Growth in Growing Heart Valves

Image of anatomical heart

Take a look at the biology, anatomy, and the mechanics of the heart, and learn about the current state of replacement heart valve technology.

Transcript

John: Hi, everyone. Welcome to the latest episode of biomechanics in the wild. I’m John. I’m a Senior Mechanical Engineering major here at Notre Dame, and I’m going to be your host for this episode. I’ll be sharing research and information on our topic today. With me is my sister Christina. She has not too much experience in her subject. How’s it going, Christina?

Christina: It’s going pretty good. How are you, John?

John: I’m doing well, doing well. So yeah, do you have a lot of experience in biomechanics of heart valves.

Christina: So I like to think as a graphic designer that my work is really important to the biomechanics of heart valves. But sadly, I do have no experience in this field. So I really don’t know what you’re talking about. Hey,

John: you know, speaking of graphics, we’ll have a lot of graphics in the show notes at the end of our show, which will be very, very useful to everyone for learning more about how heart valves work. So this episode, as we kind of alluded to, is called growth in growing heart valves. So we’re going to talk about the biomechanics of tissue engineered heart valves, and learn why they’re so useful, particularly for pediatric patients. We’ll first look at the basic biology and mechanics, and then look at how tissue engineered heart valves are being developed right now, this is a really important topic because researchers from the group Williams at all have found that there are as many as 1.2 million heart valve replacements in young and middle aged patients in lower income countries. So any way to make them easier and more successful is very helpful. Also, I should mention that the links to all the sources from this podcast, like I said, can be found in those shownotes. So first off, let’s talk about the biology of the heart. You might remember from anatomy class, how your heart has like four chambers, these are the these are the right atrium, the right ventricle, the left atrium, and the left ventricle. For our listeners at home in the show notes, there’s a link to a webpage from the Cleveland Clinic if you want some nice images to go along with this to help you differentiate if you aren’t familiar, Christina, do you remember some of that? From anatomy?

Christina : Oh, I mean, you know, I don’t really remember too much, considering I never took an anatomy class before. But I do you remember from the lovely show, Schoolhouse Rock, that you have a great song called Circulation. It really teaches you how that blood gets pumped in. You know, I don’t think I learned a lot from it. Nor do I remember much about it. But I do remember sounds a lot like Elvis, so is a, it’s a good jam that I recommend to everyone to listen to.

John: Hey, that sounds awesome. Yeah, we’ll be sure to link to that too, in the show notes so that people can check that out. The atriums, they serve as kind of the welcoming areas of the heart, the blood enters first through here. So the ventricles then are the parts that like contract and really pump blood throughout the lungs and throughout the body. Blood without oxygen first enters through the right atrium, that is pumped by the right ventricle into the lungs. So that’s right atrium, RA to right ventricle RV to lungs, RA to RV to lungs.

Christina: All right, but like how exactly does the blood move from like, the atrium, like to the ventricles is just kind of like plop? Like what is it flowing like a river? Like how does that work?

John: Yeah, so the atriums, they contract but it’s like to a much lesser extent than the ventricles contract, but kind of push a little bit. And then it also helps that the atrium is kind of situated like on top of the ventricle. So gravity kind of pulls the blood down as well. So it drips out. Gotta love it. It works really well. Yeah, it’s very reliable. So blood grabs oxygen from the air in your lungs, and then goes to the left atrium and is pumped by the left ventricle throughout the body. So the left ventricle heart muscle is like really big. And then that whole blood flow, it goes right atrium, right ventricle to lungs, then to left atrium, left ventricle to the body.

Christina: That goes like, right, left body, but like your lungs are in the middle there somewhere.

John: Yeah, so it’s like, okay, right lungs, left body. Yeah.

Christina: Are R L L B, baby?

