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MANDEEP SINGH: Hi, everyone. My name is Mandeep Singh. And I am a professor and director of the acute coronary syndrome at Mayo Clinic in Rochester. And it's my distinct pleasure to invite-- but he doesn't need introduction anymore. He's been a lightning force for our acute coronary syndrome webinars. And today, Dr. Gersh will speak on long-term cardiovascular complications of COVID-19.

This topic has made headlines since the onset of the pandemic. But little is known on what happens after the acute events have passed. We know from the literature that people who present with acute coronary syndrome present less, present late.

We also know that most people are mildly symptomatic or asymptomatic. And then, there is a gradation of severity from mild to moderately severe, which needs hospital stay to an ICU-like care. But we don't know what happens to these individuals after they are discharged or when they have this COVID and then what happens to them afterwards.

Dr. Gersh has highlighted in his recent paper and has done a lot of research not only on the acute events but also what happens long term. What are the complications? What are the cardiovascular complications? We need to look at these patients, what kind of additional research we need to do in order to better understand and then focus on where our research strategies should be on these patients long term.

Dr. Gersh, it is my distinct pleasure to invite you, again, in this forum. And I would like to-- I mean, it's an honor. It's not a pleasure. It's an honor to have teachers like you who then illuminate all of us on the themes that nobody thinks about. And this is one of them, that long-term complications. Nobody thinks about what happens after the acute event is over. So Dr. Gersh, help us understand, what are the long-term complications of COVID-19?

BERNARD J. GERSH: Thank you, Mandeep. And as always, it's a pleasure to be here. Long-term cardiovascular complications of COVID. Now, the pathophysiology and manifestations of what are called cardiac injury in COVID-19 is a bidirectional interaction. And I'll explain that as I get towards the end of the slide.

The pathophysiology is really very complex. Severe sepsis, hypoxemia, cytokine storm, the bradykinin hypothesis, autoantibodies, coagulopathy, endothelial and microvascular inflammation dysfunction-- all of these pathophysiologic entities probably take place to a greater or lesser extent in patients with COVID-19 who have cardiac injury.

Cardiac injury, other manifestations of it, type 1 myocardial infarction due to sympathetic nervous system activation. Inflammation in itself can cause plaque rupture. Hypoxemia and increased myocardial oxygen demands due to tachycardia and sepsis can lead to a type 2 MI. Takotsubo is being clearly reported in increased numbers during the pandemic. Not surprising given the stress of the pandemic.

Myocarditis is the usual suspect, but it's actually an infrequent culprit. And I'm going to come back to this, because there was a huge amount of publicity about myocarditis early on and late. Thrombosis, arterial and venous, probably plays a critical role in the cardiovascular manifestations of COVID. It tends to be more platelet-dependent. It may be viral-mediated platelet inflammation. There is also evidence for hypercoagulability of red cells. But the end result is an increased rate of thrombosis, arterial and venous.

In terms of the clinical outcomes, the commonest manifestation of cardiac injury is just a troponin rise, chest pain, MI, heart failure, shock, RV dysfunction, arrhythmias, pulmonary embolism, frequently reported stroke, and microvascular dysfunction, and pericardial involvement.

Now, why I say it's a bidirectional interaction are these modifying factors, because what has been associated with the epidemic has been a delayed presentation to the emergency department, delayed diagnosis, late treatment, which, in fact, can contribute to exacerbating cardiac injury, pre-existing comorbiditites, fever, drugs, including antiviral drugs, some of which may have some cardiotoxicity, electrolyte abnormalities, and simply logistical constraints in health systems that are overwhelmed by the magnitude of the pandemic.

So this is from a recent review by Dr. Satterfield, one of our fellows at Mayo, myself, and Dr. Deepak Bhatt, from the Brigham. The acute CV complications, arrhythmias, myocardial infarction, pericarditis, left and right ventricular systolic dysfunction, stroke, and deep vein thrombosis. And the question is, what is their long-term impact? We know a fair amount about what happens acutely. But what is the long-term impact?

Now, myocarditis does occur. And this is one report from New Jersey-- two cases, no prior CV history, shock presentation a week after COVID diagnosis, treatment with steroids and inotropes. LV function on echo, look at the proBNP, 53 2005 pg per ml. And then, four days after admission, a significant improvement in ejection fraction. In case number two, the same kind of presentation. 45% to 55% after discharge. And this is very consistent with acute myocarditis.

What is interesting is this entity of delayed onset myocarditis following COVID-19. This is a study from the UK, nine patients. Black African ancestry in seven. Mean age, 36 years. And they all had acute cardiac decompensation with the clinical features of recent COVID infection. Follow-up, complete recovery was noted in four patients.

