In Conversation With Peter Liu

The heart expert from Canada talks to MEDICUS about his work on COVID and heart inflammation and his paradigm-shifting project to bring the brain closer to the heart
A picture of heart expert Peter Liu from Canada

While the world heaved a sigh of relief when the first mRNA vaccines against SARS-CoV-2 emerged triumphant from clinical trials, their unprecedentedly wide and simultaneous use threw the spotlight on a rare but potentially dangerous side effect: inflammation of the heart. MEDICUS talked to Professor Peter Liu, the chief scientific officer and vice-president of research at the University of Ottawa Heart Institute, about the links between COVID, vaccines and heart inflammation as well as an exciting new research initiative that he’s spearheading as the director of Canada’s national C-CHANGE Initiative to harmonise and integrate heart and brain prevention and treatment guidelines. Liu was previously the scientific director of the federal health funding agency, the Institute of Circulatory and Respiratory Health at the Canadian Institutes of Health Research.

MEDICUS: Welcome to Singapore. We’re delighted to speak with you. Researchers at Duke-NUS recently published a paper in Med documenting a case of heart inflammation, or myocarditis, following a COVID booster shot. But it is not just the vaccines that can cause heart inflammation, the virus itself can too. So, can you help tease apart the relationship between COVID, vaccines and myocarditis?

PETER LIU: I think there are two things that we learned during the pandemic: one is the fact that SARS-CoV-2 is not just a lung infection. It is a very important trigger of inflammatory responses in the vascular system, what we call endothelialitis, which is inflammation of the lining of the blood vessels. And that’s why we end up with complications, like early stroke, heart attacks in young people and myocarditis. And then in terms of long COVID, many of the symptoms, for example, tiredness, dizziness when we stand up, brain fog or even the loss of taste and smell, are likely related to small blood vessel inflammation around the nerves.

The second is that the vaccine has really transformed the face of the pandemic. mRNA vaccines are relatively new and when they were being rolled out, we discovered that young men, particularly between the age of 12 and 29, can have this rare complication of myocarditis. The fortunate thing is that we tracked a lot of these patients, so we know that most of them recover and that is important. And the frequency of myocarditis from the vaccine is less than the COVID-related myocarditis, so it’s way more beneficial to get the vaccine.

When we looked into this, we found evidence to suggest that a combination of things may lead to this. One is the fact that after vaccination, you get a huge rise of the spike protein, which is very similar to how the virus infects you. The other aspect is that some of the small particles, the lipid nanoparticles, probably exert some influence because the frequency of myocarditis between the Moderna and Pfizer vaccine is different. And, then, of course, there are genetic differences between individuals as well.

MEDICUS: We now have a window where SARS-CoV-2 continues to circulate but it no longer poses the same threat. Can we seize this opportunity to improve our vaccines, and perhaps better protect ourselves against coronaviruses?

PETER LIU: Yes, we are now looking at these components—what is it actually about the spike protein that triggers an inflammatory response? And what is it about these lipid nanoparticles that trigger a cardiovascular and immune response? So that we can figure out what is the combination that maximises efficacy without the risk. 

A heart sits on a wooden plank with a brain on the other end. The wooden plank is placed on a fulcrum

Credit: iStock.com / Hryhorii Bondar


MEDICUS: Apart from concerns about the impact of infections on the cardiovascular system, research is pointing to a connection between climate change and cardiovascular disease. What are your thoughts on this?

PETER LIU: In colder countries like Canada, we’ve known for a long time that the mortality from cardiovascular disease, from strokes and heart attacks and things like that, has seasonality and locality to it. But also for example, in Japan, the northern parts tend to be colder and at the same time, the food tends to be saltier because traditionally you tend to preserve food longer that way. So you have completely different habits versus the South, somewhere like Okinawa, where people live the longest. They have lots of fresh tropical fruits and vegetables. All these things are related to climate but we don’t think about them.

We also know that in Canada, the heart attack and stroke risk, as well as deaths from these, increase by 25 per cent in February compared with August. But the interesting thing about this is that it has not only to do with the average temperature but also the change in temperature. For every five-degree drop in temperature, your systolic blood pressure goes up by three or four millimetres. This is why you have an increased number of people dying of heart attacks during a snowstorm or big cold spell. And this is not just in colder areas of Canada, it’s the same wherever you are.

MEDICUS: Our colleagues from the Health Services and Systems Research Programme here at Duke-NUS have found that even a small drop in temperature in a tropical climate like Singapore’s increases the risk of a heart attack among people aged 65 and older.

