 Welcome to Texas Heart Institute Educational Programs. I'm your host today, and co-host and moderator with me is Dr. Stephanie Coulter. My name is Vanu Kreesha. I'm an Interventional Cardiologist at Texas Heart Institute and CHI, Baylor St. Luke's Medical Center. My co-host is Dr. Stephanie Coulter. She's an Assistant Medical Director at Texas Heart Institute and Director Center for Women's Heart and Vascular Health, and also Program Director, Cardiology Disease Fellowship. She's also Director of Cardiology Education. Welcome, Dr. Coulter, to join me at this event. Thank you for hosting us all, Dr. Karajan. Our special guest today is Mohamed Majid. He's an Assistant Professor of Medicine at McGovern Medical School at the University of Texas Health Science Center in Houston, Texas. Welcome, Dr. Majid. It's a special pleasure to have you today at this special event. For those of you that don't know, Dr. Majid was our cardiology fellow several years ago, and we are very proud of his achievements. Thank you very much. Thanks for having me back. It's good to see you on the small screen. Hopefully, life will come back to normal and see you again during conferences. Thank you, Dr. Majid. The topic of our discussion today is cardiology in the time of COVID-19. Here we can see what is the current status of COVID-19 pandemic. It's a serious, serious illness that's affected all the world countries, as we can see. And we can see from this information that it has exponential growth worldwide as far as infection is concerned. We have not seen anything of this degree and size as far as humans are concerned since 1918, or so-called Spanish flu epidemic. One of the greatest concern is that, as we can see here, the U.S. curve of growth and expansion as far as incidence of infection when COVID-19 is concerned is exponentially growing faster than almost in any other country. From John Hopkins' information from about two days ago, we can see the information as far as global incidence of this pandemic is concerned. We are seeing here the total number of confirmed cases over 700,000, which is clearly seen on the left-hand side, and is divided by different countries. And we can see that U.S. is leading as far as the incidence of COVID infections are concerned. Now, on the right-hand side, we can see the mortality or total deaths that are currently close or over 34,000 patients, which is a scary, scary number. And again, this is rapidly rising in all the countries, but also in the United States. On the right-hand side on the bottom, we can see pension and exponential growth as far as incidence of COVID-19 infections are concerned in the last two months, starting from January until March. And we can see that this exponential growth is rapidly rising in March. So what is the current status of COVID-19 pandemic in the United States? We can see two epicenters. The first one on the left-hand side, in the upper corner is Washington State, or Seattle, that was the first state and city where the diagnosis of COVID-19 infection was confirmed in the United States. And now on the right-hand side, we can see New York area with significantly larger number of patients that were infected with this virus. And then we can see that the virus has been spreading extensively throughout the United States and also as you can see in the state of Texas. And we can see on the bottom, the state of Texas, just until a day or two ago, had 2,700 cases with 37 deaths. We can see that New York is leading as far as confirmed cases are concerned and also as far as mortality is concerned. So the major concern at the present time, as far as United States is concerned, that this pandemic will be expanding very rapidly all over the United States and that actually the infection rate and mortality might exceed all other countries, including Italy, Spain, and also China. As far as what does the future look like when we look at the forecasting model is concerned looking at epidemiology type of assessment, we can see that in the United States we have roughly 120, maybe 130,000 cases that have been confirmed. But it is estimated this number can rapidly increase in number over a million and probably even higher somewhere in the range of two to three million. So that is obviously of concern. The issue is how to prevent this rapid and exponential rise in the number of infection with COVID-19. It is estimated again from an epidemiological point of view that we are just at the beginning of this pandemic issue and problems. Some of the cities and states are ahead of us as far as Texas is concerned. And it is estimated that New York will probably reach the peak somewhere within next couple of weeks and maybe a little bit later it will happen also in Washington state. We can anticipate that if we continue with the same growth in the state of Texas that we might not reach the peak until May or maybe even later. Obviously all of those assessments depend on how do we approach this pandemic problem and how do we control this rapid rise and what preventive measures do we include to prevent this from becoming a reality. So one more time as far as COVID-19 pandemic forecast is concerned and the projected infections we can see again that the minimum number of simultaneously affected people could be between 6.7 to 14 million. Now this number is scary but the reality is and you will see as Dr. Majid will present in his information it is estimated that approximately 80% of the population that gets infected will be minimally symptomatic or asymptomatic. So obviously we are concerned about this group of individuals because they could actually spread the disease extensively without even knowing. So it is a special honor to ask Dr. Mohamed Majid to talk to us about his recent publication in JAMA cardiology from March 27, 2020 related to this particular topic. Dr. Majid and his collaborators looked at the