Transcription:
It’s all in the Genes: Knowing Your Risk for Heart Failure

Melanie Cole (Host):  The relevance of gene mutations leading to heart disease and hence heart failure has become evident in recent years.  This is Better Edge, a Northwestern Medicine podcast for physicians.  I’m Melanie Cole, and today, we’re discussing the genetics of heart failure.  Joining me is Dr. Jane Wilcox.  She’s an assistant professor of medicine and cardiology at Northwestern Medicine.  Dr. Wilcox, it’s such a pleasure to have you join us today.  What is the average person’s risk for heart failure over their lifetime? 

Jane Wilcox, MD, MSc (Guest):  In some ways, we’re all at risk, especially as we age, which is one reason it’s so important to, you know, develop these heart healthy habits earlier in life, which is something that we can’t stress enough, but the average person’s risk, believe it or not, is 1 in 5.  After the age of age 40, 1 in 5 Americans will be at risk for heart failure over their lifetime.  

Host:  Tell us about the role of genetics in the etiology of heart failure.  Why would someone be more genetically at risk?

Dr. Wilcox:  We’re products of our families and our environment, and heart disease tends to run in families.  Specifically, heart failure tends to run in families.  Your father or mother had some hypertension and developed congestive heart failure.  I always tell my patients, you know, you are at particularly at higher risk for heart failure simply because of your relation to, you know, your parents.  What we’re learning is that genetics specifically are due to sort of rare variants.  We’re all actually 99% the same if you think about it, and we have small variants that make us unique.  That’s what makes us different and unique, but we’re all the same, and that’s really important.  You know, evolutionarily, it’s been important to maintain sort of the same DNA and proteins and genes because that’s what makes the tissues sort of normal, but if you have a rare variant in a gene that is related to the heart, that gene, that defect, can cause cardiomyopathy, which just means heart muscle dysfunction, and that puts you at risk for heart muscle dysfunction, and those rare variants run in families.  So, that’s what we mean when we think genetically at risk.  It’s a rare variant that runs in a family in a gene that makes, you know, proteins that are in the heart.  

Host:  Well, speaking of cardiomyopathy, are you using genetics to diagnose risks for these types of heart failure? 

Dr. Wilcox:  Absolutely, and we’re using it more and more.  It’s really exciting actually.  The idea that we could prevent heart failure and particularly in family members that may be at increased risk.  So, absolutely, we’re using genetics in the clinic everyday when I see patients.  I talk to them not only about their environmental risks.  You know, are you hypertension, obesity, diabetes, but what’s your family risk?  Even if we can’t identify a particular family history in young patients, and when I say young, this is less than age 55.  Sometimes even, you know 65, if a person’s been very healthy with no risk factors, I will in fact do genetic testing in them because sometimes these rare variants that I talked about can be de novo, which just means that, you know, you’re sort of the first person to carry this or develop this rare variant and that may be what’s causing that person’s or contributing to that person’s cardiomyopathy or heart muscle dysfunction.  So, absolutely, we’re using it in the clinic.  We use it for various different reasons.  First and foremost, patients want to have a diagnosis.  They want to say, “So, why did I develop cardiomyopathy or heart failure?” and it additionally helps us talk about prognosis and family member risk—lots of things.  

Host:  Well, then tell us some of the challenges that exist in identifying the genetic determinants of complex diseases such as congestive heart failure, and while you’re telling us that is it important for physicians to talk to their heart failure patients about that genetic risk? 

Dr. Wilcox:  Genetics are simple, and they’re complex.  I think in heart failure, they can be more complex than simple, and that’s because the field is sort of rapidly expanding.  So, we now have over 100 genes in our commercially available gene panels that we can test for, and sometimes, we’ll get results back that aren’t very straightforward.  They may have what’s called a variant of uncertain significance, and that doesn’t mean that that variant is not causing that person’s cardiomyopathy or contributing to their cardiomyopathy.  It just means that we don’t know enough about the variant, and so the field is rapidly expanding, which is why it’s super, super important to be at a center or refer patients to centers that do have expertise in genetics and have an excellent genetics counselor that can, you know, work with the family to determine an individual’s risk for cardiomyopathy.  So, I think it’s rapidly expanding, but that’s a good thing because we’re learning more and more, and we’re going to be able to offer more and more personalized medicine for our patients.  Some of the challenges that go, you know, go hand in hand with screening someone’s genetics or doing genetic testing, or particularly, you know, not necessarily in an affected individual, in a patient or what we would call a proband, but it really relates to when we test family members.  So, I always recommend to my patients that if we’re going to do what’s called cascade screening where we’re going to test an unaffected family member for, you know, to see what their genetic risk is, I always recommend that they have a life insurance policy in place because life insurance companies can ask about your, you know, “genetic risk” even though the law of the land is GINA right now, and medical insurance companies cannot discriminate against you because of a certain genetic risk.  Life insurance companies can, so I do make that recommendation, but in general, I think there are much more positives than negatives with genetic testing because we can learn much more about a family and hopefully prevent heart failure in the future.

Host:  Well, I certainly appreciate that answer, and it is an important point about life insurance.  Thank you for that.  Then tell us about your Northwestern Medicine Cardiovascular Genetics Program.  Tell us a little bit about how it’s done, and how much it costs, and the services that you offer. 

