Dr. Mario Gaudino set out early in his career to study the difference between doing coronary artery bypass surgery through veins versus arteries but when he started to review the research findings he noticed something strange: there was no data on how coronary bypass surgery was different for women and people of color. As a matter of fact, the only thing doctors knew about coronary bypass surgery in women was that they had worse outcomes. Dr. Gaudino decided that needed to change and has since launched multiple studies focused on understanding the health outcomes of women and people of color undergoing coronary bypass surgery as well as working to define an improved, patient centric approach for clinical research.
Dr. Mario Gaudino is a cardiac surgeon at NewYork-Presbyterian/Weill Cornell Medicine and the Director of the Joint Clinical Trials Office at Weill Cornell Medicine. There he oversees ongoing improvement and enhancements to existing clinical infrastructure and is currently leading research on the effects of coronary artery bypass surgery on women and people of color. His work not only focuses on groups that have been historically underrepresented in research, it also takes a patient centric approach to outcomes focusing on how a patient feels in addition to clinical metrics. His research contributions have potential to change how doctors approach treating huge swaths of their patient population and how they analyze that data.
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Catherine: In 2017, Dr. Mario Gaudino began researching the differences between using veins and arteries in coronary bypass surgery. But when he was setting up his trial he noticed something: less than 20% of the people who had enrolled were women. This meant that his study would only be able to show reliable outcomes in men.
So Dr. Gaudino turned to the research of others for more information and as he sifted through their work, he realized it wasn't just his study. There was no reliable research on coronary bypass surgery in women at all. He decided that needed to change.
I'm Catherine Price and this is Advances in Care.
In this episode I talk with Dr. Gaudino, a cardiac surgeon at NewYork-Presbyterian/Weill Cornell Medicine. He shares how that first trial opened his eyes to a glaring problem in coronary research and recharted his career,
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motivating him to focus on coronary bypass outcomes in women and people of color.
Catherine: Welcome and thank you so much for making the time to speak with me today.
Dr. Gaudino: It's my pleasure to be here, Catherine. Thank you so much for having me.
Catherine: Ok lets start way at the beginning - what led you to cardiology?
Dr. Gaudino: Well, if you're asking why I got into cardiac surgery, I don't know. When I was, like 10, I told mom I wanted to be a cardiac surgeon. I didn't even know what a cardiac surgeon one
Catherine: What?
Dr. Gaudino: Yeah, my dad was a physician, but he was a radiologist, he was not a surgeon. So I cannot tell you what was, what clicked in my brain. But, that's then what I did. I mean, I, in the end, I kept my promise and I became a cardiac surgeon.
Catherine: [laughs] That’s such a specific, sophisticated goal for a 10 year old.
Dr. Gaudino: Yeah. And I did not want to be any other type of surgeon, only cardiac surgeon. it is absolutely the thing I was born to do and
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I like to do. And yeah, no, this one I got it right. Then I got a lot of other things wrong, but this one, this one I got it very right.
Catherine: So what brought you to NewYork-Presbyterian?
Dr. Gaudino: I am from Italy originally, from Rome in particular, the Catholic university and moved to Cornell in 2014. And my plan was to stay one year. I'm still here.
Catherine: What do you mean when you say you only meant to come here for a year and yet here we are Today because it seems like it's been more than that.
Dr. Gaudino: Exactly. Well, so I was very happy in Rome. I was having a good career there and there was no reason for me to move. I came to Cornell for a very specific reason because this institution, has a great reputation for a specific field in cardiac surgery, aortic surgery.
Catherine: Is there something about the institution in particular that really made you want to stay on?
Dr. Gaudino: Yeah, it's the collaborative atmosphere
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and the sense of, being a part of a community that always, aim at doing, better and as, as good as possible. You know, there are amazing people with very different expertise here. if you send to any faculty member an email saying, look, I'm doing something where, you probably have a specific experience and expertise or you have done something.