John: Yeah, that’s the one we can write, we’ll get a get a memorization tool going. So then the left ventricle heart muscle is really, really big. Because the oxygenated blood needs a lot more pressure to get all the way around the body, the blood without oxygen just has to get like to the lungs and back in the heart is like right next to the lungs. But the blood with oxygen has to go like all over the place every every area of your body.

Christina: Okay, so it like needs. Okay, I guess that makes sense. So easy to do a lot more work when it’s trying to push out to your body instead of just pushing right there. I never really thought about.

John: Yeah, and that’s kind of why there’s like two different chambers is because you only need a little bit of pressure to get from the heart, like kind of around into the lungs and back, but then you need a ton of pressure to get from the heart all the way to the edges of the body.

Christina: So like if This was happening in, say, a giraffe, like a really tall animal. It would need a lot, I guess like it would kind of be like, if it works the same way, which I’m assuming it does. I would like to think that it would need like a lot more pressure to shoot up like to the top of the head and the bottom of the feet.

John: I am so glad you asked. Yeah, that’s exactly right. You nailed it. So in like a giraffe heart. They have a really overblown left ventricle because it has to pump that blood. Like really high up exactly. Like you said, there’s any animal with a really large body, you have to do it, but especially one with so much. Gravitational Yeah, energy to overcome.

Christina: Yeah, if there’s like, say, an animal that doesn’t have it just gonna be like a hippo, or like something that’s flat. I don’t know if you know the answer to this, but like, Would it work kind of the same way? Since it still has to go? Like, far but maybe not is like tall? Yeah, it’s still?

John: Gosh, that’s a great question I, I would assume that you would still have, you know, there’s kind of two different forces that the body’s counteracting, when it increases that pressure. There’s the the gravitational force from like, you know, that’s like pulling the blood down, because it’s like, mostly water, in waters pretty dense. So there’s the gravitational force. And then there’s also the friction force. So that’s because like, as the bloods traveling through those vessels and stuff, it would, it kind of wants to slow down, it tends to like, not want to move as quickly. So in our case, in like the case of an alligator or hippo, you would probably see friction forces dominate. And so in general, you probably wouldn’t eat less like less of a pressure difference between the right and the left chambers. But also, you would like you would notice, and the mechanics, you would notice that, like the friction force was a lot more important that it was mostly slowing down to the fraction that it wouldn’t matter as much like what height you were looking at.

Christina: Okay. Yeah. And then like, so for how the blood is moving? Does it just kind of like, is it like a constant flow? Or does it like, you know, like, is it just like, it always just kind of keeps moving? And it never really stops?

John: Or like, yeah, yeah, so it is a continuous pump, in the sense that like, all of the liquid that, like, you know, there’s no, there’s no buildup of blood anywhere, right? So that means that like the velocity, they kind of have to push through the same volume of blood in the left ventricle as the right ventricle, the left ventricle just kind of generates more pressure while doing so. Because you wouldn’t want like, if there was more pressure, or excuse me, there’s more liquid coming out of your left ventricle than like, they’d be more liquid in your body. And then it would like come back around, and it’d be like, more liquid on the other side, right? Yeah, we don’t want that. We want it to be like all the same continuous all the way through. And so in terms of speed, and probably, I would assume it would be really fast near the aorta, and then like, it would kind of slow down near the capillaries and like, near the extremities and stuff. Yeah, cuz you’d have like less energy in general. Yeah, that’s a great question. So just like you have your four chambers in the heart, they’re also for heart valves. The valves make sure that the blood goes like where it’s supposed to go. And there’s at the right pressure for the different areas of the body. Like we talked about that it has those right specifications. And they basically work like doors for the different chambers.

Christina: Did it does it like kind of, is it kind of like almost like a sliding door? Where it’s kind of just, like, open all the time? Or like, is it like, open and close in both directions? Like how, like, what’s it? How does it work?