But this is what is interesting. Acutely, they had multiple negative SARS-CoV-- COVID 2 rapid real-time PCR testing. But subsequently, the CARS COVID 2 antibody levels were extremely high in all patients. So this is an example of delayed onset myocarditis.

One of the early histological autopsy studies on 21 patients who died of COVID, using morphology and microscopy and looking at the composition of the inflammatory cells. What they saw in terms of cardiac pathological changes was RV strain in 19%, focal pericarditis, 19%, endocardial thrombosis in 14%, diffuse macrophage infiltration in the majority, small vessel thrombi, which, I believe, are an important pathophysiological feature, in 19%, but only 14% had lymphocytic myocarditis.

In this study from the Mass General Hospital, another autopsy study of 41 patients with fatal COVID-19, virus was noted in the heart with the histological features of myocarditis in four patients. Virus in the heart without myocarditis noted in 26 patients. And no virus, no myocarditis in 11 patients.

And their conclusion was that cardiac infection with SARS-CoV-2 is common among patients dying from COVID-19 but often with only rare infected cells, even though a cardiac infection and virus is present. But cellular infection with myocarditis is uncommon. And at the time of the start of the epidemic, I think we all felt that we would see a huge number of patients with myocarditis.

And then, this rather definitive autopsy study from Johns Hopkins, 227 autopsies from nine countries. And the conclusion was that the initial review of the data indicated that myocarditis was present in 20 hearts, 7.2%. But closer examination of additional reported information revealed that most cases were likely not functionally significant. And the true prevalence of myocarditis is likely much lower.

In conclusion, across 277 cases, COVID-related histopathological findings were common, but myocarditis was rare. And these are the various autopsies. And what you see is the impression of myocarditis really came out of only one or two autopsies shown in orange here. The rest demonstrated no evidence of myocarditis.

So what I really want to talk about in terms of this spectrum of the cardiovascular sequelae of COVID-19 survivors is described on this slide. There are two large groups of patients. One are patients who had an acute illness, mild or asymptomatic, outpatient case. And what is the incidence of long COVID in these patients?

The other group are those that had an acute illness. It was severe. They were hospitalized, and they had evidence of cardiac injury. And the question is, in these people who had an acute illness, what proportion of these patients and these patients will have long-haul COVID with basically non-specific symptoms? And the other key question is, in those with acute cardiac injury, with structural involvement acutely, do they continue to have structural cardiac involvement and late cardiovascular complications? Or does this resolve?

And there are some reports now of some patients who had a mild acute illness who don't just have long-haul COVID, but there is some evidence of late structural cardiac involvement. And we need to realize, and I need to emphasize that we're in a changing world. This is all new. And there's a great deal we have to learn. And I'm trying to summarize at least to some extent what we know at this point in time.

This is a recent report from the National Center for Health Statistics. And what you see are weekly death rates in the United States by cardiovascular cause, per 100,000 of the population. Yellow is 2019. Orange is 2020, encompassing the epidemic. And what you see is a striking increase in late mortality due to ischemic heart disease. Heart failure, no different. Hypertensive diseases, another increase. Cerebrovascular and other circulatory diseases, no increase.

Now, that doesn't mean that in a year or two years' time we may not see an increase in heart failure. But at least these are cardiovascular deaths in the first few months of the pandemic. Conclusions, causes are multifactorial, including the avoidance of hospitals, delays in seeking, and deferral of outpatient and procedural care. Plus, the cardiovascular sequelae perhaps of undiagnosed COVID-19.

Now, I want to focus on an entity called collateral damage. And this is a paper from the United Kingdom that I was part of. It was published by Dr. Kite, who is a fellow of Dr. Anthony Gershlick. Dr. Gershlick was a real pioneer of interventional cardiology in the UK. I think the first implanted stent has done wonderful trial work, and he's a very good friend.

And what he did, he set up this registry of 55 interventional centers in Europe, the UK, and around the world to look at what happened during the COVID pandemic, to patients with an acute coronary syndrome. The sad and the personal part of this is the last conversation I had with Dr. Gershlick, he was in the ICU that he set up 25 years ago. We were discussing the review of this paper and how we should respond to the reviewers. And Tony died of COVID in Leicester, England. This was pre-vaccine.

Now, what we were able to do in this study was compare the results during the COVID epidemic with two large databases pre-COVID in the UK. And these were databases of everyone in the United Kingdom that had an acute coronary syndrome. COVID in orange, pre-COVID in yellow.

