Heart Health During and after a Stem Cell Transplant

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Heart Health During and after a Transplant

Sunday, April 18, 2021

Presenter: Saro Armenian DO, MPH, Director, Center for Survivorship Outcomes, City of Hope

Presentation is 35 minutes long with 22 minutes of Q & A.

Summary:  Transplant recipients face several risks to long-term heart health arising from their cancer treatment. This presentation identifies these risks and offers strategies to minimize them and foster healthy, long-term survival.

Highlights:

• There has been significant progress in preventing and treating cancer and blood disorders over the last three decades. Most patients with blood disorders are now expected to become long-term survivors.
• Long-term transplant survivors have a two-to-four times greater risk of developing cardiovascular disease than the general population. Treatment with radiation and anthracycline chemotherapy in particular elevates this risk.
• Heart problems tend to develop at a younger age in transplant survivors than in the general population.

Key Points:

(05:23) With more survivors, attention has turned to identifying, preventing, and treating longer term complications in these individuals.

(06:33) Despite recent progress in treatment, many transplant survivors will develop one or more long-term health problems.

(10:14) Cardiovascular disease can arise during transplant but more typically arises five to ten years after treatment.

(16:19) The range of cardiovascular problems include heart failure, coronary artery disease and valvular disease.

(12:44) In addition to treatment risks, certain patient characteristics can also increase cardiovascular risks

(21:36) Even moderately intense exercise is the best preventive medicine. This should ideally combine aerobic exercise and resistance training.

(24:16) Exercise routines should build up gradually and be something survivors enjoy.

(26:06) Avoiding inactivity is essential; individually tailored exercise programs for cancer survivors are ideal. Many simple, gentle activities are good starting points for exercise benefits.

(28:44) Survivors need to be well informed and actively involved in their long term care. An empowered patient sharing ownership model can coordinate care from cancer centers and primary physicians.

(30:45) Remote technology is an evolving care strategy that can empower patients and detect problems early.

Transcript of Presentation:

(00:01) [Thom Stewart]       Introduction. Thank you. My name is Thom Stewart, and I would like to welcome you to the workshop Heart Health During and After Transplant. It's my pleasure to introduce Dr. Saro Armenian.

(00:13) Dr. Armenian is the Director of The Center for Survivorship and Outcomes within the Hematologic Malignancies and Stem Cell Transplantation Institute at the City of Hope in Duarte, California. He oversees follow-up data on one of the largest databases of pediatric and adult cancer and transplant survivors in the US. Dr. Armenian's research focuses on risk factors for cardiovascular diseases such as heart failure and stroke in the survivors of childhood and adult-onset cancer and novel strategies to prevent them. Please welcome Dr. Armenian.

(00:58) [Saro Armenian]     Overview of talk.  Hello, Thom. Thank you so much for the very nice and kind introduction. Good morning and good afternoon for those of you who are on the West Coast. As Thom mentioned, my name is Saro Armenian. I'm a Pediatric Oncologist by training, but my research really primarily focuses on long-term survivors of cancer, with a special focus on long-term survivors of stem cell transplantation. It's a real pleasure, and a treat, and an honor, actually, to be presenting today and going over some general topics pertaining to heart and cardiovascular health during and after transplantation.

(01:40) There has been significant progress in treating cancer and hematologic disorders over the last three decades. Meetings such as the one we're participating in really give us an opportunity to take pause and just appreciate how much the landscape has changed for the treatment of cancer and hematologic disorders.

(01:53) Let's just take a look back over the last two to three decades or so. The way we treated cancer was primarily based on location, characteristics, how the tumor itself, or the cancer itself, looked under the microscope, and the size of it. There were very few biomarkers that informed us how to treat people, which is very different.

(02:15) There were roughly 250 fewer treatment options than there are today, and there were really three basic treatment options: at the time it was surgery, chemotherapy, radiation. But bio-immunotherapy and the addition of combined modality approaches have fundamentally revolutionized the treatment of cancer and hematologic disorders, as well. At the time, when we were first thinking about advancing our treatments there were limited supportive care options; but that's changed.

(02:45) There are many measures of this progress. We can look at progress by a number of measures. We can look at them in terms of advances and treatments we've made in terms of new therapies, better imaging, radiation oncology, and surgical advances, precision medicine, and the introduction of immunotherapy.

(02:59) We can think about it in terms of prevention. We're doing a much better job of intervening early for infection-related cancers, thinking about cancer susceptibility genes, and how do we counsel individuals for early detection and screening. Then thinking about drug and surgical risk reduction strategies in terms of giving less of a specific drug that we think may be toxic, avoidance of certain treatments, or reduction of total doses.

(03:27) Then improvement in the quality of life. We're doing a much better job of toxicity management during treatment. Increasingly we're considering less intensive therapies when that's an option. And then palliative care has been integrated into our frontline therapies now, which is something that we've only thought about in the context of end of life.

(03:48) Finally, survivorship, which is one of the main reasons for what we're talking about today. We really didn't talk about survivorship two to three decades ago, but now clearly it's a growing area of research. We have started to recognize that there are late effects of therapy that need to be screened for, monitored, addressed, prevented, and treated. Then we have started thinking about how do you monitor individuals, and that's part of what we're going to be talking about today.

(04:14) The reality is the general message over the last two to three decades is that mortality has been down, survivorship is up, which is phenomenal. It's truly one of the great advances in medicine that we've had over the last several decades.

(04:28) The majority of patients with hematologic disorders are now expected to become long-term survivors. If we turn our attention to patients with hematologic malignancies and disorders, what we can see is that over the last several decades the expected survival for individuals with myeloma, Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma, acute and chronic leukemia has steadily increased. In fact, the majority of patients diagnosed with these cancers are expected to become long-term survivors, which is really remarkable. In fact, we have not seen these types of advances in patients with solid malignancies.