Dr. Wilcox:  So, myself and my colleagues, we hold monthly meetings for particularly difficult cases, and we will give a patient and each of their family members detailed recommendations about how to reduce their risk for developing heart failure if they are gene positive.  So, as far as cost, genetic testing is actually becoming much more cost-effective and relatively inexpensive in terms of the tests that we do.  It’s anywhere between $200 and $250, actually, out of pocket for some companies.  Most insurance companies will pick up the cost and most of my patients actually don’t pay anything out of pocket for genetic testing, which is really an outstanding advance in recent years.  Our team then previews the results, and our team consists of myself and three other cardiovascular geneticists and our amazing genetic counselor, and we really try to provide care for the entire family.

Host:  Well, then for other providers, how should physicians answer the following question if they’re asked by their patient:  am I at risk for heart failure because it runs in my family?  Tell us a little bit about which patients should be screened and followed and what do you want other providers to know about counseling their patients about genetic testing.   

Dr. Wilcox:  So, if a patient comes to you and says am I at risk because of my family history; the answer is possibly, or we need to look into that further.  Not every patient—it’s not all doom and gloom because it runs in your family, you are destined to be diagnosed with cardiomyopathy or heart failure.  However, what we should be telling our patients, and what I really stress to other providers is, you know, we need to delve deeper and that includes screening.  So, there’s genetic screening and clinical screening, and they’re separate but related.  As far as clinical screening, if you have a family history of cardiomyopathy or heart failure, the guidelines tell us that family members should have a screening echocardiogram as well as an EKG and a clinical exam, and we want to pay particular attention to the age in which your relative was diagnosed.  If you were, for example, if your father had cardiomyopathy at age 55 and you’re 30 years old, just because you have a normal echo at age 30 does not mean that you won’t develop cardiomyopathy, and so the guidelines, again, reinforce that family members of affected patients with cardiomyopathy should have a screening echo every sort of three to five years.  Now, in terms of genetic testing, we always try to test the patient who is affected—the patient who has cardiomyopathy.  So, we test the bare genetics, and if it comes back gene positive, that’s when we do what’s called cascade testing where we test unaffected family members to see what their genetic risk is—if they in fact carry that genetic mutation, and that’s where screening is different there.  If you are at genetic risk, then we tend to follow those patients much more closely with an echo every one to two years looking for subclinical myocardial dysfunction.  We use something called speckle tracking echocardiography where we look at strain to see early signs of heart muscle dysfunction.  In which case I would recommend starting medical therapy to prevent the progression to heart failure.  So, it varies based on sort of the age of diagnosis and the actual genetic mutation and then a person’s lifestyle as well.  You know, a person who may be genetically at risk, but then is also hypertensive, obese, diabetic may develop heart failure much earlier than a patient who is gene positive and doesn’t have those other risk factors.  

Host:  So, before we conclude, how have you seen genetic testing play a role in improved patient care?  What do you see when you look at other providers who have referred their patients to you, and you’ve done genetic testing and now they’re following that patient?  Tell us a little bit about how it’s improved patient care and possibly prevention. 

Dr. Wilcox:  So, I have so many wonderful stories about sort of a shared care model where a provider has referred a patient to me because of, you know, concern for a genetic cardiomyopathy maybe at a young age.  So, I’ll tell you this story.  I had a young man who was referred.  He had a family history.  We in fact did genetic testing, and he had a mutation in what’s called the lamin gene.  LMNA is gene that is particularly arrhythmogenic causing a lot of arrhythmias and sudden cardiac deaths, and I got to know his family.  We ended up screening his siblings, and he had a sibling who had some mild myocardial dysfunction.  You know, an ejection fraction of 40-50%, no heart failure symptoms, clinically asymptomatic, but was gene positive, and we actually ended up putting a defibrillator in this patient who was an unaffected sibling simply because lamin mutations are at much higher risk for sudden cardiac death.  This is where the care of the family is so important to prevent not only heart failure, but sudden death associated with a genetic mutation causing heart failure.  So, it’s super, super important that we risk stratify our genetic mutations including the risk for sudden cardiac death.  

Host:  So, conclude for us with a summary for other providers and when you feel it’s important that they refer a patient to Northwestern Medicine for genetic testing.

Dr. Wilcox:  If you’re unsure, I’m happy to see this patient in clinic, but in general, a patient with dilated cardiomyopathy who’s been diagnosed under the age of 55 with no real precipitant cause.  Even if they’ve had some, you know, mild hypertension, or perhaps they’ve been deemed alcoholic-induced cardiomyopathy, the data are coming out that show us that even in hypertensive, in alcoholic induced, in peripartum cardiomyopathies, that up to 20-40% of those patients will have an underlying genetic mutation and an underlying genetic cause, and so if you are suspicious at all or don’t have a real reason for this person’s cardiomyopathy, these are the patients that we want to see.  We want to do genetic testing, and we want to offer screening for their family members.  So, it affects prognosis.  It affects risk for sudden cardiac death in patients and in family members, and also, I think what’s really a key point is that we’re doing clinical trials based on certain genetic mutations, and so even if we don’t have a clinical trial for this person right now, in the future, we may have a clinical trial based on someone’s genetics that this person could be enrolled in and so lots of opportunities to improve patient care based on their genetic risk.

Host:  Thank you so much, Dr. Wilcox, for joining us.  What a fascinating topic, and that wraps up this episode of Better Edge, a Northwestern Medicine podcast for physicians.  To refer your patient or for more information on the latest advances in medicine, please visit our website at heart.nm.org to get connected with one of our providers.  Please remember to subscribe, rate, and review this podcast and all the other Northwestern Medicine podcasts.  I’m Melanie Cole.