John: Yeah, so it so the heart valves are really unique in that they kind of have like a, like a cone shape, they kind of come into a point. And so they when there’s high pressure on the side, where they’re supposed to be, like, blood flowing in, you know, kind of push the valves open. But then once there’s like, once blood starts to try and flow backwards, it’ll kind of close itself shut, it’ll like catch on kind of the the tip of the cone. And so yeah, it’s really effective in that way. It only only really permits flow in the direction that it’s supposed to, and it kind of is specified for the pressure that the heart wants it to be at. Yeah, so when you when the ventricles in the heart and atria contract, they cause the pressure that’s needed to like open up those doors, and only works in that one direction. For the most part. You can have like leaky valves, certainly. So there are two doors that are between like the atrium and the ventricles called AV valves. And these are the tricuspid valve on the right side and the matrial valve on the left side. These ones they’re, they’re kind of hard to remember, I don’t there’s not like they’re not directly connected to any like other areas of the body. They’re just both AV valves and then the tricuspid is on the right, and the neutral is on the left.

Christina: I’d like to say that LM goes together in the alphabet. Okay, mutual.

John: That that’s a good point. No, yeah, so l and m are close to each other. T and R are also pretty close to each other, we will take a letter off. Okay, that’s honestly pretty solid. I like that little mnemonic there. Yeah, uh huh. Yeah, solid. Okay, so they’re not that hard to remember. But they’re a little bit more tricky. There are also the semilunar valves, which are their valves or doors that work between the ventricles, and then the rest of the body. These ones are really important because they release the like, the high pressure flow, right, they release, like the sort of the blood that has to get really far somewhere else either has to go or I mean, not that much farther, but like it has to get at least the lungs, or possibly to all those different areas of the body and our systemic circulation. So they’re very, very key. Fortunately, the the semilunar valve names are kind of easy to remember, because they’re named for the tissues or areas of the body that they open into. The pulmonary valve is the door between the right ventricle and the lungs. So pulmonary means like lungs. And then the aorta is the artery that carries blood from your body to the heart. So the aortic valve is between the right ventricle and the aorta. And it kind of that’s the the left ventricle in the aorta. The image of the heart from the shownotes indicates the kind of locations of these valves as well. In these Yeah, in the location of these four chambers in the four valves are important for understanding why like tissue engineering valves are so useful.

Christina: And so key, I would like to point out another great alphabetic conclusion as the aorta goes to the body. So A B sure, like to bring that up again, because I feel like the alphabet has been very helpful in my discoveries today.

John: Yeah, yeah. Honestly, I bet you could tell like all the old biologists that they missed that, because they probably did not know when they went work through the first time. Yeah, that is too funny. I would have thought about it. Yeah, that’s just I guess you will, probably Alright, so um, so anyway, that is the basic rundown of the anatomy and the biology of the heart, that’s kind of where everything is located, what stuff does. So now let’s break down kind of what happens in the heart mechanically. The hearts mechanical function is to create pressure, essentially, fluids flow from areas of high pressure to areas of low pressure, that’s fluids, meaning like, both gases and liquids. So in order for our body to get blood to flow, our our body creates pressure.

Christina: So like, I kind of I understand that from like, a level of reading it in physics and whatever in high school, but like, what is like a kind of, like, good example of like that inaction in everyday life.

John: Yeah. So um, so I think though, the wind is probably a pretty common example, because like, what’s happening there is that there’s like an area of, of high pressure, like a lot of air. And there’s another area of low pressure, like relatively, like fewer air molecules. And so the air like wants to move from the high pressure to the low pressure, it’s kind of just like, like diffusion of a gas, if that makes sense. Yeah. Um, another way to think about it is, it’s just like, there’s like, if you have a, maybe like a pipe, and then you kind of like push on one side of the pipe, then like, that will kind of force the water to move out the other side.

Christina: Okay. Yeah. So then, like, how does the heart then kind of create any of the pressure needed? Like, how, how does it do that?