If you look at symptom-to-admission time, it went from 179 to 339 minutes. So it doubled, partly, I think understandably, due to perception by patients that hospitals are a dangerous place to be. And they delayed presentation. If you look at the door-to-balloon time, it went from 37 to 83 minutes, more than doubled.

And this was striking. In-hospital mortality pre-COVID for all comers with acute-- this is just the STEMI data. In-hospital mortality, 5.7% increasing to 23%. And cardiogenic shock, 8.7% to 20.1%. So this is what I call collateral damage. And one of the unresolved questions here is, in those patients that survived, are we going to see a late epidemic of heart failure and arrhythmias? And that remains to be determined. So this was the experience during the early phases of the pandemic.

And what is important, I think, to emphasize, this paper by Greg Stone of 10 randomized trials of patients undergoing reperfusion therapy stratified them into quartiles of infarct size. And if you look at the one-year mortality, in those in the highest quartile, greater than 29.8% of the left ventricle involved, almost 9% mortality, in those in the lowest quartile, less than 1% mortality. And again, I want to go back to the study I've just shown you, with a tripling in the incidence of cardiogenic shock. I think we will see amongst the survivors a significant number with very large infarcts and late complications.

Another less, perhaps, dramatic but equally important aspect of collateral damage is written in this paper by one of our fellows, Dr. Oren, and myself, and others. And that is the cardiometabolic toxicity of social isolation and emotional stress, and particularly amongst the elderly. And we state in the conclusion, understanding social isolation and its public health consequences is a key to minimizing the late cardiometabolic burden of COVID-19.

But it's also fundamental to optimizing cardiovascular health outside the context of COVID-19, going into the future. And what we really meant was during the periods of isolation, blood pressure was not well controlled. People did not come for regular outpatient evaluations. And in many cases, hospitals were ill equipped to undertake those outpatient evaluations. People exercised less, smoked more, gained weight. And these are the cardiac metabolic consequences which may translate into adverse cardiovascular health outcomes.

To go back to this slide again, I've dealt with collateral damage. And really, what I want to focus on now is the post-acute illness manifestations, cardiovascular manifestations, namely, long COVID. And what happens to the patients who have acute cardiac injury. Do they get better? Do they get worse?

This is a quote about influenza. If influenza is a riddle wrapped in a mystery inside an enigma, then the viral genes are the riddle, the variable surface antigens for which they code are the mystery, and the course and the cause of epidemics, the ultimate enigma. Well, isn't this surely an apt description of the clinical characteristics of the multifactorial pathophysiology and etiology of long COVID?

I might add this quote about a riddle wrapped in a mystery inside an enigma was first made-- or the initial quote was by Sir Winston Churchill in the 1930s, when he was asked to explain what he felt about Russia. But I think it's a very apt quotation for what we're dealing with today.

So if you look at post-acute and particularly long-haul COVID, they have cardiovascular symptoms-- pain, palpitations, breathlessness, orthostatic intolerance. Some of these patients may have myocarditis. We'll come back to that. Arrhythmias, LV and RV dysfunction leading to heart failure. But the majority, basically, we see nonspecific findings on imaging and no heart failure.

What are the causes? Question marks. Long-term tissue damage. Perhaps unresolved inflammation. I think very possibly an autoimmune phenomenon and clearly autonomic dysfunction. But I might add, despite the severity and severity of the symptoms that really limit the quality of life of these individuals, the findings in most cases from a cardiovascular standpoint are relatively nonspecific. But we really need to study in these patients the autonomic nervous system in more detail.

Postural orthostatic tachycardia syndrome, POTS, I call it the electrophysiologist's nightmare, because POTS is a very difficult disease to treat. And it, again, has a major limitation upon quality of life, but it's not an electrophysiological disease. It's not an arrhythmic disease. It's autonomic dysfunction and a neurological disease. And it overlaps with chronic fatigue syndrome and post-COVID-19. And we are clearly seeing increased numbers of these patients with the long-haul syndrome.

Well, this study gained a huge amount of attention. 100 patients came from Germany, Frankfurt [INAUDIBLE]. 100 patients, 33% were hospitalized. Mild or no symptoms in the majority. Mean age, 49 years. Frequent comorbidities. And then, they had C MRI, or cardiac magnetic resonance imaging at 71 days median after the acute episode.

At the time of CMR, 76% had an elevated high-sensitivity troponin. And the findings were in 78%, there were abnormal CMR findings. Increased native T1 mapping, increased native T2 mapping. And late gadolinium enhancement, which was not really nonspecific in 32 patients. And this literally frightened the daylights out of all of us, because suddenly, we now look at the spectrum, and particularly the fact that a number were relatively mildly symptomatic, had mild disease. And we now are looking at the specter of 78% with long-term cardiovascular manifestation.

