 Welcome to Texas Heart Institute Educational Programs on Innovative Technologies and Techniques. I'm Zvon Rekreysha, I'm an international cardiologist at Texas Heart Institute and CHI Health Baylor St. Luke's Medical Center. The topic of today's presentation is arrhythmia and AI in COVID-19 epidemic. Joining me for this program are Dr. Wilson Lam, he's a Texas Children's Hospital, Texas Adult Cardiology Health Center physician, also working in combined adult pediatric cardiology and clinical cardiac electrophysiology. Also joining us is Dr. Mehdi Rizavi, he's a director of electrophysiology clinical research and innovations at Texas Heart Institute. And also joining us expert in artificial intelligence, Surrender Magar is the president and CEO of Life Signals from Fremont, California and he'll talk to us about technology that is currently available and what does the future hold as far as detection of arrhythmias are concerned. So gentlemen, welcome to our Texas Heart Institute Educational Programs. Thank you. So Dr. Rizavi, let's start with information on arrhythmias, how do they originate as far as particularly malignant arrhythmias and how this will impact our patients during COVID-19 epidemic. What is the substrate as far as electrophysiology is concerned for malignant ventricular arrhythmias? I think, first of all, thank you for having me. In one word, I would say it's chaos or dyssynchrony. What happens in the setting of some of these lethal arrhythmias is for one reason or another, the normal rhythmic activity of the cardiac electrical system is altered. So if we put this in the substrate of COVID-19 viral infection and we have had actually our program recorded on it with our former fellow Mohammed Majid who published an article in a recent JAMA that was March 27th JAMA cardiology 2020 where he actually reviewed all the cardiac effects of COVID-19 infection. And there are multiple. Some of the important ones are obviously elevation of troponin by itself either due to obstruction and STEMI or non-STEMI. But there are also several other ones. Of course, arrhythmias are very common in patients with COVID and particularly malignant arrhythmias. Can you just briefly mention how common are arrhythmias in patients with COVID infection? So one of the concerns that increases their arrhythmic geneticity is prolonged QT in a disease state. And as a matter of fact, maybe you can elaborate a little bit more on this particular item and how it affects different anatomical structures in the heart. So really the so-called long QT is it's essentially what I was discussing, the analogy I was using before. It's a prolongation in the refractoriness of the heart tissue. So that's what you call heterogeneity. Yes, correct. Or dispersion of action potentials. And then that, I guess, increases the automaticity as well. That's correct. And the way that it can do that is it can actually, now you're focusing on a different type of cells. These are the normal impulse formers of the cells. So again, the sinus node or the AV junction. And what happens is in those cases is if you have an over, you know, high levels of calcium, for example, extracellular and intracellular calcium, what that does is that can actually spark an independent heartbeat. And that's called automaticity. And then when that happens, that heartbeat, normally it would spread smoothly across the heart. And this is where a VT and a VF happens. That's correct. Exactly. Exactly. So-called wave breaks. Interesting. I think this explains for those of us that are not in the field of electrophysiology, what really happens in sick myocardium due to a variety of causes. But nowadays we are constantly on COVID-19 that can certainly affect the myocardium and all the cardiac structures to a significant way. Let's move forward and ask Wilson a little bit about inherited arrhythmia syndromes and how do those patients fare in the era of COVID and what cautions do we have to take into consideration when we are dealing with patients that could have inherited arrhythmia syndromes, Wilson? Wonderful. Thank you for letting me join on this conversation, Dr. Crazier. Yes. At the Texas Adult Congenital Heart Center and the Texas Children's Hospital, we're familiar with a lot of the inherited arrhythmia syndromes ranging from long QT, regata syndrome, and CPVT most commonly. The Heart Rhythm Society had gone together and had a publication just a few weeks ago about the things that we would anticipate and expect in this population. Fortunately, these conditions are rare, but as we think about the preparations that we have for this population, we can think about the risks that will happen in the general population as well. Long QT syndrome was thought to be the most frequent one, at roughly one in 2,000 of the population, and we know that, as Dr. Razavi had mentioned, the repolarization time, the refractoriness, has lengthened out, and that makes them more susceptible to multiple medications, such as the tested medications of chloroquine, hydroxychloroquine, and azithromycin. As you start to add other antiviral agents on board and some agents that we're not sure whether or not they prolong the QT or not, that's where we