Stem Cells in Heart Failure with Dr. Emerson Perin

How can we utilize the regenerative stem cells already found in the human adult body to combat the effects of heart failure? Dr. Alain Bouchard discusses this cutting edge realm of medicine with Dr. Emerson Perin, director of the Center for Clinical Research at the Texas Heart Institute.

Transcript

Announcer
This is the MyHeart.net Podcast. This show is produced by Dr. Philip Johnson in conjunction with VitalEngine.com. Please welcome your host, Dr. Alain Bouchard of Cardiology Specialists in Birmingham, Alabama, at St. Vincent’s Medical Center, part of Ascension.

Dr. Alain Bouchard
So, welcome to our podcast on the stem cell in heart failure. Today, we’re gonna—we have a very special guest, a good friend, Dr. Emerson Perin, who’s director of the Center for Clinical Research, director of stem cell center, and also medical director of the Texas Heart Institute in Houston, Texas. Emerson, thank you very much, and welcome to MyHeart.net.

Dr. Emerson Perin
Great, it’s a pleasure to be here with you.

Dr. Alain Bouchard
Thank you. So today in our podcast, we’re going to discuss first about heart failure, decompensation, and maybe what happens, why does, you know, the heart decompensate? We’ll talk after that about the stem cell, the type of stem cell that we use, maybe, for the treatment of the heart failure, and we’ll discuss one of the largest trials in stem cell and heart failure with Dr. Perin, and, you know, see what the results are.

Let’s talk about heart failure a little bit. We know that heart failure patients can be doing well for many, many years, 10, 20 years, but when they start decompensating, and require hospitals, hospitalization, require hospital admission, usually it really affects their prognosis and increases their mortality within the first year at about 20%. Five year mortalities is like 50%. So it’s a really big change. Tell us a little bit what happens when the heart start failing and decompensate.

Dr. Emerson Perin
Yeah, so… And the heart is the number one killer in the world, so this is truly an important problem for us to concentrate on. As you’ve alluded to, the heart tries to adapt to injury, usually, usually it’s injury from coronary artery disease and heart attacks. And by changing its shape, enlarging, but many of these changes wind up to not help, and that sends the patient into a sort of progressive spiral of having multiple hospitalizations. And unfortunately, many patients die.

And it’s interesting because over the years, really, the medical community has developed an incredible number of treatments for heart failure. And we have a lot of medicines that actually avoid death and help prolong life. But up until now, we weren’t able to sort of address the more fundamental issue behind heart failure, which is inflammation. So I think we’ll talk about that, and how cell therapy really opens a new door on being able to treat heart failure from a completely different perspective than all the medicines that we have available today.

Dr. Alain Bouchard
That’s great. Let’s talk about these stem cells, Emerson, if you don’t mind. We know that stem cells are key to the next generation of medicine to help with tissue repair, organ repair, personalized medicine, bioengineering and pharmaceutical development, even gene therapy. So let’s talk a little bit about what is a stem cell? What are the different types of stem cell? And what type of stem cells do you think we can use for the treatment of heart failure?

Dr. Emerson Perin
Yeah, so that’s a great place to start. Well, stem cells, their fundamental property is that they can self-renew. And so—and it’s very important to know that in every organ in the body, there are stem cells, we didn’t used to know this. And so we have an incredible healing power already inside our bodies that is as a source that needs to be explored to approach disease and aging and other things.

And so, I always say that everybody on this planet is made of two cells, you know, so if you can make a person, you can certainly heal the tissue and do other things. It’s just a matter of, which is tricky, figuring out how we’re going to do this, but it’s not a question of will this work. It works. The question is, how do we make it work? And so that takes a while and we keep working at it.

Dr. Alain Bouchard
The treatment of heart failure, what best stem cell do we have? I mean, I know you, you’ve done a lot of work in that field, particularly, I think you’ve been involved in stem cell in heart failure for like 20 years.

Dr. Emerson Perin
(laughs) Yeah.

Dr. Alain Bouchard
Even somebody in Brazil, right?

Dr. Emerson Perin
Yeah, that’s true, we treated the first, you know, human with heart failure with stem cells back in 2001, in Brazil. And at that time, we were using a fairly simple product, which is sort of filtered bone marrow cells called autologous bone marrow mononuclear cells. And over the years, we have attempted using different cells, some specifically selected from different tissues. And we’ve learned a lot.

And we’ve kind of come from an initial, more naive notion that we just kind of threw the cells at the problem, and maybe some magic happen, to a much better understanding of the mechanisms at play, and I would say that today, the best cell that we have against—to treat heart failure is an anti-inflammatory cell, and that the mesenchymal cells are fantastically anti-inflammatory, and, very importantly, they can read their environment.