aspect of potential effects of coronaviruses on the cardiovascular system. It's a very extensive review and I'm sure it was a very cumbersome task, Dr. Majid. I have to congratulate you on this tremendous work and from my point of view looking at this and analyzing this information I think it's the best and the most condensed and appropriate information with up-to-date information related to COVID-19 infections particularly related to the cardiovascular system. You have gathered extensive number of publications for your analysis. I believe it's something like 85 different publications related to this particular topic. And in a very objective way you have assessed that literature primarily constantly on the peer review journals and extracting the most pertinent information related to this disease. So Dr. Majid, this is Dr. Stephanie Coulter and it's so good for you to be with us today. And I was really impressed as well with your paper. Could you tell us, how was this project initiated and what was the role of each author? Thank you very much for this opportunity. Well, the work started possibly 20 years ago. So actually I was looking at the papers we referenced. I realized the first paper we published on flu and cardiovascular disease was 20 years ago exactly. So when this COVID came actually it was not a surprise. It was something we expected. We always expected the next pandemic of flu or emerging infectious agents and we still got caught by surprise when it comes to the level of preparedness of our healthcare system. But as I mentioned, I've been working on influenza and cardiovascular disease continuously for the past 20 years. And that gave us a very good understanding of the mechanisms how the viral infections can affect the cardiovascular system and what to expect when we are heading into such actually unfortunate pandemic and the way that we are seeing. As the world is seeing more and more cases of cardiovascular complications from the virus, can you explain potential effects that the coronavirus has on the cardiovascular system? Correct. So we have a lot of preliminary studies, a lot of them coming from China showing that actually the virus has very severe inflammatory response. Actually the body goes to this hyper inflammatory, hyper immune status. We call it as cytokine storm that affects multiple organs in the body. As we are all cardiologists, so we are always think about the heart as the center of the body. We have our own biases, but obviously that's one of the biggest contributors to the patient's mortality and morbidity that we are gonna talk about it soon. But we know that viral infections, especially influenza that we have worked extensively on it, have multiple effects on our cardiovascular system. As we said, they have direct very severe systemic pro-inflammatory stimulation that can cause plaque rupture. Actually increases the risk of myocardial infarction, something we very reproducibly we have seen with influenza. We know that there is direct vascular injury and in case of influenza, direct vascular infection that you can actually find the virus inside the myocardium or inside the heart arteries that can cause actually very severe exaggerated local inflammation at the artery level and the myocardium. For example, we gave this virus, influenza virus, to the hypercholestromic mice and when we looked at the arteries, they're full of macrophages and inflammatory cells. A picture very similar to what we see in the patients who die of acute myocardial infarction. On top of it, we know that there is severe sympathetic stimulation. We know that there are other effects. For example, in COVID, we have ARDS, hypoxemia that further stresses out the heart. We know that there are superimposed infections on top of COVID and other viral pneumonia that can further damage the heart and actually cause myocardial damage, myocardial injury and myocarditis that we're gonna review some of the data for them. So over the past 20 years, what we have realized is that viral infections, especially influenza, SARS and now COVID can cause myocarditis, myocardial injury. We have seen a lot of myocardial infarction with influenza and we are going to see how much we see with COVID. And also arrhythmia is something that has been neglected for quite a while because my interest was always on atroscarosis and vulnerable plaques and high risk plaques and I worked with Dr. Willerson many years on it and he supported on my research for years. And then I realized over the past few years, oh, we have a lot of potential for inducing arrhythmia with this. Last year with Payam Safavi, who has been working for me and the EP Group for years, we published the first paper that during flu seasons. We have increased risk of having ICD sharks. We presented that ESC conference last year that we saw a very strong effect on increasing the sinus tachycardia. And we had another paper coming up on increasing risk of atrial fibrillation that was supposed for one of the AHA conferences that we canceled because of this pandemic. Hopefully we'll present it later on. So viruses are bad. Some viruses are really, really bad like influenza for the heart and unfortunately COVID is showing signs that it really affects the heart in a very bad way. So Mohamed, I wanted to ask you, can you go back to the diagram? It has been also reported that pericardium can be affected and some of the patients present with pericarditis. And actually there has been some confusion in certain instances where there's ST segment elevation and the interventionalists were thinking that this is related to a STEMI. And as a matter of fact, it was pericarditis that was causing ST segment changes. I couldn't agree more with it. Actually when we were talking about myocarditis, pretty much it's always myopericarditis. And you have very good point. I have myself tapped multiple patients who