2020 Wrap-up: COVID-19's Effects on Cardiology

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This transcript has been edited for clarity.

Robert A. Harrington, MD: This is Bob Harrington from Stanford University on theheart.org | Medscape Cardiology. This is the second part of my conversation with Mike Gibson around cardiovascular medicine during 2020. In the first episode, we talked about all of the non-COVID-related issues and concluded that the science is really moving forward. We learned important things in antithrombotic therapy and lipid management, and maybe particularly in heart failure.

Now I want to talk about COVID, largely from the perspective of a cardiologist. I will break our conversation down into several areas. First, the early signals out of China, and then from Italy, around the increased risk in cardiovascular patients and their outcomes from COVID. Second, the increase in thrombotic events — myocardial infarction (MI), stroke — that then set off the search for antithrombotic therapies that might be beneficial. Third, this whole issue of myocarditis, and fourth, the unintended consequences in which people did not come to the hospital because they were scared, and so MI and stroke presentations dropped. The final topic will be lessons generally learned. You and I as clinical researchers are particularly interested in some of the research issues that were learned.

My guest is Mike Gibson from Harvard Medical School, where he is a professor of medicine at the Beth Israel Deaconess Medical Center in Boston and an interventional cardiologist. Mike is the director and CEO of the BAIM Institute, an academic research organization, and a longtime friend, collaborator, and colleague. Mike, thanks for joining us on Medscape Cardiology.

C. Michael Gibson, MD: We're here now for our COVID-ologist segment rather than our cardiologist segment.

Early Pandemic Response

Harrington: Yes, it's been quite the year. Let's back up to February and March. This viral pandemic is hitting. Early reports out of China were that patients who had cardiovascular risk (eg, hypertension, heart failure, coronary disease, diabetes) seemed to be at an increased risk of both getting the infection and doing worse with the infection. This raised all sorts of questions about angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). We know that the virus enters the cell through the ACE2 receptor, so were ACE inhibitors bad? We have learned a ton since February and March, but during those early days, what were you thinking?

Gibson: It was a riddle wrapped in an enigma that was a mystery that was topped with a secret sauce. It was so confusing. Was hypertension a risk factor, or was it the fact that you were on an ACE inhibitor or an ARB that was mediating the adverse outcome? We had a plethora of observational data, but we really did not have the science behind it to begin to nail down causal pathways. We still have a lot to learn. There was a fascinating article about identical twins. They were 60-year-old men and they contracted the same strain of the virus from the same person. One got severely ill and the other one didn't. It raises questions. Is it genetics? Well, these are identical twins. Is it environment? They had the same environmental exposures; they lived near each other and had similar jobs. Is it all of those chronic risk factors you mentioned? Well, no; they had similar blood pressure and diabetes and all that. It makes you scratch your head about what really is mediating a lot of this. It makes me wonder whether some of this is immune priming from different exposures to different coronaviruses, perhaps. It's quite a bit of a mystery.

It was a riddle wrapped in an enigma that was a mystery that was topped with a secret sauce.

Harrington: Back in the spring, from the American Heart Association (AHA) perspective, we were being called on to answer the question of whether patients should stop their ACE inhibitors or their ARBs. And early on we said that there is no evidence [to do that] and that you should stay on those drugs; the consequences could be worse. Fortunately, the observational data suggested that the drugs themselves were not problematic. Kudos to our friend Renato Lopes and the Brazilians who did a randomized trial that helped us show that it was not a problem.

Gibson: Absolutely. I was part of the BRACE-CORONA trial, and we randomized people to continuation vs discontinuation of ACE inhibitors/ARBs and saw no difference in outcomes. Kudos to the Brazilians. In our country, one of the biggest failures was the lack of organization. One of the biggest successes was the unparalleled organization in places like Brazil, with Renato and others leading the way there, and in the United Kingdom. They just simply beat the pants off us. It was amazing.

Harrington: I agree with you, Mike. Our good friend Martin Landray, from the United Kingdom, tweeted that they have gone over 20,000 patients randomized at only 174 sites in the RECOVERY platform.

COVID-Related Thrombosis

Harrington: Early on we began to see MIs and strokes. Learning from our colleagues who were really getting inundated with the disease, we started treating people with antithrombotic therapy. The challenge was that nobody was quite sure whether this was prophylactic or therapeutic antithrombotic therapy. We were seeing arterial thrombosis but we were also seeing venous thromboembolism and pulmonary embolism. How do you put all of that together now? Judy Hochman is leading a National Institutes of Health trial comparing prophylactic vs therapeutic doses of anticoagulants in the hospital. Around the country, I know people are doing really different things. [Editor's note: Since this recording, the REMAP-CAP, ACTIV-4, and ATTACC studies have been paused because of futility and safety concerns.]

