How Does COVID-19 Cause Cardiovascular Disease? (John P. Cooke, MD, PhD) May 11, 2020

[Music] welcome to DeBakey cv education I'm your host dr. John cook I'm chair of the department of cardiovascular sciences here at methodist Houston Methodist Research Institute and today at the cutting edge of our our program today we are going to be speaking to three experts in cardiovascular medicine who are going to be talking to us about kovat 19 and cardiovascular disease first we'll be speaking leslie cooper dr. leslie cooper's at Mayo Clinic he's chair of cardiovascular medicine there and subsequently we'll be hearing from dr. Martha Gulati dr. Martha Gulati is an expert in women's health at University of Arizona where she's also the chief of Cardiology and finally we'll be hearing from dr. Jeffrey Barnes from the University of Michigan who is an expert in vascular disease let's talk about kovat and cardiovascular disease let me go to the first slide so COBIT 19 as you all know is disease that is caused by this virus Tsarskoe v2 and this virus is enters into the vascular system the cardiac system the lungs the mucous membranes through this spike protein that's pictured that gives a characteristic crown appearance of the virus and it's becoming clear that in addition to causing respiratory problems this virus also causes cardiovascular problems let me just show you this slide from the CDC data mortality data that shows something at once fascinating and also quite alarming and and that is the non kovat deaths in New York City and what you're seeing there is a timeline and in from the period of April 2019 - April 2020 and on in red is the weekly deaths from heart disease in red and of course the weekly deaths from heart disease are its the largest cause of death in New York City and eniac in the US and throughout the world so it's no surprise that you see in April of 2019 cardiovascular disease at the top and in blue is pneumonia death from respiratory disease due to various kinds of pneumonia non kovat pneumonia and you know that does cause death throughout the year but at a very low level and what you see happening in 2020 and particularly in March and April when the kovat epidemic was hitting New York City you see a spike in non kovat related deaths as well you see a spike in cardiovascular disease death and in deaths due to other causes of pneumonia other than kovat 19 so we're gonna talk about that today we're gonna talk about what was what does this phenomenon mean what does it do to is Kovan 19 causing a dramatic increase in deaths from heart attack and stroke and to kick off our session dr. Leslie Cooper from Mayo Clinic we'll be talking about his paper he and his colleagues published this very nice paper and circulation just a couple weeks ago this is a preprint on the description of proposed management of acute kovat 19 cardiovascular syndrome so dr. Cooper thank you for joining us today and tell us a little bit about the spectrum of carven cardiovascular disease in kovat 19 John thank you so much it's great to be with you here on your show and to be able to share some of the observations that we put together in this really expert opinion paper at the time in mid-march when all of these reports were hitting the world's literature about the SARS Kobe - virus particularly in the lungs and the very sick people who are in the ICU developing sepsis developing cytokine release syndrome we realize this stan shal minority of these patients had cardiac involvement and that there was a very wide spectrum of cardiac involvement and so we sought to put together an opinion piece take a deep dive into organizing this literature beacon Bhaskar Marc Dresner and I with the help of Nick hendren really put this together and at the time which is now about two to three weeks ago I think it represented our state of knowledge about this particular corona virus and you can see in this figure which comes from the paper that one of the most dramatic and acute presentations is an acute coronary syndrome often with ST segment elevation Illustrated on the left side that's due in the it sometimes in patients who are older who have underlying and pre-existing coronary artery disease who in acute thrombotic occlusion that and certainly in the setting of acute SARS - gobe infection however there's another group of patients who have a similar presentation with what looks like an acute coronary syndrome chest pain often with ST food depression or elevation but on coronary angiography there is no thrombus and this is remarkable that report initially from New York ascribed this where perhaps it's due to micro vascular disease and we'll hear from Jeff Barnes a bit about that perhaps it can be due to stress related cardiomyopathy and it sometimes it could be due to myocarditis as you can see in the bottom of the figure on the left there that's my particular area of interest we'll talk a little bit about it them all in separate but related can be arrhythmias atrial are ventricular arrhythmias which can be made worse in the setting of hypoxia from lung disease but not just intrinsic lung disease related to the virus but also thromboembolic disease this is the virus that causes a hypercoagulable state you can get venous thromboembolism causing pulmonary emboli and acute right heart failure and finally toward the middle the end of these very sick patients course you can get a cardiac depressed cardiac function sometimes it's due to demand ischemia in the setting of hypertensive heart disease or or underlying coronary disease but it can also be due to myocarditis and finally some people get inflammation with a capillary link syndrome and sometimes in inflammation around the pericardium not common but we haven't seen case reports of tamponade so that's really the spectrum of acute disease with with kovat some of these patients most of them are older with underlying comorbidities but a few of them are quite young and have very little in the way of sepsis or underlying lung disease we have the next slide please so when we thought about the mechanisms of injury starting on the left there's a great paper by Mandy Mehra and then in the journal last week looking at a large multicenter database of the Cova patients showing that pre-existing coronary diseases ridiculous association with cardiac injury and all cause mortality micro vascular injury we touched on with venous thromboembolism toxemia