This transcript has been edited for clarity.
Robert A. Harrington, MD: I'm Bob Harrington from Stanford University and theheart.org | Medscape Cardiology. Today I want to talk about myocardial inflammation/myocarditis in athletes. What should we be worried about in athletes who have had COVID-19 infection? What are some of the screening tools we can use to guide our recommendations? What conversations do we need to have with patients and their families? What do the latest data tell us about the incidence? And the important question all athletes want answered: When can they get back to participating in the sport they love and excel in?
I'm privileged today to discuss this with my good friend and colleague, Dr Manesh Patel from Duke University. Manesh is currently the Richard Sean Stack Distinguished Professor at Duke. He is chief of the Division of Cardiology in the Department of Medicine at Duke and the co-director of the Duke Heart Center. Manesh, it's a pleasure to see you on the screen. I can't think of a better person to help us sort out this issue, given your background in clinical cardiology and cardiac MRI.
Manesh R. Patel, MD: Thanks, Bob. When you said "no better person," I'm glad there are better athletes but I certainly am trained in cardiology and MRI, so I can help with that.
Harrington: Manesh, in some ways this has been a remarkable year in terms of knowledge accrual on COVID-19, but in other ways it's been a tedious year. When COVID first came onto the scene last late winter/early spring, one of the things many of us in cardiology were struck by were the early case reports on the cardiac involvement of patients who had COVID-19. I'm not talking about the myocardial infarctions or strokes that were observed; that's for another conversation on thrombotic complications. I'm talking about the inflammatory complications, particularly myocarditis, which was something that raised a lot of antennas when it first appeared. What were your initial thoughts when you saw those reports?
Patel: We all realized quickly that COVID-19 was more than a respiratory infection and that people were coming in to the hospital and eventually having cardiovascular collapse. We also recognized that there were many mechanisms through which, at least biologically, something that binds to an ACE2 receptor to vascular endothelium could affect the heart. The first MRI study, from Germany, included 100 patients who had left the hospital; 78% of them had abnormalities on MRI. I looked very carefully at that study and thought, clearly some people have myocardial involvement. But when I looked at the images and other information, I couldn't tell whether it was myocardial involvement from COVID or something they had because they were in their 60s and had previously undiagnosed cardiovascular disease. Some of those findings are very sensitive. Immediately we were concerned about myocardial involvement with COVID and also about how we could sort this out to help inform our colleagues and our patients.
Harrington: It's a classic issue in imaging — what happens when you pick up abnormalities you didn't anticipate picking up, and how you deal with that information.
Patel: It's a constant in all of medicine and certainly in cardiology. I'll call it screening for evaluation of some involvement. With COVID-19, we understood that there were symptomatic and asymptomatic individuals. Certainly that study included a lot of symptomatic individuals leaving the hospital. But as we get into the athletes, we'll start talking about how you evaluate people who may be very high functioning. Should you be screening them? This is obviously a controversial topic.
Harrington: I am always telling the residents and fellows, do not get a test unless you know what you're going to do with the results of that test, because of this issue of dealing with findings that may surprise you. As you pointed out, the German study included a broad spectrum of patients. But then a report appeared from Ohio State University. This cardiac MR study found a high incidence of abnormal MRI findings in a group of competitive collegiate athletes. Now, these were nonconsecutive cases, not great controls, with a lot of the caveats that have to be applied. But it raised a lot of questions because of the unique nature of competitive athletics, which involve strenuous exercise and a return to that exercise at some point. Let's deconstruct that study, Manesh. What did you think when you saw it? Why would we care so much about myocarditis in athletes?
Patel: As with much of our understanding of COVID, this came from a confluence of science, a bit of the economics of how universities and programs must work, and then making sure we protect our young athletes who may not always have protection. I have to give tremendous credit to the investigators at Ohio State who published this research letter in JAMA Cardiology; they rapidly agreed to screen their athletes, evaluated those with COVID, and performed a cardiac MRI study that raised awareness of these abnormalities in athletes.
In fact, 26 COVID-positive athletes across multiple different sports had cardiac MRI. They used the Lake Louise Criteria, which look at T2 and T1 weighted MR imaging. For those at home, this is related to the water content of the cells. When you get inflammation in the cells of the myocardium, it can change the water content of the cells. And they looked at late gadolinium enhancement; gadolinium contrast is given to reveal cellular membrane damage or fibrosis. With these measures, they identified findings consistent with myocarditis in four of those 26 individuals.