Gibson: You ask 1000 doctors what they are doing and they are probably doing 2000 different things. It's quite variable. I was very confused by all of this. At the beginning, we wondered, is this disseminated intravascular coagulopathy (DIC)? When you look back at the early reports from China, they applied the International Society on Thrombosis and Haemostasis definitions and said that when they looked at autopsy studies, 70% of their cases were DIC. I thought, Well, if it is DIC, maybe all of these antiplatelets and antithrombins are not going to be that effective. But the story changed a bit and now it obviously looks like there is probably a diffuse endotheliitis that is activating the clotting cascade. Probably all of the complement getting released is also activating the clotting cascade. So, yes, we can give a lot of these drugs. But you do wonder: If we work our way proximally and reduce some of the inflammatory response, could we downwardly attenuate the need for some of these drugs which do cause bleeding? I worked with you on a medical prophylaxis trial and wow — now is the time to roll out those drugs and see if we can prevent some of those pulmonary emboli.

Harrington: There are three great trials going on, sponsored by the National Heart, Lung, and Blood Institute. Our mutual colleague, Paul Ridker, is looking upstream, trying to identify people who are at high risk by elevated biomarkers and then randomizing them to a variety of approaches, including placebo against antithrombotic therapy. Dr Hochman's trial is in the inpatient setting, and our former colleagues at Duke, led by Tom Ortel and Tracy Wang, are looking in the outpatient setting. This is where you and I have done a lot of work, because there is no question that if you have had heightened thrombotic risk, when you leave the hospital, at least for another month to 6 weeks you still have heightened thrombotic risk that can be attenuated. This was the case in the project you and I worked on with betrixaban, a factor X inhibitor. So, stay tuned.

Gibson: If I were sick, and I'm just talking about me, I would probably want to get prophylaxis. Every patient is different; you have to look at the risks and the benefit for every patient. But overall in general practice, I lean a little more toward prophylaxis.

Harrington: Yes, this will be interesting. We will see what the trials show us, and in the meantime, let's keep investigating the science. There were great papers on this topic from your Boston Brigham colleague, Peter Libby, on looking at the endothelium damage and trying to help us understand why the clotting occurs.

Myocarditis or Not?

Harrington: Let's move from the vessel to the muscle. Over the summer, a series of reports came out showing the relationship between infection and abnormal signals on cardiac MRI, suggesting myocarditis. And then a couple of things happened. One was that the well-known Boston Red Sox starting pitcher Eduardo Rodriguez was pulled from the season because he had myocarditis following COVID, and it sounds like he was symptomatic. And then a group from Ohio State University published a series of MRIs on athletes who had recovered from COVID, again showing high rates of signal on MRI. What did you make of it at the time?

Gibson: At the time I found it very concerning, and it really got my attention. There were some criticisms of those studies, but where there is some smoke there is probably some fire. I think there really is cardiac involvement. I'm not personally sure about the magnitude at this point; I'd like to see more data. But one area that was really confusing to me (and the lay press confused this quite a bit) was saying that the virus was infecting the heart. I got really annoyed reading that. When you really looked at it, the virus was in macrophages around the myocytes, not in the myocyte itself. Then some studies came along and did seem to indicate that there may be some viral particles inside the myocytes themselves. Nonetheless, it added a lot of confusion. When you are in the emergency room and you have a COVID-positive patient with chest pain and elevated biomarkers, are they having a STEMI? Are they having myopericarditis or takotsubo cardiomyopathy? It was a very complicated picture.

Harrington: It's still complicated. Follow-up pathology studies have shown that there is not that much true pathologically defined myocarditis, certainly less than would have been suggested by MRI. Mike Bristow, from University of Colorado, was funded through AHA to look at myocardial samples in people with COVID. There is still more to come. The myocarditis does not look to be as common as the imaging might have indicated. But trying to figure out what to do with competitive athletes is tricky, isn't it?

Gibson: It's really tricky. I grew up in Boston in that area where some pro athletes died, with a lot of controversy about whether they should be out there. I think until this is settled, I would urge people to be cautious.

Harrington: There were a couple of great papers in JAMA Cardiology, including from one of your Tufts colleagues, Jim Udelson, that tried to frame up how to look at these myocarditis and competitive sports issues. It's worth taking a look at.

Gibson: I'm not gonna get out on the football field. I'm gonna stay put.

Harrington: Despite the fact that you are a retired running back, if I remember, from University of Chicago?

Gibson: Yes, a starting halfback at the University of Chicago. But I'm gonna stay on the couch.

Harrington: Can you give me that Heisman pose?

Unintended Consequences

Harrington: I was hearing from colleagues, mainly in places that were getting hit hard, like Boston and New York, that during the height of the pandemic, they were seeing fewer cases of STEMI and acute stroke. That was observational. And then the national data started showing fewer 911 calls for evaluation of acute chest pain and acute stroke symptoms. And it does look as though there were fewer MIs presenting. The pullback of that was that people were afraid to go to the hospital. And then we started hearing things. One of our surgeons here said, "I've done a couple of cases of ventricular septal rupture repair in MI patients that I haven't done in years because of rapid reperfusion. But now these people are presenting late." I'll call all of this the unintended consequences. You were in the middle of it in Boston. Is there truth to all of this?