from the intrinsic lung disease as we move from left to right across the figure all of these contribute to acute myocardial injury in individual patients to a different degree let's not forget in the septic syndrome a cytokine storm that in and of itself can depress myocardial function and finally direct myocardial injury by the virus that could be a viral cardiomyopathy or viral myocarditis remarkably with over 4 million cases now and over 280,000 deaths in the in the world we've only seen a handful of true myocarditis cases confirmed by autopsy we know that it can happen but it doesn't happen frequently and the question is why and is it a kind of myocarditis that we wouldn't typically recognize either by MRI imaging or by biopsy next slide please and so this slide is really what is my only man mechanistic slide it shows fayek myocytes and these are very sick Maya sites they are they originally induced from pluripotent stem cells in culture and then infected with the SARS Kobe virus in a BSL level 4 facility and there you can see multinucleated giant cells those are the blue nuclei you see with the red actin and finally the sorriest Co b2m protein all together this caused the cells to fuse together into this sin system it was highly dysfunctional and if this happens in vivo it happens in even to a small number of cardiac myocytes that could cause substantial proa rhythmic tendencies as well as cardiomyopathy we don't know yet if this happens in vivo but we're looking right now at translational studies next slide and I'd like to mark and Jeff to kick in and just talk about their approach to management yeah yeah I just had a quick question les back to you the cardiomyocytes do we know and I think Martha's gonna be touching on this a little bit later do we know if the cardiomyocytes Express the ace 2 receptor which is the way the virus gets in we know they do what they do ok so it's possible they do it I think it's a bit higher in female than male cardiac myocytes I don't know in vivo if that's true the biggest issue is really is it really a macrophage or for a fibroblast infection that's driving this the data the ITM studies from Italy some data from Germany would say that macrophages and five or less to some degree are more likely to be infected than cardiac myocytes and so we can talk about that if you want to at some point but this is the management slide and three weeks ago I just walk you through the first of the left sides we get as we join together to talk about this but the first box that left is supposed to say be aware the first thing you need to think about is in patients who do have an acute infection with Tsarskoe b2 is their cardiac involvement and if there is a cardiac clinical syndrome than to investigate it and to put that investigation in the second box there in the context of the overall patient needs is this someone who's in their 80s who has different life expectancy or vols than somebody in their 30s for example and we think that if troponin and now with point-of-care ultrasound would be the early diagnostic test to look for cardiac injury any thoughts from the group well I think you know it's interesting because as this evolved and we've been learning more initially you know when we were having difficulty protecting all our physicians we were told you know don't don't do an echo on everyone then if you had pocus okay yeah we can do point of care ultrasound if you had it we didn't have it so that became a big issue for us and then even about Kath when we were listening to our Chinese colleagues who were teaching us before we even saw a they were suggesting to us to not you know that they were using thrombolytics and of course when we talked about that just even as a potential of course art our cath lab team pushed back and said no way where you know we're gonna take them to the cath lab to see and I think that it's nice to have those that outline that you showed there about making those decisions because it certainly helps I think initially I would say we were kind of all doing whatever we wanted and I would just add to that I think the idea of having a plan in place and having the team be thoughtful is really critical whether your volume is low or volume is high I really like the idea that the troponin is early on in the the pathway however we also see that these components are elevated in lots of patients just like other biomarkers d-dimer and whatnot so it's really critical that we as the cardiologists are providing reassurance that not every positive troponin means an acute coronary syndrome and even some of the abnormal EKGs that we see may not necessarily represent that true acute coronary syndrome pattern that were used to so it's really important to be thoughtful to have a good plan in place and to understand the entire clinical picture as you're evaluating I think that yeah I think that's a really important element taking the the clinical history the lab data the vital signs and then the other studies the EKG and the echo I think you can rapidly get all of that information together in order to make an informed decision is this a patient that needs to go to the cath lab is this somebody for whom we can think about medical management and monitoring it's it's even more important in this setting not to rely on just one piece of data but really to get that full package together are though would be if a patient's unstable like if they're in ventricular tachycardia or v-fib I mean then we don't always know is it myocarditis is it you know is it coronary disease and I think these are where the dilemmas have come in place but I agree that a lot of young people are presenting with it looking like a cute em eyes on the EKG and then they're not good discussion that's great unless did you want it a little bit farther down that protocol the algorithm you had well we need to put the slide back up have you found a reciprocal ST segment depression could you put that slide back up I have that you don't know here a reciprocal depression in the code non schema so we don't have this slide back up but I can pull it up over here and we'll go with us so as we move down the algorithm we divide into clinically stable and unstable the people who are going to the unit you identify early and you give them the appropriate level of support that's that's really what the middle part of this diagram is about the bottom left emphasizes that the end