That was a higher rate than one would have expected in a COVID-positive population, remembering that these young athletes with COVID-19 may not have many symptoms. So that was important. And then, we confront the issue of getting them back to playing their sport. We know from autopsy studies and others that if an athlete has myocarditis, when sudden cardiac death risks exist or the athlete has symptoms, we usually keep them out of athletics for 3 months or so.
Harrington: Let's talk about that. For the primary care doc who is doing a lot of the screening for sports teams at the collegiate and high school levels, maybe even younger, why care about myocarditis, specifically in athletes? What's the risk?
Patel: Our understanding is that as the myocardium and the cells themselves get inflamed, ventricular function may change. So even though the person is actively exercising, sympathetic tone goes up and down in these young athletes and they may experience an arrhythmogenic effect. They may have a very scary sudden cardiac event that can lead to cardiac arrest. That's what we fear most in athletic evaluations: Is there a substrate, is there an underlying mechanism by which someone could have an event? Before COVID, when we looked at series of athletes who had certain cardiac events, between 5% and more than 20% of them may have had myocarditis underlying the event. That's led to broad return-to-play recommendations in athletics. However, one thing we've learned with COVID, and we're learning with athletic evaluations, is that there's a lot of opportunity. Partnering with some of the leaders in the field, we have an opportunity to better define how we make these shared decisions, both with collegiate and professional athletes. Certainly, parents of high school and middle school kids are worried about this, and we're all concerned about our patients and the weekend warriors we deal with.
Harrington: The American Heart Association (AHA) Scientific Statement on myocarditis says that you should avoid strenuous exercise for at least 3-6 months. That may be okay for you and me, Manesh. We'll have to skip the Peloton for weeks to months, but we're talking about young people who love their sports and who are important to their teams. So you want to be sure you get this one right.
Patel: It has been such a pleasure to work with Aaron Baggish at Harvard, and Jon Drezner and Kim Harmon from the University of Washington. They and several team physicians have highlighted that restricting participation doesn't only physically affect the athletes who don't get to play; there's a huge psychological effect on people who've trained and exercised their whole lives. There is also deconditioning. We're recognizing that things like postural orthostatic tachycardia syndrome (POTS) may develop as these athletes, who have an autonomic system that's pretty revved up, stop working out and exercising. We're now seeing post-COVID POTS. My sense is, it's a significant decision to keep an athlete out of sports, so we really want to be as evidence based as possible.
Harrington: That is well summarized; you definitely want to get this one right. Part of getting it right goes back to that "incidental observation." Several months after the Ohio State report — and I agree with you, kudos to them for putting that out there — we started to see autopsy data appearing in the literature, including a terrific pooled autopsy study that said, wait a minute; when you actually study this in a nonselected population, because these are people who happen to have autopsies after COVID-19, the incidence of myocarditis by pathologic examination was actually really low, nowhere near what the imaging might have suggested.
Patel: As is often the case, first you get case reports, but as you get larger targeted studies, you get closer to the true incidence. The German study found some abnormalities on MRI in 78% of the individuals — very worrisome. And collegiate athletes, who you would assume had no other baseline myocardial involvement because they were collegiate athletes, it was 4 out of 26 (15%) with cardiac MR abnormalities. Then you look at the autopsy series, and you quickly get to less than 5% in broader groups and now you're looking at the gold standard. Some of it is about the test you're looking at, some is about the group of patients you're looking at, and some is about what you think that incidence is. What we know is that obviously something is occurring. The exact rate of what is occurring seems to be lower than those initial studies indicated, but questions have focused on the consequences. What can we do to clear people and make sure they're okay to participate in some of these sports? Because we want to be as safe as possible.
Harrington: As you know, I'm an obsessive Boston Red Sox fan. One of the Red Sox starting pitchers, Eduardo Rodriguez, was held out last year because he had what sounded to be a symptomatic cardiac event and I'm assuming it was myocarditis. I'm particularly interested in whether he'll be back on the mound this year.
With the AHA, we put together a COVID-19 long term registry. At the virtual AHA meeting, James de Lemos and others presented the first report from the registry, which found about a 1.5%-3% incidence of myocarditis.
