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Interviewer: Heart failure is devastating no matter how you look at it. But it turns out that physicians can reverse the course of disease in a small fraction of patients. What makes these people different? I'm talking to Dr. Sarah Franklin who's researching ways to find out. So heart failure, what makes this a particularly interesting problem for you?

Dr. Franklin: So heart failure is the number one leading cause of death in the United States, and it has a significant burden on human health as well as a financial burden. And I think that one of the most exciting parts about studying the heart is that in recent years, we have started to realize that this organ which we typically have thought in the past was not able to regenerate itself or have regenerative capacity, actually is much more intricate than we thought. And we are starting to understand and realize that the heart actually is able to, in some circumstances, regenerate or essentially jump back after disease.

Interviewer: I mean this is just with a certain fraction of patients, is that right?

Dr. Franklin: Yes. So most individuals that experience heart failure or heart disease have two options. Unfortunately, these options aren't very exciting. But if you have a failing heart, you either can have a heart transplant, so have a new heart implanted, or you can have a left ventricular assist device, or essentially a mechanical pump implanted in your chest that pumps for your heart. And as you can imagine, both of these are life changing experiences and neither of them are really something that you want to look forward to.

However, there is a very small fraction of individuals that experience heart failure. But when a pump is implanted in their chest, as opposed to just maintaining function or prolonging life temporarily, their heart is actually able to regenerate itself or recover because there's stress that's actually taken off the heart from the pump. And this is the population that, as you mentioned, is quite small, but it's a really incredible phenomenon.

We didn't use to know that this occurred. And now that we know that actually a heart that's failing that we use to believe could never recover from that, actually some hearts do have this capacity. And if we can identify why and how this happens, then we can potentially understand how we can get more hearts to do this or go through this process. Or potentially just intervene at an earlier stage where maybe a lot more hearts have this capacity.

Interviewer: And so how are you looking at that?

Dr. Franklin: We are very excited to be involved in research to understand this phenomenon. Our lab is primarily using proteomics, a mass spectrometry. And as an LVAD device is implanted in someone's chest, naturally a piece of the heart tissue must be removed for that pump to be placed. And so we are able to take a piece of that tissue and to look at all the proteins that are expressed in the heart. And we look at thousands of phosphorylated proteins, we identify what the protein is. We identify how abundant it is. And then we actually compare between samples, and so this gives us thousands of data points that we can use to create a very unique signature for someone's heart.

Interviewer: So it's that molecular signature that possibly could become the basis of some sort of test to decide who might get this special treatment and who may not, possibly?

Dr. Franklin: Yes. So this molecular signature has a number of advantages. So at this point, the most exciting use of it is that we actually can predict at this point, and we've done this to 10 patients so far, we can predict whether or not they will actually recover from having an LVAD implanted in their chest. And so initially, just having a unique signature, we can kind of think of something similar like a fingerprint. So a fingerprint is made up of many different lines and curves that altogether make a very unique signature that is unique for one individual.

But we can take this molecular signature at the protein level and really identify who will respond and how to these therapies. So initially, there's a predictive power here. But the other advantages of this signature is that by looking at the individual proteins, we can try to understand at a knowledge level what is happening in these hearts. How are they failing? What's the difference between those that can recover and not recover? And how are those specifically involved in the function of physiology of the heart?

So on a knowledge level, we get to understand much more about heart disease and that can allow us to even create better therapies, by targeting maybe specific proteins or pathways.

Interviewer: So when you compare the molecular signatures of those who will just recover and those who won't, how large are these differences? Are there subtle differences, or is it really a striking difference between the two?

Dr. Franklin: So we initially look at thousands of phosphorylated proteins. But our goal has been to create the smallest panel possible that still allows us or gives us predictive power. And so we've reduced this panel down to about 24 phosphorylated proteins that allow us to distinguish between patients who will recover and those that won't.

Interviewer: One thing I wanted to bring out is something that we talked about earlier that instead of you going in with a preconceived notion of what might be different between these patients, you're letting the heart tell you what's different, so it's an unbiased study. Why is that important?