of the care is not leaving the unit you do need to follow up try and if you are uncertain of the cause of myocardial dysfunction don't leave it but go on maybe to get an MRI when they're stable the imaging bindings can continue into that recovery period and finally in the outpatient setting we don't know yet whether there's going to be a long-term implication to kovat myocarditis or not and so it is important at this setting to give people a long-term follow-up that includes at least clinical assessment if not an echo then on the right side of the diagram we talked about cardiogenic shock and the importance of distinguishing basically jerk shock from cardiac dysfunction and that those are not always easy to distinguish and they often can coexist so not to overemphasize that but if you are uncertain go in the PA catheter at the bedside and finally have a upfront discussion about the need for mechanical support when is FMO indicated Thank You les and thank you for marching through those technical problems any comments from Martha or Jeff if not why don't we go on to Martha's presentation as I mentioned before dr. Gulati is chief of cardiology at university of arizona and she's gonna give us her take on Kovac related cardiovascular disease Martha yes you can go to the next slide so I mean the the cardiac injury you know there's a lot of different hypothesis of course there's the ACE to mediated direct damage that they think could be going on now I'm going to talk a little bit more about that but we also know in these patients there's what we call the happy hypoxic or that you know where they're running with very low low to saturation and there's probably myocardial injury occurring a result of that as well resulting in oxidative stress intracellular acidosis and mitochondrial damage there's also micro vascular damage that can be occurring here we'll hear a little bit more about that from Jeff but their perfusion defects and a vessel hyper permeability and even vasospasm may be occurring in addition to the whole cytokine storm or the inflammatory response that is going on and all of this together or even separately could be causing acute cardiac injury and I think we'll we'll find out a lot more as time goes on but all of these have been hypothesized as potential pathways for heart injury so we can go to the next slide so this is this is just a nice figure that the New England Journal of Medicine put out kind of describing the sort of differences in whether you know ACE two levels are good or bad and whether ACE inhibitors and they are B's are good or bad in these particular patients we know as you already heard from John with the ACE 2 receptor is the way that the Kovach 19 enters into a cell so that the ACE two levels we know are important from point.but and there is a question because ace inhibitors and a arby's upregulate ace - then the question was is there a danger in people taking these medications but at the same point in ACE inhibitors and a arby's also reduce that pathway over to the right in terms of the damage that can occur through the angiotensin ii type 1 receptor that ultimately can cause acute lung injury adverse myocardial remodeling vasoconstriction and vascular permeability so you know they were trying to in this article really nicely lay out what do we actually know is it dangerous inhibitors and a arby's dangerous or not dangerous because of the ACE 2 receptors and there had been a lot of early on information contradictory from one society to another saying take your ACE inhibitors and they are B's and other people saying no it's not safe and of course we got a lot of calls from a lot of patients saying should I stop everything and I think that then there was a nice statement both through the ESC and the American College of Cardiology and the American Heart Association saying keep on these drugs and if you go to the next slide I believe that this really this was a study that just came out yesterday but and published in the European Heart Journal but what they these were heart failure patients and what they looked at them are the people on ACE inhibitors and AR B's and look at ace 2 levels and found that there was actually no difference in the ACE 2 levels and they validated in another cohort of patients as well and that's what the figure to to the side was showing ultimately what they found is being on an ACE inhibitor or an ARB didn't increase your ACE to plasma levels certainly ace 2 levels were higher in mail and I'm going to talk a little bit about the sex differences but if okay but what they showed in that that study is that first that plasma ace two levels you know weren't changed by these medications and making those medications at least from that data suggesting that there is a reason to stop them now they did talk in that paper that you know of course that's plasma ace two levels and and that may be different than in the tissue and we don't you know measuring it in the tissue may be a different story and we need more information about that but I think that is to difference in men and women is certainly something interesting and I just wanted the chance to highlight it because again it there there is a sex difference actually in kovat 19 I think everyone's seeing this I think today the CDC was talking about it on television - how less women have died from Kovac 19 and less women have actually gotten infected and there there's a lot of different things going on here and not that we know all of them but you know the X chromosome actually holds a lot of our immune response genes and women of course we're lucky we have two X chromosomes compared with men and so and we've seen this in the past actually if you look at HIV and hepatitis C women actually have stronger immune reactions but overall there's probably other diseases as well but you know women are highly understudied so we don't always know all the sex differences but we know sex hormones have a role in modulating our immune response in this X chromosome has the high density of immune related genes and women generally mount the stronger innate and adaptive immune responses than men this results in a faster clearance of pathogens and a greater vaccine efficacy in women compared to men but also contributes to their vulnerability and other diseases things like inflammatory diseases and autoimmune diseases but we've been you know we have some animal studies some mouse