John: Yeah. So it kind of does what I just talked about with like, the the pipe, or even maybe a better example is like, he went to the dining hall, they have those like, kind of shortcuts that like push slide into each other, right? So if you had a bunch of water in the bottom one, and then you took the top one, and like, pushed it down, it was like, squeeze all the water out. So what the valves will do is they’ll keep the water in or keep the blood in, until the squeezing happens with certain rays. And or like, you know, the squeezing happens such that the blood can move through the whole body or move to the lungs, whichever ventricle we’re looking at at that time. So yeah, so that’s kind of how that how that works. Does that make sense?

Christina: Yeah, that actually makes like a lot more sense.

John: Awesome. Yeah. In the in the heart, just kind of review pressure builds up in that left ventricle and right ventricle, in particular, the atria too, but mainly the ventricles. And the heart does this so that blood will flow from the heart to the lungs, in the case of the right ventricle and from the heart to the rest of the body. In the case of the left ventricle that’s kind of gets it moving. So those valves and those ventricles and like the chambers, they all kind of work together in order to generate that important pressure and motion that we need.

Christina: What would happen if like, one of your like, if a valve like didn’t work like kind of like what would end up happening like I wouldn’t just kind of like close but it flapping flapping like never right? Stay close, like what would happen?

John: Yeah, so there’s a lot different things that can go wrong, you could have a situation where a blood or sorry, a valve is not closing correctly. And so that’s the case, that means you’ll have kind of like some blowback from the heart.

So there are basically two major areas that the heart valves can’t work properly, there’s stenosis, and there’s regurgitation. stenosis is like when the heart valve doesn’t really open far enough, it can be due to like the clot, or it can be just any other sort of kind of pathology or anything else that’s going wrong in that case. And so that’s stenosis is like one way. And then another way is that regurgitation can happen. And that’s when blood kind of flows backwards, like those valves don’t really close properly. So it’s kind of not opening properly, and not closing properly.

Christina: Is there any way to like, fix that if like a valve breaks, like are there? Like, I know that like, I’ve heard, like things I saw on Grey’s Anatomy, once they like I know, they replaced it with like a pig or something. But I didn’t know if that was like a real thing.

John: That is awesome question. No, yeah, that’s a great segue. So the what would happen is we can replace heart valves. And so in this case, you can do either a biological or mechanical replacement. And I’ll kind of break those down in the next section coming up. So like you said, heart valves often break. And it’s pretty clear from our previous discussions how important heart valve function is the flow of oxygen throughout the body. And that’s critical to so many different biological processes. In adult patients we have lots of treatment options for broken heart valves, including mechanical heart valves, which are very cost effective and long lasting, as well as biological heart valves, like from like a pig or from an adult human. That would be highly biocompatible. Yeah, so some of the research showing this there’s a lot but some of its from Williams at all as well, that group I mentioned earlier.

Christina: Would it like, let’s say, hypothetically, right now, my heart valve just like broke? And I go, Oh, now, what do I do? Would it be better for me to get like a biological one or a mechanical one? Like, is there any is there like any research on like, what is better in that situation?

John: Yeah. So there’s been like computational and like, sort of case study based research done on like, what are the benefits and drawbacks of each? One important consideration is that mechanical heart valves require drugs that will, like resist blood clots. Because otherwise blood will like solidify near the valve and clog the valve. Because whatever material it’s made out of, it’s not going to be as good at like, kind of pushing blood away as our native veins and arteries are. Cost can also be a really important driving factor, especially like we talked about some of the people who need heart valve replacements in like lower income countries. An important takeaway that I’ll kind of break down a little bit further is that the balance of needs changes for children who need those like replacement valves. There are some significant issues facing younger patients. Three, in fact, primarily, growth of the patient means that a mechanical heart valve would cause like mechanical stress, and you’d require for the surgery like you have to change it out once every year to because these mechanical valves will not grow with the patient at all, they won’t change in size as the human does. Our researchers from the group, Movileanu et al found that usage time greatly decreases for mechanical heart valves, when using younger patients, because these valves had to be replaced as the patient grew. They won’t get to like, you know, there’s some valves that can be rated for like a really high number of uses, like mechanical valves, but it’s not helpful to people who are going to outgrow them.

