Show notes
Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast, summary and backstage pass to the journal and its editors. I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: I'm Dr. Greg Hundley, the director of the Pauley Heart Center at VCU health in Richmond, Virginia. Dr. Carolyn Lam: Oh, Greg. Today we have a special episode focused on COVID‐19 pandemic, something that has just affected us so severely worldwide, it really needs no introduction. Why are we doing a special issue? Well, I think it very quickly got recognized that patients with cardiovascular disease do seem predisposed to severe COVID‐19 syndrome, and that these patients can have an acute COVID‐19 cardiovascular syndrome, in fact. We're going to be talking all about this in a series of interviews about the syndrome, the clinical presentations, what this implies for management. Is the pulmonary embolism involved in the pathophysiology of all of it? And what are ways that we should use to monitor or even screen these patient?, For example, what's the role of troponins? Dr. Greg Hundley: Yes, Carolyn. I am excited, just as well as you, and our first paper today is from Dr. Leslie Cooper, from the Mayo Clinic. He's really done a nice review describing the disease process and the management of acute COVID‐19 and the cardiovascular syndromes. Dr. Greg Hundley: Leslie, we'd like to welcome you to Circulation on the Run and just to get started, I'm wondering, could you tell us a little bit about the genesis of your paper and then also perhaps some of the mechanism, how does this virus affect our systems and promote cardiovascular disease? Dr. Leslie Cooper: In mid‐March as the COVID, crisis was taking off in this country, I was on a telephone call with Dr. [Biykem] Bozkurt and [Dr. Mark] Drazner, from Texas. We realized that there was a terrific need for clinicians to have an overview of how to manage the COVID‐19 impact on the heart. There was also, at that point, very little clinical data about the mechanisms and what the real pathogenesis was. We set about and the rapidly put together the available world's literature. That is what was ultimately published here in Circulation about two weeks ago. Dr. Greg Hundley: Tell us a little bit about that mechanism. Dr. Leslie Cooper: It became apparent that there is not one specific mechanism. We initially thought that like the Coxsackie viruses, this could be a direct cardiac damage, but clinically as we reviewed the literature, it became clear that it's more systemic. The older patients who have preexisting cardiac disease, hypertension, coronary disease, other risk factors, such as diabetes or obesity have a much greater risk of cardiac involvement and the consequences of that cardiac involvement are very substantial. Dr. Leslie Cooper: In addition, when you get a profound cytokine storm from the systemic infection, that can depress cardiac function. A combination, in individuals, of cytokine mediated damage from systemic inflammation, stress induced cardiomyopathy, as you would see in takotsubo, as well as hypoxia and perhaps increased pressures in the lung from, as Carolyn mentioned, pulmonary emboli, and finally direct viral damage. Viruses can infect macrophages in the heart. There is a growing body of literature that there can be a direct effect independent of the systemic infection. The answer is there are multiple factors each of which may have its own therapeutic target. Dr. Carolyn Lam: Oh, I love the way you explained that so clearly Leslie, and in fact, this is really bringing back sweet memories of when I was training under you at Mayo Clinic. I won't say how many years ago, but there comes the question, you know so much about myocarditis, in general, and a different viral myocarditis. Could you maybe tell us a little bit about how this one may or may not differ and also how this impacts management? Dr. Leslie Cooper: The coronaviruses have a very different mechanism of cell entry and propagation. It does not appear that this particular infection in the heart is causing the kind of antigen specific immune reaction that you see classically with a Coxsackie virus. We're not seeing necessarily a lot of auto‐antibody, molecular mimicry. We're not seeing a lot of T‐cell infiltrate. We are seeing some infection of macrophages, and it's not yet clear how many of those were infected peripherally and then migrated to the heart. The histology is quite different and the acute damage is therefore, more subtle. You're not seeing sheets of lymphocytes and the targeted therapies would not be necessarily directed at those cells. Dr. Leslie Cooper: Having said that, inflammation more broadly, for example, anti‐IL‐6, anti‐IL‐1 type, anti‐cytokine mechanisms are currently under evaluation in clinical trials, and they may be quite meaningful. Quite meaningful in the setting of the systemic inflammation. When you compare this to a SARS and other coronavirus infections, I'd like to say, we have known that occasionally a coronavirus can cause myocarditis, for 40 years. It's simply not very common. It predisposes the individual or makes the particular virus more cardiovirulent at this point. Dr. Carolyn Lam: All listeners, you have to get ahold of