had had pericardial effusion after influenza, pushing them to the edge of tamponade. And actually two weeks ago, we had actually ST elevation in 24 year old gentlemen, three of other risk factors for heart which came with a very highly positive possibility of COVID. So you're right, we are getting more and more evidence that the pericarditis and this ST elevation related to it are happening a lot. And since our paper published a couple of days ago, actually I've got emails from around the country. People are stating very, very similar experience, similar to what you were talking about. Dr. Majid, can you explain to us in one of your tables, table one, which is coronavirus is known to cause severe viral pneumonia. Not only that they can cause cardiac damage, but they also affect in almost all patients, respiratory system and particularly lungs. So you have listed three viruses there that do that. And can you talk a little bit more and explain a little bit more about this particular table and as far as incidence is concerned and also morbidity and mortality is concerned. Sure, we have multiple coronaviruses that have been known to us for decades right now. There are four of them which I haven't listed here. They cause pretty much something very similar to the common cold and are actually contribute to the considerable amount of the actual common colds that we get every year. They are endemic, but they don't cause severe or fatal outcomes. However, there are three coronaviruses that are known to humans at this point that can cause severe viral pneumonia. The most significant one very well known is SARS COVID which called SARS epidemic a few years ago which actually has very some similar features to COVID and some which are not. First of all, the case fatality rate which SARS was about 10% of people who got it actually died which is very scary situation. However, we were lucky in one way that SARS patients were not infectious and contagious when they didn't have the symptoms. So for example, with fever screening and symptom screening you could really isolate patients who could be a source of transmission and that's how actually the international community got to it very fast and stopped that potential pandemic which we don't see those cases anymore. Also, I want to know actually there is something we have called here R-NOT. That's an epidemiological variable that we want to know essentially that shows a potential for transmissibility means that if somebody has SARS it has the potential to transmitting and infecting three other page persons. So after that we had Merus Middle Eastern respiratory SARS coroner virus which actually was even more fatal disease that actually the case fatality rate was 30%. Just pretty scary. We are lucky that this disease is not that transmissible it's and we have contained it very well so far. However, the problem with SARS-CoV-2 which causes the disease now called COVID-19 and I know the nomenclature is a little bit of confusing. People say why is SARS is pretty much what happened is that the genetic sequence of this new virus was so similar to the SARS coroner virus that they couldn't just name it very similar to it. So this virus is highly, highly transmissible. Unfortunately, that's what we are seeing right now. But the case fatality rate is much lower and we are a bit lucky on that area because it's not 10% or 30%. It depends from country to country actually from beginning of the pandemic to the end and depending on healthcare is very safe, very confusing, complex situation. But the case fatality is most likely around 0.7 to 2 or 3% in severe cases, 8 maybe. But generally we would consider the around 2 to 4. I think that would happen. However, we shouldn't realize all these numbers that we give these percentages or rates are based on the known denominator. So if you go to the population and realize suddenly that and we are saying that like half of the population who get this virus are asymptomatic or mildly symptomatic, you suddenly know that you haven't diagnosed a large proportion of these patients. And the case fatality rate means that the rate of the number of people who died when they are diagnosed with drops a lot. So the case fatality rate might be much lower when we start testing in every subject in the community. And that's something that for example, the Iceland government is doing right now. They're planning to actually test every single person in their limited population, which is gonna give us a lot of information. The other thing that you want to notice is the receptor that the SARS-CoV2 and SARS-CoV2 enter the cell is called ACE2 inhibitor. That's why every cardiologist suddenly gets very interested in it obviously for ages, they have been working with ACE inhibitors. So this is true. The virus enters the cells through these ones. The medications that we use, the ACE inhibitors and ARB do not affect the entrance of the virus through this receptor. Actually, this is one of the questions that it will ask you later, but while we are still on this topic, Mohammed, I would like to ask you, there is information that actually there are two strains of SARS-CoV2, so-called S strain and M strain, S that's more deadly and M is more easily transmittable. Now, you didn't mention this in there. Can you elaborate a little bit more on it? Well, let me give you this disclaimer first. I'm not a virologist, okay? And I have cultured virus actually in a lab on Pixar's Heart Institute, upstairs actually. I've worked a lot with the virus, but I'm not a virologist. I'm not- I'm talking about published literature. Yes, so with that one in mind, that publication is very controversial. There are many other scientists who actually disagree with that. Actually, if you look at it, actually many other subsequent literature after that actually do not believe in that notion, okay? So again, with my limited