Patel: That's exactly right. I believe this is something we're going to hear more and more. Remember, these were very symptomatic individuals who were hospitalized with comorbidities and had myocardial involvement based on echocardiography and other findings. The study was really well done and found that the incidence of myocardial involvement of some sort was around 1.5%-3%, depending on whether you called it pericardial effusion, myocardial injury, or a variety of other definitions.
When I did a literature review for influenza, I found about a 0.8%-1.2% incidence of heart involvement. That was out of a total of about 800 cases. If you asked, "What's the relative rate of myocarditis with infections of any sort?", a variety have been described, including parvovirus B19. So I think this rate may be higher, given the mechanism. It is obviously significant because of all the other things COVID-19 does and also because it is so prevalent in our society right now that it matters. But I think looking at cardiac complications of other viral infections gives us some perspective.
The other thing worth thinking about is that the prevalence of myocarditis in individuals may be different based on whether or not they were hospitalized vs being asymptomatic, as we're starting to think about long COVID. Who continues to have symptoms and may have not been hospitalized? Some of these younger individuals have different immune systems, so certainly there's a lot of biology that we don't fully understand yet.
Harrington: Your flu comment is so spot-on. If you compare the point estimate and the confidence intervals you just gave me and the point estimate and the confidence intervals of COVID, they'll overlap given the state of the data today. One of the things people have been calling for is to make sure that if we're going to have these long term registries, we must include other groups: noninfected people, people with other comorbidities, people with other viral infections and other infections in general. There's still a lot of unraveling of the biology that needs to be done.
Patel: The American Medical Society for Sports Medicine (AMSSM) has quickly stood up with Aaron Baggish, Jon Drezner, Kim Harmon, and a large group of universities to put athletes' data together, and with the AHA I see that becoming a long term registry of athletes that initially was started to answer the COVID question but will answer some of these others: What are the rates of abnormal conditions in athletic hearts? How do you participate in shared decision-making for people who want to play sports? And how do we learn that? All the way from high school to older adults. That's a big step forward. One of the things we've learned from COVID is that we need to identify the control group. How do I compare this information? So we're also thinking about that for a study we're doing called "Hearts of Athletes" for which we hope to image athletic individuals who haven't had COVID so that we have control groups. I know Vanderbilt, University of Wisconsin, and some other universities have also done this with large cohorts of athletes with and without COVID. They have started to compare those images to get a better sense of the abnormal findings.
Harrington: And as you rightly said, we're going to get information that may well be instructive for the non-COVID–related conditions because issues may emerge in the control group. I want to talk about the most recent data that was published last week in JAMA Cardiology. JAMA Cardiology has done a good job of pulling in these papers on the cardiac imaging issues related to COVID. Martinez and colleagues focused on a very specific group. These were professional athletes with COVID-19 who were enrolled in protocols that involved ascertainment of symptoms.
Patel: They're calling it the triple screen. Early on in the pandemic, our sports cardiology group, our team physicians, and our sports medicine physicians came together and said, outside of symptoms, the three good tests to get would be an ECG, a troponin, and an echo, and if all three of those were normal, what was the likelihood that you would find something really abnormal in this person? Matt Martinez and colleagues have done a nice job of including pro athletes across several different professional sports — hockey players, football players, baseball players, basketball, and soccer, men and women — and they found that the rate of heart abnormalities is around 0.6%. Specifically, that triple screen tended to identify those who would have an abnormality quite well. This should provide valuable information to those primary care physicians and others who are evaluating players, trying to get both symptom evaluations and the testing we do.
Harrington: They did a nice job; if you were minimally symptomatic to asymptomatic and you had a negative triple screen, then you were able to return to sports pretty quickly, as your quarantine period ran out. But for those people who had an abnormality on the triple screen, they went on to have MRI. Some of them had evidence of myocarditis but it seems to be much lower than the previous data suggested.
Patel: Yes, it's definitely a lower incidence, but you know myocarditis is still pretty scary for people who have had COVID. So especially for younger individuals who are so functional at baseline, certainly for athletic individuals, the idea of making sure you get a good symptom screen and then making sure you get objective evaluations is valuable. Some of the same authors have put together another fairly large collegiate example of this that hopefully will come out soon, looking at some of the same kinds of issues: What's the testing? What are the constant long-term symptoms? Are there a number of individuals with MRI findings? I also think the Big 10 is making sure they get MRIs on everyone who is returning to play, so they're probably going to publish a larger series that will give us a better point estimate.