So they have those receptors on these cells that detect the environment they’re in, and if they see, for example, they’re in the middle of a tissue that has a lot of inflammation, will they immediately send out signals and proteins and different things to affect and change that inflammation. And we think that that is what is really helping in the clinical trial, when we put these cells in an inflamed heart, and we see that most of the benefit is in the patients that have inflammation, that they can turn that around.

Dr. Alain Bouchard
So just to be clear, I mean, from a stem cells perspective, you have the embryonic stem cell that divides itself, and then you have the adult stem cell, that mesenchymal cell that you were referring to, right? That’s—

Dr. Emerson Perin
Yes, yeah. So absolutely, you know, there’s so much power in the stem—in adult stem cells, we don’t need to even think about getting into any issues with embryonic cells and killing babies, or God knows, none of that, the cells that we each have in our own tissue have plenty of power to do a lot of good things.

Dr. Alain Bouchard
So let’s talk a little bit about the study that you and I were involved in. I mean, you were the international principal investigator, you know, the DREAM-HF clinical trial, probably one of the largest study of stem cell in heart failure. Can you tell us a little bit about this, Emerson?

Dr. Emerson Perin
Yes, absolutely. So yeah, it is the largest trial of cell therapy to date in heart failure, and, boy, we assessed over 1100 patients and randomize 565 patients, and these patients either received actual mesenchymal cells, which were directly injected, as you well know, into the heart. We do it like through a catheterization procedure, the patient goes home the next day. Or they received a scripted procedure in which we did everything but not really mapping the heart and inject the cells into the heart. And we follow these patients for a mean of 30 months. So that’s almost three years, so we really got to see what happened with the patients, both the population that got the treatment and the patients that didn’t get them.

Probably one of the most dramatic findings, when we looked at the results was that there was a very significant difference in events, such as heart attacks and strokes. So if you had gotten the stem cell treatment, you had a 65% reduction in the occurrence of heart attacks and strokes. 30 months out from this single treatment in which we injected these mesenchymal cells into the heart muscle. We also looked at composites which are commonly looked at for heart failure, including cardiac death, and MI and stroke. And that was significantly reduced as well.

So then we tried to think about, well, we know that these cells are anti-inflammatory. And so knowing that we had, in the beginning of the trial, dosed CRP, which is a common blood test, and it’s a biomarker of inflammation, and we then looked at the population of the patients that had elevated CRP, or that had ongoing inflammation in their bodies, and people that had low CRP, and lo and behold, that really has shown us the mechanism of how cells work, because all of the benefit was in the patients that had an elevated CRP that received stem cells. So, that’s just…sort of for the first time, really confirmed to us that in heart failure, if you select patients that have inflammation, with these cells, you can improve their outcomes. And I’m talking cardiac death, stroke, and heart attack.

Dr. Alain Bouchard
Obviously, that’s a study that’s going to be published pretty soon. It seems like in the patient that had more advanced heart failure, the benefit were not quite as pronounced. I mean, do you think it’s a matter of like, maybe the heart failure is more like burned out, and you think we need to intervene a little bit earlier in the heart failure with our stem cell?

Dr. Emerson Perin
Well, when we looked at these patients in terms of functional class, we saw that there was a significant benefit in cardiac mortality, in not dying, if you had a less advanced form of heart failure. So class 2 versus class 3 patients.

And we hypothesize that, really, there is more viable tissue, those patients are earlier on in their course, and the cells, when you put them there, can interact with the environment and still perform better than if you put them in sort of the end stage of heart failure, where there’s less fertile ground, if you will, for the cells to have an action.

So we think that optimally, if we can, and this makes a lot of sense, and is kind of like what we want to do, and what our patients would want also to happen, is to be able to treat people early on. Well, so we select the inflamed patients, we treat them early on, we’ve seen enormous benefit as we go forward.

Dr. Alain Bouchard
Seems like for the last 50 years or more, you know, we’ve been focused on treating patients with heart failure, mostly focusing on neurohormonal, you know, system, you know, with the ACE inhibitors, and now, you know, the Sacubitril/Valsartan, it seems like this study really kind of uncovers a different mechanism that is very important in the development and the compensation of the heart failure, that is, the inflammation, you know, that you very clearly exposed. Even some previous study had not shown that much effect for the different anti-inflammatory agents that were used. Maybe it was not powerful enough. Maybe the stem cell is a better way.

Dr. Emerson Perin
Yeah, so you’re absolutely right. So there have been three prior studies, and really, maybe a fourth one, but three prior studies, studying anti-inflammatory treatment in heart failure that were negative, actually, they were stopped ahead of time. They antagonized something called TNF alpha, and they were stopped before they ended because of lack of benefit. And so the community in general, I would say, that the heart failure community thinks, oh, well, there’s no way to really treat inflammation.