Can you help me? Well, you, nine times out of ten, you will get an immediate reply saying, yes, let's do it. Let's just jump on zoom and try and work together. This is very unique because in a lot of academic institutions, you know, there is so much competition. On top of that, there was this focus of the institution on research, and the clinical research in particular, which is my passion. You know, the reality is that research is important, but does not pay the bills, right?
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and so a lot of institutions, a lot of hospitals are moving away from research and trying to generate clinical revenue as much as possible. And this is bad for people like me who would like to do research. At Cornell, there was a different culture. And so that was a key reason.
Catherine: Speaking of research, I understand that you recently secured funding from the patient centered outcome research institute for a set of studies called RECHARGE that’s looking at an unusual set of outcomes. Can you tell me about those?
Dr. Gaudino: RECHARGE is probably the trial I am most proud of.
Dr. Gaudino: Recharge, it's like a dream. And if we are successful, it will be a game changer. And for two key reason, one reason is the study population recharges a trial comparing a stent versus bypass surgery in women or in
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black and Hispanic patients. So it's actually two trials separate. There is the women trial and there is the black Hispanic patient to trial. There is some overlap because women who are black or Hispanic will contribute to both trials. So it's again, it's a new design. That increases efficiency because essentially the same patient can contribute to two trial. So that's, it's very innovative. And I was shocked when I learned, you know, stent and bypass surgery are the most common intervention for to treat coronary artery disease. There are hundreds of thousands of procedures performed every year in the United States, and there have been dozens and dozens of randomized clinical trial comparing one to the other in different variations. No one in women, no one
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in racial and ethnic minorities. So our first idea was, well, this need to be done. Let's design it.
Catherine: I mean I love that your response was “I can change that!” So walk me through this trial - how are you designing and recruiting for it?
Dr. Gaudino: Yeah. The patient population is, again, either women or black and Hispanic patients that have a coronary artery disease. They have done cardiac catheterization, so they know that they have severe coronary artery disease and that they need revascularization.
So at each site, we have more than 60 sites all across the nation. There is a heart team. The heart team is essentially a clinical cardiologist and interventional cardiologist and the cardiac surgeon. They review every single case and they define if there is equipoise. Equipoise meaning they believe that they can achieve
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the same success, the same procedural success with both intervention.
Dr. Gaudino: So if this is not the case, if they believe that one technique is better than the other, in their hand or in general, then the patient will not move forward with the study and will just receive the intervention that is clinically indicated. However, for those patients where, the local heart team believe that the two intervention are similarly effective in revascularizing the coronary arteries, then if the patient consent to be part of the study, there will be randomization. And so the randomization with the will be between bypass surgery or stent angioplasty.
Catherine: So can you quickly clarify why someone might choose stent angioplasty?
Dr. Gaudino: It's an alternative coronary revascularization technique compared to surgery. It has the great
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advantage of not requiring surgery, right?
Catherine: Yes, that does seem nice [laughs and crosstalk] given the choice of surgery versus non and the same outcome.
Dr. Gaudino: Exactly. The problem is the duration of the result with stent angioplasty seems to be not as durable as with surgery.
Catherine PU: I see … ok thank you for clarifying that. So I actually want to ask you about something else that seems really innovative about the trial, which is that you're measuring outcomes in a really patient centric way. Can you tell me a bit more about that?
Dr. Gaudino: The idea was that we have used a very new, innovative and unique primary outcome. So let me be a little bit boring here, but the primary outcome…
Catherine: No, you're lucky because people who are listening are not going to find this boring, so you can go for it.
Dr. Gaudino: Thank you for that. So the primary outcome
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is what you are measuring, right? In, in your study. And traditionally, stent versus surgery trial have used a composite of cardiovascular events, generally including mortality, myocardial infarction, so heart attack, stroke, the need for repeated coronary revascularization, in different iterations. This is what is called the classic MACE outcome, where MACE stands for major adverse cardiovascular events.
Dr. Gaudino: There are several problems with using this approach. First of all, we don't have a very good definition of nonfatal events. So like, you know, a myocardial infarction can be a large myocardial infarction that put the patient at risk of dying or for heart failure, but it can also be totally asymptomatic just with a small bump in Troponin or in biomarkers
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that doesn't affect the patient's quality of life in any way, shape or form.