experience, but I pretty much read everything that has been out there. I don't think that we are facing that two strains. I wouldn't put my money on that issue that much. Now there are thousands, if not hundreds of thousands of coronaviruses in the animal world. And the question is whether the new ones will appear in the future that will be even more concerning that COVID-19. That's a very, very smart and right question. That's what we have been asking forever. You know, in 2004, I wrote a letter to the Lancet, the type, actually it was, it was of birds and men. It wasn't mice and men because we're dealing with the avian flu at that time. And it was type of mice and the role of cardiologists during the influenza pandemic. So that was written for this situation that right now we are talking about the pandemic preparedness. So back to your question, we were facing the threat of the avian influenza pandemic. It was highly violent, very fatal. We were really, really lucky that it was not transmissible easily from person to person. Mortality rate was 30 to 40%. We would have been devastated if it had a transmissibility such as this coronavirus. And again, this means that any year, any day, the humans are always susceptible to another pandemic. We don't know when is it, we're gonna sit back after this is over hopefully soon and see what has happened, what are the shortcomings, what were the strengths and plan for the next one. We hope that we wouldn't face that situation very soon in the next generation or next one, but we have to be prepared for it. Dr. Majes, one question I am very puzzled by in relationship to the way that the flu virus can mutate season to season. Have we seen mutations within the COVID-19 virus as it spreads from country to country or is it maintaining the same RNA structure as it spread? It's having a lot of opportunities to mutate from person to person through each country. Have we seen any evidence of this so far? That's a beautiful question. I bet you there are many, many leading scientists around the country that are sleeping every night with that question there. As Dr. Fauci said that the being of the pandemic, he was right, he said the good thing about flu is that we know how it behaves, we know how predicted, we know that every flu season our CCUs are full with it. That's where our search capacity is built for, for influenza and we can completely actually ad-recede when it comes. Problem is that we don't know. Fortunately so far, no major mutation, no clinically significant one or let's say epidemiological significant one has been found with me. And in my limited virology knowledge, let me tell you, this is a single stranded RNA virus. First of all, RNA replication is a defective one. It's not like DNA, which is very well preserved. So RNA viruses, whenever you hear it, you know that there might be defects in the translation and reproduction of the virus, but flaws can come and mutations. But influenza virus has eight strands of RNA. You know, if I put it in my mind, I always say like, it's like shuffling carts, whenever that, so every day somewhere around the world, mainly mostly in China actually, there is a newest strain of flu virus being built, you know, but fortunately it's either not transmissible from first from the actual animal host today, humans and this more important from human to human. So I really hope that we wouldn't have that. It's a problem, you realize that the flu, the disease was named COVID-19. So the question is that is COVID-20 gonna be, will we see a COVID-20? Would it be fundamentally different? Do we need a different vaccine? Nobody has that answer. Hopefully we would not have that problem. So Mohammed, let me ask you something very, very important and you have a slide there that shows this exponential growth of the instance of COVID-19 infection in different countries and the United States now is the leader in this pandemic, which is really scary. Now, we have learned from a Chinese experience and also from Italy and Spain more recently about clinical manifestations and the population at risk. And now this population at risk is changing because what we are seeing in United States in particular, it's affecting a younger generation, younger population, I think that the average age is somewhere around 50 or 55. So what is going on? Okay, this is a case fatality. We are talking about death rate to actually COVID. Here we see that actually in almost every country, the elderly are at higher risk for death. You see people above 80 years especially and it's pretty much a significant increase over 80. But you see, it's like J-shaped, it's not U-shaped. When we are talking about influenza, we see it in a U pattern because the children under age of two actually are high risk for dying from influenza. Fortunately, I'm a four year old son, I'm really actually happy about this one at least. We are always more afraid about the children than ourselves and fortunately we are here dealing with the adults, not the little children. There are reports of children dying and actually this is but on rare occasions. Is this related to innate immunity or anything? That's something for immunologists to work with. However, if you look at the next slide, this is the data from actually United States so far. And we talked about the fact that the death is higher in the elderly. But if you look at ICU admission and hospitalization because of the COVID disease, pretty much you see half of the disease happens in the people younger than 50 years old. And the hospitalization rate and ICU admission is really not that different between different ages. So that's very, very actually awakening message for the public. That's why when the governor of New York comes and tells people to stay at home, that applies to every single person at every age, okay? And we know from the past that we have learned our lessons