Join science journalist Catherine Price as she sits down with top physicians from NewYork-Presbyterian Hospital to discuss the latest research, complex cases, and what it means to deliver patient-centered care.
Welcome to Advances in Care
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Catherine Price: On a chilly spring morning, Dr. Nir Uriel rose before the sun came up. He put on his workout clothes, threw his cycling shoes in a bag, and headed out the door. But he wasn’t going to just any morning workout class. He was about to lead a room full of cardiologists and heart surgeons in a cycling workout, that he himself had designed, to mimic what it feels like to experience heart failure.
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The class was a combo of intervals and hills, where the incline increased every minute, so participants had to go fast with what felt like lead in their legs, making their hearts work harder and harder. The workout was grueling, but the physicians got through it. And they came away with a newfound appreciation for what it feels like to be in the shoes of a patient with advanced heart failure.
Dr. Uriel is not actually a cycling instructor. He’s the Director of Advanced Heart Failure and Cardiac Transplantation at New
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York-Presbyterian, Columbia and Weill Cornell Medicine. This class was just his own out-of-the-box way of delivering a keynote lecture about advanced heart failure treatments. And yes – he literally gave the lecture WHILE leading the spin class. For anybody who knows Dr. Uriel, this anecdote isn’t surprising – because he’s a physician who knows that the best way to treat his patients is with humility and empathy.
THEME
I’m Catherine Price and this is Advances in Care.
On today’s episode, more about Dr. Uriel’s empathetic, team-centered approach to treating his patients. And how he’s embracing technologies like AI and Machine Learning to push forward advances that are allowing patients to live long, full lives despite their diagnoses.
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Catherine Price: So Dr. Uriel, thank you so much for joining me for this podcast. I am really excited to get to talk to you today.
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Dr. Nir Uriel: Catherine, thank you for having me. I'm actually excited to have this conversation and to brainstorm together a little bit about heart transplant, heart failure.
Catherine Price: I don't know how much I will be able to add to this, this, uh, conversation.
Dr. Nir Uriel: You will be surprised that, uh, actually what’s driving a lot of science is actually ideas that come from whoever you meet in the street.
Catherine Price: Huh!
Dr. Nir Uriel: So some, sometimes a great idea starting by watching something that is completely not related and trying to take it into your direction. So I'm actually, I'm sure that I will get a lot from you, Catherine. I trust you.
Catherine Price: Okay, All right. Well let's kick this off! Can you tell me a little bit about what you do, what your specialty is?
Dr. Nir Uriel: I'm specialized in a disease that, uh, is a tough disease to handle: heart failure. Heart failure is, um, one of the most common disease in United States with more than 8 million people living with heart failure here in the United States, more than 24 million people worldwide with heart failure. Unfortunately, it's also the disease that is the most
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common disease on a death certificate in the United States.
Catherine Price: Hmm.
Dr. Nir Uriel: Let me give you some grim statistics, a little bit about what's really going on in the United States. Only the minority of heart failure patients in the United States–probably around 8%--have been treated by heart failure specialists. And only something like 20% of the heart failure patients are being treated by cardiology in general.
Catherine Price: Wow.
Dr. Nir Uriel: So the majority of the patient doesn't get to the right people to treat them. What's so amazing with this disease that if you treat it right, you actually change all the course of this disease. If you don't treat it, it's devastating. But if you get involved, it'll always be there, but they can live with it, a normal life and, uh, a long life with uh, being with their family, friend and do whatever they want to do.
Catherine Price: I mean, that's amazing. But can, can you gimme a sense of what the advances have been in the past decade or so with mechanical devices, like ventricular assist devices,
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that have allowed you to, to get to this point?
Dr. Nir Uriel: So let me take you a little bit back in time. We develop, um, continuous flow LVAD left ventricular assist device, and uh, those LVADs actually have a continuous flow. Our blood in our body is pump, and the pump is, we have heart rate and it's going up and down, up and down, a continuous flow that instead of having a heart rate of 80 beats per minute, we have a pump that is rotating in speed something like 9,000, 10,000 revolution per minute. So of course you cannot feel the pulse. What you're going to have is a continuous flow because it's so fast.
Catherine Price: Hmm.
Dr. Nir Uriel: As a result of it, part of the problem of those pumps, they could have developed actually a clot inside of those pump.