Now, there've been some other more recent studies. And I do think that first study had its limitations in terms of there was a lack of controls. But now, there are more recent studies. This one from Norway, 204 patients, 20% in the ICU, 12% intubated. And at three months, these are the findings. LV systolic dysfunction was uncommon. RV systolic dysfunction and LV diastolic dysfunction was present in 50%, probably associated with pulmonary pathology and RV strain and dilation, which can also interact with the LV.

Cardiac arrhythmias of uncertain clinical significance were common, PVCs, and non-sustained VT. Persistent dyspnea in 50%. Fatigue in 2/3. And I might add that these were not associated with echo features of cardiac dysfunction. So we have a large number of patients with persistent symptoms, dyspnea, and fatigue, and a significant number of patients with nonspecific findings in the left ventricle and the right ventricle that are really not correlated or associated with the symptoms of shortness of breath.

This has just been published. It's a preprint from Oregon Health Sciences, 1,355 patients and controls, COVID-positive in 24%, and there were a mixture of symptomatic and asymptomatic. The primary outcome was CV morbidity and mortality. And at six months, COVID-positive, the primary outcome of CV morbidity with less mortality but significant morbidity.

In those who were COVID-positive, it was 12%. In those who were COVID-negative, 6%. And the adjusted hazard ratio was 1.71. So for COVID-positive patients, there was a 71% increase in morbidity and mortality at six months, or cardiovascular morbidity and mortality. All-cause mortality, after adjustment, they showed that the time to all-cause death was 65 days less in COVID-positive patients. And this is in people followed beyond six months [INAUDIBLE].

And then, this huge study published about a week ago in Nature from the VA health system. 154,000 patients with approximately 5.5 million controls who did not get COVID and approximately six million historical controls from 2019. The majority were not hospitalized. And that's important. And only a minority were in the ICU.

At one year, there's a two-fold increase in incident cardiovascular events listed as cerebrovascular disease, dysrhythmias, ischemic heart disease, pericarditis, myocarditis, heart failure, and thromboembolic disease. But we don't really have any details of these specific cardiovascular morbidities. They say it was present in non-hospitalized patients but increased in a graded fashion with increasing severity of the initial disease, which you would expect present in all age groups and in younger patients without risk factors such as obesity and diabetes. So concern. Two, three papers that really are of concern. And obviously, we need more information.

So I would summarize some of the studies to date by saying, abnormal imaging findings in recovered patients are frequent whether it be MRI or echo, other imaging tools. What is the clinical significance and lack of-- and the fact is many of them had a lack of controls. And this applies specifically to athletes who do have high grade, highly-- competitive athletes do have abnormalities on their MRIs and echoes if you look for them.

What is the correlation of these findings with symptoms and the severity of the initial illness? And what is the natural history? Do they resolve? Do they persist? I've seen several reports now of late gadolinium enhancement in a nonischemic distribution, something we see with dilated cardiomyopathy. And it's an adverse predictor. And it may predict later arrhythmias, question mark, shown here. Do they lead to late heart failure? Don't think so, in the majority. The arrhythmias, if it's just PVCs and atrial [INAUDIBLE], of no concern. What's the impact on full activity in regard to athletes?

This was a large study from professional athletes in the US, professional sports leagues. COVID-positive, this is a misprint. Prior acute illness. 58% of these athletes were symptomatic. Almost 1/2 were asymptomatic. They had cardiovascular testing at 19 days. And it was completely normal in the vast majority, 759 out of 789.

30 athletes had one or more abnormal test results. That's 3.8%. Either a transthoracic echo, EKG, five had troponins, three, the combination of an abnormal EKG and a transthoracic echo, and one transthoracic echo and troponin elevation. And using standard AHA/ACC guidelines, there were 2 out of 789 with myocarditis and 2 with pericarditis. Pretty reassuring, by and large. And we really don't know what most of these nonspecific findings on echo and ECG mean.

And then, Dr. Jim Udelson from Tufts wrote this very, I think, good some summary, Return to Play for Athletes After COVID-19 Infection, The Fog Begins to Clear. Studies on total 6,753 athletes, and this is the prevalence of myocarditis on CMR imaging.

And what I want to point out, there are two outliers. The vast majority of these studies showed evidence of myocarditis in basically null to 4%, and several with 0%, a couple 1.4%, 3%. These two studies seem to be outliers. Total myocarditis, 2.8%. And of those patients, 31.9% were asymptomatic. 2.8% on CMR studies, which is this graph. But if you look at myocarditis in the full cohort, including those who did not have MRI, only 0.94%.

