AI and the Future of Healthcare: Cardiologist Dr. R. Scott Wright

This is Dr. R Scott Wright, who is a professor of medicine and consultant in cardiology with the Mayo Clinic College of Medicine. He's a fellow of the American College of Cardiology, the European Society of Cardiology, and the American Heart Association. He is a distinguished cardiologist and professor with the Mayo Clinic College of Medicine in Rochester, Minnesota. And his extensive research focuses on acute coronary syndromes, dyslipidemia, type two diabetes and valvular heart disease. He's renowned for his leadership in clinical trials and database studies investigating innovative treatments and healthcare policies. Thanks for coming on today. Dr. R Thank you, Lisa. Pleasure to join you. And wow, what a great introduction. That's really nice of you. Thank you. This for us is a little bit of a change because we don't often talk strictly about medicine per se, even though I am a physician and my long-term, life has been in medicine. But when we think about creativity, we don't often think, oh, medical research. We don't think about creating, designing and trialing new medications. We don't necessarily think about teaching. And when I met you actually through my husband and through your ham radio connections, I said, this is a person that I'd really like to talk to because I think the way that I experience medicine is very different than the way that you experience medicine. And I want to learn more about that. So thank you for being willing to have this conversation with me. Dr. R A pleasure, thank you. One of the things that I know about your background and that was very interesting for me to learn, was where you grew up and how it impacted your decision to work with the organization that you did and even do the work that you do now. So I'm wondering if you wouldn't mind exploring that a little bit with me. Dr. R I'd be happy to. If you've read JD Vance's book, hillbilly Elegy, you can get a great insight into my background and that of my generation who grew up in Appalachia. I grew up in eastern Kentucky and like in Vance's book where his family moved a fair amount. My parents were migrants, they were school teachers who went to work in Ohio because there were no jobs in Kentucky. And I was born in Ohio. And then after second grade, my father had decided that he wanted to move his family back to Kentucky. So we moved next door to my mother's mother in a small town near the Kentucky, Tennessee border in the Appalachian Mountains. And it was a wonderful experience in many respects. Family was a priority, community was real. People were kind and friendly to one another and everyone was poor. And no one realized just how poor we were. Dr. R I think in the 1970 US census, the county that I lived in was considered the third poorest, but I don't think anyone felt that poor, but also no one really had a lot of money. And I think when I look back now to some of the things that were discussed in my early high school career, it's very clear that it was Appalachia and its impact. So for example, probably two thirds of the students in my high school class had never been outside of the state or commonwealth of Kentucky. A third to half had never left. That county where we grew up in Kentucky is centered more by county than by city. And certainly a small percent had traveled outside of the us, maybe 1% or less just wasn't common or wasn't part of the cultural thing. But I was a bright youngster and the school teachers really poured a lot into me, which helped me get a great education. And I really developed an interest in science thanks to my high school biology teacher, Mrs. Clark. And got a great background in mathematics, thanks to a high school math teacher, Mr. Loudermilk. And I had him for three or four classes. We had a dozen or half a dozen to a dozen young students who were college bound at that time. So in our senior year, he decided to teach calculus at night so that we would understand it and be ready for it in college. Dr. R By all external appearances, I grew up in an impoverished community with few resources. The community spirit was rich. The teachers really poured their heart and soul into helping students. And if students were motivated, there were plenty of opportunities to learn. And I think compared to my own children, there were some experiences I had that are better than anything else life can give you. We spent a lot of time in the public library, a lot of time in the school library. Our church community was important and that's where we had a lot of our socialization. We had a lot of common values. And in many respects, that also creates some degree of xenophobia because you think the rest of the world should be like you even in the United States. And then as you become an adult and become exposed to different ideas and philosophies and things, you realize that there are a variety of ways that people in this country and in this world think and act and not all are wrong. Dr. R And certainly some are better than what you were accustomed to growing up. And so you become much more heterogeneous than homogeneous. But I think if there are any traits that sort