Breaking down the latest stats, cardiologist Clifton Watt, MD, sheds light on which chronic conditions raise the risk of serious consequences from COVID-19 infection. His update answers concerns about common heart drugs, looks at heart attack outcomes during the pandemic, examines heart damage from COVID after recovery, and assesses anticoagulation therapy in COVID patients.
so I'll go ahead and get started. I don't have any relevant disclosures. Um, so tonight I think that some learning objectives would be to learn about the cardiac manifestations of covert 19 as well as some of the common medical corps mobility's that we see in patients who have the infection. Um, I think another learning objective is Is one that's dear to me is toe Look at trends in heart attack, hospital care and out of hospital care during this pandemic will obviously get into that. You know that Trump eso I promised. This will be my only virology slide. But, um, this is, uh this is a slide of SARS cov to which is a single stranded RNA virus. And it has a a crown like morphology, which you can see here on the left. Um, and, uh, it has various a makeup of various proteins. Um, and we know about this spike protein. We've heard of that one. Probably the most, because it is directly related to how it how its infectivity is. But it also has an envelope, protein membrane, glycoprotein and nuclear capsules protein. But I'll point you to this. The right side of the slide, which shows how we think that the SARS cov to virus causes the Copa 19 infection, which either is through endo psychosis. Aziz. The virus gets taken up taken by the end of homes, but I think primarily the the hypothesis is that it's infect. It's infected. It infects cells directly through membrane fusion. So you can see how in this cartoon, the despite protein binds to, um, the ace two receptor and then directly, you know, fuses into the cell membrane and gets gets into the cell. That way, um, I bring up the ace two receptor because it's thought to be a big part of how it infects cells on gets into cells. Um, this receptor is prevalent in lots of different parts of the body. Um, it's in obviously, the cardiovascular system in endothelial cells. Cardiac Maya sites, the EPA, cardio adipose cells. But also it's present in lung tissue, Andi kidneys, the vascular system, the vascular endothelial cells as well as the G I tract. I bring this up because, um, there's been a lot of discussion about how a sin inhibitors or angiotensin receptor blockers, you know, by Sina Pro. But as a parole low certain those types of drugs affect the ace two receptor. Specifically, it was early on during the pandemic. It was thought that potentially these drugs that the use of these drugs could up regulate the expression of this is to receptor. And if it did, then would it increase the infectivity of the virus? Um, so there's been lots of lots of studies looking at this. Uh, um, these are these are primarily retrospective studies looking at a inhibitors air bob, angiotensin receptor blockers. And these studies have really not shown any correlation between the use of haste inhibitors, angiotensin receptor blockers and outcomes like morbidity mortality. Um, so at this point in time, we still recommend that if there is a clear indication for the use of these drugs in patients, for example, hypertension or heart failure that these these drugs not be stopped. Um, and there was one actually the first randomized trial looking at this topic from Brazil. It it included about 600 patients random i those 600 patients with Kobe 19 infection who were hospitalized. And these patients were randomized to continuing the ace inhibitor Air Bob or stopping the drug and the outcome was in hospital mortality, and there was no difference between the two groups, the group that were the group of patients that was on the drug and the group that was not on the drug. So again contributing to the the guideline from the A. C. C. American College of Cardiology that you should not stop base inhibitors. Airbnb's in patients who have coated who need the drugs. Eso Now I'll talk a little bit about SARS cov to and how it affects the heart, and I'll admit that we don't know exactly how it actually is dangerous to the heart. But we have some speculation that, you know, it could be from direct injury from the virus entering the cardiac Biocyte. Um, certainly we've heard of site a kind storm and inflammation from the virus. Um, you know these general inflammatory syndromes that I'll get into later That can certainly affect the the heart and also demand ischemia from hi poxy mia from acute respiratory failure. So these air, some possible, um, you know, direct cardiac effects from the virus. This is a cartoon showing not specific to COV SARS. Kobe, too. But just in general viral infections and how they can impact the heart. Eso showing that way. See, we've known that viruses viral infections can cause acute my they can cause myocarditis. They can cause a