The Future of Cardiac Care: Genomic Insights and Precision Therapies

Podcast Transcript

Announcer:

Welcome to Cardiac Consult, brought to you by the Sydell and Arnold Miller Family Heart, Vascular and Thoracic Institute at Cleveland Clinic. This podcast will explore the latest innovations, medical and surgical treatments, diagnostic testing, research, technology and practice improvements.

Samir Kapadia, MD:

Hi, welcome today. I'm Samir Kapadia, Chairman of Cardiology at Cleveland Clinic, and I have with me Dr. Krishna Aragam. He's our section head for a new Section of Genetics and Precision Medicine. We are going to talk about this to try to understand what this really means. Krishna, can you, first of all, introduce yourself a little bit to say what is your background and where you came from? So people get to know you a little bit.

Krishna Aragam, MD:

I am originally from Boston and spent the past decade at Mass General Hospital developing a interest in and practice in cardiovascular genomics, both clinically and on the research side. I’ve come here to the Cleveland Clinic to start this new section in clinical cardiovascular genomics.

Samir Kapadia, MD:

So wonderful. Thank you. The first and foremost question is, when you talk about cardiovascular genomics and precision medicine, how is it different than what we used to do in the past? How is it advancing the care in a different way and in a more modern way of thinking?

Krishna Aragam, MD:

First, I think cardiovascular genomics, what is it really? It really is just the idea of taking genetic information into account, these small letter code changes in our DNA, and using that to help understand an individual's risk for developing a heart condition. In some cases, if someone already has a heart condition, to better understand the condition itself.

How's that different? The analogy I sometimes give is, if we want to check the weather today, on a given day. We in cardiology are very good at assessing how someone's doing at the present point in time. That could be checking their cholesterol and blood pressure, to much more advanced things like looking at their heart structure and function, or looking inside their blood vessels, seeing how much plaque they have, how that looks. But genomics is a bit more about understanding what climate we live in, in some sense. It's not going to tell us exactly what temperature it's going to be tomorrow, but it gives us a general sense of what to expect. We're much more prepared to know what might be possible and so that we're able to be more proactive and thoughtful in our care then.

Samir Kapadia, MD:

It's not just how people will respond to different therapies, different treatments, maybe different. One is to diagnose the problem. One is to try to understand what condition they have and how it is going to progress. But it's also important to say what treatments would be better suited for certain problems. This is very common in cancer genomics, where people are trying to have precision medicine to say that this is how they will treat. It is happening in cardiology also.

Krishna Aragam, MD:

Absolutely. That's the second part of this, the precision medicine aspect of it. So, if cardiovascular genomics is giving us a sense of one internal environment, it then is also giving us a better lens into the biology of what is causing a particular person's condition. That's ultimately what allows us to be more precise in our therapies. As you mentioned, it's been happening in cancer, and there's much more happening now in cardiology to tailor a treatment strategy to someone's biology based on their genomic signatures.

Samir Kapadia, MD:

Exactly. When people think about genetics and cardiovascular disease, they always think about young people and say that if you're young and if you have a problem, then we talk about the genetics. Is it true? s it all ages or just the young people? And how do you see which people benefit from this particular effort?

Krishna Aragam, MD:

Traditionally, we think about genetics as something that is more likely to play a role for folks when disease manifests at a young age. That's generally true that it's more likely, but not that it's absent for people who are developing conditions later in life. It really is a spectrum with regard to how much it's playing a role. I think that the greatest benefit is going to be in early detection and in preventing disease, because again, for a lot of people, the disease is happening before the risk factors even develop. If genetics is your first risk factor, then you have the ability to identify this beforehand and act at an early age.

But lots of times genetic risk is latent. It's not present. It's not manifesting until several decades later. The information which you might have from, again, it's present at birth. This genetic risk, if you identify it early on, you may only develop that risk in your 50s and 60s or the actual condition in your 50s and 60s, but now you may have decades to prevent that outcome.

Samir Kapadia, MD:

Exactly. What kind of diseases are we targeting? If you say that cardiovascular diseases is heart attacks, lipids, aorta, valve, cardiomyopathy or all of them, what is the real target that you're looking for in your focus?

