Selected Podcast

The Center for Inherited Cardiac Disease at Penn Medicine

In this panel discussion, Anjali Tiku Owens MD and Sharlene Day MD speak about the interdisciplinary team at the Center for Inherited Cardiac Disease Program at Penn Medicine. They examine the importance of family members being evaluated and how the program identifies those who may be affected. They offer the latest treatment options and research available for patients with inherited cardiac disease in their family-based approach to inherited cardiac care.
The Center for Inherited Cardiac Disease at Penn Medicine
Featuring:
Sharlene Day, MD | Anjali Tiku-Owens, MD
Dr. Sharlene Day is the Director, Translational Research, Division of Cardiovascular Medicine and Cardiovascular Institute at Penn Medicine and Presidential Associate Professor at the Perelman School of Medicine at the Hospital for the University of Pennsylvania. She attended medical school at New York University Medical School and completed her residency and fellowship at University of Michigan Medical Center. Dr. Day is board certified in cardiovascular disease. 

Dr. Anjali Tiku Owens is the Medical Director for The Center for Inherited Cardiac Disease at Penn Medicine and an Assistant Professor of Medicine at The Perelman School of Medicine at the Hospital of the University of Pennsylvania. She attended Duke University School of Medicine and completed her residency at the Hospital of the University of Pennsylvania. She is board certified in Cardiovascular Disease.
Transcription:

Melanie Cole: Welcome to the Podcast Series from the Specialists at Penn Medicine. I'm Melanie Cole, and I invite you to listen in, as we discuss the Center for Inherited Cardiac Disease at Penn Medicine, joining me is Dr. Anjali Owens. She's the Medical Director of the Center for Inherited Cardiac Disease at Penn Medicine and an Assistant Professor of Medicine in the Perlman School of Medicine at the Hospital for the University of Pennsylvania. And Dr. Sharlene Day. She's the Director of Translational Research in the Division of Cardiovascular Medicine and Cardiovascular Institute at Penn Medicine. And she's a Presidential Associate Professor at the Perlman School of Medicine at the Hospital for the University of Pennsylvania. Doctors, I'm so glad to have you join us today, Dr. Owens, what's the difference between inherited cardiac disease and congenital heart disease? Tell us a little bit about inherited cardiac disease, the prevalence, and what types of diseases fit under this umbrella?

Dr. Owens: Great question, and a source of confusion for both patients and healthcare professionals. Congenital heart disease is really a group of conditions that are present at birth and relate to structural abnormalities in the way the heart forms in utero. This includes the pumping chambers, the valves, the connections between the chambers and the blood vessels and common congenital heart defects include atrial septal defects, ventricular septal defects, coarctation of the aorta. And then also more complex congenital heart disease, such as to Tetralogy of Fallot or transposition of the great vessels. The prevalence changes the type of condition that you look at. In some cases, the abnormality is the result of a genetic abnormality, but in many cases of congenital heart disease, the cause is unknown. Patients with these conditions are treated at the Penn Center for Adult Congenital Heart Disease. Inherited heart conditions, develop as a result of a genetic abnormality or change in the DNA.

That's passed along from generation to generation. If a patient has the condition, there's a 50/50 chance of passing on the genetic abnormality to each child, that child can then develop the inherited heart condition at some point during their lifetime. Although the genetic abnormality can be detected at birth, the heart condition itself may not be evident until years later, which is why we recommend ongoing screening for development of the heart condition. The most common inherited heart conditions are abnormalities of the heart muscle or cardiomyopathy inherited arrhythmias or familial hypercholesterolemia. If one of your patients is diagnosed with these conditions, we recommend tests to check family member's hearts and genetic testing. To see if we can identify the genetic variant that is responsible for the condition.

Host: Dr. Day, tell us a little bit about risk as Dr. Owens just mentioned with parent and familial genetic predisposition. Tell us if there's a demographic for inherited cardiac disease.

