Cleveland Clinic Heart, Vascular and Thoracic Research: Our History and Future

Podcast Transcript

Announcer:
Welcome to Love Your Heart. Brought to you by Cleveland Clinic's Sydell and Arnold Miller Family Heart, Vascular and Thoracic Institute. These podcasts will help you learn more about your heart, thoracic, and vascular systems. Ways to stay healthy, and information about diseases and treatment options. Enjoy.

Eugene Blackstone, MD:
Today were talking about research in the Heart, Vascular and Thoracic Institute at Cleveland Clinic. Let me introduce to you this panel. At the far end is Tara Karamlou. She's a pediatric and congenital heart surgeon who came, what, two years ago or so?

Tara Karamlou, MD:
Two years ago. Yeah.

Eugene Blackstone, MD:
...at this point and heads research in congenital heart disease, but also is part and parcel of clinical investigations, which we'll discuss shortly. Next to her is Michael Lincoff who's vice-chair of Department of Cardiovascular Medicine and director of the Cleveland Clinic Coordinating Center for Clinical Research and really oversees essentially HVTI research. Aaron Weiss, one of the new cardiac surgeons at Cleveland Clinic, and he is... Are you getting yet, your PhD?

Aaron Weiss, MD:
It's actually getting submitted…

Eugene Blackstone, MD:
We are trying to force him to finish his PhD with a focus on machine learning. I'm Eugene Blackstone. I head clinical investigations and a full-time clinical researcher with a cardiac surgery research career that dates actually back to 1959 So I'm the old person here on the podium. So let me kick this off with one organizational structural idea. When it was thought that we should become institutes there was a discussion between Mike and me about the research organization here, and it seemed like we had little pockets of clinical trials, for example, in cardiothoracic surgery, pocket... Another pocket in vascular surgery. Mike had his big pocket of it in cardiovascular medicine. And then we were all doing some sort of clinical research and quality organizations like, and we said, "You know, this is not the way to organize things because all the regulatory and other aspects of clinical trials are totally different from, for example, reporting to national organizations about quality and taking care of, why do we have so much bleeding so long, respiratory stuff and the like." So we said, "Let's split this naturally into clinical trials and clinical investigations, and when we have clinical trials going, like we have with the NIH and the like, let's work with the clinical trial group." When we're doing clinical investigations we work the clinical trial group. And I think that has worked, I'd say remarkably well so we're going to start off with Dr. Lincoff telling us as a little more about the organization and research within HVTI.

Michael Lincoff, MD:
Thank you, Doctor Blackstone. As Gene pointed out, the Heart, Vascular and Thoracic Institute does in fact involve cardiology, cardiac surgery, thoracic surgery and vascular surgery, what in many institutions and traditionally have been separate departments, are departments but are all within our Institute and all are within the same structure for clinical research. So we roughly break our clinical research into three main areas. Clinical investigations, which Dr. Blackstone heads and we'll talk about just a few moments, is the group which handles and deals with all of the observational data that we derive from the large population of patients that we take care of at the Cleveland Clinic. Data that either is directly from our medical records that is entered into a specialty specific registries or research specific databases. And this is... These are data that we obtain as part of clinical care and then use to improve clinical care to learn from our practice of medicine.

Michael Lincoff, MD:
The so-called learning health system that the FDA and others have pointed out as the appropriate way that we should be conducting research as part of clinical care. We also have a group known as clinical trials, which across the different departments is the group that conducts studies, prospective studies, studies that are planned and are carried out with enrolling patients at many times to be randomized into different groups of therapies, but of all patients that are undergoing these types of investigations and being part of our investigations within the Heart and Vascular Institute. And that represents a group that of coordinators and financial specialists and project managers about 35 to 40 personnel who then provide the infrastructure for us to conduct our trials with our patients here at the Cleveland Clinic.