of typify people who leave Appalachia, it's feeling awkward and not like they belong in any successful situations, you're constantly wondering what's going on. We had a young man in our community who was the star basketball player in Kentucky, and basketball in Kentucky is like football to Wisconsin or the Green Bay Packers. Every high school kid playing high school basketball wants to play at the University of Kentucky. And he actually was Mr. Basketball and played there, but he left after two seasons. And I was having a discussion last week with two friends from my community who happened to be at Mayo Clinic site in Florida where I was working last week. We were talking about him and why he transferred from a division one school to a division three college at the end of two years. Dr. R And I never knew, and my perspective was that likely it was just sort of the typical and what we would call today, imposter syndrome. I don't belong here, therefore I'm leaving. I want to go somewhere smaller. And he's a successful adult now, so his life has gone well. But that's just sort of typical of that background. But I think in my own work now, it's made me more appreciative of people, their struggles, understanding the people who are less affluent, who can't afford their medications or can't afford to get healthcare, who can't afford an extra hotel room a night in the hotel because they'd spent their entire budget for healthcare coming to see me, and we need to finish their evaluation in two days instead of four days. So I think it's provided a sensitivity and a compassion that I wouldn't have had if I'd grown up in a urban area, the child of affluent individuals. Dr. R And it's made me a value and appreciate education as well. And that's how I got into ham radio. I don't know if Kevin, your husband knows that story either, but in seventh grade we had a substitute teacher, so I went to the school library to get some books to read so he would not assign extra homework. And there was one on ham radio and I started reading about it and within I think a few days I'd learned morse code and I was ready to get into the hobby. And so I've been doing that since that year as well. I'm always impressed with people who can do Morse code. I know Kevin can do Morse code and he's been getting himself back up to speed. But it's a whole different language and it's something that it doesn't get used as often, well, I would assume as a cardiologist you probably don't use Morse code probably at all, but it is something that's still used quite widely within the ham radio world. Dr. R Yeah, it is. Thank you. It is, and it's used widely, I think as a backup communications modality. Now, there are much better digital modes for commercial reasons. And when we think digital, think email, think small sentences like Twitter, like tweets that you can send out better, much easier than having to decipher it with the headphone and listening to the high pitched sounds. But there is a real parallel with cardiology. We use something called continuous wave of doppler to interrogate cardiac valves, to look at gradients, to look at pressure changes. And that's just simply the same theory as Morse code. And there are many analogies between cardiac physiology and RF communication. The heart is a pump that has to match its output to the vascular system, and it deals with impedance, it deals with reactance and inductance and medications that we prescribe that slow or raise the heart rate can change inductance and diuretics and vasodilator therapies if you're taking losartan or an ACE inhibitor or something like that that alters the reactants or the capacitance rather, not the reactants but the capacitance of the body. Dr. R So there are lots of analogies. And when I was training in cardiology, it sort of dawned on me that there were a huge amounts of parallel there. And so it's helped me sort of understand how we design therapies and how we match therapies for the problems that individual patients have. And I'm still working on an idea which is to try to be able to measure the coupling of the heart to the vascular system in a noninvasive way so that we can then tailor the medications for what the patient needs rather than every patient throwing every medicine at every patient. As a family physician, I think that was your background, if I remember correctly, the patients not only have to take all of these medicines, they have to deal with the side effects, the nausea, the feeling of satiety and also the cost. And every new medicine that comes out seems to cost between 6,000 or 12,000 a year. And if you have five of those to take without insurance, you suddenly can't afford to take any of them. So I think it's behooves us in medicine to try to find therapies that fit a specific niche of a problem and use only what is needed rather than just blindly prescribing everything. That makes a lot of sense. And I think we have gone through a phase where we were using broader spectrum, whatever it was, broader spectrum antibiotics or a broader spectrum, blood pressure medication, maybe even broader spectrum anti-cancer agents. But the more that we can bring them back to an individual, and even