may get into more trouble. A lot of times with fever, many of these channels can be affected and become less functional, and we know that COVID happens quite frequently with fever as well. Fever is notorious as being a trigger for the Brugata syndrome, which is also one in 2,000. And with it, we end up seeing that we have to treat extremely aggressively to make sure that these episodes don't cause that. Short QT syndrome is extremely rare. It's only about 100 cases in the literature, and fortunately, these medications may actually prolong the QT and take them out of the range of dangers. That's the one population that might do better, but there aren't many of them across the world. Lastly, CPVT happens in about one in 10,000 patients, and we know that exercise and emotion are triggers, but as patients get sicker and get moved to the intensive care unit, they may require inotropes, such as epinephrine. And if we ever have to do a resuscitation, epinephrine is usually the agent that we use to code the patient. Unfortunately, it's also the agent that's used to prove if a patient has CPVT by inducing polymorphic ventricular tachycardia. This is one of the cases that they caution that you would not want to use epinephrine in a resuscitation case because of its potential lethality. Tell us a little bit about the ACC and AHA guidelines that were published recently in Jack related to COVID and QT propagation. Sure. Just a week ago, the American College of Cardiology joined with the American Heart Association and the Heart Rhythm Society to put out a set of guidelines for people that are going to be using these agents. We have EKG monitoring, and if the QT corrected is greater than 500 milliseconds, we should withdraw those medications. We should work aggressively to keep the electrolytes, such as potassium greater than four and magnesium greater than two. If there's any possibility of stopping other QT prolonging agents that can be found at crediblemeds.org, then we really ought to minimize the possibility of prolonging that QT. It is recommended that if these medications are used, they should be done in a clinical trial or registry where these are being monitored, but if someone chooses to use them outside of a clinical trial that an infectious disease or a COVID expert should be involved in conjunction with the cardiologists for the monitoring of the QT. Now, there are also other risk scores out there. Dr. Tisdale developed in 2013, one that you can enter a patient's age, their gender, and several other risk factors to find out the likelihood that the QT will prolong greater than 500 milliseconds, and that might gauge how frequently and how intensely we should monitor that QT. More recently, there were a couple of studies released this week, one out of Brazil that stopped their study enrolling early because a high dose of chloroquine at 600 milligrams twice a day, roughly three times the standard daily dose, ended up having about 20 to 25% of their patients had a QT that prolonged greater than 500 milliseconds, two of them having sustained ventricular tachycardia and dying subsequently. So let me ask you, Dr. Razavi, this question, because you are an adult electrophysiologist. If you have a patient that has several comorbid cardiac conditions, ventricular, history of ventricular tachyarrhythmias has a baseline borderline or slightly prolonged QT syndrome as coronary disease. Now, obviously, I would suspect you have to be even more cautious in this particular scenario, is that correct? Yes, absolutely. You're adding additional substrates, so, absolutely. All right, so Wilson, let me ask you now. There are a lot of drugs that can prolong QT syndrome, and there are certain ones that can shorten QT syndrome. And the important thing is for us, cardiologists, to be able to identify and know them and pay attention, particularly when we get a patient in the hospital with a COVID infection. And so, can you go a little bit over the list of drugs that we have listed here that could be potentially a problem in patients with COVID-19 infection? Certainly. So, if we think about the list of medications that are out there, beta blockers in general are useful agents that can calm some of the catecholamine surge and try to calm some of those arrhythmias. Many of the medicines that we use as antiarrhythmias are actually proarrhythmic as well in different ways. So, when we think about agents that are potassium channel blockers or class III agents, they will prolong the QT and can make things worse for people who are receiving agents such as chloroquine or hydroxychloroquine. That includes medicines like sodalol, amiodarone, and dofetalide. Some of the class I sodium channel blockers, as they're metabolized, they also can become potassium channel blockers and prolong the QT as well. So, many patients are on these medications for atrial fibrillation, and others of them have been on them for ventricular tachycardia, particularly if they have had ischemic heart disease. So, those are the medications that we really want to take caution. There are many other agents that are used as psychotropic agents and as antidepressants, anti-medics such as on-dancetron or Zofran, and