models showing that the InSAR is not not this infection but SARS which is very has a similar makeup to kovat 19 is that the male mice were actually more susceptible than female mice to SARS infection and again there's differences that they saw in terms of or involvement and when they did a good ad a neck t'me on male mice it didn't really affect the disease outcome but if you did an oophorectomy on these female mice they actually were more susceptible and more likely to die from the SARS infection so I think that you know understanding these sex differences will help us actually at potentially identify treatments and and potentially tell us that different ways that you know different ways that we need to go about it now I will say that we don't know again plasma aced levels may be different than tissue asa levels and I think that's one thing we really need to see even from a cardiac involvement but any organ involvement to tease out what's actually happening in the organs so I will now pass it on to Jeff Barnes from University of Michigan to talk about more of the venous thromboembolism before we do that Martha I think we can have a little discussion about what you just presented it's really interesting and before we do that though I do want that people at home to know that they can text us text DeBakey two three seven six zero seven or online pol le v.com slash DeBakey so you can ask us questions if you're interested to do so Martha you met you talked about the ACE two receptors so this is a receptor on ourselves and on many of our cells that is involved in an important physiologic process turning angiotensinogen to angiotensin one and that also is apparently a receptor for the virus the viruses found a way to use that that receptor that ace two receptor to get into the cell through its spike protein you mentioned that there's some evidence that there might be differences between men and women in an ace to receptor how strong is that evidence it's very strong I mean we have the we have a lot of data that h2 receptor is higher in men overall and even in that that paper that was just published you know again those were heart failure patients but they confirmed that too that just that there was a higher ace to level in the men in that they were studying compared to women so if there's a higher ace to receptor on tissues in men and they're more likely to be infected I guess is that is that what you're saying that's what it seemed I mean this again is plasma levels so I think tissue level we also need to know a little bit more but that's what it seems if there's more ACE to there's more you know more ability for this virus to enter into the cells that's fascinating less Jeff any comments on that you know we'll mention one thing related Martha there was a really nice paper a couple weeks ago in Lancet by Frank which it's guy who's professor at the University of Geneva he showed in that paper at autopsy that virus is getting into the endothelium and he postulated that viral invasion of the endothelium which is the lining of our blood vessels might be causing a lot of the problems that we're seeing in our kovat 19 patients with venous thrombosis arterial thrombosis etc what do you think about that I think again the vasculature does carry a space to receptors so it is very likely the endothelium would be a great and easy entry point both from a cardiovascular point but also from a lung standpoint as well so I think that that's that I saw that paper I and I think that that is one of you know everyone's trying to figure out where you know what what's the what's going on but the entry point seems pretty clear I mean those crowns like you said are the place that cat latch on to the h2 receptor and make their way in so fascinating I wonder you know once the virus is inside inside you have to sell Machinery what it does to the mitochondria if you've got more of my time drill dysfunction in men because the hormonal milieu and the as opposed women in this setting that could give you a higher degree of myocyte dysfunction that's been shown in in my apprentice in some models trusting well I think we'll move on then to dr. Jeff Barnes from University of Michigan who's going to be talking about another cardiovascular problem that we're seeing in our patients with kovat nineteen and that is the venous thromboembolism deep venous thrombosis pulmonary embolism and also micro vascular thrombosis so Jeff tell us about that yeah thank you so much for for having me and I think what we've heard so far has really set the stage for this we can go to the the next slide you know these ACE 2 receptors are found in so many different organs including the endothelium and I think it helps to explain some of what we're seeing this is a slide just to let you know that some of what I'm presenting here comes from a multinational sort of collaboration of experts across the world trying to address antithrombotic therapy and thrombotic risk and coulded and i want to give a shout out to the two lead authors dr. Vik Delhi and dr. madhaven who led this up for not in New York and it was really a worthwhile I encourage you to check it out and Jack let's go to the next slide when we think about venous thromboembolism we tend to think about clots in the large veins of the legs and then embolizing to the lung but one of the interesting things we're seeing in kovin 19 with at least some early reports is that there may also be a thrombus in sight to process especially a micro thrombi process similar to what you've been hearing from the last two speakers here is a a past specimen a gross past specimen on the Left showing with the arrows some micro thrombi in different areas of the lung tissue and then on slides you can actually see the micro strom by in the small vessels on the right so raising this question about endothelial dysfunction and thrombus insight to being a contributor to some of the disease that we're seeing at least from a lung and a blood-vessel standpoint let's go to the next slide when we think about venous thrombosis and we think about it in the setting of Kovac there's a gradation of risk and that gradation of risk seems to correlate with the severity of the Cova 19:00 infection many people we believe may be asymptomatic but perhaps infected or have a mild case of kovat 19:00 but it's when you get to that orange and the red at the top of the screen where you're getting the moderate