Dr. Day: Most of the inherited heart diseases really have no specific geographical predilection. Their prevalence is very similar, really across the globe in all populations that have been studied as far as whether they affect more women or men, most of them affect both equally because the majority of genes are involved are located on the non-sex chromosomes. There are a few of these that are X-linked, which means that males generally are more severely affected. This would include a disease such as Dan and disease, which is a glycogen storage disease that affects the heart. And as far as when the diseases manifest in life, as Dr. Owen said, it's really highly variable and individuals are born with a gene variant or mutation that can lead to a particular condition, but sometimes this condition may not manifest itself at all. Maybe it'll manifest itself sometime during adulthood, or it could manifest very early during childhood. And generally speaking, the earlier the disease manifests, the more severe the course is.

Host: Dr. Day, Sticking with you for a minute. So in that case, is there a screening, is there any way to tell what's going to happen down the line?

Dr. Day: Obviously, we recommend screening as soon as it's recognized that somebody carries a genetic mutation or has a family member that carries a genetic mutation or has a specific inherited heart condition. So we recommend screening during childhood, typically at least once a year, if there are no manifestations of the disease at the time of initial screening, and then later into adulthood, sometimes that period of time can be extended maybe up to five years, again, depending on the condition and the family, it's all very much individualized. So we don't have a specific rule for how often and in what manner people should be screened. It depends a lot on the condition itself and the individual family.

Host: So then do you screen family members? Is there an importance to family members being evaluated by a physician? How do you identify those family members who are affected?

Dr. Day: Absolutely. So it's very important to provide care to the family and not just to the individual who's affected because we know the pattern of inheritance and families. We can pinpoint that individuals who are at risk of developing the disease. So for example, if Dr. Owens or I are seeing a patient in clinic and they have three children, say they're ages six, 10, and 14, and we know that 50% likelihood for each child who have inherited a genetic mutation from their parent. Then we would recommend either genetic testing, if we have the genetic information for that particular family, or we would recommend clinical screening with typically testing that includes electrocardiograms and echocardiograms, and sometimes additional testing beyond that. And then we refer those children to our colleagues over at Shaw and the pediatric side, or to a pediatrician in their local area, depending on where they live.

Host: Dr. Owens, while we're talking about structural changes in the heart, or cardiomyopathy's, can you tell the difference between familial dilated and hypertrophic cardiomyopathy?

Dr. Owens: Sure. The difference between familial dilated cardiomyopathy or DCM and hypertrophic cardiomyopathy or HCM really comes down to the underlying structure and function of the heart dilated cardiomyopathy results in a weakened heart muscle with dilation of the left ventricle and a reduction in systolic function or contractile function. On the other hand in hypertrophic cardiomyopathy, what we see is asymmetric hypertrophy, usually of the left ventricle resulting in hyper contractility and often very abnormal diastolic function. Although the structure of the heart is very different in these two conditions, some of the symptoms can be the same with patients reporting breathlessness, exercise intolerance, and general symptoms, palpitations. And even in some cases risk of heart failure and the risk of sudden death.

Host: Thank you for that answer. And Dr. Day, as Dr. Owens was just giving us some of the clinical presentations, tell us a little bit about what you do. If someone comes to you with some they present with any of those symptoms that Dr. Owens just mentioned, tell us what you would do and assess for a specific treatments that you would use once you detect what's going on.

Dr. Day: So, the diagnosis sometimes can be challenging because as Dr. Owen said, patients present with the constellation of symptoms that can be similar across different conditions. We get clued into a diagnosis by evaluating a bunch of different pieces of information. For example, we're going to always start with a thorough history and physical examination. In this case, the family history is really important because that'll give us clues about the specific conditions that run in the family and also what the pattern of inheritances. And then on the physical exam, there may be some characteristic features like a heart murmur, for example, that could clue us into a particular diagnosis. And then typically the next piece of data that we get as an EKG, which is often abnormal and the presence of different heart diseases, it's abnormal in different ways, but it's often abnormal in some way. And then for the cardiomyopathies imaging of the heart is obviously a critical tool. We usually start with echocardiograms to characterize the size of the heart, wall thickness, and ejection fraction or contractility of the left and the right ventricle.