Michael Lincoff, MD:
Our Institute here at the Cleveland Clinic is somewhat unique or unusual in that we have a third group. A group that is known as C5Research or the Cleveland Clinic Coordinating Center for Clinical Research. And this is an academic research organization. This is an organization which manages, designs, administers and operationalizes large scale trials that we conduct in many centers throughout the country. We've done studies as small as one center our own, but as large as a thousand centers throughout the world. Most of these are industry sponsored, some are NIH sponsored or foundation sponsored, but these are large studies and we have a group of about 85 to 90 professionals that are physicians, nurses, technologists, financial people, administrators, et cetera, database specialists that constitute this group.

Michael Lincoff, MD:
And there are limited number of academic research organizations actually throughout the world. There probably 10 or so in the United States and perhaps a similar number scattered throughout Canada, Europe, and Australia, et cetera. So this is an unusual aspect of what we can offer with research at the Cleveland Clinic. And these are the trials that we usually have industry sponsored that are often large. Because of their size that offers investigators the opportunity to have very high impact in medical practice and often publications within the highest tier medical journals because of the size and the complexity and the rigor of the trials that we can conduct through this organization. So with that, I think I'll turn back over to Dr. Blackstone to talk about the clinical investigations group.

Eugene Blackstone, MD:
Yes. So let me go back a little with some history, because it started with transdisciplinary focus, which is sort of interesting two cardiologists and a cardiac surgeon, started the... What is known as CVIR or the Cardiovascular Information Registry. Royston Lewis, William Sheldon and Fred Loop, and that was in about 1972, but they went all the way back to the 1950s, so that they captured every single cardiac operation that had been done at the Clinic. And one of the interesting operations devised here at the clinic was the Vineberg Operation where the internal thoracic artery was embedded within the muscle of the heart, if you can believe, and I think that's why the Cleveland Clinic very early on adopted the internal thoracic artery anastomose to the left anterior descending coronary artery because they were already used to grabbing that ITA and putting it in inside the heart.

Eugene Blackstone, MD:
So we actually have all those Vinebergs and the people... All the data on their follow-up and so on, which is sort of interesting because some of them still have patent anastomosis between that ITA and coronary arteries, which is interesting. So that's the way things got started with the collaboration, people involved with coronary angiography and coronary bypass grafting. Initially it was all a cardiac registry and then just like is happening today, there were little pockets of people then making their own separate little registries in, for example, valves and then, and thoracic aorta disease and the like. That was all consolidated about the time I arrived and it was all housed in medical records with zero, no medical person assigned. There was a surgeon that was supposed to answer any questions that would come up, and that was maybe once a year or something like that.

Eugene Blackstone, MD:
So what we... And they were about ready to now join STS, which is a Thoracic Surgery Society to submit data. So the first thing, when I came, as I said, this is crazy having people in medical records who don't know about all these new operations because gobs and new operations were done. When I went over there, they said, "Can we ask you about this?" And started listing... There were mitral valve repairs. Where's the mitral valve? What is a P2 prolapse? Is this having to do with a gun or something on a ship? What is... What is this? What is all this stuff? So we said, "We've got to get somebody over here who knows something," and grabbed a person who's still working with us, Michelle Edwards, out of ICU's and the like and get her over there to get things going.

Eugene Blackstone, MD:
They had also some people who were fantastic about following-up people, they read obituaries, they called relatives and everything. Everything that HIPAA says we can't do any more and people loved it. That's what the regulators don’t understand. I found that there were nurses, floor nurses, who were doing that primary generation of making databases, of all things. Now, the problem is I came from an atmosphere where IBM's think skunk tank was working on the absolute latest in technology for data and the like, and had matched 20 million of UAB money with 20 million of IBM money to develop medical records for what they viewed be the 21st century. So that was the... That was the involvement I had. We had involvement in machine learning back in the 1980s.