from influenza, for example. Because that's the best study thing over the past 50 years. We know that this, you can get the disease and get sick with it. Also you can get the disease and transmit it to somebody else. Even if somebody is totally healthy and no comorbidity and young, first of all they can get sick, they can die and they can die of it. But even if they are a symptomatic or mildly symptomatic, they still can give it to the other people in the society. That's very important. Dr. Magid, that brings to mind, this whole spread of the illness throughout our country seem to correspond to spring break. And I have two daughters in college right now. And I had a daughter who returned to Vanderbilt University and was well and had a series of friends that had relatively minor symptoms were very lucky enough to be on a very good college campus with excellent administration and a good health center. And she had in excess of 20 colleagues in her senior class that tested positive for COVID-19 over two weeks ago. So occurring really just after spring break. So I think that people traveled, they weren't following any recommendations because there really weren't any at the time and they returned to campus and spread the bug. I'd like to know if you think that that may have been part of the spread here in America. I'm quite worried. Unfortunately, that's true. And we know that, for example, most likely Margie Grodd contributed to the situation to our very dear state next to us in Louisiana. And that's happening everywhere. That's extreme. I think going to the spring break or what actually I heard on the news, what they call it as COVID party, that's extremely socially irresponsible. Okay. And we actually, this morning I said news that some actually college kid was admitted to the hospital after going to the COVID party. Well, I can't got it, but you don't know actually multiple people are exposed to. This is the time for everybody to wake up and I can't tell you how happy I am that the sitting situation is extended through the next month. There wouldn't be any more wiser decision than that. You know, and this is the, it comes with all the hardships and all the prices we pay, but by not observing it, the price in the long term might be much, much higher. Mohamed, let me ask you something that has appeared in the literature and was a total surprise. And you have mentioned there are certain predictors or certain risk factors, advanced age, comorbid conditions, immunosuppress patients and so on. This is no surprise because any viral illness and any other condition can make the suggestion worse. But what was totally surprising to us when this appeared first from China then later from other countries in Italy that hypertension is also one of the predictors. So let's mention briefly, what is your opinion by reviewing the literature as far as hypertension being one of the risk factors for COVID? That's a beautiful question. So there's a data frame that was released by China CDC on about the more over 40,000 people, one of the biggest data sets that we have got so far. And as you said, people with cardiovascular disease expected to have 10% case fatality rate, that people with diabetes, with COPD, with hypertension cancer. There is one problem with this one. This is true. This is the description of the statistics that they had. But what we don't know is that they are not exclusive of each other. In other words, let's talk about it. We have been writing papers together for many years. This is like the multivariate presentation of the data. It's not a multivariate adjusted information. So having hypertension also is, we don't know if it's controlled hypertension or uncontrolled hypertension. There is a major difference between them. And having hypertension usually is a sign of aging too. Possibly, is it seriously related to aging? And it usually comes with other communities, diabetes, heart disease, kidney disease, CKD if it's uncontrolled. So we really, this is very good to give us the idea what to look for, but we are waiting for more solid information coming from other countries like South Korea, Italy. I'm waiting for them almost any day to come out. And unfortunately, now we have it in US. We're gonna have a lot of more information from here. It has been also postulated and stated, particularly related to China and Italy that actually, hypertension might not be a very reliable predictor because more than 40% of the population that had a COVID infection in China and Italy were actually smokers. So maybe tobacco is also one of the factors rather than the hypertension by itself. You have a very good point because especially what was not in the previous slide was that men had two or three times higher risk of dying from COVID in China. And we have to realize that in China, the rate of smoking in men is more than 50 or 60%. In women, it's less than three to 5%. So that might explain a lot of it. The other concern that we have, for example, in younger patients in US, why they're getting a lot, we don't have data yet completely, but there is a suggestion that maybe vaping is contributing to this one. That's some hypotheses that we have to look at. There are a lot of theories about the effect of androgens and hemorrhagic. The effect of androgens and how the androgen receptors and other things can change the behavior of the cells when they're infected with the virus. But I really want to back off on the basic science still we have very good clinical data for you. Well the good thing about having a large number of cases in the United States is that we've got the mechanism and the research capabilities here to help look at these kinds of questions with our electronic medical records which should be useful in the future. But Dr. Magic, could you explain to us which measures are being taken in different countries to control this epidemic