Balanced, Healthier Lives with the Science of CINEMA

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Dr. Dan Simon: Hello everyone. My name is Dr. Daniel Simon. I am your host of the Science at UH Podcast sponsored by University Hospitals Research and Education Institute. This podcast series features university hospitals cutting edge research and innovations. Thank you for listening to another episode.

Today I am happy to be joined by two guests, Dr. Ian Neeland and Dr. Sadeer Al-Kindi. Ian and Sadeer are the co-directors of the Center for Integrated and Novel Approaches in Vascular to Metabolic Disease, what we call CINEMA at University Hospitals Harrington Heart and Vascular Institute. They're two terrific rising superstars.

Ian is a Prevention Cardiologist trained at Mount Sinai in Emory, who came to us from UT Southwestern, and his expertise is in Cardiometabolic disease.

Dr. Al-Kindi received his medical degree from Weill Cornell, Qatar in 2013, and is trained at Case Western Reserve University. He is very interested in the social and environmental determinants of cardiovascular disease and the utilization of computational approaches for precision diagnostics. It's really a pleasure to be able to be with both of you today.

In 2019, University Hospitals invested to support the development of academic centers of excellence as a mechanism to align research activities with clinical excellence, promote team science, and impact standard of care, not only in our own community, but around the world.

CINEMA was one of the very first two centers of excellence founded by Dr. Sanjay Rajagopalan, our Chief of Cardiovascular Medicine at University Hospitals and now, this program is currently led by both doctors Neeland and Al-Kindi. The establishment of CINEMA is to bring together multiple disciplines in a unique platform to advance the understanding and treatment of cardiac and vascular complications of metabolic disease, mainly diabetes.

Share with us, what are the barriers for treatment and prevention of cardiovascular disease that complicates diabetes? What are the innovative approaches that your center has taken to tackle these challenges? And who are the key players? Ian, maybe we could start with you.

Dr. Neeland: Sure. Well, thank you so much Dan for having us on today. It's a real pleasure to speak with you. In 2020, when CINEMA started, the state of diabetes care, much like, chronic disease management in general was very fragmented, very siloed. Diabetes, like many diseases, has multiple complications, cardiovascular, kidney, across the many organ systems. And so because of that, patients tend to see multiple specialists in addition to their primary care physician. And unfortunately things get missed, miscommunicated, errors, and generally the care tends to be substandard in many, many situations, which leaves patients at high risk for worsening complications and death.

So CINEMA was started really to address those key issues and key barriers, and tried to bring together a program that's more multidisciplinary, integrated, and patient-centered. So the idea behind CINEMA was born out of a plan to have the central team that consisted of multiple specialties, but with all being able to talk to each other, communicate with each other, and really bring the patient into the center to try to provide optimal evidence-based medicine care more easily for the patient, more accessible and greater resources for the patient. So this consists of a team that's made up of cardiologists who also have expertise in diabetes care.

And the reason that's important is because… diabetes is the number one killer for patients, with diabetes it’s cardiovascular disease. So to have that complication and that potential sequelae out in front is really key to reduce complications and improve outcomes. So that's the core team…is five cardiologists with expertise in diabetes care, but we really are connected to a nurse navigator who really takes the patients not just medical issues, but holistically personal, mental physical issues into account, and really helps guide the patient through and navigate them through the care systems. We have a registered dietician who also is certified for diabetes education, and she's an excellent individual to help with lifestyle modification, counseling, help with titration of insulin, for example and is able to, discuss with the patient on a different level, a different way than the medical providers, the physicians.

We of course have a pharmacy champion who is key. Diabetes, unfortunately requires much like other chronic diseases, multiple medications, often polypharmacy becomes an issue, interactions and such, and especially with these new medications, novel medications for diabetes, which have cardiovascular and kidney benefit there tends to be issues with access and affordability. So having a pharmacy champion really allows us to be evidence-based and be as aggressive as we can. In that context, we also have individuals who help with mental health or partners who do nephrology or endocrinology.

And so it really is a multiple disciplinary program to try to address the multiple complications of comorbidities while not just focusing on the blood sugar, but focusing on one's complications and outcomes. And so our goal really is to, really make the patient healthier, happier, and live longer. That's the goal of the CINEMA program. That's what we set out to do when we started it.