Catherine Price: Gotcha, so you were concerned about clots actually in the devices?
Dr. Nir Uriel: Yes, and the problem was how to diagnose those clots because those pump make from metals, so of course, no x-ray or nothing can go inside and see what's going on in the pump.
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And I remember I was driving my car and I start going uphill, and I had to push more on the gas in order to maintain the same speed. So actually I thought to myself, what is, this is what we need to do with the LVAD in order to learn if there is a block inside of it.
Catherine Price: Hmm.
Dr. Nir Uriel: Because if there is a thrombus inside of it, in order that the pump will maintain the same flow capability, I will need to increase the speed much more in order to overcome this flow. So actually we developed the RAMP test, meaning ramp up the speed of the pump and see how it change the flow. If you, despite increasing the speed, you have the same flow, it's meaning that the pump is obstructed.
Catherine Price: Huh.
Dr. Nir Uriel: And actually we develop this and we create a mathematical equation, and if it's a normal pump that doesn't have any obstruction, you increase the speed, you get more flow, increase more and more flow, more flow. And we saw that it'll be linear and then we can create
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a slope.
Catherine Price: Huh.
Dr. Nir Uriel: But it all start by driving a car and trying to go uphill.
Catherine Price: I love the idea that your brain in some way made the connection between your foot on the gas and what might be happening in someone's heart and how to figure out if there might actually be some kind of blockage. That's really interesting.
Dr. Nir Uriel: It became one of the key studies that teach us how to detect device thrombosis. It was used all over the world, not only all over the country, to detection of device thrombosis. People start doing ramp test. I remember I, the first time after I published a paper, I got a phone call from Norway,
Catherine Price: Uhhuh,
Dr. Nir Uriel: And uh, they said, ‘oh, we want to talk to you. We did this ramp test, but we don't know how to read it.’ They sent me the ramp test and said, ‘oh, it seems to be that there is a pump thrombosis.’ They took the patient to the operating room and there was a pump thrombosis to fix it, and they called me after and I felt wow, this is actually can touch patient without touching the patient. It's not your patient that you taking care, it's patient that you take care in so many different places because of methods and technique that you can develop.
Catherine Price: Wow.
Dr. Nir Uriel: So
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that's what is how it originally was born, but it's actually take its own way. The ramp test itself is something that we, the first paper was published in 2012, so more than 10 years ago, and it was to detect pump thrombosis. But from there we understand something much more important than detect device thrombosis. Eh, the current situation is that what ramp test allow you is to set the right speed.
Catherine Price: Okay, so the RAMP test doesn’t just detect clots, but you actually use it now to set the right speed for the pump. So why’s that so important?
Dr. Nir Uriel: Think about yourself. You're now sitting in the studio and you're talking to me, you’re very relaxed. You have a cardiac output of five liter, but then you are going to go to a little jog, and you need a cardiac output of to 10, 12 liter, and then you're going to sleep and you need only 3 liter. Our pump run the same speed all the time, so how can we find a speed that will give you enough comfortable to be at rest,
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to be at exercise, and what is the right speed that will be associated with the reduce of those adverse events that I start talking about. So the ramp test that was born originally to detect device thrombosis turn shape, and now is a test that we set the speed up.
Catherine Price: Ohh.
Dr. Nir Uriel: We identified what is the right speed for the patient because we learn how the heart is behaving each one of the speed. We look at the heart from an echocardiographic perspective, what happened to the size of the heart? What happened to the function of the valve during this change? Parallel to that, we have a catheter inside of the heart now that will measure the pressure and we learn where is the optimal pressure setting for this specific patient. We can significantly reduce the rate of adverse event and heart failure relation admission.
Catherine Price: Wow. And I understand since you started your research, you’ve refined how the pumps were actually constructed so that bleeding and clotting
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are not as much of a problem as they used to be. So your patients are actually living a lot longer with their devices, so can you tell me about those advancements?
Dr. Nir Uriel: Yes, we developed this pump that's called HeartMate3.
Catherine Price: The HeartMate3, okay.
Dr. Nir Uriel: It's a completely magnetic levitated pump. What does it mean? It mean that there is a cage and there is a motor inside the cage. The motor that rotate in speed between 4,000 to 6,000 or 7,000 revolution per minute doesn't touch anything.
Catherine Price: Oh.
