John Dykes, MD, pediatric cardiologist with Stanford Children’s Health, talks about a new system aimed at matching heart donors for children awaiting transplant
What is the background on pediatric heart failure? How many children undergo a heart transplant over the year?
Dr. Dykes: Thankfully, it is a relatively rare condition to undergo a heart transplant. Even most children who are born with some type of congenital heart disease ultimately do not have to undergo a heart transplant. There is a subset of patients that are born with specific cardiomyopathies that can advance to the point of heart failure that does not respond to medications. That type of heart failure is what we call refractory to medical management and may ultimately require a heart transplant. At Stanford Children’s Health, we have one of the largest pediatric heart transplant programs in the country. We do anywhere between 20 and 30 heart – pediatric heart transplants a year. In general, there are over 400 pediatric heart transplants done in the country per year.
Typically, how long does a child have to wait for a transplant?
Dr. Dykes: There are a lot of components that go into how long you wait for a transplant, some of them are predictable and some of them are very unpredictable. Certainly, the age of the patient and the blood type of the patient play major factors. Whether or not that patient has any antibodies would limit the type of hearts that patients could receive from a potential donor and cause them to have to wait longer. You’re looking at a timeframe that’s usually in the realm of months but sometimes we get very fortunate. If a heart becomes available in a shorter amount of time, we certainly take it as long as it’s compatible with the recipient. I think the thing that really limits us in pediatrics is that the number of pediatric donors is much smaller than the number of adult donors. Fortunately, there aren’t as many tragedies that occur to children but when those tragedies occur, there are people that make the ultimate gift, which is organ donation. When you look at the grand scheme of things, the number of donors for pediatrics is much smaller. So, when you look at things like size constraints – because we need smaller hearts for smaller children – those really limit the number of donors that we’re thinking about for kids. When we talk about the size-matching that we’re doing, what we are ultimately trying to do is to get access to a larger donor population for an individual recipient that is on the heart transplant list. For potential donor hearts, along with those factors that have to do with age, size, blood type, and what we call sensitization, or the number of antibodies that the recipient has, the other factor that comes into play is their listing status. So naturally, the children that are deemed sicker and at higher risk of potentially dying on the waitlist, are listed at a higher status. So, if you are being controlled with your heart failure therapies and not in the hospital, then you are lower on the list than somebody that’s potentially in the intensive care unit (ICU) that’s waiting in more urgent need of heart transplantation. For the highest status you’re looking more in the realm of months and then as you get on the lower statuses, you may be looking at years, many years.
Tell me about size-matching.
Dr. Dykes: For pediatric heart transplant donors, traditionally the way we’ve thought of size-matching is using what we call surrogate markers that have to do with the basis of body weight and height. One of the things we all know, and it’s very intuitive, is that as you grow, your organs grow with you. Your heart gets bigger as you get older, and you gain weight and height. The problem that occurs in pediatric heart failure is that you have a split between the heart getting very dilated, but the children have also stopped growing to varying degrees, so, the predictability of how enlarged their heart is in relation to their body size is really lost. Furthermore, we don’t have a lot of normal data on how we predict a 17-year old’s heart size. We have these traditional markers that we’ve used that have guided us in the past, but we really don’t know quite how big we can go for an individual patient who’s in heart failure. When we think about size-matching, we’re typically talking about a donor to recipient weight ratio and a donor to recipient height ratio, but the weight ratio is really the one that people have traditionally targeted. In pediatrics, most people will go up to around 1.5 or 150%. Some programs will go higher to 200% in terms of their upper limit for what kind of heart they will evaluate. But those are based on assumptions about the relationship between the weight and the heart size. We found that, like many others, when we perform advanced imaging, CT scans or MRI, on these children in heart failure, their hearts are enlarged due to their degree of heart failure. That results in what we call an enlarged total cardiac volume. Whereas you may have a 10-year old that is in heart failure and they may have the heart size of somebody that’s a young adult. That’s because they’re in heart failure and their heart gets enlarged in relation to their body. Furthermore, when they stop growing, that makes that discrepancy even bigger. So, what we started doing is actually measuring the total cardiac volume by utilizing an advanced imaging technique where you look at a CT scan or an MRI and you measure the heart volume. All of our recipients get a CT scan at the time of heart transplant listing to get an idea of how large their heart is and then we compare this to the size of the donor’s heart. We have to list a maximum weight ratio that we are willing to evaluate for all donors that are available for a given patient on the transplant list. That weight ratio used to be much more conservative in our program and in many other programs. We’ve been able to increase that upper weight ratio so that we can evaluate some of these donors that were previously deemed to be too big by weight and height based criteria, but were actually appropriately sized hearts for the pediatric recipients when matched by total cardiac volume as assessed by CT scan.
What happens if a patient has an oversized heart, like the size of a teenage heart?