to severe forms of the disease that's where patients seem to be having this high risk of venous thrombosis and it's probably because it's this perfect setup for thrombosis think it back to Berk house triad when you have stasis of blood flow when you have hypercoagulability and when you have some sort of vessel wall injury that's the the perfect setup for a thrombosis these moderately severe or critically ill patients are often immobilized when they're intubated these are patients for whom there may be some endothelial dysfunction due to the direct action of the virus as we've been talking about with that East to receptor and the endothelium and then of course these are patients who get this overwhelming inflammatory response the cytokine storm that makes them hypercoagulable and so you can see all of that coming together and really creating a set up for thrombosis let's go to the next slide and we can explore that a little more there are a number of risk factors that these patients have now any patient whose critically ill in the hospital is at risk for venous thrombosis and certainly any patient whose critically ill with an infection or a pulmonary infection is at high risk but there seem to be some extra elements that may be playing in and some of our early reports suggest that the venous thromboembolism risk is at least as high and possibly or probably even higher than that that we are seeing in other non kovin severe infections you can see there may be genetic components there's dehydration there's sepsis there's underlying diseases these are patients who often have kidney disease have lung disease other cardiac conditions that put them at risk not just for covin 19 complications but also for venous thrombosis you can see on the bottom left some proposed mechanisms and especially the inflammatory response we see a number of different markers that are quite elevated and elevated for long periods of time in these patients probably representing that inflammatory response making these patients hypercoagulable and so in the middle we see the micro Samba in the lungs we're clearly seeing some coagulopathy it's not a pure di c picture but it's something similar we see myocardial injury we see the elevated biomarkers and in particular the d-dimer seems to be quite elevated and that results in a number of outcomes venous thromboembolism myocardial infarction and again this di ste or I've heard it referred to as like a a sepsis intravascular coagulation or even a kovat intravascular coagulation process so it's something that's a little bit unique but certainly concerning let's go to the next slide one of the big questions of course is if these rates of thromboembolism are so high how do we prevent them and I think one of the the keys is good use of prophylactic anticoagulation is absolutely necessary and we have good evidence this is a paper that just came out last week in Jack out of New York saying what about using therapeutic or treatment doses of anticoagulation and could that be beneficial and what you see in the two graphs on the middle of the screen is that the patients who received treatment dose anticoagulation in the blue line seemed to have better survival whether it's all patients admitted to the hospital which is column a or if you just limit to the patients who got mechanical ventilation in Figure B they seemed to do much better and so the main conclusion was that there was a reduced mortality associated with treatment dose anticoagulation but they also noted a higher risk of intubation and I think it's really important that clinicians not draw too strong a conclusion out of this use our observational data where there's a significant concern about confounding and selection bias the patients who don't get anticoagulated yet are critically ill probably have a reason to not get anticoagulated that may also be a reason that contributes to death and so there's certainly concerns we have about over interpreting this data it also comes from a single Center however I think it very strongly justifies the need to study this question what types of prophylactic anticoagulation are needed to prevent these venous thromboembolism events whether they be large venous thromboembolism events like we traditionally see or it's the smaller micros around by that we're seeing I know of at least two different randomised trials that are in the process of getting started or already undergoing right now and I think this is going to be critical information we're going to learn here in the coming weeks to months to help us guide therapy in the future John we'll turn it back to you there Thank You Jeff that was great any discussion from the panel remember seeing when the when China was sharing their information with the ACCC and they they showed that nice slide of you know when certain I can you remember the cutoff though but when the d-dimer was elevated and they did use anticoagulation and it was just observational as well they didn't tell us what they used or anything but there was definitely with a d-dimer cutoff there's people that did better but then without elevated d-dimer they actually saw a lot more bleeding complications as what I remember them showing us and so our is it is your in your in your practice right now were you anti coagulating everyone or were you using like all those risk things that the risk markers that you listed as well as if they're you know they're intubated was that enough what was it that you used to decide I'm gonna start anticoagulation yeah I think it's a really good question and we know that d-dimer is a risk factor for venous son Wamba lism yeah we also know that it is a nonspecific biomarker and it's elevated in lots of different situations and so it's certainly concerning and I've seen some of the highest d-dimer levels I've ever seen in our patients with kovat 19 so it certainly raises concern we don't however have good data to tell us that using the d-dimer alone to guide therapy is efficacious and so it's for me a part of the the general picture in how I'm making a decision our institution decided that we were going to be somewhat regimented every patient with kovat 19 must get venous thromboembolism prophylaxis in the hospital no questions asked and we tried to use methods that would minimize the number of nurse to patient interactions because we wanted to minimize that exposure risk so we really tried to encourage use of