many of the antibiotics, such as fluoroquinolones and azithromycin, can prolong the QT as well. And so, unless we're certain what the infectious agent is, we really want to take caution in combining these agents with our patients. So, Medi, let me ask you this question. We have a number of patients in hospital with COVID condition at the present time, and I don't know if you have admitted or you've been consulted on some of them, but would, therefore, your approach would be when you see it with COVID infection patient, you immediately look at his or her drug regimen and figure out what is absolutely needed, what is not needed, what could be potentially hazardous to patients' health, and then would you switch into different medications or what is your strategy at the present time? I think, yes. I mean, that becomes, I think, a secondary issue. If they're critically ill, you have to obviously make changes with data blockers and calcium channel blockers and things of that nature and have to put them aside. So, acutely, you try to go for, obviously, the best hemodynamic support you can. But kind of in a subacute management of these patients, I do tend to... Most of these drugs that, you know, as Dr. Lam was pointing out, a lot of these drugs can have effects on that QT prolongation. A lot of these drugs can't be used in patients with any structural heart disease. So patients who've had a history of blockages and so that becomes, that makes things somewhat more challenging. But there are still regimens, there are still individual medicines that even though perhaps in the long term toxicities acutely in the more short term are both effective with management of arrhythmias and at least acutely don't offer as much toxicities. And I think that those types of medicines become things like amniodone, for example. We may not like to use as much in the middle-aged patients, but in the short term, it's something that I would consider strongly. I see. So now we are dealing with this complex scenario where patients has multi-organ issues and frequently multi-organ failure, not only just cardiac, but respiratory, renal, and liver involvement, which is very common with COVID patients. So the question then is how do we, how do we from the cardiac point of view stratify patients to determine what degree of monitoring is needed to make sure that we're actually not doing harm when we institute a certain therapy. And as Wilson mentioned, hydroxychloroquine all of a sudden was popularized and there are other drugs as well that have been used and emdesivir and so on. And some of the patients don't have really severe symptoms that would necessarily require hospitalization, but somebody somewhere decided to start them on one of the medications that could potentially do harm and prolong QT syndrome and so on. So how would you approach this? Do you approach it with hospitalization in this typical scenario for monitoring? Do you just do an electrocardiogram to make sure QT before and after? Or do you use some kind of a monitoring modalities with one of the wearables to follow that patient? And Wilson, let me ask you first and then, Madi, you can make your comments on it. Sure. I think that it makes perfect sense to take the entire patient together. I think using a risk score such as the Tisdale risk score can help to predict what's the likelihood that QT corrected will be greater than 500 milliseconds. In a person who's relatively low risk, perhaps using some agents on an outpatient basis with electrocardiograms may be reasonable. But for anyone who's in a high-risk category, I think bringing them into the hospital and having monitoring makes sense and making sure that kidney function and liver function are also doing well as we take into consideration what other medications are they on? How are those medicines metabolized and how do those also impact QT? Madi? Yeah. I just want to both temper perhaps enthusiasm for some of these drugs, but also temper the kind of immediate blowback, especially with this most recent study that wasn't peer reviewed, but nonetheless the incidence of arrhythmias. If my understanding of the doses, again, Dr. Lam was pointing out, these are very high doses that were being used in this particular study at least. And certainly far greater than what we clinically use when we use these drugs for a variety of reasons. So that's just the temper. I don't think that if I do agree, if we monitor, we pick the patient as a whole and if we monitor them appropriately, I think this can be done with relative safety. I do think that the scoring algorithm to predict a longer QT is extremely helpful in this situation because you have so many variables not coming at you from different directions. So in essence, I think what I completely agree with Dr. Lam on this. Very good. So AI is getting more and more popular and bringing more and more information and modalities in patients with cardiac disease. And I would like to ask our guest today, Surrender, if you can mention to us what is the technology at the present time where we can record reliably arrhythmias and how will this impact not only treatment of patients with cardiac disease but also patients that might