And even more clearly,
I can use another example of stroke. So you can have a stroke that is devastating and that leaves the patient hemiplegic, but you can have also a stroke that is totally asymptomatic and that you find out only on a control MRI because there is a small signal in the small image, but nothing has happened to the patient. So first of all, we do not know how to define a lot of the events. And that's problematic.
Catherine: So they all get lumped together as if they're equivalent.
Dr. Gaudino: Exactly. Exactly. And then the other question is okay, but what about non cardiovascular events that are important for the patient, but we are not measuring it. What about, for example, a renal failure and dialysis, arrhythmia or, re hospitalization for heart failure of any reason, wound, wound complication, bleeding.
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I mean, all those events that are very important to the patient, we are not. They have not been measured. Well, they've been measured, but they're not been formally compared because the primary outcome was only focused on cardiovascular events.
So what we did, and this is thanks to the PCORI mechanism, because, you know, PCORI required a very close engagement with patient during the design of the study. So we have listened to the patient and we have asked the patient, what is important for you? What are your expectations? What's your goal and your hope? Undergoing either stenting or bypass
surgery. And essentially the answer we got, I think I can summarize in the sentence. I want to live longer and to live better. That was the constant answer. And so we design our primary outcome
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around this. Our primary outcome is survival and quality of life.
Catherine: So that actually reminds me of a question I wanted to ask you just about how you actually got the input from the patients, because you were alluding to actually talking to them….
Dr. Gaudino: Oh, it was one of the best things in my life. We did those, focus group and interview with the patient and patient representative from all over the country, mostly women, black and Hispanic patients. And we asked them questions like, what's important for you? What do you value the most? What are your expectations? And, you know, we, as physicians, when we started, we all thought that, okay, you have coronary heart disease. So what's important for you is a heart attack, chest pain, that kind of stuff. And I remember, these men telling the group, look, I can take a little bit of chest pain now and then, but I really
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want to be able to go dancing. I love dancing. I go there every Saturday night. For me, if I cannot dance,
that would be, really, something that make my life, uh, miserable. And, you know, we have never looked at dancing in our study, but…
Catherine: You need to have them, the mace-d, you can put the D at the end, right?
Dr. Gaudino: Exactly! Exactly. So we have learned so much from those patients and I am really grateful for the time they spent with us and they gave us a different perspective.
Catherine: Okay and is enrollment open now or when does this start?
Dr. Gaudino: We are in the startup phase. So we are finalizing the regulatory part of the contract with the participating side.
Catherine: You know, I have to say as a, as a patient and a person who enjoys dancing I am just I'm so grateful that you're doing this and I can't wait to learn what you learn from the recharge trials.
Catherine: And I also wanted to ask you about something I believe you have already studied, which is the question of whether veins or arteries are best to use in coronary bypass surgery. Is that right?
Dr. Gaudino: Yes, that's exactly right. So I do coronary bypass surgery. And for this operation, you can use either arteries or vein to bypass the blockage in the coronary artery. And it was fate or chance because For many years, veins have been used and there was no alternative to veins. And then in the early nineties, some pioneers in Europe, in Australia, and also in the United States, proposed the use of arteries, which require… it's a different technique. It's a different, uh, they require a specific training. And I was lucky enough to actually train with, pretty much all of almost all those pioneers. So I was exposed to the use of artery from the very
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beginning of my career. And so, this is what I've been doing for most of my career.
Catherine: So I'm curious - what's the difference between using veins and arteries? Is one option better?
Dr. Gaudino: I think the key benefit of using a vein rather than an artery for a surgeon is that it's much easier technically. There are a lot of veins that you can use, a lot of options. The arteries are smaller, more fragile, um, a little bit more complicated to harvest and more complicated to deploy. And there is a learning curve and, um, during the learning curve, the risk of operative complication, it's higher with arteries rather than vein. On the other hand, We have seen how arteries, once they are deployed correctly in the coronary circulation, then they stay open and so it's a more
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durable benefit for the patient, compared to the use of vein.