arrhythmias. Andi stars Kobe to is no different. Eso clinically what types of cardiac manifestations do we see in Cove in 19? And I'm sure some or all of you have seen or read about thes things. Eso probably the most common manifestations from a heart standpoint are acute heart failure, Myocardial tous, um, stress induced cardiomyopathy or talk it soup. Oh, or a pickle Ballooning. Um, atrial and ventricular arrhythmias air also fairly common. Certainly atrial fib Relation in acutely ill person with Kobe 19 is is not uncommon. Um, more rarely. Cardiogenic shock, um, is a is a manifestation. Patients sometimes need to be put on ECMO. Andi need advanced therapy. Um, okay. And we've also observed that the risk of non ischemic myocardial injury is higher in cove in 19 patients. Um, come, you know, compared to ischemic mile cardio injury. Um So there was an observation. I'll study of 28 patients with S T elevation and my from Italy, um, in cove in 19 um, and showing that about 39% of these cases with S t elevation M I did not have any culprit lesion on angiogram even though they presented with S t elevation and my and and cove it to give you ah kind of background in patients without co vid with with stem E S t elevation and my typically, we see rates off. Around 90% of these patients have a total inclusion of their coronary. So it's a much, much lower percentage on these co vid 19 patients who have a culprit lesion. Um, we we speculate that you know, Kobe 19 patients have, you know, higher, um, incidents of, you know, from biotic or thrown bomb bolic disease. They have a higher, you know, inflammatory milieu. Because of that, they're probably growth robotic, Andi. They also can have a cute plaque rupture. So they probably do also have a higher risk of, you know, ischemic injury. Um, if someone has an underlying ischemic pred election, um, so it's certainly something that we need to watch out for. You know, we need to do our due diligence and look for a ski mia in a Kobe 19 patient if our clinical suspicion leads us that way. Um, so now I'll talk more about common co morbidity is for Kobe. 19 infection. Um, so this is actually a common probably one of the most common questions that I get in the outpatient setting, Um, in the clinic and the cardiology clinic. So I get asked, um, by patients, you know? Oh, I have I have high blood pressure. I have diabetes. I have I had a heart attack five years ago. Am I at higher risk of contracting over 19. And so we have data for this. Um, this This is data, actually, you know, earlier on from China from Wuhan, China, in 168 patients who actually died while hospitalized there on, Do you concede? E. First of all, you can see in this top panel you know, the average age of these patients who died of covert or from Cove it. Andi, you can see obviously the bias towards the population older than 60 years of age. But what I'll point out to you is this middle panel showing that in these patients, you know, almost 50% of them had hypertension. Almost 25 to 30% of them had diabetes and about 15 to 20% had the scheme IQ, heart disease. Eso um you know, certainly there is a high prevalence. Or was the high prevalence of thes co morbidity ease in these Kobe 19 patients? Um, now, one cabinet caveat, I'll say, is that you know, the data that we have primarily are from in patients there from hospitalized patients. So e think we're still gathering data from the outpatient setting on one on outpatients with cove in 19 infection and there their risk factors. Um, this is a busy slide, but I'll point away point out sort of the key points. So this is a This was a study looking at 1500 patients who were admitted to I c use with Kobe 19 in Italy. But I'm going toe show you similar, um, findings that in these patients ICU patients hospitalized with Kobe 19 similar numbers. 49% of them had hypertension, 21% had cardiovascular disease that included coronary artery disease, cardiomyopathy and heart failure. Um, 18% of them had hypercholesterolemia and 17% have diabetes. So again, you see, you know, similar numbers of these common co morbidity ease in Kogan 19 infection. Um, in case you thought, Oh, that's China. That's Italy. That's Europe. We have similar data from New York City of the U. S. Eso these air. This is was analysis of 5700 patients with hospitalized with Kobe 19 in a cluster of New York City hospitals. Yeah, I think over the period, you know, I think March or April, Um, and I'll point out similar numbers that, you know, Of those patients, around 56% had hypertension, 11% had coronary disease and around 7% had congestive heart failure. Um, and in fact, you know, about 90% of us patients hospitalized for Kovar 19 have had at least one underlying co morbidity. So this is this is a question that I get a lot from patients and and hopefully that can help you council your patients when they ask you this. You know, there was also a fairly high prevalence of obesity 41% and diabetes, about 34% in this population. And