and the effectiveness that you expect from these measures? That's a very good question. I think some of the best samples that we have had is, for example, from South Korea with aggressive disease identification, drive-through testing, identifying the index cases, quarantining them, actually they have been able to flatten the curve. And let me explain to flatten the curve for those who are not very familiar with it. But essentially, let's imagine the disease is coming to get us. And if there is no vaccine, there is no antibody from prior exposure. Look at the way that it's happening in New York. That's when the curve is not flat actually it's a disaster because our hospital systems are not ready for this surge in capacity. And however, if we can contain it and have the quarantine actually done in the proper way, people will get it very slow. That's gonna buy us time till we can build our hospital capacity, till we can hopefully have a vaccine in the population till actually we have enough ventilators, enough PPEs in the hospital for our doctors to take care of them and they'll be having investigational drugs being studied and we know how to deal with them. So if the patients, if we are successful in delaying this till the day that, oh, actually I've never been happy ever in my life, I've lived in Houston for many, many years, never been so happy to wait impatiently for the weather to get 100 degrees. I'm counting till it gets, I always was wishing that, okay, you have two more months, I'm praying for 100 degrees right now because most likely by this, most likely that's gonna affect the actually virus and we're gonna see actually dampening of the epidemic. So Muhammad, let me ask you something that it's a hot topic and is discussed by layman and also by physicians with experience and cardiologists. Let's talk a little bit about ACE inhibitors and ARBs that we use commonly on daily basis for treatment of hypertension. Those medications are very effective and there has been some speculation and rumors rather than any clear scientific evidence that they could be potentially harmful and I want you to give your opinion on the basis of the published information. What is the status of ACEs and ARBs in high-pretensive patients? That's a very good question. I'm getting it like almost every day from family, from friends on social media and email and well, here it is. We talked about ACE to receptor. I think that starts the whole thing and there is a knee jerk reflex that actually as soon as we think about these ACEs. So there are two theories, you know that positive ACEs and ARBs are beneficial or harmful. We know that it doesn't prevent the entry of the virus then down the road how it affects the metabolism of the cell and can it worsen it or improve it. We don't know, everything is totally especulating and everything is like based on some molecular, but we have to see that our molecular biology is very complex, highly overlapping and if you ask me, my answer is that there is not gonna be any significant effect but the data so far we know that from a paper by Dr. Gu published in JAMA Cardiology last week, they looked at the people who died versus those who survived, they actually in take out this medication were not harmful or beneficial. It was a small study, but we're gonna see it in more studies coming up. Currently the joint leader by the leaders of President of American Heart Association, American College of Cardiology and HFSA actually they expect opinion right now actually notifies us that most likely the intake of the medications are not harmful or beneficial from the virologic point of view. So if the patients are on it, let's continue now. Right, excellent. I think that that should be emphasized because we have millions and millions of patients on anti-hypertensive therapy that are using either ACE or ARBs and we certainly don't wanna stop this medication and cause a lot of harm with strokes, heart attacks and other problems. So there is absolutely no clear cut scientific evidence that they are harmful and I agree with you. There's a potential benefit not related to the virus or virology here. We are gonna talk right now about the cardiac injury that we know it actually we, actually I was talking to Stephanie a few weeks ago and she said, okay, we had these patients coming with 4 million myocarditis after influenza. Well, you know, actually I've been talking about it for ages and so let's put these patients together actually write on it, you know, how important it is. So we also see a lot of cardiac injury. Hypotetically, do you want to be on ACE or ARB when you're heading into an acute viral disease that has the potential to cause cardiac injury? We know that these medications help the heart to recover and help the whole ring model. So most likely there is a lot of benefit from that parts you know, that we are talking about. So Dr. Magic, can you tell us more about upcoming clinical trials? There's been a lot of interest in the media and with our politicians hyper-pervalating about whether or not one treatment may be beneficial and our sister hospitals on the street here in Houston are using immunoglobulins derived from patients who have recovered from Corona COVID-19 and trying this as a treatment in, you know, deathly ill patients. What do you think about the future of what we're going to be doing for treatment trial? Oh, that's the very, very good question. I wish I had to answer. I don't think anybody has it but we know that there are several classes of medications which are extensively being used for it. In our paper, we have a very long list of the randomized clinical trials which are out there testing pretty much everything which has been promising in this situation. Some of the most widely used medications include remdesivir. That's a medication that has been developed first to work against Ebola but it has