And now we’ve really hit on something that…this is what is very interesting, is it treats the inflammation, it does not treat the volume overload. So you talked about, the body compensates, but the heart gets bigger, and you try to do all these things, to make it—the heart failure better. And so all the medicines that we have address, try to block these bad things that the body does to the heart, and actually improves heart failure. But it doesn’t address the primary problem. So we know that Entresto and all these newer drugs that we use, ACE inhibitors, beta blockers, they’re very successful in dealing with that volume overload, and they’re successful in dealing with recurrent hospitalizations for heart failure, but they’re less successful in dealing with mortality and subsequent cardiac events. And there’s a big difference there.

And I think, for the first time, we’re seeing…”Wait a minute, let’s not mix up recurrent hospitalizations, repeat visits to the emergency room with sort of interrupting that what is maintaining the heart failure fire burning in the heart,” and that we can do with cells.

Dr. Alain Bouchard
Interesting, also, I’d like to know a little bit your impression on the reduction of stroke, I mean, the reduction of myocardial infarction and stroke, how do you see this kind of remote effect on the cerebral circulation?

Dr. Emerson Perin
So that’s very, very interesting. So these cells, they have an action…so when they get activated, when we put them in the heart, they get activated by—let’s say that the patient has inflammation going on. They’re activated and they put out signals which circulate throughout the whole body. And atherosclerosis, which is the buildup of blockages in the hearts causing heart attacks, but also in the brain, when they occlude, causing strokes, are a consequence of inflammation in plaques inside the arteries. Well, we can clearly see in this study that when you give this cell treatment, that anti-inflammatory effect reaches beyond the heart and to the large blood vessels in the body. So we see a anti-atherosclerotic effect by reducing inflammation in large vessels. And that’s how I think we can explain this decrease in heart attacks and decrease in strokes.

Dr. Alain Bouchard
Perfect. Well, you know, I think we learned a lot from that study, we learned that, you know, first of all, it’s safe. You know, I mean, the patients really tolerate it very well. We learned that maybe we need to kind of intervene a little earlier, and we learned a little bit more about the mechanism of inflammation. So where do we go from here, Emerson? I mean, what is the future? I mean, do we need better stem cell, more powerful? Do we need, like, these exosomes? What’s the future like?

Dr. Emerson Perin
Well, I would say, well, first of all, a very important thing to realize is that cell therapy works in a parallel fashion to all the medicines that we use. So it’s additive. So it’s not like we’re saying, “Oh, we don’t need to—” No, we want—this trial, all the benefit that we saw from the cells we’re on top of patients that were on maximum medical treatment. So it’s additive to the medical treatment. So we want all those good medicines for the volume overload, but then we also want something that gets to the cause and the maintenance of heart failure. So that’s a very important concept.

In terms of the future, well, we are definitely slated to do a confirmatory trial. So now, we have the elements with—this is, we’ve been, you know, for the last 20 years really searching for a path into treating heart failure. We have found it.

And I have the perfect roadmap for a next trial in which—would be very similar to DREAM-HF, that’s fine-tuned a little bit to really highlight and confirm what we’ve seen, that really doing what we think we’re doing that we’re going to improve these endpoints again. And if we can do that, well, then the FDA is going to say, “Okay, well, then this is obviously a very good treatment. And it’s something that can be approved.” So that’s number one on my list is to get a mainstream cell therapy approved for heart failure, and I think these mesenchymal cells definitely are on the shortlist.

As we go to the future, we can think about things that you mentioned, let’s say, more potent cells, and also gene therapy, the combination of cell and gene, the combination of different cells, and we’re really in the very, very beginning of a long, long process of discovery. I’m sure you know, 100 years from now, they’ll look back and say, “Oh, man, those guys, they tried really hard. And now they understand how things work.” But you know, you do what you can with the knowledge that we have, but I think that the future is very bright, I think these cells and other cells, and in combination with gene therapy, really hold a lot of good things to come as we gain knowledge from the things that we do, so… The future’s good.

Dr. Alain Bouchard
Well, as a clinical researcher and cardiologist, I want to follow you and I want to do everything that you do, you know, clinical-trial-wise, because, obviously, you know, you have a very kind of a good vision of what’s the future, you know, for the treatment of heart failure. Emerson, I want to thank you very much. I mean, you know, Dr. Perin, a world specialist in stem cells, particularly in the field of heart failure. Incredible knowledge, great experience, and with a bright future. Thank you very much, Emerson.

Dr. Emerson Perin
Great, thank you. It’s a pleasure being with you here today and talking about my favorite subject.

Dr. Alain Bouchard
Thank you very much.

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