(05:02) The reality is that this has led to a growing number of long-term survivors. If you actually look at the number of long-term survivors in the US today, the overwhelming majority of them are going to be more than five-year survivors. This means that there are new issues that many of these survivors will be dealing with in the decades after their cancer treatment.

(05:23) Attention has turned to identifying longer term complications in transplant survivors. Let's turn our attention specifically to stem cell transplantation and bone marrow transplantation. We at City of Hope and others have spent a considerable amount of time cataloging the specific issues that could develop either shortly after their transplant, a little bit in the two years past, or very late effects that can happen. We have categorized these according to these general areas, but we can have any of these issues that develop across the entire spectrum of the survivorship journey for many of our patients.

(05:56) We know that many of our patients struggle with respiratory complications, chronic GVH and infections, ocular complications. And then there are the delayed events that can happen, so health conditions that may not have developed during treatment, but they can develop after treatment either two years or in some cases 10 years afterward, including cardiovascular disease.

(06:19) Clearly, we know that these health conditions in and of themselves, if they're severe enough, have a substantial impact on physical and psychological performance of our survivors, as well as quality of life and social integration.

(06:33) Many transplant survivors will nonetheless develop one or more long-term health problems. The reality is, many long-term survivors will develop one or more long-term health problems that are in part related to the intensity of the treatments that they received. Many of these conditions are often underappreciated in the general medical community, especially if we think about who these cancer survivors are, and especially the transplant survivors. They could be one of 100 or one out of several 100 in a busy primary care practice. It's often going to be underappreciated and underdiagnosed.

(07:02) Early detection of these problems is important. It's really important to catch these problems early when they're most easily treated, and that's what we're doing as part of this session today is really educating providers, patients, and survivors about what are the issues that we should be monitoring for and what are the issues that are unique to the transplant survivors and why is it so important to pick them up early?

(07:24)  A case study illustrates the dangers of not detecting problems early. I'll digress briefly and present a case to sort of help illustrate the importance of long-term surveillance and monitoring for our stem cell transplant survivors. This is a patient that was seen here at City of Hope. She was 27-years-old at the time of her initial diagnosis of lymphoma. She had a relapse and was treated with additional salvage therapy and then underwent autologous stem-cell transplantation.

(07:54) It was about six years later, or so she started complaining or having symptoms of worsening shortness of breath, easy fatigue, and she used to love soccer, and that's what she used to do. She used to play as a hobby as part of a weekend league. She noticed that this was something that was substantially impacting her ability to keep up with others.

(08:18) Now she had moved away and was seen by primary care physicians who essentially said it was just fatigue or deconditioning, or some would actually listen to her heart and lungs but it really wasn't a thorough investigation, and she, in fact, did not share her past medical history. She contacted us, and we were able to evaluate her immediately. Brought her in for a comprehensive assessment knowing that there are specific issues that could develop in this particular population that is often underappreciated.

(08:50) I'll orient you. This is her chest x-ray from the end of her treatment. She had completed her cancer treatment. This is just the simple x-ray that we pulled, and what you'll see on the x-ray is essentially normal heart size in the middle. The rig cage is sort of the lines going across. Clear lung fields, and by that I mean that the darker the lung fields are the clearer they are because that means they're full of air. This was a normal chest x-ray that was immediately after her treatment.

(09:19) Then fast forward to several years later when she came to us having those symptoms that she reported and this is what her x-ray looked like. What you can see quite clearly is that the heart has dramatically increased in size. It's much wider. It's nearly twice as large as it was at baseline, and then the lungs are full of fluid and that's why they're not dark. Full of air. In fact, the reason why they're so hazy and white is because they're full of fluid. In fact, she had developed congestive heart failure.

(09:50) Now, that's a condition that you don't typically see in the general population until people are in their eighth or ninth decade of life. In fact, what we actually saw is it in someone, it developed in her three to four decades. Before you would typically expect it. Again, an underappreciated health condition that is likely exacerbated by the treatment that she received upfront.

(10:14) Cardiovascular disease can arise during transplant but more typically five to ten years after treatment. I'm going to be talking a bit about cardiovascular disease in the context of transplantation. What are the cardiovascular issues that we see in our transplant survivors? And again, these are issues that could develop either during therapy, but typically they develop five, 10-years after the treatment has been completed, so well into the long-term survivorship journey.

(10:34) There are several kinds of heart disorders that may appear. Survivors can develop cardiac dysfunction, which is what happened here. It just means that the heart is not pumping adequately. Another word for that would be heart failure where the heart muscles are weak and are not able to adequately pump the fluid out of the chambers. Atherosclerosis, otherwise known as coronary artery disease, that's narrowing of the coronary arteries. Cardiac arrhythmias and then valvular disease, so aortic stenosis, and mitral stenosis, mitral valve prolapse. These are various valvular disorders that can develop and have been recognized to occur in our patients with hematologic malignancies.

(11:12) Long-term transplant survivors have a two-to-four times greater risk of developing cardiovascular disease. Let's contextualize this for our transplant survivors. Long-term transplant survivors, overall, have a two-to-four times greater risk of developing cardiovascular disease compared to the general population. When we do these types of comparisons we compare them to their peers. We don't compare them to ... These are age-matched and sex-matched population controls, and what you see is that there's a substantially higher risk.