At the end of the day, the clinician is going to be wondering, Okay, I'm in clinic, and I have this 16-year-old high school soccer player; what should I do? Besides understanding the symptoms, there's doing some of these tests that we just described, getting an ECG, symptom tracking, and maybe an echocardiogram. I'm not sure you have to do the troponin in that individual; it's not easy to get back. If the ECG and echo are normal, you should feel pretty comfortable for that individual given the data that we have. If they are abnormal, then you may get nearer to an MRI, although that is not always easy to do. Thinking about how you coordinate that will be important. Of course, when someone has or is recovering from COVID, even without myocarditis we still do a lot of work on understanding their heart rate recovery, their ability to exercise to peak, and those kinds of things that help us understand their physical ability.
Harrington: That's important. Even the person who's had frank myocarditis is given a graded, well-monitored return to exercise plan. It's slow exercise, gradually increasing the activity level. That still may have value, and it may even have value in a formal, observed exercise period.
Patel: Thinking about the number of people who are in and out of our healthcare settings and people we're caring for who will have COVID, how are we going to evaluate their hearts and get them back to doing the things they want to do — what I call return-to-play/return-to-work? That's why these athletic registries are so valuable, because they're collecting the information carefully and, of importance, in athletes who have fewer baseline cardiovascular abnormalities than our cohort of 50- and 60-year-old individuals who are in the hospital.
Harrington: To help the primary care doctors seeing young athletes in their offices, troponin levels are pretty easy, if you're able to get them, because it's either normal or it's not; echo is pretty easy to have interpreted; you're looking for wall motion abnormalities. What should they be looking for on ECG?
Patel: Great point. Just to mention, on echo, a certain number of these individuals in the studies had a pericardial effusion. So any amount of a pericardial effusion might raise your awareness, especially when you're thinking about pericarditis/myocarditis. So on echo, no pericardial effusion, no wall motion abnormalities, pretty normal-looking ventricles. You have to be careful about what you start looking for because you're going to see a thickened septum and you're going to be wondering, do I have to start thinking about other diagnoses? So, as you said, be careful when you order the test that you know how to interpret it. Asking your cardiologists to read it will be important.
The ECG can reveal a variety of things that go with myocarditis/pericarditis, but these studies looked for any abnormality. We know that athletes have bradycardia and large right ventricles. They have things that will look abnormal on ECG, so you have to be careful there too. Early repolarization will be common, so we're not looking for that as much as significant changes that may be consistent with pericarditis, or if you are actually starting to see T-wave changes that you don't think are associated with repolarization.
Harrington: The other thing I'm looking for is any evidence of heart block. Do they have a prolonged PR interval? If you are lucky enough to have a prior ECG, take a look at that and the ST segments. Also, is there any evidence of AV block? You want to be very careful as you as you look at their ECGs.
Patel: We're going to get a fair amount of data as these groups carefully look at the ECGs using the athletic ECG screening criteria compared with what's different in the COVID ECGs to discern how we should screen. For a long time, there's been controversy about whether we should use ECG or echocardiogram to screen athletes. As we delve into that for COVID return-to-play, I think we want to be aware of that available literature.
Harrington: Manesh, this has been a fantastic conversation about a lot of information that's been gathered over the course of the past year. We've learned a lot since last March, and we still have more learning to do. Fortunately, people have invested in doing the right kinds of research to try to understand this, and kudos to the professional sports leagues and athletes who are allowing their data to be published so that the rest of us can learn from it. As you said, there's something to be learned here that goes beyond the athlete, or even if it's strictly confined to athletes, it's not just the pro athletes; it's the middle- and high school athletes too.
Patel: I appreciate the opportunity to talk about it and certainly enjoy working with our team physicians and sports cardiologists, the foundations and professional societies, the AHA and the AMSSM, that have taken the lead here and are trying to make sure we go forward and figure this out.
Harrington: My guest today was Manesh Patel, the Richard Sean Stack Distinguished Professor, chief of the Division of Cardiology at Duke, and the co-director of the Duke Heart Center. Manesh, thanks for joining me here on theheart.org | Medscape Cardiology.
Robert A. Harrington, MD, is chair of medicine at Stanford University and current president of the American Heart Association. (The opinions expressed here are his and not those of the American Heart Association.) He cares deeply about the generation of evidence to guide clinical practice. He's also an over-the-top Boston Red Sox fan.
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Cite this: COVID and the Athlete's Heart - Medscape - Mar 25, 2021.