Dr. Dan Simon: Well, Ian, I think it goes without saying, as someone who refers a lot of patients to CINEMA, that the one comment that I get back is this incredible confidence in coordinated team-based care, high touch, high accessible, easy to follow up and frequent touch points.

Sadeer, maybe you could talk to our listeners about how important this navigated high touch care is, especially for the kinds of patients that you're focusing on, where social determinants and access is really key.

Dr. Sadeer Al-Kindi: Yeah. Thank you. And again, I reiterate what Ian said. Thank you so much for having us today. Basically, diabetes is very complicated as all of you know. And it requires not only polypharmacy, that does not only require kind of multiple interventions, but it requires us to do so at a specific pace, right. So, we often see in traditional clinical care we see that there's clinical inertia and patients come and see physicians every year, every six months, and at every time point there is a hurdle or an obstacle to actually up titration of medications or implementation of new medications.

Oftentimes these patients have issues with prior medications that are, have caused side effects, so they may be wary of starting a new medication. So it does require an intensive discussion and intensive treatment of sorts that helps us achieve the goal of the program, but also putting the patient at the center. For many of our patients especially at Cleveland Medical Center and in Cleveland in general, they have a lot of, in addition to medical issues, they have social and environmental determinants that can really impact their trajectory over the lifetime.

So what we have been doing, and we've realized this a long time ago, and that's where the nurse navigator is really instrumental in doing this, but having the frequent multiple touchpoints between the physician, the other clinicians who are involved in patient care, and where we communicate with them directly. But also having that patient get communication through a channel, an open channel, with the nurse coordinator is critical.

More recently, we've started to integrate additional resources, including a community health worker referral, to resources that are available broadly at the federal, county level and local level, and even within University Hospitals Health System that helps address some of the adverse social determinants of health because we've realized that it's not only medical care that's necessary, but without addressing the social needs it becomes extremely difficult to address diabetic complications.

Dr. Neeland: And I would just add that, diabetes self-management is a real key piece in bringing patients into their own care and helping them manage to the degree they can, I think, that improves health disparities and leveraging technology to do so, in a way that's cost effective as well. I think is an important piece of what we do.

Dr. Dan Simon: You know, one of the things Ian and Sadeer, is that I don't think people really appreciate that one of the underlying problems that we have here is really obesity and insulin resistance, and you're really at that cutting edge of seeing patients who are obese without overt diabetes, or who are obese and have diabetes or pre-diabetes. And the one things I really, want our listeners to understand is that you literally change people's lives. I have sent you patients with hemoglobin A1C’s and the high eights who've lost 40 pounds under your care and now have hemoglobin A1C’s in the sixes completely change their whole approach to life.

And obviously the intensity of their diabetes management is changing their future cardiovascular outlook. At the same time though, you've really helped patients who are just obese, who are at risk for problems and diabetes in the future through very, very novel programs with GLP-1 receptor agonists. We can't not turn on the television now and see Wegovy or Ozempic or Mounjaro, and so maybe you could talk to our listeners how have these new medications that are very favorable from a cardiovascular standpoint, how are they changing people's lives with respect to this whole issue of obesity?

Dr. Neeland: So the main driver for cardiometabolic disease, that's cardiovascular, kidney and diabetes, is what's called dysfunctional adiposity or fat where it doesn't belong and is not function the way it should. Many people think that fat is not an organ…just sits there and, holds triglyceride, but in fact it's a very active organ. It secretes, a lot of different cytokines, different hormones, and it really is the driver for many of the complications. So targeting the visceral and ectopic fat, ectopic being fat, where it doesn't belong such as the liver or the skeletal muscle…targeting that and trying to improve that profile can really make a big difference in terms of complications and just people feeling better and being healthier. So the idea for these novel medications, which impact not just the blood sugar and, one's handling of blood glucose, but rather really attacking visceral and ectopic fat and trying to reduce that, that goes a long way in both improving patients with obesity as well as reducing their complications, and that's one area I think that if we think about integrating and systems coming together is going after that system, that pathophysiology is really the key to improving one's cardiometabolic health.

Dr. Dan Simon: That's terrific. So Sadeer, in 2020, CINEMA joined the Cardiometabolic Care Alliance as a key strategic partner. Tell us a little bit about this national Alliance and what impact it brings to CINEMA and to UH?