to note, uh, about 22% of these patients hospitalized had an elevated proponent. All right, so moving on to kind of one other. Another topic that is really interesting to me. Which is how cove in 19, the cove in 19 Pandemic has affected how heart attack, um, numbers and treatment has transpired. S so this is a data coming from the UK um, looking at hospitalizations, or I should say, admissions for heart attack. My acute myocardial infarction in in the United Kingdom on dso eso these air four different panels, acute coronary syndrome. Any acute m I stem me and and stem me on Dukan. See that? You know, the beginning of these curves start in January, Andi, Then you know progress to at the end of the line or the curve. May Andi thes vertical dotted red lines correspond to the date of Actually, when the UK initiated, they're locked down their national lock down. And so you could see how and when we all know that you know, covert 19 infections started to increase around in the UK around February march. Andi, you can notice the point of these curves you can see, is that the heart attack numbers actually started to come down dramatically as corresponding to the peak of Kobe 19 infection. And you can see that in all four panels. You can see how the numbers of admissions for heart attack, um, trending down dramatically. Um, And then, you know, you could see how it did start. Thio. These numbers started to increase towards April May, um, and but they did not return to their baseline. Yeah. Did not refer Return to baseline. And so So the hypothesis behind me, this is is that patients tended to try to avoid getting hospital care, um, for their heart attack, even if they had symptoms because they were afraid of contracting the virus in the hospital. Um, and this was recognized not just in the UK, but in other countries. Andi, I think that, you know, health health systems started thio, you know, reassure their patients or I guess, you know, instruct their patients that they shouldn't postponed their, You know, their presentation with chest pain because they're worried about catching the virus. They needed to get there, care it was imperative. And so that could explain how the numbers and started to go back up, But they still did not return to baseline. Uh huh. Um, this is similarly this is, uh, this was a study from April from a hospital in Hong Kong, China. Andi, this This looked at actually time from different times from presentation, um, to treatment of their heart attack, you know, so onset of chest pain to first medical contact, for example, the er um when we say door the device once they enter the hospital to having a stent placed in their heart Andi also cath lab revival These air all heart attack patients acute my patients and these columns are time and minutes, um, of these three separate categories and I'll just point out that comparing. So, this column here, the second column here is during the pandemic. Um, and this this third column is last year. Uh huh. Prior to the pandemic. And you can see how the times off, you know, each of these time to treatment essentially has increased dramatically during the pandemic compared to pre pandemic eso 82 minutes versus 318 minutes during the pandemic. So door to device, you know, 84 minutes before the pandemic, compared to 110 minutes during the pandemic. So this is to illustrate that the you know the time to treatment off someone's heart attack can be influenced. Bye. The pandemic. And one can speculate there are different factors. Maybe patients, when they roll into the ER, they need to get screened for Kobe first before they get their treatment. That can provide a delay. It could be that PPE needs takes time both for the patient and for the providers. So maybe that took time. Onda caused a delay in their treatment. Um, but it's it's really interesting. Interesting to see, you know, that time to treatment has been influenced. Um, and, you know, finally, you know, this is actually US data, and I wanted to show this just because it doesn't apply to us here, Um, the the in the US This is a study similarly of patients for a cross sectional study of possible is ations, um, in the United States across, uh, several different hospitals in Alaska, Washington, Montana and California. Um, admissions for acute and my and similar findings. You can see how off point out. You know, in January, February and then starting in February march, you can see a precipitous drop in the admissions for acute M I, um you know, reaching its lowest point in around end of march. And then you can see how it again has picked up, but not has not returned to baseline. Okay? And actually, at UCSF, we've seen that in our clinics in our clinic volume, where, um, you know, our clinic volume dropped precipitously during the peak of the pandemic. And only recently has our have our numbers gone back. Thio pre pandemic. Um, and this is data from also the, uh, from Italy looking at out of hospital cardiac arrest, That's what Oh