I thought this was a very good editorial, which basically emphasized the significance of COVID-19 associated myocardial injury, how over-interpretation of scientific findings can fuel media sensationalism and spread information. When the first data came out on MRI findings, and particularly in athletes, there was a huge media and public response, and one of great concern, which I think is to a large extent now being delayed. And not completely, but at least reassured.

This is from a widely read blog, "Setting the record straight, there is no COVID heart," from John Mandola. After a year of frightening headlines, widespread concern and countless retweets that the virus that causes COVID-19 may attack the heart more aggressively than any other viral illness. The verdict is in it doesn't. Well, I don't agree with that totally. I think it does affect the heart. The question is, how frequently? And I'll come back to that. But it's not to be ignored.

So if you look at the late CV complications of COVID-19, I think in all likelihood, we will see serious late cardiovascular complications of COVID-19 infection. The question is, will it be frequent, uncommon, or rare? And that remains a question mark. I intuitively feel it will be uncommon or rare, but it's a question mark.

And so to summarize, what do we know? Cardiac injury during the acute phase of COVID-19 is common and an adverse prognostic factor. The etiology is multifactorial. In COVID survivors, cardiac abnormalities on imaging are frequent, irrespective of the severity of the acute illness.

What don't we know? We really don't know the natural history and clinical significance of the abnormal findings in acute survivors. We do not know the late natural history of survivors of acute coronary syndromes who had delayed therapy, as shown in that UK study. And I might add, that study of Dr. Gershlick's has also been repeated by Dr. Tim Henry in this country.

The mechanisms and etiology of the different manifestations of virus presence in the heart are really unknown. And the approach to competitive athletes and whether prior guidelines on myocarditis are applicable to the COVID population, I think they are. I think we do have guidelines about the return to play for athletes who have the flu and other viral illnesses. And I think those guidelines are probably going to be applicable to the athletes with COVID-19 infection.

Mark Twain made this tremendous prescient quote, "What gets us into trouble is not what we don't know. It's what we know for sure that just ain't so." And I think what we can conclude with this, this profound thoughts, what we do know for sure is that there is a great deal more that we do not know.

And so my final slide makes the plea for more data. We need prospective, large, specifically phenotyped, longitudinal follow-up studies, including athletes and different ethnic groups. This is a really important entity to emphasize. And the question mark. The questions, symptoms, functional limitation, morbidity, and survival.

And these are the imaging endpoints that have to be collected, CMR, event monitoring, and stress testing. The duration of follow-up needs to be not just months, but years. And I'm pleased to note that these kinds of very large studies are now ongoing. NHLBI is a very large study in this country. But there are several ongoing studies such as this in different parts of the world. And we will get the answers in the not too distant future. But I think it's really important that these studies are not just short term. Thank you for your attention.

MANDEEP SINGH: Thank you, Dr. Gersh. It was a very illuminating and fascinating talk, as always. I think for the audience, I think it's very important to differentiate the risk from the burden of disease. So risk being-- for example, you said myocarditis, the hazard ratio for myocarditis in this recent VA paper has been 5 as compared to arrhythmias or, for example, ischemic heart disease, where the hazard ratio is about 1.7, 1.8.

But the burden of disease is very low for myocarditis long term. Whereas, the burden of disease for more common problems like arrhythmias and ischemic heart disease is much more than less common problems like myocarditis. We did report last month on a 32% reduction in patients presenting with ACS. But then, there was a relationship of the decline in their presentation with the lockdowns that happened statewide.

There are several questions from the audience. And I'll go over one by one. The first question is by Dr. Strauss. And she says, now, in the MDH study, you said there is no virus. There is no myocarditis. And then, how are they attributing the deaths to cardiovascular complications?

BERNARD J. GERSH: Effectively, the MDH study was 41 patients. Four of them had clear viral myocarditis. A significant majority had evidence of virus in the heart but without myocarditis. And that means that there was virus in the heart without the histological appearance of viral myocarditis. And then, there were about, I think, 11 patients that had no virus and no myocarditis. So I think it is certainly possible to die from an acute viral infection of the heart or even from a late viral-- or the late complications without having myocarditis.

And it may be-- now, I emphasize the may be, because these are the unknowns. It may be that virus in the heart causes microvascular dysfunction, endothelial dysfunction. Or endothelial dysfunction leading to thrombosis, both in a macrovascular and the microvascular level. So yes, you are dying of-- you're dying of-- thank you very much. Let me just-- I'll go to that slide. Yes, you are dying of a COVID infection of the heart. But it may be that it's not myocarditis at all. And this is the study you're talking about here.