I know that there's been a lot of work being done with individuals genetics and the way that individuals metabolize things, I think the better off we're going to be. Because when you use things that are very broad, then as you've pointed out, you can actually get a lot of side effects and they may not even be the best medication for the patient. But it's taken us a while, I think, to get to the level of technology that we've needed in order to tailor things to individual patients. It sounds like this is something that you've been working on for a while yourself. Dr. R Well, it's an idea and I proposed thoughts about how to test it many years ago, and I've been distracted along the way with other things, including one of the new cholesterol medicines we'll talk about I'm sure in a few minutes, but it's still something I hope to work on before I finish my career. I think you're exactly right that we do need to tailor medicines for individual patients. We have a whole center at Mayo Clinic in Minnesota called the Center for Individualized Medicine, and their goal is to combine genetic testing, genomic testing, patient prior responses, and AI to sort of say what's optimal for you rather than just try everything. And I think it's especially true with high blood pressure. I'm sure many of the listeners today take high blood pressure medicines, but they might be shocked to learn that typically we have to prescribe three because the first one will lower blood pressure, but then the body has a counter regulatory physiologic reaction to that medicine. Dr. R And so then you prescribe the second medicine to counter that counter reaction, and then the body does a counter reaction, you prescribe a third, and then eventually you're able to stop the body's resistance, so to speak to all these medicines and get the blood pressure to the appropriate level. So if patients who are listening or any of us who are listening who take medication ever find themselves frustrated, just remember the body is a pretty well designed human engineering system. It's designed not to have its ecosystem tilted by medication or other things. That's why it fends off invaders like viruses and bacteria and it sees medicine as foreign. And so we have to recognize that there will be counter responses, side effects, it's often called. And so you have to prescribe things to manage that or even remove that medicine if the side effect is too strong or too harsh for the person to tolerate. Because I think that one of the things that often happens, obviously within primary care, because we're dealing with all of the things all of the time, so we're always translating back what big names of medications mean or what different ways that the body acts, how this happens. And we're always trying to bring complex ideas into something that's understandable for people who have a broad range of ways that they understand. And I think that what you are describing is incredibly important for all of us to know because sometimes when people walk into an office, whether they're seeing a nurse practitioner, a physician, they're really relying on somebody else to make a judgment on their behalf because they don't feel like they have all the information they need. And it would be much better if we can bring things to a level where people understand they're actually agreeing to so that if they start taking a medicine or if they start engaging in other types of therapies, they know what the possibilities are for things going wrong. And this I think really gives people back their ability to make their own decisions with the help of their healthcare team in a pretty significant way That's become increasingly important with people's greater access to knowledge and information. What do you think? Dr. R I fully agree with you. I think what you've just articulated much better than I could ever have done is critical. I think that every person in training, whether it's a medical student, a PA or a nurse practitioner student, really needs to be taught that at the end of the day, we're all here to serve people, to serve the patients, and they are partners. They are actually in charge of their own healthcare. They're coming to us and trusting us for advice. And I always tell my patients, look, you're putting a lot of trust in me to give you advice, but also to spend your money and to pick appropriate testing and to pick appropriate therapies. So I like to pick the greatest value in testing for you. I work at an organization where I'm salaried, so I don't have any necessarily incentives to do things that are more expensive or less expensive, whether it's a fee for service or a managed care type organization. Dr. R It's just we're salaried and we like to think that we do what's optimal for people. I'm not criticizing others, but that's just a system that I've chosen to work in and I like it. But also I tell patients that I really try to pick the medication that offers you the best value. Most of the time it's a generic medication that also has evidence that it will lower your risk of stroke or death or heart attack, and that we really should get a benefit from anything we prescribe. It should do more than one thing. It