Christina: To like biological heart valves go with the patient or is like, is there the same sort of issue of it won’t really grow? Yeah, you get it when you’re younger?

John: Yeah. So as of right now, tissue engineered heart valves like they could grow with the heart of the current research from, like, Movileanu et al, does not directly measure the growth. Rather, they focus on solving those biocompatibility challenges. Which is kind of Yeah, we something is really important to figure out is like, is it possible to develop a heart valve that can kind of take advantage of the biological machinery already in place, we can probably assume that like the only kinds of heart valves that really could grow with a patient would be ones that could interpret those biological cues. I would imagine that like it’d be extremely difficult to manufacture a heart valve that was like fundamentally mechanical, that could interpret say, like a growth factor like a hormone. Whereas if you had like a, sort of like a some sort of allograph like a like a heart valve from another human, that would probably be much more likely to interpret those hormones to take in and like processes biological cues. That makes sense. Yeah, yeah. Additionally, that group found that mechanical heart valves require anticoagulation drugs that would cause a significant burden on younger patients like I talked about, sometimes even daily doses of vitamin K. This is a substantial problem because the patient would have to take these drugs for like the rest of their life, unless they later underwent surgery for a biological valve. older patients can take such drugs with like a standard pharmaceutical regimen, but there’s gonna be a serious financial and medical burden for our young patients. As you understand I’m sure, this is a critical issue regarding the use of these valves. The third major issue for pediatric patients is that collagen is a fundamentally important protein. And like the mechanical behavior of heart valves, really in the performance of like all soft tissues, researchers in the group Oomen et al found that stretching a biological heart valve causes substantial growth and remodeling collagen fibers. Mechanical valves would not experience that stretch. And so they wouldn’t really change properties during like the natural aging process either. We don’t really know the extent of like this remodeling, but we can imagine that like, it could be really important for like long term performance in people in different age groups and different demographics. So all in all, there are like three major issues facing current engineering research for heart valves. The valves are important because their fundamental role in controlling blood flow throughout the body and they make the awesome and impressive heart what it is. Do you have any other questions

Christina: and no, I don’t. Thank you.

John: Thank you. And thanks, everybody for biomechanics in the wild. This is John. And keep checking out those biomechanics in the wild

Transcribed by https://otter.ai

References

  1. Williams et al
    1. Williams DF et al. (2021). “Long-Term Stability and Biocompatibility of Pericardial Bioprosthetic Heart Valves”. Frontiers in Cardiovascular Medicine 8. DOI: 10.3389/fcvm.2021.728577.
  2. Cleveland Clinic (heart anatomy)
    1. Cleveland Clinic. (2018). Heart Valves. DOI: https://my.clevelandclinic.org/health/articles/17067-heart-valves
  3. Circulation, Schoolhouse Rock
    1. https://www.youtube.com/watch?v=1_22fZdI_vA 
  4. Movileanu et al
    1. Movileanu I et al. (2021). “Preclinical Testing of Living Tissue-Engineered Heart Valves for Pediatric Patients, Challenges and Opportunities”. Frontiers in Cardiovascular Medicine 8:707892. DOI: dx.doi.org/10.3389/fcvm.2021.707892 
  5. Oomen et al
    1. Oomen P et al. (2016). “Age-dependent changes of stress and strain in the human heart valve and their relation with collagen remodeling”. en. Acta Biomaterialia 29:161–169. DOI: 10.1016/j.actbio.2015.10.044.
  6. Texas Heart Institute (stenosis and regurgitation)
    1. Texas Heart Institute (). Heart Valve Disease. DOI: https://www.texasheart.org/heart-health/heart-information-center/topics/valve-disease/