MANDEEP SINGH: Yeah. That one, the 11--

BERNARD J. GERSH: Viral in the heart, four patients, viral in the heart without myocarditis, 26 patients, four patients with myocarditis, and 11 patients without. And I actually think, if I go back to this very complex first slide, I do think that-- let me just bring it up here. I think this is-- not just I think. I mean, many people think. This is a very important entity, thrombosis, arterial and venous. And it may be viral-mediated platelet inflammation.

And then, I think this is really important as well, endothelial and microvascular inflammation and dysfunction. And that may be in the long term an important-- a really important cause of long-term morbidity. And we have seen reports of patients, and I've heard of this on a personal level, of patients who were perfectly healthy before COVID who developed classic microvascular angina who at cath have acetylcholine vasoconstriction, which is how we define vasospasm. So I think that myocarditis is the usual suspect, the obvious suspect. But it's relatively infrequent.

MANDEEP SINGH: So just getting this forward, Dr. [INAUDIBLE] asked, how do these COVID-19 cardiovascular complications compare to other COVID variants and also more recent Omicron? Have we learned from, or are there studies published on different variants of even COVID-19? How does that affect the cardiovascular? Or we don't have that?

BERNARD J. GERSH: I don't really know the answer. I think I know about as much as you do about the virology. And obviously, none of us are virologists. What I do know is the prevailing viewpoint is that Omicron is a much more benign variant. It's much more infectious, but it's more benign.

Having said that, in older patients with comorbidities, it may still lead to a very severe illness. What I don't know is any study that has looked at cardiac injury is defined by proponents and drawn the conclusion that it is less. There's less cardiac involvement with one variant versus another.

What we do know, I think, generally, is that Omicron is associated with less hospitalization, a lower duration of hospital stay. It is a more benign condition or benign variant. It doesn't mean that some people won't have severe injury. But I don't know of any, I mean, severe disease. I do not know of any direct comparison of, at least published, of cardiac injury in Delta versus Omicron. My own impression would be that it's more severe and more frequent with Delta.

MANDEEP SINGH: Now, Dr. [INAUDIBLE] asks, is there a difference between when you get viral myocarditis versus those infrequent cases of vaccine-related myocarditis?

BERNARD J. GERSH: Yeah. I think there is. It's a very good question. I think vaccine-related myocarditis is really probably an autoimmune-related inflammatory condition of the heart. No question. It's not new. It's been seen-- it was described with chicken pox vaccine years ago. So it's not new. It tends to affect young males and teenagers.

And it's very self-limiting, at least, I think, in all the cases I've seen published. I think that myocarditis, when it occurs with COVID, is a marker of more severe inflammation plus perhaps inflammation and maybe other cardiovascular manifestations.

What we do know is, from the center-- I think it's from the National Center for Health Statistics, that the likelihood of myocarditis with the vaccine, which does occur in young people-- tends to be males, tends to be teenagers-- it is still less than the incidence of myocarditis acutely in COVID-19. So even with a vaccine, it's still less frequent than in patients that get severe COVID-19 infection. So I think that the documentation of myocarditis and pericarditis with the vaccine should not be used as an excuse not to have the vaccine.

MANDEEP SINGH: Very good. Dr. Marks asked about POTS. And he mentions that, shall we do cardiac MR in those patients? And then, also, what is the role of inflammatory markers for a routine surveillance in these patients?

BERNARD J. GERSH: I absolutely don't know. It's a very good question. And this is being looked at right now in these long-term prospective studies that are collecting evidence for acute cardiac injury acutely, namely, troponin elevations and seeing what happens to them over time and how they correlate with persistent symptoms, because it is possible that some people with persistent symptoms may have ongoing inflammation.

Well, I think it's probably autoimmunity. So we don't know at this stage what the role is of the cardiac biomarkers late. Personally, I would get a measurement of troponin and perhaps CRP in these patients. Would I do MRI in people with POTS routinely? No. I think if they had an abnormal electrocardiogram and if the echo was abnormal, then I think it's reasonable to get an MRI. I wouldn't do it routinely.

I think that I've seen POTS-- working as an electrophysiologist, I've seen POTS frequently after undisclosed viral illnesses, whether they be flu, Coxsackie, who knows. But typically, women in their 30s, educated, many of them active athletes, quite serious athletes. And it's a debilitating condition. And the reason I say the electrophysiologist's nightmare, there's not much we can do for them. They have these postural tachycardias. Ablating these patients would be a disaster.

And what they need is really-- POTS was first described at the Mayo Clinic in detail by Dr. Philip Lowe, a neurologist. And it's a disease of the autonomic nervous system. And neurologists take care of them. But one critical aspect of POTS is a very comprehensive multidisciplinary rehab program with graded exercise, sometimes aerobic exercise in water, in a pool. But it needs a comprehensive multidisciplinary group to treat POTS.