been promising in the cell cultures against coronaviruses and it is in active clinical trials right now. Actually, the first patients in the United States actually were enrolled in this medication in clinical trials. Soon we're gonna get the result pretty imminent results from. We know that let's rather HIV anti-HI medication has been used very extensively in China and other places. One preliminary report that was published in New England just recently didn't show that much effect but it's still under further clinical trials in combination with other medication and different populations. Let's wait for it. Interferon beta has been used for many, many viral diseases. We are waiting for clinical trials again. Hydroxychloroquine is possibly the most controversial and possibly very promising. We have to wait. Let me tell you, there are countries that this is used almost as routine therapy right now. But the problem is that if you use it in 100% of patients or a very big majority, you don't know if it really works or not. You don't know if you get any harm from it or not. And some of the early reports that I've published are not something to justify to go and widely use it based on what we call evidence-based medicine. So we need data. As somebody said, they actually put it out there very nice. He said, in God we trust for everything else. We need data. So we really, really need a good clinical trials and there are more studies. I think the hyper-inun antibodies antibodies are very, very promising. The convalescent plasma is very promising, has been used a lot in the past. Monoclonal antibodies against IL-6 and other actually inflammatory pathway, immune pathway have been used and been treated there. There's a lot, pretty much everything that is out there is being tested right now by the scientists all around the world to see. WHO has started a very, very smart initiative, the Solidarity Clinical Trial, in 45 countries with a combination of this medication that we just talked, the four or five medication which are the most promising one to see in different population, different combination to see which one is the best. Most likely till we get very specific anti-viral, my hunch was in feeling is that we're gonna use a combination of different pills with different mechanisms that we do the key. There is another medication, Comostat, which is not available in the US. I've never heard of it, none of us, but it's a medication used for viral diseases and pancreatitis in Japan. It is generic there, the culture studies, not human studies, but the culture studies have been very promising. So, more and more studies and more and more drugs are coming out. We are really hopeful that we'll get some good data very soon. Dr. Majic, could we go back one slide and have a little talk about the injury? Correct, I think you saved- And how much excess mortality is associated with the troponin elevation, even- Correct. That's a full slide that you're showing. You saved the best for last. There's a couple of very, very interesting and very clinically important papers that just came out in JAMA cardiology. This paper by Dr. Gu showed that actually high troponin levels is a very strong predictor of death in patients who are hospitalized with severe case of COVID. Actually, interesting is that the high troponin level is predictor of poor outcome. If there is baseline cardiovascular disease, the effect is double-dub and without cardiovascular disease. Interesting thing was that even if there is cardiovascular disease at baseline and troponin doesn't go up, the risk is not that much elevated. This is very important. It shows the myocardial injury, how important it is. So it looks like our very sick patients die of ARDS or myocardial affection or a combination of them, mostly. There is another study by Dr. Ruan, are you again, which was published a while ago, again showing the same pattern. And if you show the next slide, this is a study by Dr. Shi, actually again published in JAMA cardiology, that shows that actually elevated troponin level, significant increases the risk of dying from the disease. And this is a study from a 418 patient that shows actually housing. So what's important, first of all, it has very important prognostic information. Can actually identify the high risk patient, that can tell us how to allocate our resources. Who is at high risk, who is at low risk? It shows us new pathways for diagnosis and possible treatment of this patient. These are extremely important. We are starting some studies in our institute to tackle this particular problem, in effect on the myocardial. I'm really intrigued by this as a prognostic marker of outcome. And do you think that we should be measuring troponin teeth routinely on admission and every day? Or do you think it should be every eight hours? What do you recommend? What have they done in the past for measurement of the troponin? We don't have very solid, out of this one, we don't have any big data to show actually be shooting all comers or not. I think my own personal approach would be people who are hospitalized in severe cases. Maybe we can do it because hospitals do have the capacity. We have it actually set up in every hospital. And that's gonna give us a lot more information. Possibly we are going to use it actually, I myself are going to use it actually everybody for research purposes to get a better picture of what's going on and actually interpreting based on an in combination with other factors that we're gonna. Mohamed, so it's really interesting because I talked to some of our colleagues from Italy that have treated thousands of patients with the so-called stemming, unquote stemming as the segment elevation. And they found that 40% of them actually don't have any large vessel of inclusion. And yet they have very elevated troponins which tells you it's a myocardial injury but it's not