that simple. So at an individual level, you should be able to risk stratify these patients. And for that, you need to understand what is the role of non-invasive or invasive testing and diagnosis and management of ARVC. We routinely do mapping and EP studies in patients who are borderline. It's also very important when you want to reverse the diagnosis. Somebody has given the patient a diagnosis of ARVC, put a device, right? Now you have to go back and say, no, I don't think it is. So we need an extra level of investigations and some invasive testing to show that we've done all of this and still we don't see the phenotype of ARVC. For AC immobilizations, it's very important to understand that a majority of these are epicardial substrates. Placofilin, we talk about. Placofilin is mostly an epicardial substrate. It's possible that they may have LV VTs, but even when they have LV VTs, it often ends up being basolateral or basal epicardial. We just had another case with Dr. Merva visiting us in Mandible. We just had a patient with ARVC who had actually previously ablated on their RV epicardium, comes back in VT, comes back four years later, and now he has LV basolateral epicardial VTs. We really need to understand that these substrates tend to be epicardial. So you have epicardial ablation, expertise is critical. It's important to funnel these to a group of electrophysiologists so that they gain expertise in this. If you just spread it, it's hard to gain expertise. So it is a decision that's made as a collective group, just to identify people and start developing expertise. And as your volume grows, you may need more and more people, but it is important to sort of have some centers designated to do these cases. And of course, you need collaboration with cardiac surgery as well. Philanthropy, we always hope some rich guy will give up ARVC, right? Yes, you just said, right? And then he donates to the problem. It's very important because this is a rare disease. And it's very hard to get grants, right? Now forget about, I don't even know an NIH exists anymore. So it's getting harder in the US as well. So it is important to have this in your mind, whether you're in Africa, India, US, doesn't matter where you are. Whenever you develop a program, a new program, the patients need to be the center of it. They really need to be engaged. And many patients are, they are engaged. Even a small donation can go a long way. It will fund early stage research. It will fund you hiring people, hiring committed fellows who really want to make it a part of their career. And raise awareness. As a matter of fact, I was funded by philanthropy too when I started the ARVC programs, totally funded by philanthropy. So I think it's important to give that career boost to fellows and faculty so that they can develop expertise in this condition and move the field forward. And education is very important. You have to train fellows in there. You have to have research and publications. It's just not good to see patients, but to tell your experience of it, your experience in a very resource strapped, Africa may be totally different from a very resource rich space. So it's really sharing knowledge is very important. And have routine family meetings for patients to gain knowledge about what is important from their perspective. What are they looking for, right? It's not about what you want to give them. What do they want? Really get, find out about that. And presenting in meetings like this, AHA, CCNs, it's fantastic to have a meeting dedicated to what are unique problems in Africa. And of course, we need to have a registry. We usually have an IRB approved protocol. Often it turns out to be an observational registry. And you have to track clinical follow up. You have to create research opportunities for fellows and faculty. And it also allows for collaboration with other ACM programs everywhere. I have alluded to this is patient engagement is very important. You need newsletters to keep them focused, keep them really involved in this. Keep providing constant updates and research. Opportunities to get involved in advocacy. Important changes in how even insurance companies deal with doling out ICDs. These patients look otherwise healthy, but they are at very high risk for sudden death, and how do you improve advocacy to access to resources? Collaborate on grant proposals and social media presence. I think that's important. I think, and I'm sure in Africa, social media is important. Spread the news about the disease, the awareness of the disease, especially among athletic population. And hold family seminars to engage the families so that they can spread the word to screen first degree relatives and so on. This is the group, right there you can see. There's Sala right there in the middle of all that. This is sort of the Vanderbilt ARVC program. And it's a part of a bigger picture. This is our recent meeting in Zurich where all the ARVC experts in the world have met. It's great, I think, to be a registry, to be a program, gets you invited to all these exotic places where you can have fun. But it also is a place where you get great ideas on what should you be working next. And also to develop consensus. Thank you. Thank you very much, Professor Tandri. Any questions from the audience? Thank you. Can you, sorry, please, can you use the microphone so that it can be recorded? Do you think the voltage-oriented biopsy is critical in some patients where there is crossover of myocarditis? And you know that the difference in prognosis is quite good when it's ARV involvement, myocarditis. What do you do in these cases of doubtful? Cuz in Italy, we faced a lot of cases that have been diagnosed as arythmogenic dysplasia, but they ended up as a substrate of myocarditis. Yeah. Proven by 3D mapping oriented voltage. Sure. Endomyocardial biopsy showing myocarditis, right? I think myocarditis is a intermediary step in all of arythmogenic cardiomyopathy, desmoplacan, placofilin. They all develop myocarditis at some stage. Depends upon when you catch them. And if you do a biopsy, it will show myocarditis. But how it evolves into the arythmic substrate is very variable. Some people get myocarditis and you scan them years later. It seems like this function has recovered, especially the circumferential pattern of myocarditis that you would see. But some myocarditis leaves profound destruction. So myocarditis to me just is an intermediary step and really doesn't define it. The endomyocardial biopsy role is interesting when you're talking about infectious causes. I'm sure there's another talk about tuberculous myocarditis in this meeting where it becomes very important. They do PCR and actually find tuberculous bacilli. And there, it will significantly change treatment if you have an infectious etiology. But I'm not sure myocarditis has been incorporated in the diagnostic criteria for ARVC, so we really base the whole diagnosis on the other features that would meet task force criteria. Dr. Aghalia is running an etiology service in Egypt. She's half Egyptian, half humanist. Thank you, Naya. Thank you, Dr. Aghalia, for your comment. A question is, how do you approach when you're doing genotyping of family members? How do you approach patients who are genotype positive, but have not yet have a phenotypic expression? How do you manage those patients? So, having genotype positive doesn't always seem to be equal to developing the disease, so it's a tricky situation there. It's at the end of the day, it depends on what the family wants. I don't try to test kids below the age of 10, right? It just creates a lot of confusion. Usually say, come back when you get to your teenage years or whatever. Sometimes it helps families to steer them away from the disease or families to steer them away from competitive athletic sports. There's a lot of congregation of that. Dad's an athlete, mom's an athlete, all the kids are going to be athletes too. It's going to be hard to steer them away from that. But sometimes it makes it easier for the family to steer it away. But if a teenager is found to be mutation positive, but has no phenotype, we follow them pretty closely. But don't impose any restrictions on them. Because it just becomes a quality of life issue for them. I often see them every six months, probably do a whole tour more than anything else. If I start to see multiple PVCs, which you should not see in a 16-year-old, once you start to see the emergence of PVCs or any structural changes, that's a wake-up call for them to say not to engage in athletic activity. But I don't think we have evidence right now to say if you're mutation positive, don't do it. Okay. Very good. Thank you very much. This comes to the end of our session. Thanks all for coming. Please fill your evaluation forms. We appreciate you all coming. Thank you.

inherited arrhythmogenic cardiomyopathy

ARVC registry

PKP2 mutations

genetic insights

South Africa

Egypt

multidisciplinary collaboration

resource limitations

genetic research

Africa