Advancing Cardiovascular Care Through Genetic Testing

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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.

Dr. Krishna Aragam:

I'd like to welcome everyone to another episode where we're talking today about cardiovascular genomics, inherited heart disease risk, and in particular, familial risk, and how genomics allows us to understand not only what a patient is at risk for and might experience, but what their entire family might be at risk for. In talking about this today, I have two of my colleagues here from our genomics section here at Cleveland Clinic in the cardiovascular division. I'll introduce myself, Krishna Aragam. I'm the Director of our Cardiovascular Genomics program here.

Christina Rigelsky, MS, CGC:

I'm Christina Rigelsky. I am the lead cardiovascular genetic counselor.

Dr. Michael Hill:

I am Michael Hill. I'm an advanced heart failure and transplant cardiologist. Also, I specialize in inherited cardiomyopathy disorders within the genetic section.

Dr. Krishna Aragam:

We want to talk today again about cardiovascular genomics, and what exactly is cardiovascular genomics, and what does it entail? Why are these approaches becoming more important in heart care? Broadly speaking, when we think about the concept of cardiovascular genomics, it is the use of information that's encoded in our DNA that translates to what each person's risk might be for a particular cardiovascular condition, conditions related to the heart and/or blood vessels.

We're all composed, we all have these letter codes, these letter code changes in our DNA that make us different from one another, can influence our eye color, height, and so forth. There are also specific letter code changes in our DNA that influence each of our respective risks for various conditions, including cardiovascular conditions. Cardiovascular genomics is really the idea that we're going to capture all of those letter code changes in our DNA to better understand which of them are predisposing each of us to different types of cardiovascular conditions.

One distinction that I like to make usually is that the terms genetics and genomics oftentimes get used interchangeably. Really, the distinction is that in genetics, we’ll often think about as encompassing specific genes, single genes, and how they influence disease, genomics being multiple genes and the entire genome, and how that information interacts with non-genetic factors.

Why is this becoming more important? More and more people are now having that information readily available to them. The cost of genetic testing is coming down quite a bit. This is becoming a lot more accessible. There's just a lot more information about how those DNA changes not only relate to cardiovascular and other conditions, but also how those differences in risk need to be managed differently.

This is now entering our real-world practice as the data is rapidly changing. We're simultaneously trying to incorporate that into how we manage patients and manage patients based on their individualized risks. When we're talking about cardiovascular genomics and specifically the types of heart conditions that are involved, it's worth knowing that, again, genomics encompasses or influences a lot of different heart conditions, but there are certain ones that we think about more readily. Mike, do you want to tell us which ones?

Dr. Michael Hill:

Yes, there are. Absolutely. There are so many different domains in the heart that we take care of on a daily basis. Many of these domains are influenced by genetics and genomics. Some of these include what I see a lot every day, cardiomyopathies, which are heart muscle disorders. Some of these types of cardiomyopathies can make the heart become enlarged and stretched out. We call that dilated cardiomyopathy. There are three types of genetic disorders that can make the heart muscle wall very thick and stiff. We call that hypertrophic cardiomyopathy, among others. There are also heart rhythm disorders that can be influenced by genetics, such as QT changes or ventricular tachycardia, or even the most common abnormal heart rhythm in clinical practice, atrial fibrillation or AFib, can be influenced by genetics as well.

Aortopathies are a syndrome where the aorta, the main artery blood vessel that runs up and down, can become stretched or enlarged over time through weakness of the collagen or weakness of the structures that make up the aorta. This has an impact on when surgery might be offered for that condition.

Finally, cholesterol levels, which are something that many people are dealing with, even who don't see cardiologists, but many people are on medications for cholesterol control. The downstream effect: what does high cholesterol cause? Blockages in the blood vessels or blockages in the heart arteries. Cholesterol management or heart artery disease called atherosclerosis, these are all conditions which the genetics can influence.

Dr. Krishna Aragam:

Absolutely. As you mentioned, those are the main ones that we have testing pathways for now and have probably accrued the most information on, but the field is evolving rapidly, and we're learning more and more about other genetic markers that influence other cardiovascular conditions. We're on the lookout for that and evolving our practices accordingly.

When we're speaking about genetic information then, again, the theme here is that this information, what sets it apart from other types of testing that we do, probably a couple of things. One is that you're born with this information, so you have the ability to capture this information very early on. But then the other key piece is that that information has come from somewhere. It comes from a family member, and that's the inherent difference from other types of testing that we do and the implications of it. Christina, do you want to talk a little bit about, again, that concept of a diagnosis or extending that information to other family members?

Christina Rigelsky, MS, CGC:

Yeah. Certainly, even just knowing about your family history can help influence risk, but when we can actually find an underlying genetic answer through genetic testing, it actually helps us much more easily test other family members to know who's at risk so that we can make sure that those family members get the most appropriate evaluations and treatment so that we can be as tailored as we can about their ongoing heart care. But of course, we don't always find a genetic answer either. Even with many of the conditions that Dr. Hill talked about, particularly when they occur at young ages, we may have recommendations for ongoing screening of family members to help identify disease early as well.