Dr. Nir Uriel: It's rotate inside of a magnetic field. So if I wanted to think about it as something similar to that, think about the bullet train that exists in Asia and in Europe. The bullet train can ride so fast, 280 mile per hour. Not like the, the Amtrak train that we have here is because those bullet train actually doesn't touch the, the rails, there is a magnetic field that create,
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and they go with this magnetic field. Because of it, there is less friction. Friction is a source of heat generation. Protein can denaturate in heat.
Catherine Price: Ohh.
Dr. Nir Uriel: A lot of thing can happen to the blood in heat. So the HeartMate3 is a completely magnetic levitated pump that have a motor rotated inside of the cage, doesn't touch anything and because of it, there is no heat.
Catherine Price: Huh!
Dr. Nir Uriel: There is nothing that happen inside of it that can, uh, destroy those blood products.
Catherine Price: Wow, okay. So, so what effects has using that pump had on your heart failure patients?
Dr. Nir Uriel: So we just published in the JAMA paper, the five year survival of the HeartMate3.
Catherine Price: Mm-hmm.
Dr. Nir Uriel: And I have to admit, it start to be mirroring what we can see in heart transplantation. We need to remember that those patients are much sicker than the transplant patient. A lot of them were declined transplantation because they're too sick or because they're too old.
Catherine Price: Oh, really?
Dr. Nir Uriel: But despite that, the survival was amazing, uh, outstanding.
Catherine Price: I mean, that's just all amazing.
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Just watching you talk about this, you're glowing as you're describing how you feel about these advancements. And it's just, I'm getting very excited about heart failure treatments.
Dr. Nir Uriel: I have to say. It's, it's exciting. It's exciting to know that when you come, you know what, I'm always afraid someone will come to my office and I will say to him, ‘you have this disease. And I don't know what I can offer you and I don't have anything to offer you.’ Yes, I will escort them and I will walk with them through the journey of their disease and making sure that they have someone next to them that can give them the information they need and the emotional and social support together with their families. But I want to be the one not only doing that, I want to be the one that helps them have a long life, helps them enjoying their life. Those technology enhancement change the way we’re able to treat our patient.
Catherine Price: So tell me more about, you know, how things are changing in transplantation in particular
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when it comes to those technological enhancements. I mean, especially in regards to how you can tell when things are going wrong.
Dr. Nir Uriel: Yeah. Transplant is a magic. It's something very magical. You know, you take the most devastating thing that can happen to a person. His life, his death, and you take something from him, and you actually save someone else and give another family an opportunity to be with their member. And the challenge is that the body always want to reject whatever is not own. We love only ourself. We don't love anyone else beside ourselves. So we want to reject. So immunosuppression is the key element that changed transplantation. It's all changed in the eighties when eventually a medication called cyclosporine was developed that actually really help us control the immune system in a way that you still function enough to fight infection, malignancy, but prevent the rejection of it.
Catherine Price: Mm-hmm.
Dr. Nir Uriel: The challenge that we still rejection can happen and because of it, patient need to be monitored
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very closely. So the way they've been com– monitor is actually receiving, um, biopsies. When I was trained, we did 17 biopsy routine in the first year of every patient.
Catherine Price: Wow. 17 times. They had to come in.
Dr. Nir Uriel: They had to come in the first month every week to the cath lab. We have to go to catheterization, into their heart, take four pieces of their heart and send it to pathology.
Catherine Price: Wow.
Dr. Nir Uriel: Think about the stress those patients have to go through. Despite we think that we are the most gentle, and I think that whenever I'm in the cath lab and I'm doing this procedure, I'm sure that I'm the gentle guy in the world, but I'm sure nobody want to lie down over there on the table and get his biopsy.
Catherine Price: No, I know. I think no matter how gentle you are, if you're taking a piece of someone's heart out, it's gotta, it's gotta be traumatic on a lot of different levels.
Dr. Nir Uriel: And this can have also complication this procedure.
Catherine Price: Mm-hmm.
Dr. Nir Uriel: But in the last few years, there was a significant transformation by us being able to test the blood and see what
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we call cell-free DNA.
Catherine Price: Oh, okay. Right. I remember hearing that being able to test patients using cell-free DNA was a really big breakthrough for you. So can you tell me more about how that actually works?