low molecular weight heparin once a day or perhaps twice a day in our obese patients once patients became critically ill and transitioned into the ICU we often increase that so that they were getting twice a day low molecular weight heparin prophylaxis we actually have some data from the h1n1 influenza epidemic where we found similar high rates of thrombosis in those patients who were critically ill and we were using a low dose infusion of heparin and so that's an Astra G that was employed in some of our ICUs but we wouldn't necessarily jump to treatment doses of anticoagulation unless we thought we were empirically we're objectively treating a venous time bomb was the case so we were not quite as aggressive at the University of Michigan as they weren't some centers in in New York I think it's an important question to study but we also recognize that higher doses of anticoagulation also increase the risk of bleeding and we were really trying to balance that carefully Jeff what about let me ask you a question about the ambulatory patients someone there's kovat 19 positive and they have risk factors for venous thromboembolism maybe they've had a previous VTE maybe they're obese maybe they have venous varicosities what what when would you put some on an outpatient basis or would you on prophylaxis yeah I think that's a really good question and frankly it's a question I'm getting at an increasing rate and I really do not know the answer to that we do not have evidence to tell us that prophylaxis in the outpatient setting your respective of the Cova 19 status is beneficial and that the benefits outweigh the harms unless you're somebody who has a very high proton biotic state or you're somebody who's previously had meanest on one list so I'm using this opportunity in those patients to reassessed should they have been on secondary venous thromboembolism prophylaxis anyway if somebody had an unprovoked clock a while back and they continue to have some risk factors it may be worth having that conversation to say you know in today's day and age we have new drugs with lower bleeding profiles that may be being on something prophylactic that's beneficial but I am NOT starting people only because of co vid on an outpatient prophylactic basis I actually think we need to learn a lot more about the VTE risk in the outpatient setting we just don't have data yet you're a vascular doc there's another vascular condition that's been reported the so called kovat toes I mean compared to the RT vascular events that we're talking about it it's you know not that important but it might be reflecting a microvascular derangement that's that's causing the other problems as well this these Cova toes this erythema disappearing lesion in people's fingers and toes what do you make of that with what's going on there and how does that relate to the cardiovascular events that we're seeing in the larger circulation yeah it's a really good question and it is definitely something that is being seen I personally haven't seen a case of it myself perhaps because all of my visits with patients are video visits and they can't quite get down there to show me those images of their toes but I am definitely hearing a lot about it my colleagues in New York have told me they've seen quite a number of cases I do think it represents some combination of either micro thrombi or inflammation and what's interesting is it's not just in patients who we know have or had a case of copán 19 but we're also seeing in people who didn't know that they had kovat 19 before it may be a marker in some of our younger patients who had a subclinical course that didn't end up in the hospital who then come in with these these really painful or or just red lesions on their toes it's usually a benign course it runs it runs its course they don't have risk for losing their toes or their fingers but it may be a marker of just how widespread this virus has been and we haven't necessarily picked it up because not everyone is in the hospital it looks like something we've seen Lesley you are in Mayo Clinic with me at one point and we would see pernil occasionally right the is lesion that occurs in people that had frostbite it looks very similar to her knee Oh doesn't it yeah you'd need to do the exam I looked at that I saw the the the when that paper came across a lot on the Kovac toes and my first thought was is it you know venous congestion or is it is an arterial small vessel process and you know it would take any one of us you know three seconds for the patient to figure it out but when you're it's hard to tell from the manuscript yeah so I'm not sure but you're absolutely right so if it was a problem of basal reactivity which is highly unreasonable because this is an endothelial Cody atrophic virus it certainly could could look like bernie on and we give it card or a-- and it would get better would you anticoagulate for Cova toes that's a that's a really good question I don't think I would go there right now again I think I would try and deal with the base of reactivity and provide reassurance but again I would use it as an opportunity to reassess did this person have some other reason that really they should have been antique wagon but I wouldn't any quite get them just for the Cova toes in and uh that's you know let's just suggestion with a good one last year suggestion was a good one using a calcium channel blocker because that that does work with perennial that we I mentioned Mayo Clinic only because anyone anyone that's had a tour of duty at Mayo Clinic has seen pernil because it gets so cold there in Minnesota we do see the patients with the frostbite so maybe antiplatelet therapy as well potentially yeah you know I've had a lot of people ask about that is there a role for aspirin you know should people take it and I know in fact there was even some suggestion I believe from Anthony foul at one point saying that perhaps we should think about aspirin in our young folks who are at risk for strokes right we're seeing some young people with stroke that may be kovin related and again I think it's it's an interesting question I I always am a little concerned to get too far out in front of the data we know that aspirin is not completely benign there is some risk associated with it but you know if you're somebody who's relatively low risk for bleeding it may be a reasonable strategy to use for a short period of time it certainly