Dr. Franklin: We love mass spectrometry. It's one of the things that we get giddy about in the lab. We have lots of experience with mass spectrometry and proteomics, but we love the fact that it is an unbiased technique. We don't say beforehand we're only interested in this protein or only interested in this pathway, which in some areas can be helpful or in some labs is useful.

But we are really excited about the fact that we can go in unbiasedly and say we have no preconceived notions about what we may find. But we are going to apply this technique that will allow us to just sit back and have the heart tell us what's happening, tell us what proteins are being involved in this disease process. Have the list of proteins that are likely involved, identified through this technique as opposed to us picking or choosing what might be involved beforehand.

One of the things that I get really excited about is how impactful this study could be. As I mentioned, we're in the early stages but I can only imagine if you were in a patient's shoes, if you were the one that was having to make the choice of whether or not to have the LVAD surgery or to try and hold that longer for heart transplant, or where you might actually be listed on that heart transplant list. I can only imagine that that could be really stressful time in your life having to make those decisions.

And our hope is that we'll be able to provide more information or alternatives to actually helping us figure out who would benefit from an LVAD implantation or maybe provide additional information to influence where someone may be on a heart transplant list. And so really the idea of personalized medicine or helping the individual person and having information that would directly impact their specific situation is really what we're striving to do.

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Dr. Miller: You have advanced heart failure. Would you ever need an artificial heart? This is Dr. Tom Miller on The Scope Radio. We will talk about that next.

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Dr. Miller: I am here with Dr. Craig Selzman. He is an Associate Professor of Cardiothoracic Surgery in the department of surgery. He is also an expert in heart surgery and implantation of artificial hearts.
Craig, what types of patients that have heart failure might merit a discussion about having an artificial heart implanted?

Dr. Selzman: I t's actually lower than you think. The reality of it, there is probably about five to six million folks out there, many of those that might be listening that have the diagnosis attached to them of heart failure. But of that group, the folks that have really advanced disease, it's much smaller. Not that much smaller but probably anywhere between two and 800,000 people.

Dr. Miller: Nationally, that's a big number.

Dr. Selzman: It's a big number. It's a big number. And then the folks that really have really bad stuff, it's probably about 80,000 a year. But the important thing to know about that is that everybody thinks, "Well, if my heart goes bad, I'll just get a heart transplant. That's what they do, right?" The only problem with that is there is only about 2000 to 2500 hearts a year. So you can see the disparity right off the bat that if there are only 2500 hearts that are available for transplant for the entire country, and there are 80,000 to 150,000 patients that could potentially benefit, we got a real problem there.

Dr. Miller: Well, we see that with all type of organ transplants now. Whether it's liver or kidney or pancreas or lung, there are not enough donors. But it sounds like the artificial heart is a way for people to have advanced therapy who might not be able to get to a heart transplant right away.

Dr. Selzman: Yeah, that's true and that's how we use not just the artificial heart. Artificial heart is often used to symbolize a lot of things. There are heart pumps or internal or external pumps that support your circulation is used. The artificial heart, the original one, the ones that we associate with Barney Clark and others, actually you remove your existing heart and you put in two ventricles, two pumping chambers that are combined to make a total artificial heart.
The way the majority of patients use . . . about 95% of the folks that need assistance, we use devices that support a single ventricle. And the most damaged ventricle, typically, is the left ventricle. So that's why we developed these devices called LVADs or left ventricular assist devices. That's what we most commonly use.

Dr. Miller: How does a patient with advanced heart failure and the need for surgical treatment make their way to you or a specialist?

Dr. Selzman: There are fantastic doctors in the community that can manage the early stages of heart failure. Early stages are folks that might just be on some blood pressure medicines and they get some shortness of breath, maybe they're put on a water pill that help them deal with that. But what we find is that when patients get a little bit sicker and they're going up on some of these medicines and then even worse, when they are unable to tolerate some of these medicines because their blood pressure is a little bit low or they're still fatigued, these are kinds of patients that we would recommend to be seen by someone with some experience at advanced levels of heart failures.