Dr. Nir Uriel: The DNA is sitting inside the cell. So when it's outside the cell, it mean this cell die. All of us have cells that die every day. That's part of nature of life.
Catherine Price: Mm-hmm.
Dr. Nir Uriel: But suddenly, if there is an area that will die more, there will be more of it. We have a DNA. The donor have a different DNA, so if we can identify how much of the DNA that we found in the blood is not a DNA that belonged to us, it's mean that it have to come from the donor.
Catherine Price: Huh.
Dr. Nir Uriel: So if this level is elevated, it's mean that the donor going through a process that the cells of there die and the process most of the time will be rejection.
Catherine Price: I see. Okay. So you're saying you test to see if there's more dead cells than normal, and if those dead cells are the donor's DNA, then it means a rejection is
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probably taking place.
Dr. Nir Uriel: Yes. It's completely transformed the way that we do our transplant today at NewYork-Presbyterian. If you get a heart transplant, you get only four biopsies.
Catherine Price: Wow.
Dr. Nir Uriel: And all the rest will be only cell-free DNA and if necessary we’ll do that. We sometimes do even less than four biopsy.
Catherine Price: Wow. And I mean, understand that you've adapted post-transplant medication, too. So can you tell me about that?
Dr. Nir Uriel: The main problem of heart transplant is what we are doing after. We are so afraid of rejection to give a lot of immunosuppression. And it's true because we don't want rejection.
Catherine Price: Right.
Dr. Nir Uriel: But, but there is going to be a lot of people that are not going to reject so fast. They don't need so much immune suppression and immunosuppression have a big price.
Catherine Price: Huh.
Dr. Nir Uriel: Malignancies and infection. And I said, ‘maybe this test can guide us how much immunosuppression we should give
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to the patient, and maybe we can identify the patient that are low risk, give them less immunosuppression.’
Catherine Price: I mean, that's, that's amazing. Because like, what I'm hearing you say is that you're not just currently able to get a sense non-invasively of whether the body's protecting the heart, but you're saying you're now working to personalize immunosuppressive therapies for transplant patients so that you're, you're not just like blasting them, you're actually titrating the medicine.
Dr. Nir Uriel: You, you just used the right words: Personalize.
Catherine Price: Mm-hmm.
Dr. Nir Uriel: We need to stop treating everybody as the same. We have to do precision medicine, personalized medicine. That's what we have to do.
Catherine Price: Huh. I mean, that's just mind blowing to think about the implications of that just across all fields.
Dr. Nir Uriel: Oh, it's exciting. It's exciting. And that's the reason I'm saying that it's exciting and that's the reason we need more new people that think different. We need people that are actually willing to challenge the paradigm.
Catherine Price: Yeah. And you're also using technology to challenge the paradigm of how patients receive
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care too, right? I mean, like with your remote patient monitoring program. Can you tell me a bit about that?
Dr. Nir Uriel: Yes, you're right. Uh, nobody want to sit in an office of a doctor for two hours waiting for his appointment to happen, so we establish a remote monitoring program, a way to handle the heart failure patient remotely. I'm not going to be able to see you and physical exam you, but it doesn't mean that I cannot have a lot of information about what's going on with you.
Catherine Price: Mm-hmm.
Dr. Nir Uriel: So today we are very fortunate. There is a lot of technology that we can put in the patient or in the hand of the patient. So let me give you an example. It can be as simple as a scale and a blood pressure cuff and a video chat as we are doing now, or as sophisticated–this was something that I like to do a lot–I can put a tiny, tiny chip in a size that is less than a dime and I can put it into the pulmonary artery of the patient
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in a procedure that take 45 minutes and very simple.
Catherine Price: Huh.
Dr. Nir Uriel: And when the patient go home, every morning, when he wake up, he lie on a special pillow that I give them and this tiny chip that I put serve as an antenna, measure the pressure in the pulmonary artery, send it to the pillow, the pillow send it to the cloud, and I have my team of PAs looking at those numbers and I say, ‘if the numbers are in this range, Wonderful. If it's too high, change the medication. If it's too low, change medication. If it's completely out of range, call me and let me know.’ We call this CardioMEM.
Catherine Price: CardioMEM…
Dr. Nir Uriel: Yes–
Catherine Price: Okay.