Dr. Sadeer Al-Kindi: So the Cardiometabolic Alliance is a consortium of hospitals that have this novel program in different flavors, in different locations, that target patients who have type two diabetes and either at risk for cardiovascular disease or have preexisting cardiovascular disease. So this program brings different sub-programs within it in different hospitals across the nation. With an idea that we should both integrate the data but also to provide a quality improvement initiative to understand first what is the kind of the spectrum of disease, how are we doing at the different centers, and try to align everybody at the same protocols and the same approaches. Realizing that everybody has some novel approach that they may be able to do, but providing that infrastructure for quality improvement, for ensuring everybody gets the same care, high quality care, but also being available for large registries in large interventional studies that will arise invariably in the future when it comes with new medications and new diagnostic tests and new therapies and applications and so on and so forth.

So, UH has entered into this in the very first program along with St. Luke's Center in Kansas City. And we have been really trying to integrate the protocols, trying to participate both in the protocols and for quality, but also for research and for understanding how the spectrum of disease is across the nation.

Dr. Dan Simon: Terrific. So type two diabetes and related metabolic disease are the leading causes of death and disability in the US. In fact, in Ohio, diabetes and cancer related diseases account for greater than 50% of the state's deaths. Since the inception of the center two years ago, the center has accepted more than 600 referrals. I mean, that's just, really incredible. Congratulations.

Have you observed any improvements through this patient-centered team-based intervention? What lessons have you learned, Ian? And then maybe afterwards you could tell us about some, any exciting research findings that you can also share. So what are the clinical results? Are people losing weight? Are there A1C’s better?

Dr. Neeland: Yeah, so, we were very happy to not only be able to implement our clinical program, but study it, study the process, study the outcomes, and to help educate ourselves and others on how we're doing and how we can improve. We published our year one CINEMA results in the Journal of American Heart Association just this past summer. And what we saw was that across the board markers of cardiometabolic risk; weight, BMI, cholesterol levels, hemoglobin A1C, all improved in just a three month to six month span. And this happened in patients who've, for example, seen endocrinologists and primary care doctors for years and years and have not necessarily been able to improve their markers.

But with the program because of its unique ability to have high touch points, to be very aggressive and to increase the utilization of evidence-based therapies like SGLT2 inhibitors and GLP-1 receptor agonists. In fact, we increased it by twofold… that this was really able to make changes for patients in addition to the lifestyle and getting patients involved in their own care, really make major, major strides. So… beyond the markers that improved, we increased evidence-based therapy utilization and we also provided educational resources and satisfaction for patients. And so, we are now actually working on our year two data, and we plan to hopefully present that in the American Diabetes Association Conference this summer.

Dr. Dan Simon: That's really terrific. So, Sadeer, one of the goals of CINEMA is to promote team science and align research activities with clinical needs. Can you tell us a little bit about the clinical research you are currently conducting at CINEMA and how it's impacting discovery in general?

Dr. Sadeer Al-Kindi: Yeah. We do, quite a bit of different, patient-centric discoveries that are bench to bedside. One of the programs that we focused on is utilization of newer technology to empower patients, but also to improve our ability to identify high-risk patients who may benefit from intensive, even more intensive therapies. So, and we have one program that really try to understand the protein signature in the blood and identifies patients who have diabetes, who don't have heart disease yet, and identify them to have either high risk for heart disease or low risk and try to treat them aggressively.

So that's novel proteomic signature that is built and hopefully will try to present the data in the, near future. Another arm of the study that Dr. Neeland is leading is really trying to empower patients who are not using insulin, by providing them with continuous glucose monitoring. By providing them with data on minute by minute basis to empower them to understand what they should eat, what they shouldn't eat, what type of activity will help their glucose levels and we've seen really tremendous effects in patients that we've been enrolling in this study, but perhaps one of the largest ones that we've been able to integrate with CINEMA and utilize the CINEMA platform is really the ACHIEVE GreatER program, as you know.