Dr. Dykes: We do know that as we get older we reach a point where our heart has achieved a full size and that size, in a healthy individual, generally doesn’t change too much when you’re in adulthood. The pediatric patient is still growing and developing, and their heart is getting larger. For patients in heart failure, we know that they typically have larger than expected hearts due to the nature of the disease. Thus, if you were to take, let’s say, a 25-year-old that weighed a certain amount and then took a young teenager in heart failure, their heart sizes may actually be the exact same. Meaning that the recipient’s body can accommodate that older patient’s heart just fine and they can receive that heart transplant. So, it’s not that the heart is larger, it’s that the patient’s body weight is much larger and now we just have more accurate ways of assessing the total cardiac volume. When we talk about weight ratios, we may talk about somebody that has a donor to recipient weight ratio of 250% but when we look at the donor-recipient total cardiac volume, it can be one-to-one because the older patient that’s not in heart failure doesn’t have a large heart like the pediatric recipient.
Once the recipient becomes healthier, will the space remain?
Dr. Dykes: The space will accommodate. Oftentimes we don’t actually get to a true one-to-one volume ratio with a heart transplant so there is leftover space in the chest cavity that is which up by the lungs, pericardial fluid, or scar tissue. The idea is that the recipients failing heart size is what we consider usable real estate that we can potentially be used to fit the new heart. Then, over time, the body accommodates to that heart size and the heart works just fine, the lungs work fine, there’s really no issues. What we are looking at is how large can we go to try to take some of those adult donor hearts for our pediatric patients and get them off the list? One of the struggles that we face in pediatric heart failure and transplant is that there’s a real wait-list-mortality that we fight against. The availability of pediatric hearts is much rarer than the adult population. So, if we can take a heart, even if it’s a little bit on the larger side by weight-based matching but appropriately sized for that pediatric recipient by volume-based matching, we can potentially save that child’s life and get them off of the heart transplant list.
To clarify – if you have an 8-year old recipient and the heart is the size of a 15-year old, he/she could only accept the 15-year old heart size – or could we use the heart size of an 8-year-old?
Dr. Dykes: The lower limit on sizing for hearts is not necessarily something that we are going after right now. Typically, we look in terms of weight ratios. We look at about 90% of the recipient’s weight up to 200 or 250%. We generally like to stay right around that eight-year old’s weight. So, yes, they can potentially take the heart of someone their similar age. Essentially, if you have an eight-year-old that has the same heart size as, say, a 15-year-old, they can take that 15-year-old’s heart, but they can also take a heart of someone their similar age and do just fine. What we’re trying to do is find the largest heart that they can take because that’s really the end that can expand the donor pool. There is an abundant number of adult donors that are out there. For example, there are 3.5 times as many donors in the 18 to 34 range as compared to the number of donors under 18 years of age. So, if you had a 13-year-old that had a heart size that could accommodate a 25 or 27-year-old, then it’s likely that that patient would wait much less on the list.
So, this technique is potentially a game-changer?
Dr. Dykes: Yes, I think that the idea of considering total cardiac volume in pediatric heart transplant size-matching is a real paradigm shift for us. The traditional size-matching was rooted in weight and height surrogate measurements that traditionally had served us very well and over the last 50 years, and that’s how things have been done. There are many in the field, not only at this institution, that have really grasped onto this idea. A direct measurement, something that we can tangibly say there’s 500 CC heart here and 500 CC heart there, those are potentially compatible donors regardless of the donor’s height or the weight, or the age. By getting a direct measurement it is a much better way of assessing size-matching in heart transplantation where we have a very significant wait-list-mortality and we need to get these children transplanted as soon as we can.
Tell me the steps that you go through.
Dr. Dykes: It all starts when we’re evaluating a child for our transplant list; all of our children end up getting a CT scan of their chest. We then take that CT scan and we bring it over to our 3-D imaging lab here at Stanford. We’re able to segment that heart in a way that we can create a volume measurement of everything in the chest that we would remove at the time of the heart transplant. That includes the ventricles and the atrium, and then we store that volume measurement on our heart transplant list. When a donor offer becomes available for that particular patient on the list, as soon as we can get the Digital Imaging and Communications in Medicine (DICOM) file, which is the CT scan that’s been performed on the donor who has passed away, then we can electronically import that into our system where our 3-D lab can then measure that donor’s heart. We can once again get a volume measurement; we can compare those two for size eligibility. If that volume ratio is around one-to-one or less, then we can take that heart from a size standpoint.
What is a ‘virtual heart transplant’?
Dr. Dykes: Essentially that is kind of what we are doing. On the recipient side, we’re mapping out all of the parts of the heart that will be removed at the time of the heart transplant. On the donor side, we’re mapping those same portions that we will then insert into the recipient’s chest cavity once the old heart is removed at the time of transplant. So what we’re doing is essentially performing, from a size standpoint, what would be called a ‘virtual transplant’. In the lab they can virtually do that and move the heart into the recipient’s chest electronically. What we’re mainly doing is looking to see if there enough real estate– is there enough volume or space in the recipient’s chest to accommodate this new heart which traditionally was thought to be larger by weight-based size-matching.
What are the benefits of the doctor’s rehearsing this beforehand?