should be more than treat the condition you have. It should also give you additional prevention against other disease states. Because we live in an era now, we practice in the greatest time in the history of humanity with medicine. We have all these clinical trial data and outcome studies, and we have knowledge and we have lots of people globally working on things. Dr. R And it really behooves us to use therapies that are safe and effective, but also add value to people. And I try to educate and inform my patients, and sometimes they come in with a decision. Sometimes people come in and say, I really want a Medtronic pacemaker. And I'll say, okay, I'll let the team putting the pacemaker in know that you really want a Medtronic, why do you want a Medtronic? Well, my daughter or son works at Medtronic and I understand that if we have a device like that, they'll get it, but most of the time people really trust you to do that. I remember I was in Chile lecturing and they asked me to come to the hospital to the ICU to see some patients and give them advice. And one person was having a heart attack and was getting a stent, and they had done the angiogram and I was looking at the pictures with them and agreed that he needed to have an artery and they stopped and there was a 15 minute discussion going on in there and I asked one of them, what's going on? Dr. R They said, oh, we're discussing the three stents that are available. We have the US made stent. That's this amount of money. We have a second one that this, and then we have the knockoff a third from a country in Asia that's substantially cheaper. And he's deciding which one he wants to go with because he was paying out of pocket for this. And they had that discussion. And it kind of helped me understand that even in a country like the US where we have lots of insurance, public and private, we still need to have those same discussions. And so I think Lisa, your advice is prescient and it's correct. And we do need to be treating the next teaching rather the next generation of healthcare providers how to do these tasks because it doesn't matter if we have the best medicine available and prescribe it, if people will not stay on it and take it, it does no good. Dr. R And we could talk about cholesterol medicine. You can be on the most powerful medicine, but if you're not adherent, you have the same risks of bad outcomes as someone who's taking the least effective medicine. So you really need to be able to stay on your medicines. And if you're not engaged with your healthcare provider and willing to take it, you're probably not going to stay on it. So we have to take the time and or have people in our team who can talk with them and help them understand the importance of that. And I think it's all a partnership too, between specialist and generalist. None of us live in isolation. And I always encourage patients to get a home physician, have a home primary physician, a home specialist, because most of my patients travel hours to thousands of miles to see me and I tell 'em, I can't be there. If you have a heart attack, you need someone locally who can treat you. So don't disregard your local healthcare team. Stay with them. Yes, I agree. Although as a family practice doctor, I think of myself also as a specialist. I just specialize in a kind of broader range of things than somebody who perhaps is a heart specialist as you are. So I do think it is important for all the teams to be able to communicate and to work together well. And one of the things I'm interested in with regard to your work is that you are doing things that are both kind of more on the scientific research side, but you really want to bring them into the medical realm and the clinical realm, and you're really trying to create value with the medicines that you've been working on. So in the most, I guess, understandable way possible, could you help us understand what it is that you've been working on most recently and what the process has been like as far as creating a new medication that people can use and what this is used for? Dr. R Oh, sure. I'd be happy to, and please interrupt me if I go too long because you put a nickel in and we can give you $2 worth of output sometimes talking about these sorts of things. In 2015 or 16, I was invited to a small meeting in London during the European Society of Cardiology that I typically attend, and some individuals that I have immense respect for who had worked in the pharmaceutical industry at Roche had transferred to a small US company at that time called the Medicines Company. It was founded by a physician from the United Kingdom who wanted to bring disruptive therapies to the healthcare arena and do things differently in a more affordable cost-effective and generally easier way. So he had a small pharma and he was living in Boston when he started the company, and he had some fellow physician friends who worked with him, one of them who turned out to be a ham radio operator by the way. Dr. R So if any student or young person is listening to this, a ham radio is a great way to boost your career, it seems. It's worked for me. But anyway, they were showing us some new data on a therapy