Krishna Aragam, MD:

I’ll start by saying we think that genetics is playing a role in pretty much all cardiovascular conditions. How much and in what manner differs. We do know that more classically in what is even tested for currently, there are probably four or five major areas, well-established genomic markers for dyslipidemia, lipids and plaque formation atherosclerosis, as well as for heart and muscle disorders and heart failure, the cardiac arrhythmias, so rhythm disturbances, electrical abnormalities in the heart, and aorta. Aortic enlargement and rupture is another classical one.

Those are probably the four, and some other vascular conditions. Four or five major areas where there are already a lot of genomic markers that we know about and test for. But again, there's a vast body of science that suggests that many other conditions that we don't test for conventionally have a lot of genetic determinants, including valve disease. We're eager to be on the lookout for that and have that inform our care soon too.

Samir Kapadia, MD:

How easy or difficult is it to test for this genetic marker? So if I'm a patient and I come to you and say check my genetics, what, really. do you do?

Krishna Aragam, MD:

Actually, it's become quite routine. It's quite streamlined now. Really, it can be done through a blood test or a saliva test. It's not that hard, if the setup is there. If someone comes in for a clinic visit, they can walk out with a genetic test order and then the results back in a matter of days to a couple of weeks.

Samir Kapadia, MD:

If we collect this genetic information, and let's say we also collect the genetic information from the siblings or from their family, how does it affect their overall psyche or overall outlook? Because some people are scared of having genetic testing because they think that they don't want to find out things that they currently don't have and get all upset. How do we communicate to them? How do we deal with this genetic information?

Krishna Aragam, MD:

That's one of the areas that we're thinking very hard about in terms of how to approach this and communicate this appropriately, because you have patients coming in at different points of their journey. One is, you mentioned family members. For a lot of people, they're coming in because say a family member or several family members have been affected with a given condition, maybe over some generations, and they don't really know why that's happened. We find out that there's a genetic driver for this.

Depending on how you frame it, either that's cause for fear or it's viewed as an opportunity. That's how we view it, that it's an opportunity not only to identify what has happened and explain what was a mystery beforehand, but I think the other key part of it is that oftentimes people think of these DNA changes, genetic changes as somewhat deterministic, that it's their destiny now.

In fact, that's not the case. In fact, even for these very high-risk factors, it's not a given that someone with a particular genetic marker will inevitably get a condition. There's so many other factors. Those are the opportunities for us to intervene.

Samir Kapadia, MD:

And you can change them.

Krishna Aragam, MD:

We can change them. They're modifiable. Other modifiable factors can then influence whether someone with genetic risk actually goes on to that condition. That gives us the playbook then to say, "Here's how we can try to be more aggressive and avoid an outcome so that it's not deterministic."

Samir Kapadia, MD:

In our setting, what we are planning to do is to collect all this information and we'll somehow store it in an appropriate way. We'll make it analyzable, so, even if in the future, new information becomes available. Because currently we understand so many genes from a large genome, so many sequences. How do you see that we will expand our knowledge and communicate the knowledge back to the patients in case new things become available in the future?

Krishna Aragam, MD:

This is a critical point and one that has to be navigated even right now in genomics. Even in the current day with current standard of care testing, people can get a result back about a particular gene and it gets a genetic change, then new information comes out about it and we have to, a few years later, update our thinking around this and return that to a given patient. This is already something that people have to navigate. I think it's going to become even more so later, but I think we'll be more equipped to do that going forward. There are new genes being identified linked to various cardiac conditions, new types of genetic tests that are out there, and these are all changing.

So, what we have set up and are setting up to do it in more scale now is, as you said, to not only collect information, but have a system within the section so that within each of those domains, those different cardiac domains where genetics can play a role, we've got our expert teams updating every six months, one year, the new information, new genes, new genetic tests and so forth so that we already have records then of who all who've gone through our system have tested positive or negative for particular gene or gene variant for that condition. If there are relevant changes that we know about, we are able to go back and say, "Who does that affect now? Who do we have to reach back out to to then tell them that now we have to think a little bit differently?"

Samir Kapadia, MD:

Wonderful. What is our center? This is our, as we have stated, the Haslam Family Center for Cardiovascular Genomics. Explain to people what exactly we are going to do, at least what our goal is in the future, because we have worked very hard to make this a reality. How do you see a patient flow or a patient journey in this center, so people can understand?