Eugene Blackstone, MD:
So I came here and here were nurses who are trying to work with data. So it took about a year to recruit person in machine learning, a person we stole from what is now CMS to handle data management. I thought that I could probably teach masters level statisticians statistics up through about the level we were doing with PhDs. They may not be able to develop techniques, but they could work on that. And then we, of course, came not too long after that to a JJ idea, the idea of building a building and JJ existed before institutes existed, but that's when we said we ought to separate all of these things out. And at that time too we had as many as 18 artificial intelligence PhDs working with this here on things and so on and so forth. So there was just this huge effort of looking at what are our results? How do we improve results? How do we document it? How do we be transparent about it? And how do we apply the latest in terms of machine learning?

Eugene Blackstone, MD:
You were in on some of the machine learning we were doing with congenital stuff more than a decade ago. So that's sort of how CVIR came to be in six different locations, a half a mile scattered apart. When we came together in the JJ building, none of us had ever been physically together. And we didn't know whether we would fight like cats and dogs or just what. And since then hundreds of papers focused on what the FDA now calls real-world data with real-world inferences continuous right till today with NIH funding for advanced analytics. And that's what CVIR is about. Okay. So now what we need to do is, among each other I think, is talk a little bit about the kind of research we do. What are the highlights of what we’ve produced, and even where do we think we're going in the future and so on. So it's just... You two guys are the new ones, Mike and I are the old ones. And we can try to moderate between you folks.

Tara Karamlou, MD:
Well, thank you, Gene and Mike. This is really a phenomenal place for clinical research and translational research. Aaron and I, I think, have a very tall task ahead of us in terms of maintaining and hopefully even growing this amazing research enterprise that both Mike and Gene have spearheaded. I think for me, it's where do we go in the future with all of that legacy in the past is a challenging question to answer, but I think it's a very exciting one. There is a lot of new data visualization techniques. Aaron is sort of at the forefront of some of these. And we are also on the precipice of globalization of cardiac surgery, for example, which means a much larger theater for us to both investigate and disseminate our research. We, I think here at the Clinic, are very blessed to have the volumes of patients, the expertise that we have in so many niches of cardiovascular and thoracic care, but also this wonderful pool of learners and students and residents, which gives us a very rich environment.

Tara Karamlou, MD:
And one of my students, a couple months ago, asked me and I'm sure Aaron can relate to this, we wear several hats as both surgeons and scientists, but my student asked me, "Well, why do you want to... Why do you bother with all this? Why do you want to be a surgeon-scientist?" And I thought to myself, and then I answered. I said, "Because I want my footprint to extend beyond my fingertips." And I think that that is something that resonates with all physician scientists. And I'm hopeful that the team we've put together here is going to be able to bring the Cleveland Clinics footprint to the world. So, Aaron what are your thoughts?

Aaron Weiss, MD:
It's interesting you say it like that, because what I had always said, was the reason why I got into medicine, was I wanted to be a heart surgeon since I was very young, but I wanted to impact medicine in a way that went beyond what I did with my own two hands in an operating room. And it goes to show the commonalities we have amongst ourselves and the driving influences that we all have to help progress forward for our patients. Amongst the panel that's up here, we all prioritize translating what we do with the progress we find to our patients at the bedside. And I think that's incredibly important because patient centric care is the motto of the Cleveland Clinic and we embody that even on the research side. And I can't say enough of how much I've experienced that since coming here and it's been really enlightening as well as motivating for me to continue to do this in unique and interesting ways.

Aaron Weiss, MD:
Some of the ways that I see the clinical investigations, and just clinical research at the clinic, progressing forward really entails evolution of our data management, as Dr. Blackstone already articulated, and it's integrating the electronic health records that are sort of omnipresent now, but it's utilizing those in a manner that facilitate real-time feedback to physicians, to clinicians, as well as to our patients. And right now I think we have a lot of work to do. We stand on the giants that came before us, and we only can do this stuff because of the infrastructure that has been set forth, but we can utilize newer technology and newer initiatives to help streamline progress, research, integration amongst all the various different players, and collaboration amongst all the different players.