this beautiful paper. As Greg was actually suggesting a little bit earlier, they're this beautiful figure that you have to refer to that shows a management pathway and considerations. Also, very lovely illustrations of potential mechanisms. Leslie, could you also let us know then, in the overall management, not just treatment, where is the place then, for things like myocardial biopsy? Dr. Leslie Cooper: I think you have to start with the clinical presentation. COVID‐19 as a syndrome, and SARS‐CoV‐2 as a virus, can present with multiple cardiac syndromes. The first would be ST segment elevation, like myocardial infarction with normal coronary arteries. In that setting, it may be microvascular obstruction, or it could be myocarditis or stress cardiomyopathy, perhaps in a younger person who doesn't have risk factors. Dr. Leslie Cooper: Can also present with a primary cardiomyopathy, a heart failure presentation, shortness of breath, systolic dysfunction. And finally it can present as a pericardial effusion, not the most common presentation, but it's important to realize that just like other viruses, this can cause an epicardial or pericardial inflammation. Dr. Leslie Cooper: Management really depends on the clinical syndrome and I'd emphasize guideline‐directed medical management. If it's an arrhythmia, a ventricular tachycardia or heart block, manage that per the current guidelines. The same is true for systolic heart failure. Dr. Leslie Cooper: In addition, I would say that since most patients with COVID infection do not have cardiac involvement, you should first treat the whole patient. First, see the clinical syndrome. What is the dominant problem? Is it a lung problem? Is it kidneys? Then, if there is a cardiac manifestation, we recommend starting with a troponin. If the troponin is elevated, proceed to a point of care echo. Dr. Leslie Cooper: We do want to minimize exposure of allied health staff and physicians to the virus. We do not recommend multimodality imaging or heart biopsy upfront. Having said that, if the patient has substantial left ventricular systolic dysfunction, and they're already in the cath lab, because you're excluding coronary disease, our paper does recommend that you consider an endomyocardial biopsy to find the mechanism of left ventricular dysfunction. Dr. Greg Hundley: Very good, Leslie. Dr. Greg Hundley: Could you close this out, a little bit about therapy when we have patients with this severe hypertension, respiratory abnormalities requiring ventilation, and then also these devastating cardiovascular effects. Are we looking at anti‐inflammation is primarily the target as opposed to antiviral therapy? Dr. Leslie Cooper: Right now, there are a couple of clinical pearls. Number one, as in all cardiogenic shock, you don't have... Sinus tachycardia is not a therapeutic target. You may need that because of low stroke volume. You want to allow when it's compensatory for the tachycardia. Once you've treated with guideline directed therapy, the arrhythmias and the cardiomyopathy appropriately, specific mechanistic interventions, such as antiviral therapy or anticytokine therapy should be given within the context of a clinical trial, wherever possible. Dr. Leslie Cooper: Our article recommends that if you have access to a clinical trial and in this country, the convalescent plasma trial, is up and running. Mayo is leading that for the country. It's available at approximately 600 sites. We would recommend, first of all, enrollment in a trial because we then will understand the mechanisms and the best treatment. If you don't have access, it really depends on the clinical syndrome and how sick the patient is. Patients who are less sick have been treated with things like hydroxychloroquine. People who are more sick, we move on to a convalescent plasma and anticytokine therapy such as tocilizumab. Dr. Greg Hundley: Very good. Well, Leslie, we want to thank you for sharing this wonderful review with us at Circulation. We feel very privileged to have the opportunity to publish this and also to share it with our readership. Again, thank you for all of your frontline work at the Mayo clinic and helping participate in trials and things of this nature to combat this terrible disease. Dr. Leslie Cooper: Thank you so much. Dr. Carolyn Lam: Greg, from acute COVID‐19 cardiovascular syndrome to now, all about troponins. I am so, so thrilled that Dr. Nicholas Mills is here with us, not only our associate editor, but also corresponding author of the next paper. He's from University of Edinburgh in UK. Nick, I love the question that you asked in your title, "Are troponins an ally or a foe in the fight against COVID?" Explain, please. Dr. Nicholas Mills: I strongly believe that they can be an ally, but I recognize amongst cardiologists and clinicians around the world that are grappling with this new condition, that the use of biomarkers can be contentious. We're still learning very much about this condition and how it affects the heart. Therefore, it's difficult to provide very clear guidelines. It's how you interpret the cardiac biomarkers in this condition. The reason I feel strongly that they can be an ally is, they're easy to measure, they're