develop COVID. Okay. Yeah, thank you, Dr. Treasurer. It's a great pleasure to participate in this panel with some elite people. So Life Signals, we've been developing a platform technology in general to do serious clinical monitoring. And so I'll basically provide introduction to the technology and then briefly discuss how we are taking the technology and quickly morphing it into kind of creating products to specifically help the COVID-19 situation including some other things you've been discussing. So anyway, the slide which you are seeing right now, it really outlines the vision with the dream we started this company about more than 10 years ago. I think the whole idea was that, hey, a lot of patients, they are monitored today mostly in hospitals. And they are typically tethered to some kind of monitoring devices where the infection issues come up and because many wires are touching the body and the patients are not mobile, they can't go to bathrooms. And so the productivity is low because the wires get pulled off and so on. So there are a lot of issues. So our dream was, can you really create a world where all these patients are untethered? And we really were to study the problem that what problem we're trying to solve, we kind of looked into physicians and especially the people of your class. What do they look for really? What signals are most commonly monitored? So we kind of did an analysis and really collected the data from 2030 reports that what disposable biosensors get sold and mostly they're connected through the wires to patient monitoring equipment. You can see this brief chart which is not very visible but you see that we figured out that about 5 billion ECG electrodes get used per year and they're connected through wires. And then SPO2 and some other vital signs, that really tells a lot that what Common Leads practiced in the clinical world. So our idea was, can you create a patch, a wireless patches which are really working at same clinical accuracy, same level and you're really displacing this kind of monitoring which goes on in hospitals really using wireless patches or biosensors, whatever you call. So to create that word, we said, this is what we deal with because these are the procedures that go on in hospitals. One to twelve lead ECG, actually one is not really conventionally done in hospital, it's normally three to twelve leads. SPO2 is a very important signal, heart rate, respiration rate, temperature is monitored, blood pressure is monitored and stethoscope or heart sounds of different kind, the blood flow, those things are very key when you're seriously diagnosing patients or really in a disease management category when you're really trying to provide therapy and then monitor at that time. So our dream was really to create a technology which really has the characteristics shown on the right hand side because our idea was this should be able to scalable to where millions and millions of people can use it. So number one criteria was actionable reliability. It has to be so reliable that serious clinical actions can be taken. You're basically doing life and death situation, basically decisions you're making. Must be disposable because that's what hospitals like it. You place on a body then toss it out and no recharging or re-changing batteries, all that is tough. Clinical accuracy, highly robust wireless connection even when there are, let's say, twenty-thirty people in close proximity in an emergency room, each one maybe wearing a patch, how do you make it that the data wirelessly flowing from the each patient continuously into the monitoring device of some kind. So what we wanted to basically do was take some of that technology and quickly kind of try to morph it where it can be used for COVID-19. So you see these ideas we came up with were, hey, where is the bottleneck in COVID-19 today monitoring? First we found, first we figured out his screening people is tough and people are not feeling well. They're very anxious. Am I getting symptoms or is something going to go wrong or even if you're giving some people drugs and they may be at their home or whatever, can they be monitored and how their symptoms are doing. So the idea was we called it a kind of symptom monitoring just as a classification. So this patch and we are creating now, we had a lot of already kind of remote monitoring apps and so on for physicians and other things also our partners have then we created a kind of consumer oriented app for this patch where you can see that common things which COVID-19 really the symptoms produced are the temperature, body temperature of course the respiration rate, heart rate, cough frequency we are about to add and then we added the QT prolongation tracking what you were just discussing that if really indeed the different doses of the drugs are being tried. Well, Surrender, thank you very much. This is very informative and this is exactly what we need in our practice a patch that's disposable that adds many different components not just one because there are companies that offer that as well but this one is unique in a way I would like to ask co-participants Wilson if you want to comment what you think about this technology