We still don’t fully understand why the SARS-CoV-2 virus is so transmissible and causes severe disease in some people but not others.
But Dr. Philip Adamson, chief medical officer of Abbott’s heart failure business, said he’s amazed by how quickly we’re learning about COVID-19, building off our prior knowledge of coronaviruses and other viral pathogens.
“We have more of a handle on the mechanisms, and that’s where I think we are beginning to have hope for clarity,” he said. “In just about every disease that we are able to treat, we develop those treatments because we understand the fundamental mechanism of the disease.”
Adamson warned of increasing rates of heart and lung failure due to COVID-19 when Medical Design & Outsourcing interviewed him last year. We’ve checked in for an update on the latest about COVID-19’s cardiovascular impact and how medical devices can keep patients alive.
The following conversation has been lightly edited for space and clarity.
MDO: What have you learned about COVID-19 since we last spoke?
Adamson: The receptor that this virus utilizes to get into the cell is part of the system we call the renin-angiotensin-aldosterone system. It’s the angiotensin II receptor. That’s really all over the body, but mostly expressed in the lungs, so that’s why it focuses on lung damage when it sets up an infection. But the process, we’ve now learned, is there are both direct and indirect effects on the heart and blood vessels. We talked a lot about the indirect effects of the cytokine storm and the intense inflammation that occurs typically in some people with this disease and syndrome. That is well defined now through multiple different inflammatory mediators that actually could be targets for therapy in the future. But that inflammatory mediation is maybe more exaggerated in people with preexisting cardiovascular inflammatory states like metabolic syndrome or other syndromes that would cause this underlying, low-burn inflammatory state that we’re aware of. Clearly, those that have cardiovascular disease seem to have a higher chance to have severe disease when they get COVID-19. What we were worried about early on is that we can fairly commonly see and detect injury to the heart during a severe COVID infection. When patients are having COVID and feeling bad but not going to the hospital, nobody tests those folks for heart inflammation as a result. But when the moderate to severe disease that lends itself to hospitalization occurs, the cardiac community has been interested to see how that’s mediated, how many people get it, is it only found in moderate to severe disease? We typically make inferred diagnoses in cardiovascular disease. So if we measure a blood component that is a biomarker like troponin that is only in the bloodstream measurably when the heart’s damaged, or we measure a protein called B-type natriuretic protein — which really is only in the circulation in higher levels when the heart has stress on its filling — we then take those essential measurements and make diagnoses or inferred diagnoses from that. We find that troponin I — which is a significant marker of myocardial injury or heart muscle injury — is elevated in many people with moderate or severe disease. We thought that the total inflammation plus the direct effect on the heart might cause a marked increase in myocarditis, which is a global inflammation of the heart muscle itself, and it is associated with other viral infections. That’s not been what we see in these infections. But there’s clear evidence that in about 20% of people there’s an elevation in troponin, which would be a diagnostic criterion for a myocardial injury or myocardial infarction. And that then leads to a higher risk of death. It’s pretty clear actuarially that if a moderate or severe COVID syndrome is associated with an elevation of troponin then the prognosis is much poorer. It is associated with higher risk of death through a variety of blood vessel and heart muscle abnormalities that can cause cardiovascular disability as well as death.
MDO: Anything new on lasting cardiovascular effects from mild COVID-19 cases?
Adamson: I am still concerned that any kind of inflammation or any kind of direct injury to the heart muscle — we know this from other diseases and other situations — sets up this potential for long-term myocardial damage and nonischemic cardiomyopathy. It’s just too soon. That takes years. It is theoretically possible and certainly there’s a lot of evidence to suggest that could happen. The data is still accumulating about how severe the heart is involved in mild to moderate nonhospitalized cases. There are studies that would suggest that there is some probable inflammatory injury. But I don’t think that we have enough definitive information to make a conclusion yet.
MDO: We initially thought of COVID-19 as a respiratory disease, but is it more helpful to think of it as a vascular disease in that it touches everything the vascular system touches down to the smallest capillaries?