(11:39) Radiation and anthracycline chemotherapy pose particular risks. Who is that risk? We know that certain treatments put you at risk for developing premature cardiovascular disease. Radiation, which is often used in the treatment of lymphomas, especially if the primary disease in the mediastinum, or in the chest near the heart, can impact the heart itself. High dose anthracycline chemotherapy is drugs like doxorubicin, daunorubicin, mitoxantrone. These are typically the ones that you would see hanging that looks orangish/reddish, so many people will remember it that way. The higher the dose of the anthracycline therapy you receive, the higher risk of developing cardiovascular issues including heart failure.

 (12:22) In the older treatment era, individuals treated in the pre-1990s has a much higher risk for several reasons. One, because they're longer-term survivors and so there's a longer period of which they can actually develop this, but also radiation techniques were quite different back then and, those have evolved and, I'll show you some examples of how those have evolved.

(12:44) Certain patient characteristics can also increase cardiovascular risks. Those are treatment characteristics. How about patient characteristics? Individuals who were very young at the time of their treatment or much older at the time of their treatment. Those represent the two vulnerable spectrums of cardiovascular disease.

(12:56) Individuals who develop traditional, you know the established cardiovascular risk factors like hypertension, diabetes, obesity after their transplantation. These risk factors, in addition to what we consider cardiotoxic treatments, put you at an exponentially increased risk of developing cardiovascular disease.

(13:17) Then lifestyle factors, being sedentary, smoking really exacerbate the risk for many of our patients.

(13:24) In an earlier era, higher doses and poorly targeted radiation was especially risky. When we talked about the earlier treatment era, I think it's important also to understand why we are singling out individuals treated in older treatment eras or earlier treatment eras as being at risk. Part of this has to do with the fact for those individuals who have received radiation in the 70s and 80s, there was a substantial amount of radiation delivered to non-lymphoma tissues, for example. As a result, the heart ended up being a bystander and received a substantial amount of radiation exposure.

(13:55) What you'll see on the left, Panel A and Panel C, is sort of the traditional mantle radiation that many individuals had received. Then that yellowish/orange hue is essentially the radiation that's delivered. As you can see, if the lymphoma is in the middle, there's a substantial amount of lymph nodes and non-lymphoma area that is essentially receiving radiation that potentially puts health tissues at risk for dysfunction later on.

(14:24) Panel B is site radiation where we actually were, over time, able to decrease the amount of radiation to the healthy tissues without compromising the quality of cancer salvage.

(14:36) Now loser doses and new techniques for delivering  radiation have reduce the risk of heart problems later.  On the bottom right is what we typically see. Panel D is what we typically are doing now, which is involved node radiation, which is typically identifying a very specific area being much more localized in how we treat. Sparing much of the heart, which you see in purple below, but targeting the tumor itself. Radiation fields have dramatically changed over the years, and this hopefully will result in improved outcomes for many of our patients.

(15:01) It's not that we're reducing the total dose of radiation in the field, but we're also changing our practice. Simple strategies such as breath-holding, holding your breath when the radiation is delivered. On the left panel, top and bottom, you see free-breathing. In the red is essentially the highest dose of radiation that's delivered to the heart and nearby structures. If you actually, on the right panel, top and bottom, look at breath-holding, if you just hold your breath, change the physical structure of the chest wall cavity, you can substantially reduce the amount of radiation to the heart and its associated structures. We've gotten much better over the years and this will hopefully result in improving outcomes for our future long-term survivors.

(15:52) Cardiovascular disease typically happens more than five years after transplant rather than earlier. Let's take a few minutes to talk about what are some of the issues that come up, and what are the things that we could be monitoring for. When we think about cardiovascular disease, for many of our survivors it's not that it develops during the cancer treatment, but really that it's much more of a longer-term issue. Typically, it happens more than five years after the treatment is completed.

(16:19) Symptoms of cardiovascular problems. What are the symptoms? For individuals who develop heart failure, as I mentioned, for example, for the woman that I gave in the case you can have swelling of your extremities, shortness of breath, reduced ability to exercise, participating in strenuous activity, and then you can have fatigue and weakness persistently.

(16:39) For coronary artery disease. So what I mentioned was premature atherosclerosis. Individuals can have chest pain or discomfort, shortness of breath, pain or discomfort, especially in the arms and the shoulder that radiates ,nausea and weakness.

(16:53) For valvular disease; if it's severe enough, you can have shortness of breath, chest pain, fatigue, irregular heartbeats, and then fainting and dizziness.

(17:01): There's a lot of overlap that cause these conditions and there's a lot of general symptoms that you're having, but this sort of gives you some guidance about what are the troublesome signs and symptoms you should be monitoring. It's important to note that these signs and symptoms are no different than if they were to develop in the non-oncology population. It's the same conditions that you would expect in individuals who didn't have cancer, or who didn't go through transplantation. It's just that what's happening is that it's happening much more frequently in our population at an earlier time point than what you would expect for the general population.

(17:37) Prevention is key and screening is recommended for some individuals. Prevention is really key. Many of our patients clearly, because you're a long-term survivor, obviously that's the most important milestone; is actually reaching survivorship. Clearly, there are a number of treatments that individuals have received that are irreversible, obviously. But there are some things that you can do to help improve your health and decrease your risk of cardiovascular disease. I'll talk about a little bit later, that for certain individuals who we consider high risk for developing cardiovascular disease, it's important that you remain engaged with a primary care provider and someone who is aware of your health history.

(18:20) For certain individuals, we recommend routine echocardiography, which is the ultrasound of the heart, as well as EKGs, electrocardiograms to monitor heart rhythms for looking out for cardiac arrhythmias.

(18:33) Managing modifiable risk factors is key. But if there's any message that I can convey today, it is the importance of management of modifiable risk factors. Many individuals will develop hypertension, diabetes, dyslipidemia after transplantation at a disproportionately higher rate than what you would expect for the general population. It's so important to have many of these conditions well-controlled, aggressively managed.