due to in all the patients a large vessel of inclusion but maybe small vessel occlusion, a microvascular type of effect with elevation of troponin. So that's an important thing to consider because we otherwise would have a tendency to very aggressively treat a large number of patients that do not actually have a classical acute myocardial infarction due to large vessel occlusion. I couldn't agree more with it. That's true. That's what we actually, if you go back to figure one, that's why I was telling you all these different mechanisms that can contribute to it. And we would expect type two MI with such severe disease patients are ventilated, hypoxic with the white lung as we call it, call it called neonotic. And all the very severe lung involvement and severe inflammatory response. It's not surprising at all and it is expected, unfortunately. So I would add one more thing here on this diagram. I recently had a good friend of mine from Colorado that elderly lady that presented with a DVT and pulmonary embolism as a first presentation of this or COVID-19. So it does affect venous vasculature and it does affect pulmonary vasculature. Well, you have a very good question. I just reviewed all that data for, there is a group of scientists who are working solely actually with purpose of developing data what to, on the effect of the COVID-19 entombo from the symbolic events. And we know that with SARS, we had anecdotal reports that there was extensive venous and arterial clotting on autopsy. We have seen case reports of PE and DVT in patients with COVID-19. There is a lot of changes on the immunostasis and coagulation factor. We know that the majority of them have been dimer elevation, for example. And there are a lot of coagulation factor that have been measured actually over all tendencies to have a pro-coagulant pro-traumatic effect from COVID-19. So you couldn't say better and we have to face it and expect these problems. I think I imagine it because with what Dr. Crazier was suggesting about the microvascular injury, if that were true, one might expect more women to have more symptoms of that and that might more events. And yet we see the great number of terminal events occurring in men and not so much in women, which leads me to believe that the troponin elevation is really probably more related to myocardial injury and myocarditis than to microvascular injury. And it's gonna be interesting to see how the data plays out as we diagram the outcomes during this pandemic. Well, you have a very good point. I think I'm airing on the side of it by the spread my cardio damage and injury. But we are waiting to get a lot more information to clearly understand what's going on in different sub-population. Well, I think we have come to the end. We could probably discuss this for hours and not being able to answer all the issues and all the questions. And I again, thank you very, very much. Number one, for your excellent work on this manuscript and I would like to congratulate your co-workers on it as well. I think, and I know for sure it was a joint effort. And not only that you had a cardiologist involved, but I think you also had a pharmacist involved in or PhD in pharmacology. And there were multiple institutions involved. So that obviously offers a more objective assessment and more expertise to it. And I think this manuscript will be well received in the cardiology community and it will be of great benefit to a lot of physicians to guide them as far as assessment is concerned and also management of patients with COVID-19 and other coronaviruses that might appear in the future. So unless Dr. Coulter has any other questions, we... I only have one question and which is that I'd like to ask Dr. Magid to come back after we've gotten more evidence and more data to come back and remind us what we've learned from this because we have a lot to learn and we could really benefit from his expertise. So thank you so much for participating in our first cardiology in the time of COVID-19. Thank you very much. Thank you. Just want to add, you know, when you're talking about my colleagues, you know, let's add someone. So what we have learned over the past few decades from effect of influence on cardiovascular disease that has helped us to better understand how COVID-19 works on the influence on the cardiovascular system. That's why, you know, my colleagues, Dr. Vardhani and Dr. Solman, world leaders in influenza research and its effect on cardiovascular disease, they're conducting very large, actually, clinical trials to identify the effect of influenza vaccination in preventing heart disease. And that was the foundation why we got together, tried to learn from what we have observed in the past and look for the future with this medication with this situation. Thanks a lot. And hopefully I will see you in better circumstances very soon. Well, Mohamed, stay well and stay healthy. And thank you once again. And for those of you that have joined us for this Texas Heart Institute Educational Program, thank you very much for participating in this program and make sure to join us in the future for other Texas Heart Institute Educational Programs. We will have several of them with the title of Cardiology in the Time of COVID-19. And within the next few days, Dr. Coulter and myself and our colleagues from Texas Heart Institute will join us on the specific topic of Ecolab in the Time of COVID. How to organize the Ecolab, how to make it efficient and what is the most appropriate way to use Ecolab during COVID infection. And there will be other ones as well as far as COVID-19 is concerned in cardiology. This will be related to cardiac catheterization lab, how to organize it, what is the best way to use a cardiac cath lab during COVID-19 and there will be many other programs in the very near future. So once again, thank you for joining us for this program.