Dr. Dykes: There are benefits of doing that because it is a process with a lot of steps with the sort of ultimate step being that, when the DICOM file is available for us, we have to make a decision and we have to make that decision quickly. Rehearsing the process of doing the mapping for the volumetric assessment is extremely important because it allows the team to be extremely efficient when we have that file and they can get us the numbers as quickly as possible, so we make that decision. We’ve got it down to about 15 minutes by the time the file’s in the system to when they can give us an actual measurement on the size of the donor’s heart. I think the biggest issue right now is just the electronic transfer of the image itself.
Tell me about the quantitative imaging lab.
Dr. Dykes: The idea of thinking of total cardiac volume in pediatric heart transplant is not something that started here. It’s something that the field has been thinking about for years and other people have done and have participated in the research. What we’ve been able to do in 3-D imaging is expand the work and implement it into a real-time process. The 3-D lab at Stanford has been available for us 24 hours a day, seven days a week. We can’t predict when a heart becomes available – it can happen in the middle of the night, it can happen during off-hours. So, having a 3-D lab that has a staff that’s capable of doing these measurements quickly and at any time of the day has allowed for us to be ready to measure those hearts when we need to. Not every single heart that we get offered has to be measured, but certainly the ones that are on the higher end of our acceptable size range.
How long has this been implemented at Stanford?
Dr. Dykes: We’ve been doing this for a little over two years now. We’ve certainly ramped up the number of hearts that we’re measuring and right now we’re in two phases that are going side-by-side. We currently have the protocols in place that when we have the DICOM file available to us on the donor at the time of transplant, we can measure that donor and compare it to our recipient heart volume and see if that virtual transplant is good from a size perspective. We’re also measuring a lot of normal hearts to develop what we would call a ‘healthy heart library’, where hopefully some day you can identify a person of a certain age, height, weight, and sex who has a compatible heart size to our recipient waiting for a transplant. So that potentially, down the road, when we measure enough normal heart volumes, we can predict in a normal individual that’s a 27-year-old male of a certain height and weight, and determine what their total cardiac volume would be possible without advanced cardiac imaging. We really just don’t have that data yet to know if that’s possible. There are a number of factors like obesity that likely play a role in the total cardiac volume of donor hearts that we are looking at now. Hopefully, after we complete measurement of a large number of donor hearts we will better understand the influence of these factors on total cardiac volume. If we can develop a way to predict total cardiac volume in a normal individual, then we can measure hearts of kids listed for transplant and then know what age, height and weight range that we should target for those in regard to size matching for heart transplant. Ultimately, I think we’re still going to be left with the gold standard being a direct measurement of both the donor and recipient, but it would be nice to measure the recipients and potentially predict the donor heart volume.
Are there additional uses for this type of technique?
Dr. Dykes: I think the 3-D labs have opened up the quantitative assessment of organ size which can play a role in other forms of transplantation. I know that the lung transplant teams have shown interest in it. There are also some people that have an interest in terms of liver transplants. We really have to be able to measure size and space in pediatric solid organ transplant, it’s such a precious thing that affects the process, and these advanced imaging techniques that are so abundant now really give us the opportunity to do that. So, I do see it expanding beyond heart transplantation, for thoracic organ transplantation, in general, I think it’s very useful.
How many other hospitals use this innovative technique?
Dr. Dykes: It depends on in what capacity because many places have 3-D imaging labs that may have the ability to get a total cardiac volume. The problem at some of those other institutions is that the 3-D labs are not as robust and developed as they are at Stanford, and the 24/7 coverage is a real limitation. We’ve been very fortunate that our team has been able to provide that for us, and I think that’s where we’ve been able to take off running with this and open it up to all of our patients.
Have more lives been saved as a result?
Dr. Dykes: Yes. I do think that. Ultimately, our job is to get these children transplanted in the safest way. I think that when we have the ability to open up more potential donors for patients, it allow us to be more selective on other risk factors that may contribute to poor outcomes after transplant. We potentially open up the door for more local heart donors that are beneficial for our patients and ultimately, get them off of the heart transplant list. In pediatrics, where our options for mechanical circulatory support are sometimes limited, we need to make sure that we’re utilizing every heart donor that we come across for an individual patient that could potentially get transplanted. Right now, in the United States, we utilize somewhere around 60% of all pediatric heart donors, and I think we can do much better than that. More donors for a patient listed means a higher chance of finding a match, which in turn helps us get patients off the transplant list before they become so sick that we need to do things that are very risky, like certain types of pediatric mechanical support. I do think that this is saving lives. Instead of measuring the person, that’s basically just height and weight, we’re measuring the heart and that’s the biggest thing. The bottom line is that we’re not assuming that just because you’re tall and you weigh a lot that your heart is big. While that usually is the case, we can’t rely on those assumptions because we don’t have the data to make those assumptions yet. We also know that there’s variability in heart size for a given size person. We’re not using those surrogate measurements to assess the total cardiac volume, we’re specifically measuring it using advanced imaging techniques in both the donor and the recipient patient, which allows for an improved size-matching criterion. Ultimately, all of us are looking to get that healthy heart for these children that are dying and allow for them to recover safely after a heart transplant, so they go on and lead long and lovely lives.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
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