Hcea stands for out of hospital cardiac arrest numbers comparing them during the pandemic to last year, similar times last year. So the blue, if you could see the blue columns, are the rates or numbers of out of hospital cardiac arrest this year. And the orange bars are the numbers from last year. So suffice it to say you can clearly see a a dramatic increase in the out of hospital cardiac arrest in Italy during the pandemic. And that mirrors the this red line showing the case Cove in 19 cases cumulative Kobe, 19 cases in Italy. Um, so actually, you know, we see close to a 60% where we saw the closest 60% increase in the cardiac arrest rates this year compared to last year in Italy. Um, and so one can speculate, you know, and I think it makes sense that, you know, as a corollary to the decrease in the hospital, admissions for acute M I. You know, these patients might be afraid to go to the hospital. Andi. They might be suffering an M I at home. And if they're suffering an M I at home, they have a higher risk of having a cardiac arrest due to thank curricular. Take a cardio are ventricular defibrillation. Eso. This is another reason why we need to counsel our patients and tell them you can't ignore your symptoms of chest pain during the pandemic. You need to get this addressed on bond promptly. Um, so you know, that's that's a little bit about acute. My and on and cold it. And, you know, this is way in the cath lab. Do, um, have to spend, you know, a lot of effort in time, you know, putting on the PPE. And, um, you know, it does change our workflow significantly. Um, and when we have patients who roll into the cath lab, We, you know, sometimes see pretty unusual things. This was a case report from Europe of a patient who had a spontaneous coronary artery dissection. Um, and co vid in the setting of cove it eso things. Person came in with chest pain, was tested positive for cove it, um, and had, you know, a new urgent coronary angiogram. And you can see here, this is this is a non angiogram. Looking at the left interior coronary. Let led the left anterior descending corner. You can see you know, this dissection here, Um, and to compare this patient actually had a coronary angiogram three years prior, showing mild after a sclerosis in the same location. Um, and spontaneous coronary artery dissection, or scat, is quite rare. So, um, so way see rare things in in these covert 19 patients. This is a This is a patient who came in to the hospital in Europe, also Europe with chest pain, and was found to have s t elevations on E k G. And, you know, urgent coronary angiography showed a plaque ACLU sieve plaque in the right coronary artery here, which had to be stent ID and showed a non inclusive thrown. This here in the l a. Andi, this was confirmed on O C t eso. Certainly we have toe watch out for you know, our bread and butter acute M I and ischemic causes of an acute Emma. Um, one other thing that was published fairly recently. Waas this'll paper from Germany looking at how the Kobe 19 infection can affect the heart long after recovery. Clinical recovery of the infection. Um, and this this study, I thought was quite interesting. Um, it was one of the first studies looking at patients. Um, this study was done in Germany. On there was an observational study looking at 100 patients who had who had prior cove in 19 infection confirmed by PCR, and they were enrolled in the study. If they were at least food two weeks out from their original diagnosis, and importantly that they no longer had symptoms of, you know, they had no longer had any symptoms. They were asymptomatic. And also they had a negative repeat PCR test after after isolation. S o. You know, the majority of these patients recovered at home and were not hospitalized. But what was interesting to me was that these patients all underwent cardiac Marie as well as proponent testing. And there were in addition to these patients, there were healthy control, healthy controls as well as risk factor matched controls. Um, so the study, um you know, the study results showed that the mean duration between the positive Kobe test and the memory was actually 7 71 day, so it was quite some time out from their infection. So that's important to keep a note of. Um, What the study found was that high sensitivity troponin INTs were elevated in 71 71% of these patients, um, also notably 78 out of the 100 patients had abnormal cardiac Marie findings. I'll get into this in a second, and this included a decrease in their LV ejection fraction increase in their LV volumes. And you know some other parameters. Um, just Teoh give you a brief intro If if you don't know, LG stands for late Catelyn IAM enhancement, which really corresponds to scar scarring of the mile cardi um, which can occur in ischemia or in a non ischemic ideologies such as myocarditis or other things like that. Cardio authorities. Um t one and t two r are, um parameters from cardiac emery, and I'll keep it simple. You know, these Kenbrell