that you could inject that would lower cholesterol 35% to 40% for 12 months if you had a single injection of it. And we were all intrigued by that because injectable therapies for cholesterol, didn't exist, and for most problems outside of say, osteoporosis, just were not being utilized except with chemotherapy. So they started teaching and explaining to us that this was a new class of therapy based upon a discovery in 1999 by Craig Mellon at one of the schools in Massachusetts, who discovered how viruses and other organisms can alter the cells and bodies of their hosts because they go into the cell and they alter the RNA silencing complex. And that's a mechanism that's the body's natural way of silencing the translation of message RNA. So in simple terms, we all have DNA, the DNA can create a message RNA, which allows us to have proteins and other things to synthesize things in the body. Dr. R The body has used this RNA silencing complex as a way to silence the translation of things when those things need to be turned off. I think in 2005 or 2006, Dr. Mellon and his team won the Nobel Prize, I think in medicine for this. It was a very quick thing. Well, now fast forward to 10 more years from that Nobel Prize, and now there were therapeutics being developed using this by a company called Alnylam in Massachusetts, and the medicines company had acquired the use of a drug that they were going to call Lyran. And we started looking at it, and I was struck by how easy this was to take. It was like a small vaccine akin to getting a flu shot that quick and you could lower cholesterol 35% or 40%. And I immediately said to the CEO, I said, this is going to be disruptive and this can replace statins someday. Dr. R And I said, we really need to be testing this. And he said, yeah, that's why we're here. And so we were invited and were four or five of us, and we have worked with them to help bring this medication from the concept stage, the preclinical stage through phase two and phase three clinical trial testing. And it was approved by the European Medicines Authority about a year before FDA approved it. Its approval process started coming during the pandemic, which slowed down approval in the US because the factory producing this compound was in Italy. And of course there was little travel during the early part of the pandemic. So FDA couldn't go and look at the factory and delayed the process. Now it's approved in 80 countries, but it's called a small interfering RNA compound. It silences the translation of a protein called PCSK nine. PCSK nine is probably the most important way we regulate cholesterol levels in the body, even more important than what statins do, blocking the enzymatic synthesis of cholesterol because by blocking PCSK nine, you can reduce cholesterol 50% to 80%, which is about twice what typical doses of statins will do as they're titrated up. Dr. R And when used in combination with statins, you can have fairly profound lowering of cholesterol. You can take someone with a total cholesterol of 200 and bring it down to 90 or so or 80 with both statins and these drugs. So we can bring people's cholesterols to very low values. And that's important because before we all lived in urbanized centers and we were hunter gatherers. Our natural cholesterol levels were 80 to 100. And the LDL cholesterol or the type of cholesterol that causes plaque buildup and heart attacks and strokes was in the 10 to 20 to 30 milligram per deciliter range. So what we see in urbanized areas, especially in the west, and frankly anywhere in the world that you live in an urbanized areas is your LDL cholesterol gets up to 100 to 200, and that's when it starts having to be deposited into the artery walls and other places because the body doesn't want that toxic stuff around. Dr. R So it tries to push it away to get it out of the way. And that leads to disease processes that cause stroke, heart attack, the need for bypass surgery, stents, things like that. So anyway, the best way to lower this was through statins, initially diet, then statins, and now by blocking PCSK nine. And there had been monoclonal antibodies to PCSK nine that were developed and tested and proven effective, but they were initially priced at about 16,000 a year and almost no one could afford them. Then the price dropped to seven or 8,000 a year, and they still weren't being widely prescribed. And so at the time we were developing the approach to testing this new compound, we all insisted that while we couldn't dictate a price, this had to be affordable for the average person. And so to the company's credit, they promised that, and then they also promised to bring it out in a way that most people on Medicare wouldn't have to pay excessively out of pocket for it because we felt the target population. Dr. R Now, of course, we know it's a lot of pre-Medicare patients, younger people like us who also need it. And so it works by, you get an injection now, we use it twice a year. When you start on it, you get an injection on day one, day 90, and then every six months after that. So it's a twice a year medication, typically over a lifetime, and it lowers cholesterol depending on your type of