MANDEEP SINGH: So do you think--

BERNARD J. GERSH: And the one--

MANDEEP SINGH: --predilection of this virus for the autonomic nervous system. That's why--

BERNARD J. GERSH: I think I've seen it after other viral infections. Now, what I think really is important when these patients come, and they're pretty debilitated, a significant number are told, look, you don't have an infection anymore. It's all in your head. It is not. It's real, and it overlaps, as I said.

MANDEEP SINGH: How about changing the topic a little bit? Dr. [INAUDIBLE] asked about hypercoagulability. What is the difference? Or what are the differences, you think? Or if you want to compare acute COVID infection versus long-term or chronic COVID infection.

BERNARD J. GERSH: I don't think we know that.

MANDEEP SINGH: So it has implications--

BERNARD J. GERSH: I don't think we know that.

MANDEEP SINGH: --on the anticoagulation and such, because the PEE and arterial thrombosis is much more common after COVID-19.

BERNARD J. GERSH: Absolutely. No question. And there's a lot written, and they're all good consensus guidelines on who should be discharged on oral anticoagulants, and a substantial number of people. And obviously, if they've had a DVT or a PEE during hospitalization, I think that discussion is, how long do you anticoagulate them for? Is it three months, or six months, or whatever? But I don't know of any studies on coagulation factors in patients presenting at three to six months with non-specific symptoms. I just don't think we have that data.

MANDEEP SINGH: Yeah. So there is one attendee who has-- now, you mentioned this collateral damage issue. So the symptom-onset-to-presentation time, door-to-balloon times, they're all prolonged. And he mentions that, is it because of lack of healthcare workers being present, or while they're waiting for the COVID test? So that's one part of the question.

And the second part is that knowing that underserved minority patients and high rates of COVID infection traditionally have poor CVD clinical outcomes, how can we effectively determine future incidence of CVD within that population and possibly aggressively address the risk factors at the same time?

BERNARD J. GERSH: Well, I think that's a very good-- It's not even a question. It's a statement, and It's a very important statement. I think that the collateral damage that we've seen, it's not universal. I know I presented some of these data in Europe. And in some centers in Europe, they didn't see that. They really didn't.

So it may be region-specific. It may be in part due to the logistics and the logistical constraints and the availability of resources in that particular region. It may also be patient-specific. Some patients may be more reluctant to go to hospital than others. And it may depend upon the quality of the hospital in the area. So there are multiple, multiple, factors.

The second part of your statement, I echo that. COVID has brought out disparity, so has magnified the disparities already present in our society in the delivery of cardiovascular care. And they've been magnified by COVID. And of course, these minorities are at a greater risk in terms of cardiovascular risk factors, with or without COVID.

And so I think that the impact of isolation on cardiovascular risk factor management and its late implications is profound. It's going to be very difficult to study. But it is really an issue. And that may be one of the things that is responsible in the one slide I showed for the late incidence of hypertensive deaths during the first year of the pandemic.

MANDEEP SINGH: Yeah. If we have to focus on groups, you mentioned athletes is one, which even though the overall myocarditis incidence is less than 1% but can have profound implications for that high-intensity exercise group and can be fatal, even though they may not have symptoms. And then, you brought out the race and ethnicity issue. Do you think the other susceptible group that we may need to have special focus on will be older individuals, where there are tons of comorbid conditions that make them more susceptible to long-term COVID infection sequelae?

BERNARD J. GERSH: Yes. I think so. I think that in terms of competitive athletes, there are good guidelines in focus-- I mean, in print, that are not just COVID related, related to any athlete with a viral myocarditis. And they're good. And I think they ensure safety. There's a role for stress testing. There's a role for imaging. There may be a role for Holter monitoring in some.

So what I think we haven't yet seen-- and there are a number of sports medicine individuals who are looking at this. And that is if you're a top class professional athlete, and you lose 5% of your performance, that could have a huge effect on their livelihoods and their success as an athlete. Hopefully, that's not going to be an issue, and not a long-term issue. But it's something to think about.

You talk about older individuals with comorbidities who have higher morbidity from acute COVID. And I think it's reasonable to, I suppose, hypothesize that they may be at a greater risk of long COVID. But we don't know that. That's what the studies, again, are looking at. We don't know that.

MANDEEP SINGH: And Dr. [INAUDIBLE] has asked again about, do you have any imaging or any markers? For example, you said post-vaccination myocarditis is mainly autoimmune.

BERNARD J. GERSH: They think.