present t one can represent fibrosis of the mile cardio and or oedema and t one can represent my cardio Adina A swell. So these are parameters of mile cardio injury. Um, so you know, these findings, you know, suggests that, you know, even long after clinical recovery from Kobe 19, there may be, you know, persistent either injury, permanent or not, Injury of the heart muscle long after recovery. Andi, I think that we have still a lot to learn about. Um, okay, about the clinical consequence of this, but this'll remains to be seen. So this is some data from this study from Germany, and it's a busy slide, but, you know, I'll just show you, you know, this, uh, you know, these values here, these cardiac Marie values here, All of them were significantly different in the cove. It the patients who had had Kobe 19 and had recovered compared to the you know, the control group. Um, so again, you know, LVF LV volumes t one t two and late Catelyn IAM enhancement and even pericardial effusion. Um, there was a difference in 20 patients with Prior Kogan. 19 had Corbyn s. I had pericardial effusion, whereas, um whereas none of the healthy controls had the infusion, Um, well, this is also really busy, but I'll just you know, this is just a graphical representation of how we see that, you know, the T one and T two values, which again represent mile cardio Dema and fibrosis are higher in the co vid recovery groups compared to the control groups. Um, this is this is a trend line. These trend lines of of these t one t two enter opponent values. Um, over time in the patients who had covert these air all thes air the cove in 19 recovery groups. But what I wanna point out is that, you know, if you look at the x axis, you can see the time um, you know, this is 25 days, 50 days, 75 days, all the way out to almost four months after their initial cove in 19 diagnosis. What I want to point out is, you can see you know these ab these values um, you know, don't change, you know, even 34 months out from recovery. Um, you know, even this troponin down here on the lower right. The troponin levels did not change even even well after recovery. So this is you know, this remains to be seen how clinically relevant this is, but, um, this suggests that there may be long lasting, um, effects of Kogan 19 on the heart. Andi, this is another, um, study from also from Germany. Looking at, you know, patients who had actually passed away from cove it it was 39 individuals, Andi, and autopsies were done, and genetic analysis RNA analysis was done. Um, you know, I know this is a busy slide, but I'll summarize and say that, you know, off these patients, tissue was taken from their heart and genetic analysis are any analysis, and histology was performed. Um, out of these 39 patients are in a from SARS. Kobe to was detected in 62% of them. But what I'll point out here is that, um, you know, in the patients. So this group here on the left or the patients are control groups. I guess you could say without without virus detected and on the right side, you know, with increasing copy. Number of virus. Um, thes air the patients who had virus detected in their system. Um, this row here is gene expression of cytokines and inflammatory markers. You know, TNF Alfa interfere on. You know, I'll six violate, And you could see, based on this heat map that, you know, there are higher expression. There was higher expression of these inflammatory markers. Aziz, you go from left to right. You know, in the patients who had Higher Cove in 19 virus numbers. However, this row shows theme the way also looked at or they also looked at, um, inflammatory cells. And they did, actually, they actually did not see any difference in the numbers of inflammatory cells in the cove. It negative the stars Kobe too. Negative. And the stars Kobe to positive patients. So this is interesting, because again, to summarize, we saw higher viral load correlated with higher numbers of cytokines, but not with increased inflammatory cells. So I don't think we know why. Uh, this was the case. Maybe it's a different mechanism of injury, not just, you know, ah, high number of inflammatory cells, but but something that we don't quite understand. Moving on. I have a few more slides left. Um, you know, Kobe 19. And from from Bomb Bolic and from biotic risk has been a hot topic. Um, you know, obviously patients who are hospitalized for Corbett, you know, they have a higher rate of D v t p. But, you know, there have been some case Siri's from different parts of the world, including the US showing that in general, through robotic events in Kobe, 19 patients are higher then in patients who who do not have coded. And we you know, there's not been a direct head to head comparison, but we're looking at rates of thrum bardic events, prior pre Cove in 19 pandemic um, that are lower. So So this this was an observational study looking at patients, um, this'll was in New York showing that out of out of 3000, about 3000 patients with Kobe 