And then sometimes we move to a cardiac MRI to provide a little bit more information. In addition to the structure and function. Also the characterization of the heart muscle, how much scar there is, where the scarring is, etcetera? Now as far as treatments, those vary considerably across the different diseases. So for someone who is asymptomatic and has a mild form of a disease, they may not need any treatment at all, but rather just regular surveillance and testing that we were talking about earlier. Now, in many patients, medications will be used to alleviate symptoms or improve the left ventricular function. These classes, medications include beta blockers, calcium channel blockers, ACE inhibitors, angiotensin receptor blockers, and then some of the newer drugs like Neprilysin inhibitors, SGLT two inhibitors. And there's also a new class of drugs called myosin modulators and a drug called Mavacamten within this class has shown significant promise in clinical trials for patients with obstructive hypertrophic cardiomyopathy.

Beyond medications, some patients might need a catheter-based procedure maybe to treat atrial fibrillation or ventricular tachycardia, or they may have obstruction of blood in the outflow tract. For example, if they have hypertrophic cardiomyopathy and then a catheter-based procedure called an alcohol septal ablation can sometimes be used to treat that some patients might need surgery, which could include a septal myectomy for patients with HCM and outflow tract obstruction, or even heart transplantation in patients with very advanced heart failure. And then the prevention of life threatening arrhythmias is also a really key component of treatment of all of these patients and devices called implantable defibrillators may be recommended in some patients. And then finally, we always stress the importance of a healthy lifestyle. So not smoking, not drinking alcohol to excess maintaining healthy body weight and getting regular exercise

Host: Dr. Day another group of inherited heart disease cause abnormal heart arrhythmia, but typically no changes in structure or function of the heart muscle. Describe those, and while you were telling us about the others, tell us about these and how they're treated?

Dr. Day: This group of diseases inherited arrhythmia is also known as channelopathies because they affect the way that ions like sodium potassium and calcium moving in and out of cells through designated channels. So the most well-known of this group is called long QT syndrome. They can all lead to life-threatening arrhythmia. So although often by different triggers. So, some of these patients, the arrhythmias make occur at rest or while they're sleeping. And other times they may occur with physical exertion or with startling reflexes. Fortunately, most are treated effectively with medications, particularly beta blockers, and rarely implantable defibrillators are used if the arrhythmia is a refractory to medications.

Host: Dr. Owens, tell us about the services at the Penn Center for Inherited Cardiac Disease. Tell us about the physician services. Describe some of your highlights and features?

Dr. Owens: At our Center for Inherited Chronic Disease. We offer really a comprehensive range of services and access to specialists for patients with these inherited heart conditions and importantly, their family members. We do both consultative and lifelong longitudinal care for patients who either have disease or are at risk of developing disease. For example, we consult with specialists and work in a multidisciplinary team, including electrophysiologists interventional cardiologists, imaging specialists, lipid specialists, heart failure cardiologists, sports cardiologists, genetic counselors, and geneticists, cardiac and vascular surgeons, maternal fetal medicine, and high-risk OB GYN, psychiatrists, and social workers. We also have a well-established joint program as Dr. Day mentioned earlier with our partners at the Children's Hospital of Philadelphia to care for the entire family.

Host: That's certainly a very multidisciplinary approach, Dr. Owens and once accepted for referring physicians, what's the communication like with referring physicians? And what can the patient’s family expect the support services that you offer and how they're working with that multidisciplinary team?