(19:01) Sometimes, some of the medications that we give for management of GVHD, or even prevention of GVHD, can result in hypertension, can result in insulin resistance and lipid abnormalities. Oftentimes, because we think that these are just transient side effects of the medication, we kind of let them slip by. But the reality is that we really shouldn't. We should be much more vigilant and aggressive in our management of these modifiable risk factors.

(19:25) On the right, there's a graph that shows you there's a substantial proportion of individuals who are walking around with these health conditions in whom these conditions are untreated. We have learned that when you combine these risk factors with a history of cardiotoxic therapies, your risk for cardiovascular disease increases exponentially.

(19:49) Prevention with a heart-healthy diet and lifestyle is crucial. Clearly, prevention is the goal. What do we tell our patients to do? It's so important to implement a heart-healthy lifestyle, think about a heart-healthy diet. Obviously, if you're smoking, you should not be. Increasing physical activity, and again, compliance in the treatment of modifiable risk factors.

(20:06) Some treatment factors increase the need for routine screening. A brief word on screening for heart disease. This is a bit of a gray area in terms of if we know that individuals are at risk for cardiovascular disease can we pick it up earlier? Is it just about doing close monitoring and physical exams or do we need to do more intensive monitoring such as ultrasounds and echocardiograms or EKGs, et cetera?

(20:28) We know that not everybody needs an echocardiogram. Not everybody needs an EKG annually. But there are some folks who may benefit from these screening tests so that we can pick up disease early, prior to it becoming symptomatic. Individuals treated with high dose anthracycline chemotherapy, so as I mentioned anthracyclines are the drugs such as doxorubicin and daunomycin. If you have access to your information in terms of your cumulative dose if you have had more than 250 mg per meter squared over your lifetime, especially if you received it at a young age, we recommend routine screening with echocardiography ranging from every two to every five years or so.

(21:12) If you've received chest radiation, especially in earlier treatment eras, there's a very high risk of coronary artery disease as well as valvular disease so you should be monitoring for those. Then obviously, if you have any concerning symptoms during strenuous activities you should have screening studies; including echocardiograms, EKGs, and in some cases stress tests, as well.

(21:36) Even moderately intense exercise is the best preventive medicine. What about exercise? That, I would say, is probably the best preventive medicine that you can actually implement. This is a study that was done in over 10,000 survivors of Hodgkin lymphoma and these are individuals who were treated in adolescence and young adulthood. This essentially looked at the intensity of physical activity and how it correlates with cardiovascular disease risk. On the bottom, on the X-axis, you see essentially the intensity of exercise. Just to give you a sense, nine mets per hour per week is equivalent to about 30 minutes of moderate-intensity physical activity per day.

(22:14) You can see that the cardiovascular disease trend, it's almost like a medicine. There's a dose-dependent effect. The more intensive the exercise is, the more frequent the exercise is, the lower the risk of cardiovascular disease. In fact, you can lower your cardiovascular disease risk by half just by engaging in 30 minutes of physical activity, moderate-intensity of physical activity per day during the week. That's something that can be done without a substantial amount of pharmacologic intervention or other types of interventions.

(22:48) There are specific recommendations for aerobic and resistance exercise. In fact, there have been a number of consensus recommendations and exercise guidelines for cancer survivors. While these are not necessarily specific to transplant survivors, they are broad enough that it could be applicable to any cancer survivor. When we think about what are the different types of physical activity exercise strategies that you can implement, you can do aerobic activity such as running, fast walking, going upstairs, resistance such as weights, or you can combine both.

(23:17) What I tell our survivors is that these strategies are most effective when you combine them in terms of reducing the risk of cardiovascular disease. Aerobic plus resistance has been shown to decrease anxiety, decrease depressive symptoms, fatigue, improve quality of life and perceived physical function, but importantly also reduce the risk of cardiovascular disease later in life.

(23:41) What are some recommendations? Based on this consensus guideline for cancer survivors, a recommendation is to do aerobic exercise at least three times a week, so 30 minutes per session of moderate intensity. That would be brisk walking, cycling, mowing the lawn, hiking, dancing. Resistance exercise at least two times a week, and that's 30 minutes per session, two to three sets focusing on the large muscular groups like the psoas, the abs and that's essentially using resistance bands, thinking about squats, and in some cases implementing weights, as well, too.

(24:16) Exercise routines should build up gradually and be something survivors enjoy. This is about as good a recipe as you're going to get in terms of thinking about how you reduce your risk for cardiovascular disease later on. Especially if you're at risk. It's really important to remember this that if you're going to make, and this is a fantastic quote from Anna Schwartz , if you are going to make exercise a part of your life, you have a long time to get fit and you must slowly and steadily develop a routine you enjoy. The last thing you want to do is go all out starting in the first week of this self-imposed program and get injured and ultimately set you back for weeks to months on end.

(24:51) The reality is, for many of our patients who are not physically active who have been physically inactive, who have been bedridden for long periods of time, it's a process that's accumulated over weeks and it takes sometimes months to reverse. I would just say make sure that you're patient with yourself as you start thinking about implementing exercise strategies.

(25:13) Some general guidelines for individuals who are planning to begin or intensify their current physical activity levels. It's important to stop and contact your doctor if you have disorientation, dizziness, blurred vision, or fainting. Sudden onset of nausea or vomiting, or unusual sudden shortness of breath. Irregular heartbeats, palpitations or chest pain. Leg or calf pain, bone pain, or unusual joint pain or pain that's not associated with injury. Then muscle cramps or sudden onset muscular weakness or fatigue. This could be a sign of either worsening heart disease, injury, or vascular insufficiency, that is something that happens that we can see for many of our patients who are deconditioned. It's important that you are keeping your healthcare providers in the loop as you begin to engage in physical activity.