Gibson: Back in the '90s, we had patency rates that were 15%-20% on arrival to the cath lab, mostly closed arteries. What is interesting is that over the past 20-30 years, those numbers have crept up to 35%-45%. There is something going on. Personally, I think people are getting there a little quicker and they have less mature clot, and the drugs we are giving them are reestablishing patency a little early. Fast-forward now to this pandemic and everything goes the opposite way. People are waiting at home, scared to go in, scared that they are going to get COVID. They fear COVID more than they fear an MI. We saw all of those complications you mentioned in Boston. We saw about a 50% drop in MI admissions. And that was true around the world; Italy reported a 50% drop. Everyone reported more mechanical complications. It was kind of interesting at one time to see people starting to talk about giving lytics. I was waiting on the calls because I am probably the only person who knows how to give a lytic in our hospital these days.

Harrington: I was thinking the same thing. There are not many of us left who gave a lot of thrombolysis, but there are still a few of us.

Gibson: Exactly. But it turned out that primary angioplasty is probably the way to go. Our volumes are back to 80% of where they were. We are not closing down; we're just going to continue to go now.

Lessons Learned

Harrington: Finally, we will talk about lessons learned, maybe from a research perspective. Research kept going, and certainly from a COVID perspective, wow — quite the amount of papers have come out. A lot are not very good, but some are really helpful. What have you learned, Mike?

Here is the saddest thing: Storytellers prevailed over scientists.

Gibson: There are so many lessons learned. One is that you only have one chance to make a first impression. And sadly, I think science and public health made a bad first impression. We heard, "No, you can travel. No, you don't need to wear a mask. No, it's not aerosolized, it's by contact." And when they began to change their recommendations, people got really scared. You know why? Because people love predictability and they absolutely loathe uncertainty. And we really laid down a lot of uncertainty with the public early on.

You and I like to think that we are scientists, and we welcome uncertainty and testing things out. But the public does not welcome uncertainty. That is one of our biggest limitations. Then when you had that uncertainty, I think people from all sides of the political spectrum rushed in to offer the answers, to offer certainty, even though we all knew there was no certainty. Here is the saddest thing: Storytellers prevailed over scientists. Emotional connections and tribalism sadly prevailed over science. Mercifully, the scientists kept going and have developed a lot of effective treatments. But I think we went through a period that was one of the worst I've seen in science in terms of bias, confirmation bias, and in terms of people only believing the data that supported their presumptions and their own biased viewpoints.

With the success of the vaccines, with the final triumph of science combating this thing, I hope scientists and public health officials can regain their voice so that we can establish science and the scientific approach as a trustworthy way of getting through these things. I hope we have taught people about uncertainty and about how you answer uncertainty, and it's not through the narratives we saw.

Harrington: I could not agree with you more. I think that for scientists like you and I, we welcome things changing because that means we are learning and adapting and testing new hypotheses. But we did not have consistent messaging throughout. The challenge of science literacy in the public makes this difficult, that people do not accept uncertainty as something that we really want to do. We've learned some important lessons on how one thinks about science, how one transmits science, and how one communicates science. We have work to do.

Gibson: We have a lot of work to do. You and I are both leaders and we both have difficult challenges. I had to turn a bankrupt organization around. People want two things from you, and they want them simultaneously: They want speed and they want accuracy. It's a little bit like the Heisenberg uncertainty principle, which is often misstated. The real Heisenberg uncertainty principle is that you can't know both the location and the speed of something at the same time. As it applies to politics, you can't really have accuracy and speed at the same time. We do our best to reach a compromise between those two. But if you went on accuracy, you were too slow. If you were quick, well, then you were inaccurate. It's a tough job. I really felt for all of the public health officials who were trying to lead us through this pandemic because it was a big challenge.

Harrington: It was a huge challenge. There were some important lessons learned. We need to do a better job of how we convey science and how we talk about science. We need to do better with how we teach science and what our expectations in the schools ought to be. There is still a lot to learn.

Gibson: We need to do a lot of work teaching people in medical school about observational data and its limitations.

Harrington: Absolutely. Mike, I want to thank you for joining me here on theheart.org | Medscape Cardiology. This has been a fascinating discussion. My guest was Mike Gibson, professor of medicine at Harvard Medical School, Beth Israel Deaconess Medical Center, in Boston, and the BAIM Institute. Mike, thanks for joining me here.

Gibson: Thanks for having me, Bob. Let's have a better 2021.

Bob Harrington, MD, is chair of medicine at Stanford University and a former 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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