cheap, and you don't require a direct patient contact to obtain the result of the test. It gives us some fundamental information about whether the heart is involved or not. Dr. Greg Hundley: Nick, can you tell us which biomarkers do you favor and is it high sensitivity troponin? Is it regular troponin? For our listeners in many different hospitals across the world, what would you suggest? Dr. Nicholas Mills: The evidence that has that merged very rapidly over the last few weeks and months suggests that our range of cardiac markers have very, very high prediction for poor outcome. Whether that's predicting a patient that might deteriorate and require admission to an intensive care unit for ventilation, or develop complications such as acute kidney injury or death. Dr. Nicholas Mills: There are a number of biomarkers that look very useful for predicting the course of a patient. The strongest, in most studies, is cardiac troponin. I think it's because we do have such sensitive assays now. High sensitive assays are such a fabulous way of getting a barometer of your heart health. The heart of course, is a fairly fundamental organ. If this condition is going to affect to any other organ out with the lungs. If it's the heart, you're going to be in trouble. I think high sensitive troponins, in particular, give us such exquisite information about the systemic complications of this virus that they are perhaps above all other markers, the most useful for predicting outcomes. Now, that clinical question goes beyond that. We need to understand how this virus is affecting the heart and whether we can intervene in any shape or form in response to these results in order to try and improve the course for these patients. That is a more challenging question. Dr. Greg Hundley: Nick, you've got a wonderful figure and we just heard from Leslie Cooper about the different cardiovascular disorders. Once we have elevation or experience, we see elevation in a patient with a biomarker, whether that be high sensitivity, proponent, BNP, et cetera. How does that point us in a direction of where our next move is, clinically, to combat this disease process in patients? Dr. Nicholas Mills: I think the first thing to say is that biomarkers do need to be interpreted in the clinical context and to understand that the pre‐test probability of having underlying structural chronic disease in your patient who presents with COVID‐19. That will very much influence your interpretation. If you think about the spectrum of conditions that you might see, and in fact, that we are seeing, there are a number that I would highlight. In particular, we know from many years of looking after patients with bacterial or viral pneumonia, that the pro inflammatory state of those conditions in patients who are vulnerable, older, and have underlying coronary heart disease is a really powerful risk factor for acute coronary syndrome and type one myocardial infarction. Dr. Nicholas Mills: Often in ventilated patients or patients who have clearly an alternative diagnosis, these important conditions, which are treatable, are overlooked. I think in considering the potential causes of myocardial injury of these patients, we should not overlook the probability that vulnerable patients have triggered acute cornea events in the context of their illness. Dr. Nicholas Mills: The other group that I think are really important are type two myocardial infarcts. They are an increasingly well‐recognized group of patients with the use of high sensitive tests in critical care units around the world. In the context of profound hypoxia or hypotension in sepsis, it gives the clinician managing the patient an idea about the vulnerability of the patient and their susceptibility and risk. I think that is also important. Dr. Nicholas Mills: Then, I think there's a separate group of conditions that are a direct consequence of the exposure to coronavirus and the clinical syndrome of COVID‐19. We are seeing case reports and have our own experience locally, of patients who develop myocarditis in this condition. I think it is rare, but it is real. When it occurs, it can be particularly severe and associated with prothrombotic complications. The other conditions that we are seeing are stress cardiomyopathies in relation to profound breathlessness, and that is not uncommon. Dr. Nicholas Mills: We are trying to systematically scan our more critically unwell patients in the intensive care unit to look for evidence of cardiomyopathy. Dr. Nicholas Mills: The final group that I would highlight is in those that are more severely unwell. Right ventricular dysfunction as a cost of either prothrombotic changes or of ARDS itself, is a really important observation that an elevated cardiac biomarker may be the first clue that that patient is developing cardiac decompensation. Although there's a range of different, important underlying conditions and the biomarker in itself cannot differentiate between these, I think recognizing that the patient is at risk of these underlying cardiac artery disease is an important first step. Dr. Carolyn Lam: Nick, really nicely explained. I'm going to read one of the lines f…
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