PETER LIU: Right. And with climate change, we have much more drastic changes in temperatures. But we have not adapted, so the consequences are becoming more and more dramatic.

So, we really need to find ways, on the one hand, to try to modulate these differences, and then the other, to improve cardiovascular health. I call this our resilience factor: how can we protect the population so that despite these changes, we are better prepared?

MEDICUS: So really educating people about the risks of heart attacks and even heart disease is going to be important. But what is the biggest misconception that people have about cardiovascular disease?

PETER LIU: The view that heart disease is in your genes and you can’t do anything about it.  But I would push for the fact that cardiovascular disease can be reversed. And that fate is in our own hands. In heart failure, sometimes patients are told it’s a terminal illness; there’s no hope. And they can get very depressed, so it becomes a self-fulfilling prophecy. But I have patients who had heart failure and now have practically normal heart function, having survived more than 20 years. With the knowledge we have today, we can partner with our patients to empower them to see cardiovascular disease as tameable.
A picture showing Peter Liu and his answers four more personal questions

MEDICUS: There is more than meets the eye to this self-fulfilling prophecy though—something that you’re hoping to investigate with a new grant focusing on the brain and heart. What prompted you to pursue this?

PETER LIU: Because we’re so specialised, we sometimes forget that patients with cardiovascular conditions have simultaneous risks for brain conditions and miss some of these biggest opportunities. About 40 per cent of heart failure patients have a risk for depression. And between 30 to 60 per cent of them can develop cognitive impairment. So, what we don’t realise is that when patients with heart failure forget to take their medicine, it is not that we have failed to teach them what to do, but that they may have a cognitive impairment that’s not been recognised. So, unless we address that, patients won’t get better. The same is true for patients with heart arrhythmias, or what we call atrial fibrillation. Even in patients with a risk of atrial fibrillation who never had any stroke, if you image their brain, you’ll find signs of micro-strokes. So, these are the things that we failed to realise but the tools are better now. For example, we now know that after a heart attack, there are direct changes in the brain. And vice versa, people with a stroke have cardiac changes. There are all these connections.

So, we’re looking for novel tools to diagnose cognitive impairments much more efficiently and new treatments that are synergistic for the organs involved without generating side effects that negate the benefits. And then teach the patient how to look after themselves and look out for these conditions, so that they are better off as a total individual since it’s truly a patient-centred approach rather than an organ-specific approach.

We’re also developing a few simple questions that patients can answer, so we can pick up early cognitive impairment, signs of depression or sleep disturbances and things like that, which we don’t tend to ask about when we take their history but that influence how we treat a patient.

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MEDICUS: Can you see this triggering a paradigm change on a larger scale?

PETER LIU: This is our first foray into designing a model focused on how the body cross-talks, and if we want to have adequate prevention strategies and treatments that are effective, we need to think of this as the model rather than the exception. This is the way medicine should be practised.

And it’s not going to be just the brain and heart. People with chronic conditions can also have kidney and lung impairments—and all are interrelated. We need to profile patients’ risks appropriately, rather than just look at the cardiovascular risk factors. Using a risk-stratified approach, we can apply a much more patient-centred prevention strategy.

MEDICUS: You visited Duke-NUS to forge some new collaborations, how is that going?

PETER LIU: We already have ambitious plans from the conversations we had so far. There are several really exciting studies already underway. So, we want to build working groups to bring in people with shared interests around the world to share learning, accelerate research and increase our impact.

This is an opportunity to take like-minded, talented people and create a community, where we work together, but at the same time, have diverse approaches, data sets and tools. But all trying to answer similar types of questions. That way, we can get there much faster. And probably have a much more realistic set of solutions.

MEDICUS: In pushing for this wider approach, what do you hope the wider impact will be?

PETER LIU: One of our ambitions is to change how people think about this. We still teach organ systems because they are one order of organisation, but we leave it at that stage without thinking about what is the integration, the higher level of connection. And when things go wrong, how do they affect each other? But this is complicated, so it’s easier to say that is somebody else’s problem. But the patient really suffers when care is not integrated. So I think on the care side, there can be better coordination. And in terms of education, we need to learn how to put some of these pieces together for the benefit of the patient. It’s ambitious, but it’s time to think about this. We have the tools of science pointing this way. Patients tell us it is important, so let’s just go for it. 

The interview was conducted and edited by Nicole Lim, Senior editor.

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