has evidence in reducing venous thromboembolism events we know that it has about a 30% relative risk reduction in recurrence after a VTE event it obviously has beneficial effects in arterial disease like mi for artery disease and stroke so there may be a role for that I would be careful about recommending it broadly but on a case-by-case basis it could be considered Martha you had something to add I did I'm sorry I thought I might have cut you off well I did have another question for all of you and and there's another condition Jeff you mentioned the disorders that were seeing in young people with kovat 19 what about this Kawasaki syndrome that's occurring can you tell us a little bit about what what is Kawasaki syndrome and why is it occurring in young people with kovat 19 yeah it's a really good question and and what we're seeing with these young people and I caution these are some early reports that we're we're just learning about is there seems to be a flam Ettore response that these young children are coming into the hospital way now I'm an adult doc I'm not a pediatrician and and so I'm listening to my pediatric colleagues tell me about this and they're really concerned that there there could be this overwhelming inflammatory reaction that appears similar to Kawasaki disease again another disease of inflammation that affects the blood vessels one of the manifestations we often see are aneurysms because of everything because of information of the blood vessels we do not know whether that's going to be the same thing in these people these young patients with Koba 19 or not but it's certainly something that we have an increased or heightened awareness for because of the similar patterns with Kawasaki disease so it's something that to be vigilant about and I think especially as more states open up and we start to get more interaction between children if that risk of covin 19 or the risk of the corona virus spreading may not necessarily manifest in a kovat 19 picture that we're used to seeing might we start to see some of these other manifestations we just don't know but we need to be vigilant and careful in watching for these good the the treatment of Kawasaki diseases is to treat the anti-inflammatory as a retreat of process with anti-inflammatories but that could potentially be dangerous with a viral infection do we do we have any thoughts about that yeah you know it's it's a good question and in fact to me it reflects some of the early questions I heard about just general Cove in nineteen if there is this overwhelming inflammatory response are these patients who should be getting steroids and other sorts of immunomodulators and of course you're always balancing keeping the inflammatory response from getting out of control with also making sure that you can control the viral infection and and so I don't know where where we're going I'd be curious to know you know Leslie or Martha what what you guys have done or what you've been reading but they're you I think you always have to be careful about giving too much anti-inflammatory when you know that there's infectious underlying process there's several you know in title six now on trial so I'm going right now three of them at least at Mayo and so as well as you know there were multicenter studies here and in Europe and we don't have the data yet so I think that when you're in that moderate to severe ill category you know passed the hypoxia phase then I think it's it's a really good valid question I think when you move and the kids I don't I'm also not a pediatrician that's all the report from the UK and another ones but I couldn't really know I I couldn't really comment intelligently on that but what I'd say is that we need the trial data because as you said as you point out John other other trials of anti-inflammatory therapy where there was a lot of good preclinical data turned out to be negative and and we did we need to just be rigorous and you know for now try and enroll everybody you can in a trial so we get data well we're coming to the close of our program thank you Jeff I'd like to hear from each of you had we had a little chance to talk before the program started today about how each of your institutions is dealing with kovat 19 generally and I thought that was very interesting a lot of similarities but some differences in and maybe we can start with you Jeff just think a back about the last month what's it been like at the University of Michigan yeah it's really been fascinating our entire delivery of health care has been transformed we essentially shut down all elective operations we stood up to new I see use to just prepare for the surgeon and we did get a surge we we ended up with just shy of about 250 patients in our Hospital with kuvira at one point we have to date discharged more than 450 patients with koban and we still have quite a number it has been a very interesting experience we've had a number of patients come in and require long courses of oxygen therapy supportive therapy and just do you know floor-level care general care but then we've also had the patients who just dramatically worsen end up in the ICU and have these really prolong courses and it has it has really changed the way we are approaching health care from an inpatient standpoint certainly as it's affected our outpatient delivery Doc's like myself or cardiologists were pulled in to help with the kovat care and Jen med service and it was an honor to get to do that but certainly pushed us out of our comfort zone a little bit and now we're figuring out how to rebuild and how to how to get to a new normal and so I'm going to be very curious to see what healthcare is going to look like in the coming six months because it's changed dramatically from where it was six months ago and kovat has really been a catalyst for that thanks Jeff Martha how about you at University of Arizona you're directing the cardiology program there what what surprises were there for you well the biggest surprise is we didn't get hit as hard fortunately as a lot of the other places and you know it's funny how all three of us are from different geographical areas I think that you know the thing that really was shocking for me was just how the hospital almost came to a halt and I think I think Jeff was is really right we are watching our healthcare system that had been practicing you know we all probably complained about this at some point