Dr. Nir Uriel: And this is something that we do a lot in NewYork-Presbyterian. Just to give you an example, we just analyzed our data a couple of months ago and we were blown away in our CardioMEM program. We reduced the rate of heart failure admission by 64% and we said, ‘wow, this is really changing patient life.’ They don't need to be admitted. They can be measured, they feel better,
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and they're doing much better.
Catherine Price: That is really amazing that you could actually monitor heart failure patients from home. But it also makes me think, so those people obviously know they have heart failure, but I was reading something about how you're doing work using artificial intelligence to somehow identify patients who have heart failure, who don't even know it yet. Can you tell me more about that?
Dr. Nir Uriel: So everybody have the same electronical medical record. It's called Epic. Epic have so much in it that we don't see that we can’t see because as I said, there is so much information. So what we decide of doing, we create an analytical program based on analysis on thing that we know that actually tell you that you have heart failure before something happen. If the patient have a low ejection fraction, if the patient have a blood test called BNP that is elevated, if someone is using high dose of IV diuretics.
Catherine Price: Mmm.
Dr. Nir Uriel: So we're creating mathematical algorithm that can identify the patient.
Catherine Price: Okay. You mean like it identifies patients
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with these warning signs for heart failure?
Dr. Nir Uriel: Yes. And uh, when we launch it, we launch it in Brooklyn Methodist. It was the first hospital and in the first day we did it, we identified double the amount of patient that we thought were in the hospital with heart failure.
Catherine Price: Oh, wow.
Dr. Nir Uriel: So, so, what we said is that our heart failure specialist in Brooklyn Methodist will go to those patients, see them at least once to see if the computer is right, computer is wrong. The computer was right in 73% of the cases, so actually pretty good.
Catherine Price: Wow. So what do you think going forward, this might be able to help you do, is it not just about predicting, but would this actually affect the way you treat patients?
Dr. Nir Uriel: It's going to take us to a new direction that is a little bit imaginary. So to use this artificial intelligence and to help us after we identify the patient, see if together with the computer, of course with our input, we can identify the right route for this patient, the right management track
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that we want this patient on.
Catherine Price: I mean, it’s really interesting to think about because you know, there's so much discussion about AI right now, and on the one hand that sounds absolutely amazing, but I would imagine that you probably have peers and patients who are resistant. So what's your take on that? How should we be thinking about this?
Dr. Nir Uriel: This is the revolution that we are at right now. And in medicine you have sometimes two choices. You can stand still and say, this is the way we work and this is how we are, or we need to accept the changes that happen in life.
Catherine Price: I mean, that sounds like that is foundational to your philosophy of how you think medicine should be practiced. You know, being open to change, being humble about how you're practicing medicine, and I was wondering if you could tell me a bit more about your philosophy towards treatment.
Dr. Nir Uriel: Yes, you're right. This is go-to my philosophy about medical care. Medicine historically was based as a one-on-one profession. It's like a combat fight, one-on-one, you with your patient and you alone. However,
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then it's only your skills, and yes, they're good and you are very talented, but you're limited. In a world that has so much information and knowledge exists around you, uh, it's almost impossible to cover all bases. And, uh, so my belief in medicine is general. That is, it's a team approach.
Catherine Price: Gotcha. So what does that team approach actually look like in practice?
Dr. Nir Uriel: What's unique in NewYork-Presbyterian, that it's not only one center. Uh, here at NewYork-Presbyterian we build a mega center for heart failure.
Catherine Price: Mm-hmm.
Dr. Nir Uriel: We have eight adult hospitals that are part of it. We are the biggest heart failure, uh, team in the country with more than 32 board certified heart failure attending. There is a lot of depth into this and experience. In any field of heart failure from heart failure, reduce ejection fraction throughout preserved ejection fraction, from heart transplantation, mechanicals to support cardiac amyloid, pulmonary hypertension,
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we have experts in each one of those that actually devoted their life. So when you combine all of this together, in almost every piece of information, you will have someone that will have what to contribute. You create teams.
Catherine Price: Huh.
Dr. Nir Uriel: These teams have the ability to tackle much more, in much more challenging situation and actually to bring more, uh, tools that will be able to resolve those situation. And if you work in a team, and you don't work as an individual, then you actually can make a big difference. I think that if you take your ego aside in medicine in general, you can provide a little bit better care to your patient. I think the main element in medicine have to be that it's about the patient. This is not about you in any way, shape, or form.