19, um, about 16% of them had a robotic event during their hospitalization. You you know what I've seen in prior studies? Um, you know, these rates of throw robotic events, typically in hospital, are typically around five thio 5 to 15%. So so way may see Andi increase in robotic risk in these code 19 patients on DSO. There has been an interest in, um whether you know how to treat Kovar 19 patients in terms off anti coagulation and you know there was. I didn't include this on this slide, but because this actually just came out. But there was a very recent paper, I think this'll week from New York from Sinai, I believe, um, looking at patients with Kobe 19, and looking at patients who were either not anti coagulated um, who had prophylactic anti coagulation and who had therapeutic on deck regulation. And these were all Kobe 19 patients without a diagnosis of a thrombosis or so no prior no diagnosis of a DVT or a P E. But they were treated with with anti coagulation, either prophylactic or in therapeutic. This study actually showed that there was actually mortality benefit in the anti coagulation group compared to the knowing anti coagulation group. Um, and you might say, Well, why? Why were patients put on therapeutic anti coagulation with cove it when they didn't have a reason to and the reason is because, you know, I guess one reason you can say is that these doctors in New York, you know, they were you know, they really didn't know how to manage thes patients. We didn't We didn't have a therapy for these Kobe 19 patients a time. Now we have probably mawr idea about about therapies. But at that time, you know, a few months ago, you know, You know, I think it was really sort of Ah, shotgun approach. And, you know, there were observations that patients had had more clots. They had more p. They had more DVT. And so, you know, patients were put on empirically, um, you know, therapeutic, sometimes therapeutic anti coagulation. Andi, there is some data coming out now that supports that may affect on decrease mortality. But that remains to be seen. You know, I think it's very early to say, but I think certainly what is clearly recommended now by the major societies is that, um, in patients who are hospitalized with cove in 19, they really should. It really is strongly recommended that they be on pharmacologic anti coup, uh, prophylactic anti coagulation, either with a knocks a parent or sub Q. Heparin. Um, and some there is. There's no data to support this yet, but you know, it may be considered to extend that prophylaxis with anti coagulation after the patient is discharged. If the patient has a high risk of the public's robotic event, sort of what we do with, you know, um, patients after hip surgery, for example, Hip replacement s O. This is a topic that z still being studied, obviously, but, uh, but definitely I would say, you know, if you have ah, hospitalized covert 19 patient really strongly consider, um um pharmacologic prophylactic dose in a regulation which you probably already do Almost done. I think two more slides a little bit about this. You know, the syndrome called multi system Inflammatory syndrome, Children M I s C um, this is a syndrome that's been a noted are documented more recently in patients or Children who have inflammatory syndromes. Fever, fever, shock, you know, elevated white count. But an infectious cause is excluded, you know. You know, you know, back to re mia or any other type of infectious cause of their inflammatory syndrome. Um, and these images air from the CDC website where, um you know you can. I'll point out here on the left panel here. You can see this Green Line which represents the numbers of Covad 19, um patients, cases and these vertical bars or vertical lines are the numbers of M. I s C cases. You can see how as the Kobe 19 patient numbers came down, this is from May. So it's a very different graph now, but from from you know, this is going from March to May, as the as the numbers of Kobe 19 cases started to decrease you, we tended to see us increase in the MSC numbers, which suggests that you know patients after their infection can develop these inflammatory syndromes. Onda reason why I bring this up during a cardiology talk. Is that during, you know, with these MSC these inflammatory syndromes, we see significant amount of cardiovascular involvement. Um, you know, a decrease in the ejection fraction 5% of these Children had EFS less than 30%. 4% of them had to go on ECMO. So So thes inflammatory syndromes can be very severe illnesses. Andi, there are now more recently, um um multi multi system inflammatory syndromes. diagnosis or documented and adults. This'll was from more recent you know, beginning of October, where you know a collection of patients who are adults at these, you know, non specific inflammatory syndromes after after they were diagnosed with co vid 19 eso. This is something that will that's probably going to be continue to be documented and and it needs more study.