Dr. Miller: I'm assuming that would include a team perhaps, maybe a cardiologist who specializes in heart failure as well as a surgeon and some others. Is that right?

Dr. Selzman: Absolutely, and the University Utah, we have a team of almost 70 people that are involved in the care of various patients with heart failures, from the not so sick to the very, very sick. But it does require a team to care of all this and dedicated to understanding the particular needs of this group of patients

Dr. Miller: So how would a patient advocate to see someone or a group that specializes in this type of advanced care? They are under the care of their internist or family practitioner. At some point, they may need this specialized care.

Dr. Selzman: Yeah, it's a good question because most people that have various mid-level staging of heart failures, they are not the ones that aren't that sick or the very, very sick-they are kind of that gray zone in the middle-don't really appreciate how bad their heart failure is. And maybe their primary care provider is not maybe fully appreciating the scope of how much disease they have. As such, you are potentially missing some therapies that might otherwise not be offered to you. So, we need to have people to recognize that this disease is rampant and recognize that there are more than one or two medicines that can be used for it.

Dr. Miller: Well, it also seems to me that the earlier the patient would get into a specialist group, the better chance they would have of designing the optimal therapy over time for that particular patient. So it would be better to get them mid-way through the process then later on when things are really going south.

Dr. Selzman: Yeah, I think that's a great point because the way that our group looks at it is we are partners to the providers and the community and the patient, most importantly the patient. So we try to team up with the patient and what the best thing is. At the University of Utah in particular, our scope is 14, 15 states of people coming in. So we have some unique challenges. We cannot be everyone's heart failure doctor. So we work with the group, wherever they are coming from, to try to help that patient to find what the best pathway is.
But I totally agree with you that we'd love to see these patients early on, and we've followed the patients for decades before their heart has actually progressed to the point where it needed something in an advanced therapy fashion.

Dr. Miller: And so these patients, when they do end up with a left ventricular assist device, tend to do quite well over time and the technology now allows these patients to do better, be healthier and people shouldn't really think about the old days. The technology is very different now than it used to be.

Dr. Selzman: We'd love to put on our little quarterly newsletter showing all the pictures of people doing their fly fishing, they're playing golfs, some of these got some moose hanging over them. You name it, you can do it. You can live life and mind you, that by the time we are seeing these patients, most of the people are not living life. They are basically struggling to go from the couch to get to the restroom or couch to get to the refrigerator, and these kinds of therapies give back life.

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Dr. Miller: About 32 years ago, Barney Clark had the first artificial heart implanted here at the University of Utah. We're going to talk about how things have changed since then on The Scope Radio. This is Dr. Tom Miller.

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Dr. Miller: I'm here with Dr. Craig Selzman. He's an Associate Professor of Cardiothoracic Surgery in the Department of Surgery here at the University of Utah, and Craig is an expert in heart transplantation as well as ventricular assist devices, which are the new artificial hearts.
About 32 years ago, Barney Clark was the first man to undergo an artificial heart implantation, and that was here at the University of Utah. Now a lot has changed since then, I think. Dr. Selzman, can you talk to us about what's new with artificial hearts?

Dr. Selzman: Since that time, so much has happened. It's been in two or three different areas, and the first area is just the technology.

Dr. Miller: That's got to have changed tremendously.

Dr. Selzman: It's huge.

Dr. Miller: I remember the pictures of Barney Clark. The pumps were huge. They had to wheel it around with Barney Clark. It was noisy. It was loud. It was terrible.

Dr. Selzman: It's a Zamboni machine. We still have one here in the hospital, if necessary, to clean the ice outside. But the deal now is that we have these pumps so small and they're very patient-friendly so that the patients can actually go home. They can do everything. They can play 18 holes of golf, walking. You name it; they can do it.
The one thing that is a little bit difficult is there's electricity going through this; they're not going for a swim any time soon, but that's even changing. We have pumps now that allow people to have artificial heart support that can actually go swimming with internal batteries and stuff. So it's been huge.