in our lives we're still practicing medicine like the 1800s and look what happened and not that we should you know not that Kovan 19 is good but the good that we can find is that we found our health care system can change it took a big push but it can change it's change how we deliver care outpatient has dramatically changed I I think I saw one patient in the last month in person in my clinical setting and I almost was excited by it because it's very different learning how to use telehealth has really changed our our interaction the thing that we love is being with patients and then you're you're talking to maybe their computer doesn't work and so all you're getting is their voice but everything you know whirring a convincing patients even you thinking that they're having a heart attack they're telling you on the that they're having symptoms that you clearly know is unstable angina and you're begging them to come in to the emergency room because they're scared to come into the hospital so we have a long way to go nothing's like nothing's gonna be normal for a while we've been really fortunate though in Arizona I think that we shut down early and we're shut down long and we probably opening this Friday if everything goes well but you know we've got a lot to think about a lot to learn for our future I don't think this is the last pandemic we're gonna face and we're not you know I just read something before we got on this call that maybe this states that open to soon are already seeing increases so I don't know now if we're already entering the phase two as well that's a nice segue to lastly because beaches are open in Florida now it's my understanding are you concerned about a bump or another peak in cases yeah people have displaced the the seagulls the beaches are fall and now the there isn't concern about a second wave later in fall but I'd say what I would add to what Martha and Jeff said I'd agree with everything you said and I'd add the use of effective personal protective equipment has been transformative between masks here's mine here from from clinic and eyewear where needed has and the consequences of not using that effectively and not screening patients effectively because one infected inpatient can touch fifty or a hundred healthcare workers in the course of a few days or for couple weeks and that can lead to numerous people being out on furlough or you on on quarantine excuse me and that means a huge impacts to your workforce so you need to change practice rapidly as a Martha like like you a year ago we might have done five telephone a video visits a month now we do 2,000 a week at our site more than that it's it's completely transformed way we we manage and follow-up patients to minimize risk of virus exposure so I think that's going to create and I think that's the good thing in some ways that we are going to find niches for virtual care where it's better it's more effective for people it's more efficient than we ever had before in this new model so there's good there's good that'll come out of it but we're not going back in the next year after what we used to do there's some good that's come out of this right I mean I think you all spoke to that issue the medical practice is changing has changed dramatically in response to the pandemic you know the other thing that that I've seen that that's been fascinating is how the medical and scientific communities have pulled together around the world sharing information virtually immediately and I mean we saw that today on this program less and and Jeff you shared with us two papers that wouldn't even be in published yet I mean they're there they're in pre print form and and you've given that information to us today you know it's just amazing how rapidly we're learning and how we're sharing information it's just an incredible you know the one of the areas that we're working in is is making a vaccine and it was incredible the the developments in the vaccine world which we'll talk about this program another time but just the sequence of the corona virus in January was released to the world and within 42 days and RNA vaccine was made it's incredible the light speed rate at which therapies are being developed because of the communication and the technology well we do have a couple of questions I think we have time for one and from let's direct this one to you Martha this question is about ferritin levels and the the if question is is there any relationship between high ferritin levels and cardiac injury oh well I don't know it would be my answer but I don't know if any of my other colleagues actually could answer this better than me yes the early studies you know ferrin's it's a gradation but more than a thousand more than 800 were associated in the early Chinese studies with with higher risk of adverse outcomes okay and and does is it related to my viral myocarditis or is it something else that's that's uh that's the relationship that causes this relationship between hi ferrets and levels in cardiac injury what is it what is the mechanism there why is high ferritin levels causing cardiac injury well I have to be vague I think it's an acute phase reactants and you're getting a systemic the same I think that you get high CRP you're getting high parens and it's a it's a it's a response to the systemic inflammatory mob thank you all right okay thank you for that less all right well thank you all for joining us today on the cutting edge at the DeBakey cv educational series it was great to see you all Martha nice to see you again Leslie we worked together a long time ago it's nice to see again work together again Jeff thank you for your comments really insightful really appreciate having you guys on board be safe stay well to take care thank you very much yeah you [Music]

Channel: Houston Methodist DeBakey CV Education

Views: 4,846

Rating: 5 out of 5

Keywords: DeBakey Heart & Vascular Center, Houston Methodist, DeBakey Institute For Cardiovascular Education & Training, Grand Rounds Conference, Dr. Alan Lumsden MD, DeBakey CV Education, Cardiology, cardiovascular, Cardiac Surgery, Heart Failure, Heart Disease, DeBakey CV Live, Live, dicet, Vascular Surgery, Cardiac imaging, Structural Heart Interventions, COVID-19, Cardiovascular Disease, John P. Cooke MD, Martha Gulati MD, Leslie T. Cooper Jr. MD, Geoffrey Barnes MD

Id: aKb_L1KaZ8A

Length: 59min 4sec (3544 seconds)

Published: Tue May 12 2020