Tara Karamlou, MD:
Yeah. I think it's interesting that you mentioned the integration. One of the benefits of being at the Clinic is the vastness of this place, but with that benefit comes a very real and tangible drawback, which is this siloed approach. And Gene can be a witness to this, when I first got here, and we all have the same ideas almost at the same time because those are ideas that are at the forefront of our clinical intuition by virtue of our practice on a daily basis. But I was working on something and come to find that somebody at the Lerner Research Institute and the biomedical engineering lab was working on the same thing. Similarly, we've all had the unfortunate experience of looking at a project only to find that a colleague has published on that, weeks before even. So one of the challenges that comes with the largess of this place is to integrate and really break down those silos and find a way to somehow know what's happening around you. And that's going to be a challenge as the complexity of data grows and the volume of data grows.

Michael Lincoff, MD:
I think it's also important to recognize that research brings new therapies. So the observational data that we've talked about, the real-world evidence that we've talked, about provides the ideas. They help us learn from what we're doing. But in the end, we have to definitively prove the things work and don't work. And in most cases still, despite the sophistication of analytical techniques, in most cases, to develop an evidentiary basis for approval and for the acceptance by medical community we need randomized trials. So our ability to handle large volumes of trials, which we do. We're presently conducting, just in heart and vascular, 200 different trials in devices, in new drugs, in diagnostic approaches, in all of the different departments within. So this allows our patients, the opportunity to not only help advance the field, but from the personal standpoint, to have the opportunity to have access to new grafts for aortic repairs, new devices to replace valves, new drugs to treat their underlying risk factors, et cetera.

Michael Lincoff, MD:
We're very proud of not only what we do in terms of changing the medical practice with the trials we complete and published and present at the major meetings that change practice, but also the fact that our own patients who come here have access to this. We have a website that has been developed that does have a listing of our trials and a description of what studies, and certainly patients who have issues that are suitable for that. We'd welcome their contact numbers and we'd welcome referrals for those particular issues. But really... For most conditions in cardiovascular medicine and cardiovascular surgery and vascular surgery, we probably have some trial going on and many of our patients are able to be part of that as they're being taken care of at the Clinic.

Aaron Weiss, MD:
I think one of the interesting points you brought up, the 200 or so trials you have ongoing at any one given time point, in the couple hundred observational studies that are ongoing at any point here at the Cleveland Clinic, we focus on who's running those trials, or who's running those studies, but the reality is the team-based approach to helping get these projects accomplished. Everybody from the data abstracters to the people who designed the data warehouse to the statisticians, the programmers, the registry-based people, the follow-up people. Everybody that kind of comes together for that bigger purpose. It's for us to further medicine in a manner that we can apply for patients. And it's without that big team and all those various different efforts, we wouldn't be where we are today.

Eugene Blackstone, MD:
Let me bring up one thing that you have said, Mike, that we have sort of forgotten in this conversation, and that is beside research there's also innovation here. So you mentioned the stent grafts and all this going on too, because some of our best researchers are also the most innovative in mind, all the way wiggling catheters and putting in all this hardware inside your vessels and all this kind of stuff that needs to have trials and so on. So let's not also forget the fact that, just as you've mentioned, the basic sciences and getting people who are interested in these, interested in patent ductus' too, and people who are devising these things, probably at night in the back of their mind and then into clinical trials, is actually a whole ‘nother aspect of the research and innovation that is going on in the Heart, Vascular and Thoracic Institute.

Tara Karamlou, MD:
I think the other thing about that is, in research there's innovation in how we treat patients and we have published a lot on new therapies and new operations on the pediatric side. There's three new ways to approach congenital defects that have been revolutionary. And those types of landmark things galvanize us and excite us, but we also innovate in the analytic realm and I'd like to spend a few moments, perhaps at the end, to just talk about all of the new things that our biostatistical team has been doing, because they are also experts and partner with us. And those types of technologies can help us really bring individualized medicine to our patients and to show the world our best selves, which is what we do here at the Cleveland Clinic. So, Mike, you were going to say something.