Dr. Miller: So are the pumps still external to the body, or are they within the body now?

Dr. Selzman: They're all within the body. We still have some that are used externally. Those are used for really the sickest of patients that we're really just trying to do whatever we can to save their lives. But in terms of folks that you want to actually go home and regain life, the thing about a lot of this field is that the chances of you having a long life with advanced heart failure is low. Probably the patients we're talking about, less than 10% are alive at two years.

Dr. Miller: I mean, that's as bad as many cancers.

Dr. Selzman: It's metastatic cancer. It's basically the same thing. I use an analogy a lot, and the one thing that the VADs have done in this artificial technology is that it's the therapy that is so much better than chemotherapy, meaning that you can put somebody on with an advanced cancer, and you might buy another two, three year, four months. We're talking about buying five to 10 years. And not only just years, but also quality years. These patients are back with their families. They're going back to work. They're living life. It's amazing.

Dr. Miller: Craig, does this mean that actually having a heart transplant may become obsolete?

Dr. Selzman: Ah, that's a great question, and it's one of the current debates within our community because the life expectancy, the one year survival rate for patients that are getting these machines is almost as good as getting a heart transplant. The problem with heart transplant: great therapy. There are just not enough of them.
For the last 25 years, we've done about 2,000-2,500 hearts a year in the United States, but there are probably 80- to 100,000 folks that need it today. So these pumps have really filled that gap. Early on, because the pump technology wasn't quite so good, you'd have complications. But now the complication rates are actually very manageable and the survival is quite good. One year survival is over 90% right now.

Dr. Miller: I remember in the Barney Clark days that that clots arising from the use of that type of pump were a real problem. That's pretty much eliminated now, is that right?

Dr. Selzman: Whenever you have blood that goes through a washing machine or a Kenmore or a Maytag, it's just not normal. And so we still are faced with this complex problem of hemostasis, thrombosis, and anti-coagulations. For the most part for these pumps, you will be taking some blood thinner medicines.

Dr. Miller: But the risk of having a clot is lower?

Dr. Selzman: It's much lower. I mean, it hearkens back to the old heart valve days where we used to have that had a ball that would go up and down, the old Bjork-Shiley valves and stuff. We don't use those any more, and so the whole field is new.

Dr. Miller: The whole technology.

Dr. Selzman: Yeah.

Dr. Miller: What does the future look like in terms of these devices? I mean, do you see these devices becoming smaller, like calculators becoming smaller and smaller?

Dr. Selzman: Yeah. I think there are two or three things that are going to really make a difference here, and you could actually trace back. If you look at the pacemaker defibrillator field, defibrillators used to be these big giant things that you used to put in the abdominal cavity, and now they're these little things below your collarbone.
So the same things happened in the VAD world. They're getting smaller and smaller, and because they're getting smaller and smaller, the complications are less and less, you're actually going to start putting these things in patients that are less sick to try to get them off this spiral of decline that happens with heart failure. So size definitely better, complication rate less. And then the main thing that's coming from an industrial standpoint is power. So just like you're trying to get batteries in that 747, or what was it, the 757, the lithium battery was the only bad thing.

Dr. Miller: Exactly.

Dr. Selzman: So they're starting to do the same thing with these VADs. And so a lot of the original DeBakey pump, believe it or not, was a collaboration with N.A.S.A. to help do these things.

Dr. Miller: Spinoff technology.

Dr. Selzman: Yeah, so there's a lot of cross collaboration there. The interesting thing I think really where the field is going, it's not so much about the pump because the pumps are getting better and better. But it's about the patient and the biology of the patient. And our goal is not to actually put the pump in to have them have it for the rest of their life or for them to get a transplant, but actually to get better so that we can remove the pump.
So how do we do that? Well, we're going to recondition the heart, probably use other biologic therapies to help us. So the main thing that I see the field going in the next five to 10 years is not so much about a pump, but about a patient that has a bad heart. How do you make that heart better with the assistance of a heart pump so that you can actually remove it so that patients can live long lives that way?

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