condition between 45% and 60% in combination with a statin. It's quite potent to go even lower than that. So it's a very well tolerated medicine. It is an injectable. It has to be given either in your doctor's office or an infusion center because it was tested and designed that way while the monoclonal antibodies, you self-inject every two weeks at home. So right now we're an injectable phase of treating high cholesterol where you take a pill and then you also take an injectable and you can either take it every two weeks at home or twice a year at your doctor's office or an infusion center. Dr. R And that's kind of what we're doing. So it's a small interfering RNA and I didn't think too much about it. And in terms of that, because it gets into the body, it's delivered directly to the liver, it's designed so that it's only taken up by the liver, it doesn't go anywhere else, and then it works in the liver and then after only a single dose, you get a profound effect. But it wears off and that's why we go to twice a year. So it's not like it's a permanent change to the body. People don't have to worry that it's going to irrevocably or irreversibly alter their physiology. It doesn't that we wish it would last longer, but it doesn't. And that's a safety mechanism. And so it's been tested, and at least in the initial work that we published in a large number of patients, including a publication just in May of this year, it's profoundly safe and has very few side effects except some itchiness and redness typically at the side of the injection, like almost any injectable can, whether you take insulin or other diabetes medicines or you're taking wegovy or ozempic for weight loss, those can also give you some itchiness or redness at the injection site that you don't really pay attention to. Dr. R But fast forward to the pandemic and then suddenly any use of anything with RNA became a politically volatile topic. And how do we talk to patients about this medication, which is life changing in the setting of not politicizing it and either causing them to be highly in favor or highly opposed to it. And so that made it kind of tough. But thankfully I think we've kind of moved beyond that a little bit in our country. And so now we can continue to talk about this in a way that explains the science and helps them understand. And it's really the mechanism of this is going to lead to discoveries for treating a lot of disease states, not just heart disease. Cardiac amyloidosis is a rare condition largely in older people that has uniformly been fatal. And now there is a new drug that's an injectable that was ahead of the one we brought forward that treats that, and it's sold by I think several companies now. Dr. R And then there are blood pressure medicines that have been developed and tested to lower blood pressure by blocking the conversion of angiotensinogen to angiotensin in the liver. Liver diseases are being tested for treatment with this type of therapy because the liver, it seems, has a unique receptor on the surface that's been preserved over millions of years and is expressed in high amounts, and it will take up a carbohydrate moiety inside the cell where you can then couple that with the medicine and deliver it right to the liver. So it's targeted therapy. So what with the benefit of this is that you target it to the organ where you need the medicine to work. You don't get any systemic side effects. You don't get the risks of off-target side effects typically. And so we're at the precipice of a lot of new therapies coming along. I know there's a lot of interest in gene therapy and gene editing, but I see this right now as a much safer alternative to CRISPR Cas nine gene editing because it's not permanent. Dr. R You have to continue to take it. If you get a side effect, you stop. If you get a side effect from gene editing, you live with it the rest of your life, whether it's an off target effect like a cancer or your hair changes color or something, whatever it could be, we don't know what it will be because the gene therapies haven't been approved yet and are just being tested. But I think this is the next phase. So my dream is that we can go from taking pills 365 days a year or several times a day to getting some injectables that are infrequent that make compliance and adherence much better and easier for people. I think all of us who take medications, I certainly do on a daily basis, forget to take them occasionally. You're traveling, you run out, you can't get your refills back in time. Dr. R Somebody doesn't deliver them to you through mail order on time, so you're kind of stuck. And with cholesterol medicine, if you miss it for a few weeks, your risk for heart attack goes up. And so the benefit of this too is that it keeps your cholesterol down. It may not be at 50% down because the drug is wearing off and it may be only at 40%, but it's some reduction and it protects you until you can get the refill of the other medicine or get back for your injection. So that's kind of where we are. I think that's the future. That's where healthcare is heading and I'm pretty excited about it. I think 10 to 15 years from now, maybe we can come back on Radio Maine