Dr. Owens: We try to make it as easy as possible for the patient when they come to the center. And also for the referring physician, after we provide our consultation, we start with developing a detailed plan for the day of the visit for the patient and any family members that they choose to bring with them. This is laid out in an itinerary that gives them an idea of when they're going to have their testing, when they're going to meet with the physician or the nurse practitioner. And when they're going to meet with our genetic team, and importantly, they're invited to bring any family member, either virtually or in person, that wants to be present to hear the conversation. We know that because these conditions are inherited, it's very important for the whole family to be involved. We offer same day consultation if needed with a member of the electrophysiology team, with a member of the surgical team or the interventional cardiology team. Again, if we can identify in advance, that's what the patient needs. After the consultation, we typically give the referring physician either a call or send a letter, hopefully in a timely fashion, that lays out what our thoughts were about the patient and the plan of care. And we try to do this in a shared care model, meaning that both the referring physician and also any Penn physicians and specialists are really working together to provide the best plan of care for that patient and their family.

Host: Dr. Day, tell us about any current or emerging therapies for inherited cardiac disease. Are there any game changers? Tell us about something you're doing at Penn Medicine that other providers may not know about?

Dr. Day: That's a very timely question. I mentioned earlier that there is a new class of drugs called myosin modulators, and these drugs have shown a lot of promise in clinical trials, in patients with heart hypertrophic cardiomyopathy, Penn has been instrumental in enrolling patients in these trials. And Dr. Owens is the site investigator for trials that have already been published. And also those that are actively enrolling. So what these drugs do is they bind to the heart's primary muscle motor called myosin. This is the molecular motor of the heart muscle cells. And in doing that, it dampens down the contraction. So it inhibits the turnover of ATP or energy utilization. And what that does is it just very slightly reduces the forcefulness of contraction of the heart, which in hypertrophic cardiomyopathy can actually be too forceful. And that can cause left ventricular outflow tract obstruction, which causes significant symptoms in many patients, and typically leads to the need for medications and often an alcohol septal ablation or surgery called myectomy, collectively called septal reduction therapy.

So, I think that this is really an exciting development because it's the first drug that's ever been developed specifically to treat patients with hypertrophic cardiomyopathy. And previously we've just borrowed things that have been used for other conditions. So that I think is probably one of the most significant advances that's been made in the field in a long time. As far as other things we're doing here at Penn Medicine and elsewhere, there's a lot of interest in translating basic discoveries from scientific experiments, for example, in preclinical models of hypertrophic cardiomyopathy, or dilated cardiomyopathy into clinical practice. And so it's a really exciting time to be in the field. And it's exciting time to see scientists and clinicians working together to develop new treatments for these diseases.

Host: And Dr. Owens, as we wrap up, when should patients be referred to an inherited cardiac disease specialist and tell other providers what you'd like them to know about the Center for Inherited Cardiac Disease at Penn Medicine?

Dr. Owens: It's important for any patient who's diagnosed with one of these inherited heart conditions, either cardiomyopathy, arrhythmia lipid disorder, aortopathy, to be evaluated at a center that focuses on these conditions and specializes in them. That's the best way to provide comprehensive cutting edge care to patients and their family. So I would suggest as a referring physician, if you diagnose one of your patients with these conditions to offer them a consultation at the center, and again, that can be a one-time consultation just to set things on a path, to any necessary genetic testing and familial screening, or it can be for more comprehensive longitudinal care of complicated patients that need specialized treatment that can really only be offered at a tertiary care center like Penn Medicine.

Host: Thank you doctor so much for joining us today and sharing your expertise and telling us about the Center for Inherited Cardiac Disease at Penn Medicine. To refer your patient to the Center for Inherited Cardiac Disease at Penn Medicine, please visit our website at pennmedicine.org/refer, or you can call 877-937-PENN. For more information. That concludes this episode from The Specialists at Penn Medicine, please remember to subscribe, rate, and review this podcast and all the other Penn Medicine podcasts. I'm Melanie Cole.