how you would use it and then I want to hear your comments as well. Certainly. I think a lot of the 21st century research is looking at big data and big data depends on capturing a lot of points, time points as well as data points so that you're able to bring in all of the clinical information is hopefully hopefully helpful so that we can figure out who are the high-risk patients the needles in the haystack that are otherwise attributed to being low risk but they just don't know it yet so I definitely think that there's a role a lot of the monitoring systems do very well for our atrial arrhythmias for the patients that we're not sure exactly what's causing those symptoms and we need to make a diagnosis it may have a role in determining whether they're on anticoagulation or what type of rhythm strategy we perform this is perfect for that. In the realm of COVID I think that there is a role for this the high-risk patient I think is going to be unfortunately admitted to the hospital already because of if they're really severe going to an intensive care unit they'll have their monitoring for that low-risk patient who we're not sure about or that intermediate risk patient that doesn't look sick enough to be admitted to the hospital that's a place where you can send them home with the monitoring to keep tabs of those other vital signs but I think you have to be very select knowing that many of the ventricular arrhythmias the malignant ventricular arrhythmias happen in a lot of the intensive care unit patients and the sicker patients may not be there already but there may be those in the needle and the haystack I think as studies try to determine where chloroquine and hydroxychloroquine can be used is it in prophylaxis, is it in an outpatient basis, that's where this would have a very important role to monitoring the corrected QT. Ready? I pretty much agree with again with everything Dr. Lime had to say I just want to bring out the kind of subtlety that he touched on that this is kind of the low intermediate risk patient perhaps maybe our biggest area of need and then certainly the ability to precisely call out the QT interval specifically towards COVID-19 and its treatment so yeah. I'm personally very intrigued and excited about this multi-detector disposable patches because as you mentioned the surrender not only this will be pertinent to COVID patients but to many other conditions particularly when we add all those different sensors let's say stethoscope and listening the respiratory function patient with peripheral vascular disease to have sensors and so on I think we'll be able to manage our patients better so I think the future is very bright for this in this field and I have to congratulate you and your company in your vision and moving forward with this technology in such a rapid pace. What you said is very important and really if you can get all vital signs not to put different pieces on the body so even this stethoscope the technology the way it is being integrated this team has done 10 years of work research in that area and heart sounds and how to pick up the sounds and even the very fine blood flow analysis for congestive heart failure patients and so on even correlating with ECG so a lot of good work has been done so it's really the beauty is embedded in the same patch you're seeing all these sensors because we have the silicon and take the input from all these things we have the radios which can manage we have the on chip processors where you can write any specific algorithms so I think it works very well and your comment by the way should not be really mistaken I think it was Dr. Lam made comment here that basically outpatient I think our goal was also to be equally applicable within the hospital setting as well where people are really basically move around they can go to bathroom and they're still being monitored constantly and for actually major OEM which I don't want to disclose the names which really builds patient monitors and so on I mean their goal is to really launch this as a within this year in hospital setting as a low acuity kind of man monitoring patch you know just one patch which manages all the signals you know in a kind of one patch that really some ICU and so on and they're being generally watched I think this one patch you really will keep track of everything and people are free to move around I think even your I agree I think in the hospital when there are many leads that are stuck on the body it can lead to a little bit of economy of space if you have to go into a room and take care of a patient you don't want to have to muddle muddy around with a lot of equipment and I agree I think that also if the pandemic truly surges and we have to move patients into a close to the hospital but not necessarily in the hospital because of limited resources a chip like this would be outstanding thank you yeah absolutely well gentlemen this was a great discussion and great presentation thank you very much for your generosity as far as the time is concerned and your valuable contribution to our Texas Heart Institute educational program particularly now when we are dealing with this COVID-19 epidemic thank you very much thank you