(26:06) Avoiding inactivity is essential; individually tailored exercise programs for cancer survivors are ideal. We talk about what you should be cautious about, but what can you do? What is really the ultimate message? The second most important message after the aggressive management of cardiovascular risk factors is avoid inactivity. Whatever you can do, just avoid inactivity. Get individually tailored exercise programs from a physical therapist or a personal trainer if you have one that's available who's certified as a trainer for cancer patients, if you have access to that, that's really fantastic.

(26:39) It's important to do special recommendations for survivors who are still in their cancer treatment. I think it's really important for trainers to be mindful of individuals who are going through cancer therapy and to integrate specific recommendations based on the tolerance of the patient.

(26:58) Then there are established programs for cancer survivors whether it's Livestrong at the Y, or exercise and thrive programs. There are a number of them that could be easily searched on the web that specifically target cancer survivors. This is important to consider, because not only is it physical activity that's designed to keep the survivor in mind, but also has a peer support and peer group system that's incredibly important.

(27:21) Many simple, gentle activities are good starting points for exercise benefits. What can you do? Take a walk with your friends, work out with a DVD, TV program, or YouTube. Things to think about would be, searching examples would be, low impact aerobic exercise or chair exercise. Those are really nice starter strategies to think about if you are physically inactive. Ride your bike, mow the grass, rake the leaves. There are literally limitless number of options, so it's not just about running or climbing stairs, or hiking. There are a number of strategies. Think about parking your car in the farthest parking place and then walking to the location that you're going to.

(27:55) If you have an option of taking the elevator or stairs and it's not a high rise, use the stairs. Get off the bus several stops early and try to implement walking or fast-pace walking as part of your everyday activities. Take classes at local centers in the YMCA, for example as I mentioned. Integrate gentle Yoga, Tai Chi additional strategies as a way to balance the rigorous physical activity if that's something that you're implementing.

(28:22) Again, these are gentle enough and they're a perfect place to start. The key is avoid physical inactivity as much as you can. It's something that many of us have, in the context of the COVID pandemic, adopted. For others, the sedentary life has taken over much more so than before the pandemic.

(28:44) Survivors need to be well informed and actively involved in their long term care. The last few slides I just want to talk about how are things changing in the healthcare landscape and what is its impact on cardiovascular disease and what is its impact on the overall well-being of our long-term survivors? Until recently, the primary way in which survivors and cancer patients were engaged with their healthcare providers were in this context of this traditional paternalistic model of care where there is an empowered physician, where the patient is completely reliant on the provider to receive information, diagnosis referral.

(29:14) An empowered patient sharing ownership model can coordinate care from cancer centers and primary physicians. This is really difficult for patients to navigate within and between health and social care, especially as they're transitioning from their cancer centers back into the community. If the entire source of information and monitoring is really in the hands of the primary physician, it's really hard to navigate that and transfer that information over. Typically, interventions are done in response to the person physically being there and that's really changing. We're moving more toward this empowered patient sharing ownership model, especially in the context of COVID and remote delivery of care.

(29:46) Patients are wanting to become increasingly informed of whenever, wherever regarding their health. There's increased push toward co-creation of care packages, proactive prevention, rapid access to services. Technology has really driven the support and self-management needs of our patients and our survivors, even much more so and accelerated because of the pandemic.

(30:11) This is a study that we did a few years back. The reality is that for many of our long-term survivors, when you get to five, 10-years post your transplantation, you're no longer being seen at the cancer center. In fact, there's a dramatic drop in the cancer center related visit. What we see is an increase in general practitioner visits. There is a transitional care that's happening. The more informed you are, the more informed the survivor is, the better that transition can happen, the smoother that transition can happen.

(30:45) Remote technology is an evolving care strategy that can detect problems early. We at City of Hope have embraced remote technology as a strategy, as a means to address this gap in survivorship care. During this transition we know that many survivors may fall through the cracks and not have adequate care. We believe that there's a hybrid mechanism where the cancer center can actually remotely be involved in the monitoring and the prevention of these modifiable risk factors, especially in the beginning during this transitional period.

(31:12) We have piloted several projects and approaches where we're giving individuals remote monitors, Bluetooth enabled blood pressure cuffs, glucometers, scales, Fit Bit machines, Fit Bit watches, as well as Pulse Oximeters, and this information can then be relayed in a secure platform into the medical record, to the provider and really give real-time information about how you're doing, what's your health, how's your blood pressure, how's your blood sugar, et cetera, and provide opportunities for real-time management instead of waiting for that once every three-month visit, or once a year visit to really implement that care.

(31:49) We published this in a recent paper where we actually looked at a group of long-term stem cell transplant survivors, provided them with a number of these remote monitoring trackers and then really paired them with a specific system where there were alerts that were generated if these specific parameters were out of the normal. For example, if someone's blood pressure was 180/120 persistently, a nurse was alerted and then obviously, if this was a true finding and let's say appropriate triaging was done, but if someone was having symptoms or there was concerning issues that needed to be addressed then there was the opportunity for a health professional to intervene with additional triaging.

(32:35) The reason why I mention this is that this paradigm of remote monitoring and intervention is here to stay and in fact, it's probably going to continue to grow. Demand is not just from the providers in terms of thinking about how to take care of our patients remotely, but it's also from the patients because there's a lot of sophisticated patients who are increasingly interested and engaged in their health and will demand these services and this form of triage and management.