So this is a novel program where instead of waiting for the patients to come to us, we actually go to the community and identify individuals who may be at risk and plug them into the high touch program, so that they can have a much better improvement in their cardio preventive therapies, and understand their risks, and also integrate their social determinants interventions alongside the medical interventions. So this is in conjunction with Wayne State University and Dr. Rajagopalan is the PI for the Cleveland Project. And we are very happy to collaborate with community-based partners in this program.

Dr. Neeland: And I would just add that, part of the amazing thing about CINEMA is that we're able to leverage the clinical program for research as you said, and really be a test bed for treatments and really kind of go to cutting edge with science. And so, for example, we're going to be starting a new trial looking at the impact of SGLT2 inhibitors on sleep apnea and CINEMA patients will be front and center in terms of eligibility for that trial and this is an area where this is going to be evolving and in the future, because obesity, diabetes, hypertension is inextricably linked to sleep apnea. There is no medical therapy for sleep apnea currently be beyond CPAP, which 50% of people can't tolerate long term. So this is a trial that, helps to and hopes to, really, be novel and provide new insights going forward. That's just one example of, how the clinical program links up with research in a really novel and exciting way.

Dr. Dan Simon: Well, it's very interesting that you're attracting collaborators from the sleep center as well, as you said, Sadeer, not waiting for patients to come to you, but now going out in the community to find them. So I guess I have a question for both of you before we wrap up, and that is what's next? Where do you see CINEMA going in the next five years?

Dr. Sadeer Al-Kindi: Yeah. So I think there are multiple visions that are integrated actually into the program, and one is how do we move from where we are right now, seeing 600 patients to seeing 50,000 patients, right? Because we're making a dent in the overall diabetes population, but how do we make a program that's sustainable, that is intensive, but also is very scalable? And that's really where the key is in utilizing remote monitoring, remote clinician teams that, not necessarily physician driven, but could be pharmacist driven, nurse driven, approaches with protocols across this system to identify patients and treat them and improve utilization of cardio, preventive therapies and whatnot. Utilizing some of the novel EMR based interventions as well. So that's I think part of the vision where, we hopefully will head to, gradually, but I'm sure Dr. Neeland has additional visions as it relates to the program itself.

Dr. Neeland: Yeah, I think, scalability, interconnectivity, and networking with other similar programs across the country, which they're slowly trickling in because of our successes and, putting it out there that what we do has been really beneficial for patients. And so ultimately I think trying to create a network of like-minded institutions with similar programs and scaling it up, as Sadeer said to larger populations. And also trying to figure out how we can do that, but yet be effective… and not lose the personal touch that we have with a program like CINEMA. And that's the challenge I think in the next five years is, how do we get larger but not lose ourselves and lose our vision? And so it's been a great experience.

And the biggest thing is that I think we've helped people, with impacted lives and it's been really satisfying and very humbling to help those individuals who for years have struggled with weight and diabetes and high blood pressure and really try to make impacts and do it together, patient-centered and shared decision making I think is the key. So hopefully we can continue to grow going forward.

Dr. Dan Simon: You know, I think you both have hit on a really critical topic of scalability. Investigators from the University of Mississippi have a very intensive nurse and pharmacy led, hypertension program. So, as hypertension, the number one risk factor really for heart attack, stroke, and heart failure in the US only 40% meet blood pressure targets, it costs 42,000 per quality life adjusted year to increase that adherence from 40% into the mid to high sixties. And this is not really gonna do anything unless we go from $42,000 per quality life adjusted year down to 420. So, we literally need a hundred fold reduction in cost. And that's very daunting. It's exciting because, we're at University Hospitals, which sits right next to Case Western, and we have great engineers and biomedical engineers. We need sensors, we need chat bots, we need, computing that is gonna allow us to monitor patients without actually needing caregivers doing this every day because as you pointed out, we've treated 600, but we have 50,000 that we need to treat, conservatively. So I'm so excited and look forward to bringing you back to check in on progress before that five year time point.

So thank you so much for taking the time to speak with us today, Dr. Neeland and Dr. Al-Kindi. It's really, I've watched both of you grow in your careers. I'm inspired every day that I see you, and it's these young rock stars that make it exciting for us older folks to come to work every day.

So, for our listeners interested in learning more about research at University Hospitals, please visit uhhospitals.org. Thank you very much for joining us today.

Dr. Neeland: Thank you.

Dr. Sadeer Al-Kindi: Thank you.