Catherine Price: Hmm.
Dr. Nir Uriel: So by doing it as a team, you may be able to provide a better care to the patient.
Catherine Price: I love that on so many levels. It's just so refreshing and wonderful to hear your perspective with this deep humility, uh, in terms of your role and it’s coupled obviously with deep skill and competence.
Dr. Nir Uriel: Think about it. The most important thing that we have in our life is our body, so when someone came to me and sit in front of me and he share with me the problem that he have now, and I understand this problem is not a small problem, this is a life-threatening problem, and he trusts me with that, I need to do everything that's right by him or her. So there was a record that came to my, uh, office of a patient that want like a third opinion that you need a transplantation. I look at the record and I say, wow, this is a young man, very young man. I think during that time he was only 28 or something like that.
Catherine Price: Oh, wow.
Dr. Nir Uriel: And yeah, he had a congenital heart disease with multiple surgery already in him. He also had type 1 diabetes.
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Catherine Price: Oh.
Dr. Nir Uriel: He was already blind. He born blind and uh, he was rejected from all, uh, two other centers for transplantation, and they live very, very far away. And I didn't feel it's fair for the family to come so far that they hear another rejection. So I remember the first day that they step into my office with, um, a cane, you know, because he was blind with his mother and stepfather and, um, we start talking. And I just fell in love with him and the family and the situation. So in order to overcome all those surgery that he had to do as a baby, and you know, baby wanted to peer everything, so he had to be tied as a baby.
Catherine Price: Oh.
Dr. Nir Uriel: So the way that his family–
Catherine Price: You mean like tied down so he wouldn't actually disturb his own sutures in his–wow, uh huh.
Dr. Nir Uriel: Yeah. So the family, the family, what they did, they play music to him, so he will calm down. So they play country music and
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he became a country musician.
Catherine Price: Oh wow.
Dr. Nir Uriel: And he opened, he opened to Kenny Rogers and Loretta Lynn, and he really became a musician despite being blind, type 1 diabetes, heart failure and all of this, and I said, ‘I don't give a damn. We are going to transplant this guy.’
I brought him to the committee something like seven time, and every time everybody said, ‘Nir is crazy, he is young and he is not knowing what he's doing,’ and, and every time I fail to convince the committee, but I decide that I'm going to do like one by one, I will go to each one of the committee member and I will rally them to be on my side.
Catherine Price: Oh, you, oh, you had a whole campaign. Oh, that's funny.
Dr. Nir Uriel: I did it and we transplant him.
Catherine Price: Wow.
Dr. Nir Uriel: He waited in the hospital almost a year for transplant because he had so many antibody… and I still see him. We are more than 10 year after. He's amazing. He's inspiring. The family is inspiring and you learn
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never to turn down a case because of the record and always to meet the patient. And since then I never, I always, if someone want to see you, I will always see someone because to see how they look. So yeah,
Catherine Price: I just, I just had to do a little, a little eye wipe after that one, so...
Dr. Nir Uriel: Yes, and, uh, I have a very bad habit that, uh, a lot of my patients have my cell phone, but, uh, they know what to send, and they just make me smile. Sometimes when you have a tough day, you look at this and he said it was worth it, but this is what you know, advanced heart failure is all about because it's life and death in those relationships. When the patient is coming to my clinic or I'm doing a video call with him, actually we open our life to each other and, uh, of course the patient much more. You build on it. It's not a one visit, it's not two.
Catherine Price: Hmm.
Dr. Nir Uriel: If you do it right, as I said, those patient can live a very long life and, uh, there is nothing more rewarding
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than to see them achieve their own dreams and what they want to, to do.
Catherine Price: That's amazing. I, I, It's just amazing. Well, thank you. Thank you so much for inviting me into your life for this conversation. I've really, really enjoyed it.
Dr. Nir Uriel: Thank you. I know I, I had a good time. Thank you very much.
Catherine Price: Thank you so much to Dr. Nir Uriel for speaking with us today. His empathetic approach and personal commitment to his patients really inspired me, and I can’t wait to see where he takes his research next.
I’m Catherine Price; Advances in Care is a production of NewYork-Presbyterian hospital. As a reminder, the views shared on this podcast solely reflect the expertise and experience of our guests.
To find more amazing stories about the pioneering physicians at NewYork-Presbyterian, go to nyp.org/advances.
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