(33:08) Remote exercise strategies are another evolving tool. Then sort of to round things up, we talked about monitoring blood pressures, blood sugars, scale, physical activity, et cetera, but how about taking it even further. We talked about exercise and a lot of the exercise strategies that I mentioned were primarily focusing on in-person classes at centers, et cetera. But we, at City of Hope, have increasingly investing in remote exercise strategies.

(33:37) There are two ways we can do this. Right now in the bottom is what we see typically, which are sort of traditional cardiac rehabilitation strategies that are primarily hospital-based or center-based. We believe that Telehealth and home-based exercise programs are really the wave of the future for many of our long-term survivors. The reason why we do that is because we believe that you can get similar reductions in cardiovascular risk factors if you use a Telehealth exercise versus a hospital-based program. You can get similar improvements in functional fitness, risk factors, quality of life. All of this could be done remotely. Remote guidance through Zoom or other types of platforms are clearly possible with, obviously, supervision and appropriate guidance.

(34:25) This is really going to be the wave of the future, and for those of you who are contacted by researchers or providers at cancer centers, et cetera, who are interested in looking at these new paradigms, I would urge you to consider participating in these strategies, because really, this is the wave of the future for many of our patients.

(34:42) A summary of what patients can do. To summarize everything, what do we encourage our patients to do? We encourage our patients to learn about the treatments that they receive. Get regular checkups focusing on health risks related to your cancer treatments and transplantation. Work with healthcare providers to develop a long-term follow-up plan. Obviously, make healthy choices, recognizing that you are the most important member of your healthcare team. Being a self-advocate is the most important thing that you can do for yourself.

(35:08) With that I want to thank you. This is a picture from our transplant reunion that for years had been happening in-person, last year was remote. But hopefully, we're looking forward to having an in-person reunion in the future. Clearly, it takes a village and it's a tremendous honor and privilege to be talking to you about optimizing your health. I'm happy to take any questions that may come up in the chat.

Question and Answer Session

(35:36) [Thom Stewart]   Thank you, Dr. Armenian, for this excellent presentation. We will now take questions. As a reminder, if you have a question, please type it into the chat box on the lower left-hand corner of your screen.

(35:50) Dr. Armenian, I will take the first two questions here together. One is a follow-up to the other. The first is what are the complications of chemotherapy and radiation to the heart? And the follow-up to this is can CAR T treatment damage the heart?

(36:09) [Saro Armenian]      Yeah, so those are great questions. The complications of chemotherapy and radiation on the heart, they vary really depending on the chemotherapy and the radiation. Typically, the chemotherapy-related injury that we see to the heart, that's driven by the anthracycline chemotherapy. In some cases, cyclophosphamide that's used as part of transplantation. That can cause weakening of the heart muscles, so initially termed as cardiac dysfunction.

(36:43) If there's enough weakening of the heart muscle, it can result in heart failure where the heart is not pumping adequately. Radiation, per say, can have a number of effects. It could damage the blood vessels that are feeding the heart causing premature coronary artery disease, or atherosclerosis. Radiation can impact a number of blood vessels. Whatever blood vessel is actually is near it can cause atherosclerosis type pictures.

(37:10) If someone gets neck radiation, the neck blood vessels can have narrowing, et cetera. Radiation can also cause scarring of the valves, so the valves can become stiff and in some cases they can actually be leaky. The valves just aren't working as well. If there's enough radiation to the heart muscle itself, it can cause arrhythmias, rhythm disorders, et cetera. If it's severe enough, they'll need to have interventions and ultimately the worst case would be to have a pacemaker, et cetera, that's implemented.

(37:46) CAR T. That's a black box at this point. We know that CAR T causes a number of issues that compromise the hemodynamic system. What I mean by that is that we know that CAR T can cause a number of inflammation syndromes, and these inflammation-type syndromes can have a substantial impact on the heart and the blood vessels themselves. We have had situations where individuals who are going into their CAR T transplant with suboptimal heart function receive their CAR T-therapy. Then there's the CRS syndrome that can develop, which is sort of this massive inflammatory state. They can develop heart failure and heart dysfunction.

(38:32) At this point, it's too early to know what are the long-term side effects of CAR T. Clearly, it's an emerging and very, very exciting form of treatment and has been a lifeline for so many individuals. We are going to be monitoring that at City of Hope, as well as other investigators around the country and hoping to have more data about that in the near future.

(38:54) [Thom Stewart]       Thanks. Here's another question that came in. I've had many chest CTs over the past six years for pneumonia, fungal infection, and lung GVHD. Can CTs effect heart health?

(39:09) [Saro Armenian]      That's a fantastic question. To the best of our knowledge, the amount of radiation that you get from a CT scan, a simple CT scan, especially CT of the chest, which can be relatively quick, has a slight but not substantial risk. There's been no direct between, in our population at least, between CT scans and heart disease risk later on.

(39:38) There's general information in the general population about CTs, et cetera, but at this point, there's not a lot of compelling data to suggest that there is. That said, if you've already received a substantial amount of radiation as part of your frontline therapy and on top of that you're getting additional scans, yeah, it has the potential to increase it but we just don't have the data yet.

(40:02) I think all of our physicians are incredibly aware of the need to balance the information that you're going to get from a CT scan with the potential harms of additional radiation to somebody. If your physician does not know this, does not know that let's say you've received radiation as part of your treatment initially, that's something that obviously you would need to bring up to them.

(40:31) [Thom Stewart]       Okay. Another question is what percentage of those older than 70 get these sorts of cardiovascular disease? What if you go in as a long distance runner?

(40:45) [Saro Armenian]       These questions are truly fantastic. We don't know. I'll tell you this; the one thing we do know is that the better shape you're in going into a transplant, the better your likelihood is going to be that you're going to be able to avoid many of these issues later on. In terms of yeah, if you are a long distance runner going into your transplantation, your likelihood of developing cardiovascular disease is going to be substantially less. Right?