MANDEEP SINGH: Any inflammatory or any other markers that will help the audience differentiate? Because, you have patients who received a booster or a vaccine and then got into presentation with myocarditis. Now, they are unsure whether this is a COVID infection, or this is a vaccine-related myocarditis. So are there any tests?

BERNARD J. GERSH: Well, no, there's no way you're really going to know. It's a clinical scenario. Someone in really good health, 17-year-old, excellent health, may get a vaccination. And four days later, they've got chest pain with myocarditis and, more frequently, pericarditis. That's all I need to know. And the likelihood that they will resolve is very, very high. I think probably almost universally, it'll resolve within a few days.

And that, actually, we did see with varicella, chicken pox, vaccination years ago. In fact, in UpToDate, we've got a paragraph in UpToDate on varicella myocarditis. And I actually raised the question of whether it was redundant and just a historical value, and we should take it out of UpToDate. But not. Of course, it's not, because the COVID vaccine.

Now, what is difficult, I have seen some slides of an MRI with quite extensive late gadolinium enhancement in a young individual. That individual had COVID and, subsequently, was vaccinated, without an acute vaccination syndrome. Now, there, it gets difficult. I don't know whether what we're seeing related to scarring from the original infection or whether it is related to the vaccine. But I don't think the vaccine-- my understanding is it's very short lived, severe, and painful for two or three days, as pericarditis always is. And then, it goes away.

MANDEEP SINGH: So I have a few minutes left. And it's quite unusual but I think something that I wish to ask you for a long time, as my mentor, as my teacher. And I think it'll help people who are viewing and listening to your talk is how they can become Bernie Gersh. So just let us in a few minutes-- I know you've had a career in cardiology. I just want to know-- and if you can let all the audience know, where did you start, and how did you become Bernie Gersh? And how can they become Tajik, and Nishimura, and Bernie Gersh, if they wish to? What do they need to do?

BERNARD J. GERSH: Maybe most of them are too sane to want to become-- to go through all of that. I think my children would have a different answer to that question. Well, I think the key is you have to love what you do. You have to be fascinated by what one does. And aside from being a clinical cardiologist who spent most of my time in the CCU, I just found a lot of very interesting questions to ask that come up in your day-to-day clinical practice.

And then, when you work in an institution like ours, one has the resources to sit down and say, well, we don't really know. Let's look at it. And one of my mentors, Bob Frye, who always said to me, don't just quote everybody else's data. What about our data? What do our data show? So I think you have to have the curiosity and the interesting-- There's no shortage of interesting questions.

And I had a meeting last week with some of my colleagues in the artificial intelligence group. And we've just come up with three or four really interesting questions that need to be answered. And we will answer them. And then, I suppose the other aspect of it is we're all very busy. And no one's going to do it between 9:00 and 5:00. You have to work longer hours. And for that, I'm very grateful that I've had an incredibly supportive wife and family, incredibly supportive. They've supported me in my career for 30, 40 years.

I don't really know how to answer that. It just happens, or it doesn't. But you have to work and ask the questions, because I frequently get asked some really good questions from non-academic cardiologists who say, look, I've got a patient with A, B, and C. What do you think? And you say, you know, I'm not sure I've seen that before. Maybe we should try and study that. Have to love what you do, because it is time consuming.

MANDEEP SINGH: Yeah. Yeah. So three things. Love what you do, right? Curiosity and a loving wife. And not in that order. Not in that order.

BERNARD J. GERSH: No. And loving wife and children who are supportive.

MANDEEP SINGH: Absolutely. Absolutely.

BERNARD J. GERSH: Because they're the ones that when we're working nights and weekends, sometimes, we take the time away from them. And then, obviously, you've got to have a certain amount of intellect.

MANDEEP SINGH: Yeah. Yeah. No. It's been a pleasure and an honor, again. Till we meet with another fascinating talk by you. Till then. Be well, and we'll see you soon.

BERNARD J. GERSH: Thank you very much, Mandeep.

MANDEEP SINGH: Buh-bye now.

Long-term cardiovascular complications of COVID: Seeing the forest for the trees

In this Cardiovascular Medicine webinar, Mayo Clinic cardiology experts Bernard J. Gersh, M.B., Ch.B., D.Phil., and Mandeep Singh, M.D., moderate a discussion of the pathophysiology of acute COVID-19 cardiac injury and the spectrum of late cardiovascular sequelae. A key part of the discussion is the extent of resolution of acute cardiac injury and its impact on late cardiovascular symptomatology.

For more information or to refer a patient, visit Mayo Clinic Medical Professionals — Cardiovascular Diseases.


Published

February 16, 2022

Created by

Mayo Clinic

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