Dr. Michael Hill:

Christina, I think you bring up a really important point about identifying disease in the family members, and that is something that maybe is a misconception that both patients and doctors may have, that something that runs in the family has to be obvious, that it has to be very clear that mom had this and aunt had this, and now I have this, but that's not often the way that genetic conditions present, especially cardiac genetic conditions.

We know that, as Dr. Aragam mentioned, all of this is based on your DNA, and we all have half of our genes come from mom, half of our genes come from dad, and it only takes one mutated copy or one bad copy of that type of gene in many cardiac conditions to cause disease. We call that autosomal dominant. But the reality is that it's a lot more of a murky picture because not every person in a family might express the disease just as severely as everyone else. They might not even have the same disease at all. It could be a different type of heart muscle disorder or something.

So, for many patients and many doctors who think that it has to be very clear and straightforward for me to worry about my genetics, the reality is that even in the absence of a family history, or with a mild but maybe suggestive family history, it's worth diving into, it's worth talking about, and it's maybe even worth getting genetic testing even when the family history isn't so crystal clear.

Christina Rigelsky, MS, CGC:

Yeah, actually, I would add to that too, that I often talk with family members who then say they've told their family members about our recommendations for screening or genetic testing, but they feel fine. So, they don't think they have it or need to have the testing. Certainly, your point is that it presents differently. Sometimes, there aren't symptoms that a family member might have to know whether or not they really need to be evaluated.

Dr. Michael Hill:

What does that process look like of screening for family members when you're counseling the family members of a patient who might have been diagnosed with a genetic disease?

Christina Rigelsky, MS, CGC:

Yeah. I mean, genetic counseling in general, we spend a lot of time collecting family history, certainly more than people encounter in most clinical settings. Sometimes we say it feels like taking a test, the number of questions we're asking about family members, but you really can't fail it. You just have to give as much as is known.

We take a lot of information about family history and we talk about genetic testing, and what the consequences of genetic testing are. If there's already a known genetic cause in the family, then we talk about if a family member shares that risk, the type of screenings that would be recommended or treatment down the road that they might be able to expect. Or if they're negative and there's nothing else concerning in the family history, they actually would be free from screening, and they're not at risk for that genetic condition any longer.

Dr. Krishna Aragam:

Yeah. Then, the process, thereafter, in terms of getting the buy-in and then doing the testing itself, what does that all entail then, logistically?

Christina Rigelsky, MS, CGC:

Do you mean from the standpoint of-

Dr. Krishna Aragam:

Even just getting the testing because a lot of people have questions about what is genetic testing? What does that mean? What's actually happening?

Christina Rigelsky, MS, CGC:

Yeah. I mean, truly genetic testing is actually a very simple process where we just have to get a sample that could be blood or a cheek swab or saliva. It's very simple from a patient standpoint. These are things that are usually covered by insurance. That often is a concern that people have. But once we know a genetic answer in the family, it's usually pretty easy to get insurance to cover it.

Dr. Krishna Aragam:

Are there other things people are typically concerned about from your experience, patients or families, when it comes to pursuing and deciding to pursue genetic testing?

Christina Rigelsky, MS, CGC:

Certainly, when we talk with family members who are considering having a familial genetic risk, something that was already found in the family, one of the things that we talk about is, could this impact other circumstances like insurance? There are some protections for people who have genetic testing from being discriminated for health insurance and employment, but those types of protections don't exist for other types of insurance. Those are things that we often talk about before somebody pursues testing. Truly, it's a good idea to consider it even before coming to meet with a genetic counselor. But each individual has to weigh those risks with the importance of the information that we can provide with the genetic testing.

Dr. Krishna Aragam:

I'm curious, in addition to some of those logistics, you both probably have encountered the concerns that come up of people just sometimes not wanting to know the information, and saying what's going to be done and what will that label result in. Insurance aside, that's one consideration. But just the idea that now I know that I have this potential risk, and is that just going to be hanging over my head, and not wanting to reveal that at some point? What do you say to folks in that situation?

Dr. Michael Hill:

That is a challenge and probably a welcome challenge in medicine, and in cardiovascular medicine and genetics. Because I think many of our patients, nobody wants to have something wrong with their heart, but I do think there is a point of optimism when we are able to discuss something that's reversible, when we're able to discuss maybe lifestyle that could be modified or medications that could be started.

I think genetics have the benefit, but also the scary feature that genetics are something you're born with and it's something you can't change about yourself. Although I agree that my patients as well can and have expressed fear sometimes, fear of the unknown and fear about knowing their genetic results, but I think helping to educate the patient on the different ways that genetics can actually improve their care and improve their health is the most impactful way I've been able to convince my patients and really to partner with my patients to decide that this is a path we should go down together.

I think that, between genetics for aortic conditions, for example, influencing when surgery might be appropriate for preventing life-threatening tears, or for people with heart muscle disorders, genetics could inform when they go on to pursue an implanted defibrillator to protect against sudden death. I think right now the leading areas where genetics impacts the management tend to be more preventative, which I think lines up with most patients' goals, which are using the genetic information to predict future risk and to make decisions that help prevent consequences. I think that's gotten a lot of patients excited about their genetics, even though the conversation may have started as a point of fear.

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