(41:18) Part of this has to do with what treatments are you receiving? You could have potentially a long distance runner who received a tremendous amount of chemotherapy and/or radiation that could impact the heart. Right? That person's risk, even if you are a long distance runner, you're going in with an increased risk at baseline and that increased risk is going to be more than someone who is not a long distance runner and has not received those treatments.

(41:42) I'd hate to be going around in circles on this, but part of it has to do with just recognizing that part of it has to do with the treatment. But if you balance out all the treatments across the board, the individual who goes into their transplant in good physical shape where they have managed their cardiovascular risk factors, they're physically active, and more importantly they're physically active during the transplant. That's really, really important that we get our patients up and going during the transplantation, the better they're going to do. The lower the risk of cardiovascular disease.

(42:21) The quicker you get back up on your feet afterward. That's the other thing, too. The quicker you can get back into that routine afterward, the reconditioning that you need to do, that's also very, very important.

(42:34) [Thom Stewart]      Thank you. Are post BMT patients particularly at risk for aortic root dilation due to radiation and chemotherapy?

(42:44) [Saro Armenian]       I wouldn't say post BMT in general. The aortic problems that you can see typically are going to be not too different than what you would see in let's say someone who had lymphoma, received radiation and chemotherapy for it but did not go to a transplant. We don't have evidence that suggests the BMT itself adds even more to aortic problems including aortic stenosis or dilation, et cetera. Part of that is probably from the pre BMT treatment exposures, et cetera.

(43:21) [Thom Stewart]      Okay. One more wants to know how can I find out more about Telehealth home-based programs?

(43:30) [Saro Armenian]       It depends on your location. One of the things I would do is, depending on the cancer center that you're working with, I think the best thing would be is to ask your provider. I think a lot of these areas are emerging. Many places don't have access to this technology. The reason why I put it in the slides is more just to give everyone a teaser that things will be changing. COVID has changed the landscape of how we think about health and preventive health and how much we empower our survivors.

(44:05) It's more about giving you a window of what's going to happen over the next few years or so. I can imagine these Telehealth centers and Telehealth interventions popping up more and more based on your geographic location. I would say the first question would be just to contact your primary cancer provider if you're following with them. If not, just your regular practitioner. But I would just say stay tuned. At City of Hope, we're doing this in the context of research at this point so that we can actually show that these strategies are effective. I'm very optimistic that it's going to be part of the mainstay in the years to come.

(44:41) [Thom Stewart]       Okay, and these two are sort of related to that question. I'll just give you both of them together. One is how do you find a trainer who is certified as a trainer for cancer patients? The other one related to that is who is a resource for personal trainers that work with cancer patients?

(45:00) [Saro Armenian]       Yeah, again, it depends on your geographic location. Places like Live Strong, the organizations like Live Strong or the YMCA, those are nice organizations and groups to actually contact both locally and nationally to get more information. Let's say you go to a gym nearby, you may want to ask about what level of training do they have.

(45:33) If you are in contact with your cancer center where you received your transplantation, you may ask the physical therapy folks to see if they have recommendations, suggestions, or resources based on your geographic location. Then, obviously, an online search to start may be another way to think about it as well, too. I'm not saying that is the only way to do it, but if that resource is available, then by all means, it's sort of the cherry on the top.

(46:04) [Thom Stewart]       Well, this may be a related question to that but how does one find an oncology focused physiotherapist and dietician, especially several years post-transplant?

(46:17) [Saro Armenian]       Oh, yeah. Again, I would just say depending on your location there may be an abundance or there may be a paucity of it where you are. I think your best bet would be to contact a comprehensive cancer center that's nearby, or where you had your transplant. If you moved away from that center, then you may want to contact another center nearby that does transplants or is known for doing transplants, or even a large cancer center. They will have adequate resources they will be able to provide for you. Even if you are a long-term survivor.

(46:51) It's important to recognize that survivorship is part of the language and the way that we ... It's part of the mainstream language of the cancer centers around the country. There are increasing resources that are being allocated at the cancer centers to help both in the transition for survivors, but then for certain individuals to help in providing care and preventive care, as well.

(47:19) [Thom Stewart]       Okay. You mentioned that heart issues typically show up five to 10 years post-transplant. Does the risk rate go down after that amount of time? This particular individual is currently 22 years post-transplant.

(47:37) [Saro Armenian]       Yeah, that's an interesting question. The reality is, cardiovascular disease is an aging condition. The reality of our body and our biology is that if we live long enough, we're either going to develop some form of cancer or we're going to develop some form of cardiovascular disease. That's just part of the body's aging process. Those are the two most common causes of morbidity and mortality in the United States.

(48:12) The risk, I would say is, for our cancer patients who receive cardiotoxic therapies, is high across the board. It continues over a lifetime. What happens, and it's going to be hard for me. I'm trying to motion it with my hands and I can't. The reality is that once your risk goes up, it continues to stay up all through your lifetime. What's happening is that you're essentially adding the increased risk of cardiovascular disease to the normal increased risk that happens with age.

(48:46) For all those reasons, I would say there's continued engagement, continued vigilance, increasing activity level, better management of cardiovascular risk factors. That's all you can really do. You can't go back and change the treatment, but you can be proactive about your health.

(49:05) [Thom Stewart]       Okay. Do you recommend using standard risk factor tools for cholesterol and triglycerides or are there other tools to use or recommendations for transplant patients?

(49:17) [Saro Armenian]       That's a great question. We, and others, are working on developing specific risk calculators that are tailored to transplant survivors and transplant patients. These are not ready for primetime, so until then, I would say that using standard risk calculators make all the sense.