Michael Lincoff, MD:
You mentioned earlier, and I think it goes to the point of the innovation, either biomedical engineering. We have the Lerner Research Institute here, which has hundreds of professor level bench researchers, from the most basic to us as immediately preclinical as biomedical engineering, that are our collaborators as well, and many ideas of course come from their laboratories. And then of course we have the opportunity to collaborate with our ideas with them to... particularly bioengineering for say, surgical devices, et cetera. So it's not just the clinical operation here that that is the driver, the engine of the innovation and the work that we're able to do in research. We're very blessed here at the Clinic to have the very close collaboration with our colleagues over in the basic science.

Aaron Weiss, MD:
And I think it's an interesting point. If you can be innovative but not have the infrastructure to take that innovation and run with it and take it to completion, and I think that's something that's pretty unique at the Cleveland Clinic. Is that there's established infrastructure that can then be leveraged to discover new ideas or take that innovation and apply it in a different way. And I think it's a really unique thing about the Cleveland Clinic.

Eugene Blackstone, MD:
Let me just interject another idea here. And that is, what are our pain points in research here? And I would say the biggest pain point is something that Tara is going to have to do. And that is how do you follow patients longitudinally in the long-term to see if it was appropriate to take that little baby out of the uterus and do this operation, put it back in and so on? What are the neurologic consequences? What are all the consequences of this? So what is the consequences of everything we do? Mike is a catheter wiggler too, right? And what is the consequences? What's the long-term benefit of some of these things? And I would say that is the single hardest thing to do. And that is to actually follow patients. We have thousands of patients as you can imagine, if you were going to try to even follow them every year, it would take an army to do so. So it's highly expensive, but how important it is to know that all these innovative things that we do actually have a value.

Tara Karamlou, MD:
No, I think that is really the greatest challenge that faces us as, as scientists and frankly, as people. It's ironic in today's world where you can follow everybody on Twitter or Instagram or Snapchat, which my daughter uses quite vastly to my chagrin. We have difficulty in and regulatory obstacles that prevent us from following our patients without really a lot of hurdles that we jump through. So, there's no easy answer to that Gene, but without that data, we really, as you say, we can't know what we do modifies the natural history in any meaningful way for our patients and it is no more apparent than in the realm of congenital, where we're now operating on babies even before they're born. And what is the fate of those children? And moreover, what is the fate of those families? And those siblings? And the population? What is the burden on society in general for those interventions? And while we all believe that what we do is right, because it seems like intervening as an active thing to do, it may not be always the best option for all of our patients. So a challenge for sure.

Eugene Blackstone, MD:
Well, can we have each of you just give a little wrap-up because I think we're about out of time.

Tara Karamlou, MD:
I just want to thank the Cleveland Clinic for their commitment to research. I think it has really been a very wonderful experience for me to work with this team. And I think there's... I think our future is bright and I can't wait.

Michael Lincoff, MD:
I echo that. And I think our pain points, if you want to talk about it, are also those of drinking from the fire hose. That there're more opportunities and questions. than we have people to manage the studies that we'd like to do. So we're selective, we try to do take a strategy that has the most impact, we welcome the patients and the collaborations that allow us to have the most impact on advancing the cardiologic care.

Aaron Weiss, MD:
Just speaking to the times, I think one of the important things that we've learned of being in the middle of a pandemic, is the importance of good rigorous science and that requires funding, that requires collaboration, and you just talked about, requires innovation and dedication. And I think marrying all those together is going to be incredibly important and renewing that commitment, our good high quality science, every single time we take something on is also incredibly important.

Eugene Blackstone, MD:
Yeah. And I would like to wrap up by thanking the philanthropists who have funded the research in HVTI to a huge extent that make all this possible. So there are... it's true, there are grants, there's money that comes in from industry and the like, but it's really the philanthropical gifts that is making the infrastructure happen that keeps things together. So I want to thank you for that.

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