Adamson: That’s a great question, and it turns out that it can be better understood when you understand the angiotensin receptor that’s involved in the transmission of this disease. The virus binds to this natural receptor to get into the cell, and in that process gets into the membrane and then it sets up all the inflammation, etc. And the lung, alveolar cells are really studded with these receptors, so that’s where the virus finds the opportunity into the cell. It makes sense then that most of the symptoms and developments as a result of COVID-19 syndrome are focused on the lungs. That being said, the angiotensin system is one of the most important regulatory systems for the cardiovascular system, both the heart and the blood vessels. Those receptors are everywhere, and they’re available when you inhale the virus. When it becomes systemic, then you do get direct effects on the blood vessels, on the heart, on the coagulation sequencing in the blood vessels, primarily probably stimulated by disruptions in the endothelial cells that line the inside of the blood vessels. The body doesn’t like disruptions in that. When it sees those kinds of breaks in the endothelium, it has to fix them and it starts that fix with the coagulation system. That can deplete the system of its first responders, which then causes this concept of disseminated intervascular coagulation in which you get this cascade of coagulation. And that’s most apparent in the smaller blood vessels, especially those that are going from the heart to the lungs, the capillaries in the pulmonary circulation, and that just obstructs the ability to get oxygen then into the bloodstream. Then the oxygen level drops, acid-base levels change, electrolytes change, and now you have not only systemic inflammation, but you have all the substrate for injury to the heart. That would include direct muscle injury, direct production of arrhythmias, blood clots in small vessels, deep vein thrombosis and pulmonary emboli are very common. It’s a cascading effect, a combination of both direct effects on the heart and the blood vessels, and an indirect effect of this massive inflammation that can occur along with the oxygenation, etc. It is complex, but on the other hand, it kind of makes sense if you think of it as starting with this receptor that is found in a lot of places, and every place it’s found has a potential of being impacted by the disease. And so far it’s shown great success in doing that.
MDO: The coagulation in the smallest capillaries, is that what’s referred to as COVID-19 microclotting?
Adamson: Exactly, and we all do this because our blood vessels are constantly under stress. When there’s a break in them we have this system that surveils and repairs those vessels all the time. And when that cascading of blood clotting gets out of control, then the blood clot obstructs the blood vessel. These tiny vessels where the exchange of oxygen and carbon dioxide occur are not too much bigger than a red blood cell itself, so it doesn’t take much to get a clot that destroys or blocks up those vessels. Then it doesn’t matter how much oxygen you breathe in, you can’t get it across the membrane into the bloodstream if that happens in a large enough load on the lung.
MDO: Are there tests to detect microclotting?
Adamson: You can’t really look at the tiny blood vessels, but you can see the effects of it in some of this ground glass appearance on CT scans of the lungs. Oxygenation’s a big deal in this disease. And that’s why extracorporeal membrane oxygenation has become a lifesaving intervention. Essentially it’s a bypass for the lungs. You take away that function until it can recannulate and it eventually will if given enough time. But unfortunately, the host can’t survive if it doesn’t have an operating lung system. Larger clots are fairly common and we can directly image them either with ultrasound or venography. In the veins of the leg, many times those clots break off and can go to other parts of the circulation. Most commonly, they go back into the lungs. These are big clots that can obstruct the blood flow in general to a whole segment of the lung. Pulmonary embolism can range from not even knowing you have it to death — sudden death. That component is well described with the coagulation abnormalities that occur with COVID-19.
MDO: What role can medical devices play to tackle COVID-19, both in prevention and treatment?
Adamson: The most important are supportive devices when severe disease occurs. It is absolute in my mind, it is very clear that extracorporeal membrane oxygenation is the most effective way to save a life. Early on, it was thought that when ECMO was applied, people tended to die. What we learned is that there was too much time before it was applied. It was applied too late. ECMO was this sort of temporizing medical device intervention that saves lives. We now have seen that we really have to have a broader availability of providing that therapy. And I think everybody now recognizes that we’re going to have to have that if people are going to survive this disease.
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