(49:38) Top risk calculators from the American College of Cardiology or the American Heart Association are widely available. There are a number of risk calculators. Essentially what the risk calculator does is that it gives you some boundary of action. At this point, we don't have any transplant specific risk calculators that we can use that are ready for mainstream. Until then, I would just say the standard ones should be more than adequate. Again, the lower your blood pressure, the better your blood sugar control, the better your cholesterol, the better your control your weight and more importantly increase your physical activity across the board the better you're going to do. There is no bottom to that ceiling.

(50:27) [Thom Stewart]       Okay. Another question asks are aftercare plans from the transplant center the norm today? I have experienced a big disconnect between the center, oncologist, and primary care physician.

(50:42) [Saro Armenian]       Yep.

(50:42) [Thom Stewart]        I have to chase after specialists on my own. It's been five years since transplant. Is it too late?

(50:50) [Saro Armenian]      It's never too late, but the story of chasing down providers and getting this information is one that I hear hundreds of times a year. It's the reality of the landscape, but I would say it will change and it is changing. 10-15 years ago the concept of providing individuals with survivorship care plans and guidance on what to do long-term was nonexistent. That concept was not even there. Now? It's part of the forefront. I wouldn't say that it's available at every center across the country, but there are increasing mandates such as the American College of Surgeons and other sort of initiatives and incentives, as well, that are coming down across from both local, as well as federal level that are going to mandate much more proactive engagement of survivorship care. I would say that it's continuing to evolve and for the good, I would say.

(51:50) [Thom Stewart]      Thanks. Another question is are the remote monitoring tools covered by insurance?

(51:59) [Saro Armenian]       Increasingly, yes. Obviously, for folks who have these health conditions; diabetes, hypertension, et cetera. Increasingly, depending on the health plan, they are being covered and I can see that it's going to be even more so in the future. Because I think health insurance, or insurers are recognizing that proactive management of these risk factors has tremendous downstream benefits. Preventing hospitalization, preventing illness, much more costly health conditions from developing.

(52:34) There is going to be that incentivization. I'm told technology was the barrier. It wasn't the willingness of the payers to cover these issues. Now that the technologic barriers are being removed and at a rapid pace because, like I said, the advances in technology due to the COVID pandemic, it's going to be part of the norm.

(52:54) Having a Bluetooth enabled blood pressure cuff that's going to, in real-time. Provide your doctor with your blood pressure readings over the last week or so, that's going to be the norm over the next few years or so. I'm very optimistic about that.

(53:08) [Thom Stewart]       Good. Relative to the City of Hope where you practice, are the City of Hope Telehealth exercise and monitoring programs available across the country?

(53:20) [Saro Armenian]        The short answer is no. But we are hoping as we start developing them ... The first step is development, the second step is testing to make sure they're effective and they're safe and preventing serious cardiovascular disease. The third step is dissemination.

(53:38) The NIH is increasingly interested in these initiatives. There's going to be a tremendous motivation for researchers and providers across the country to develop these platforms. Again, I put it in the talk as something to keep on the horizon. While it's not available at this moment, it's definitely something that will be in the next few years or so.

(54:12) [Thom Stewart]       The related question to that, another questioner wants to know are there exercise programs via Zoom for City of Hope patients who received their BMT six years ago? Loved music, Yoga, Reiki, et cetera. Co-treatment while I was there, now lives in San Diego.

(54:32) [Saro Armenian]       Yeah, we recognize that is a tremendous unmet need. From a program standpoint, we have not done that yet but again, I wouldn't necessarily focus just on the center itself. If there are other online platforms where you can ... You know, there are so many platforms now. Obviously, the most advanced and the most sophisticated being Peloton and all those other strategies, but having the web-based interface is something that is not just for oncology care, it's really going to be part of the mainstream for the general population, as well.

(55:15) While we don't necessarily have it as a developed program yet, it's definitely in the horizon, it's on the horizon. But there are several other strategies that you can implement. It doesn't have to be just through here.

(55:25) [Thom Stewart]      Okay. We're going to have to take one last question. We're running out of time. I found two question that look alike, so I'll give you one of them. I have found that a general internal medicine doctor has no idea of how to treat/care for a transplant survivor. How do you recommend finding a physician for general care as we transition from the cancer care center to our life as a thriver?

(55:59) [Saro Armenian]      That's a fantastic question. I think the best answer is going to be your provider is going to know who the physicians are in the community who have competence in caring for cancer survivors. That's a conversation you're probably going to need to have with your cancer provider. If not them, nurse practitioners or whoever else that you're engaged with on a regular basis.

(56:35) I wish there was a directory where you could just go and say okay, these are internal medicine physicians who have expertise in cancer survivorship. At this point, it's not formalized yet so we don't have that platform. Part of it is because it's just so complex because of provider access and coverage. Yeah, I hate to be vague about this but I would just say we don't have a good platform or mechanism to do that.

(57:05) It really is a case-by-case situation and a conversation with your primary oncology provider. Again, there's geographic location. Where are you in relation to that cancer survivor specialist? There's just a number of different barriers to being able to develop this one long list that are getting in the way at this point. Again, the NIH is very, very aware of this issue and this disconnect and they are pumping a tremendous amount of money into research to help bridge this gap between the cancer center and the primary care providers.

(57:44) There are going to be a number of innovative ways to help bridge that gap, we just don't have it yet.

(57:50) [Thom Stewart]      Closing. All right. Well, I want to, on behalf of the BMT InfoNet and our partners, thank you, Dr. Armenian, for your very helpful talks. Thank you, the audience, for your excellent questions.