Krishna Aragam, MD:

Yeah, absolutely. This section, this new, wonderful initiative and we're all very excited by this, this Haslam-Bailey Family Section of Cardiovascular Genomics and Precision Medicine, which represents the clinical hub for this overall initiative. Several providers, expert providers here at Cleveland Clinic across these different cardiovascular domains in genetics, paired with a team of genetic counselors who are able to see patients and provide evaluations simultaneously, so that it is both the cardiac evaluation and the genomic evaluation all happening there at a clinic visit. Then later, when the tests are completed, there's a full loop completed. The tests are evaluated by our team, and then the results are not just returned, but they're discussed with the other providers within cardiology to make sure that it's part of the care plan. That's been the strength of the Cleveland Clinic here, the multidisciplinary nature of care, and now it's really making genomics part of that through this entire team and infrastructure.

The second half is then the research side, just to make sure that we are up-to-date in everything, all these new developments. We have teams that are pursuing relevant research to make sure that, in all these areas, we are not only keeping up with the latest information, but helping to create it. That then has a direct benefit to the patients because given the structure, the teams are very much linked so we are in a position then to have the latest information influence what we're telling patients.

Samir Kapadia, MD:

So when you're talking about research, there are two parts, as I see it. One is to identify the genes or the factors that affect different genes together, affect the disease process. The second is to test the new genetically determined therapies. How do you see that? We have the C5, and we have our infrastructure. We are trying to organize not only detection, but also the treatment side together. How do you see that happen?

Krishna Aragam, MD:

This is a very exciting area and one that I think people in the community have been excited to make meaningful efforts on, but it requires this kind of infrastructure to really set up. On the two sides of it, I think one is just being able to identify which patients are at risk genetically for particular pathways or genes, because they might be the most likely to benefit from certain therapies. Certain types of trials may benefit from this genetic enrichment. In other words, if you're being recruited to a trial because you have certain underlying genetic risks, that will allow us to have this precision medicine concept tested in trials. We'll have data then to support that maybe this is going to work, this therapy is going to work more so for this set of patients, if we have all those patients with genetic risk ready to enroll. That's one aspect, identifying genetic risk for inclusion in a trial.

But the second part is actually creating therapies that modulate the genetics. That's where gene therapies are coming into play. If you identify that a genetic change or genetic risk is in, let's say one particular gene, we do have the ability now, and there are many, many therapies coming up in the cardiovascular space, for gene therapies. Whether that be looking to replace a gene that is not working as well, or other related types of mechanisms. But essentially focusing on correcting the genetic defect at its root source. Again, that requires identifying the patients that need it, but now having the infrastructure through C5, for example, to be able to roll this out in a trial where therapies are now emerging, and we can plug that in.

Samir Kapadia, MD:

I think this is an exciting new era where we are going to be able to treat the patients in a very precise way with the genetic information and, of course, environmental factors together with how we modulate their therapies and identify the risk. This is wonderful. What final message do you want to give to the patients that would benefit from this particular effort?

Krishna Aragam, MD:

I think with everything that's happening now, I would say that it's always to keep this concept in mind and to always to be aware of the fact that this risk is all around us and the more proactive one can be, the better equipped one is to manage one's health for decades to come. I think noticing that family members, for example, might be afflicted by certain conditions is sometimes a clue for even younger individuals to take control of their health and speculate, maybe there's some genetic risk. Maybe I can be the one that not only helps myself and my trajectory, but the people around me. That kind of initiative can go a long way, especially now in this day and age when we have all these capabilities.

The last part, as we said before, is that this risk is not deterministic. Most of it, we can do a lot about, increasingly so by the day. It's not just finding the risk and then saying, "Well, well, I wish we could do something more." It's quite the opposite. We can actually, in many cases, remove that risk almost entirely. Knowing about it is more than half the battle and then having the infrastructure to counter it is the other. I think we have that now.

Samir Kapadia, MD:

I think we have to not forget that, that we are so thankful for the general support of the philanthropy from Haslam family and also from all of the donors that have made this possible.

Krishna Aragam, MD:

Yes, absolutely. It takes a lot of infrastructure. Yes.

Samir Kapadia, MD:

A lot of infrastructure and a lot of goodwill to help us do this. Thank you again for watching.

Krishna Aragam, MD:

Thank you.

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