Catherine: Gotcha. Well, that actually brings up something I wanted to ask you about because my understanding is that you then did a trial called the ROMA trial where you actually compared arteries versus veins in coronary bypass surgery. So can you tell me more about what motivated you to design a trial like this?
Dr. Gaudino: So the ROMA trial started, in 2017 and, it essentially started because another very large trial run in the UK that was supposed to finally prove the role of arteries rather than vein for bypass surgery. So that trial failed in the sense that there were issues in the trial design that were not considered by the investigator and so at the end after Almost 20 years of running this trial was unable to provide a clear
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answer if artery were better than vein or not.
Dr. Gaudino: There was a lot of disappointment in the cardiac surgery community. We had been waiting for that trial for 20 years. And I thought, well, why don't we do another trial like that? And at the beginning, uh, everybody thought I was crazy. But, we got it done. And actually, the silver lining is that because the other trial failed, we know exactly what not to do. And so we designed a much better trial that was also larger and more ambitious.
Catherine: I mean that’s really interesting how you took the failings of that trail and then turned that into and opportunity to do something better. And it’s occurring to me that seems a theme in your work because my understanding is that you also realized when you were doing the ROMA trial that it had limitations and that led to your ROMA Women trial. And so I'm wondering can you tell me more about that trial and why you felt it needed to be done?
Dr. Gaudino: Sure. For most of my career,
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I have studied this artery issue. I knew just by reading the literature result in women were not as good as men, but that was not the primary focus of my research. And then, when I was designing my trial that is testing actually the role of arteries called the ROMA trial is a very large trial. I realized that, like in many other, like in essentially all other trials in cardiology and cardiac surgery, there were only 20 percent of women.
Catherine: Enrolled, you mean,
Dr. Gaudino: Exactly. So I said, well, okay, we don't have enough women, but Is there a reason why, results should be different in women? And so I start looking into that more granularly, more in details. And I was really shocked when I realized that We dunno anything about bypass surgery in women, except that the result are not as good as in men. That's the only
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thing we know. But we are not doing too much to change that.That was a little bit the epiphany. That's why I said, okay, this is something that needs to be addressed.
Catherine: So how much worse are we talking? How did the outcomes for women compared to those for men?
Dr. Gaudino: Well, significantly, so I can tell you that we looked at all the Bypass surgery performed in the United States the last 10 years. And each year, the operative mortality for women was significantly worse than that in men. Women in general had 30, 40 percent more risk than men of dying after the operation, and an even higher risk of having a complication. And this did not change, there was no evidence of a temporal improvement. The results were as bad at the end of the study period as they were at the beginning
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of the study period.
Catherine: How long has it been known that women have poorer outcomes, but nothing's really been done? How long has that been something people are aware of?
Dr. Gaudino: Probably three decades.
Catherine: Really.
Dr. Gaudino: Yeah. I was making the same mistake that everyone else had done before me. And that's why I said, okay, do we address that? Well, we must do another trial. You know, there is a famous, uh, quote from one of the German internal medicine editor, who used to say, women are not small men. And that's exactly right. But we have, we have made this mistake over and over.
Catherine: So how did you decide to fix it?
Dr. Gaudino: Well, the idea was simple. By leveraging the main trial, ROMA, we design a, spin off trial that is called ROMA Women, that is dedicated to women and will include women only, again, looking at the artery question, but in women specifically. What we will
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do once we close the completed enrollment in the main trial, rather than closing the site like you generally do, enrollment, we will keep all the site open, but the site will enroll only women. They will not enroll men anymore. And we will do that until we reach a number of women that give us enough statistical power to compare, artery to vein in women only.
Catherine: That brings me to my last official question for you, which is if you could fast forward to the end of these trials and studies, I'm wondering what your dreams are, you know, when it comes to what impact the ROMA trials and the recharge studies might have on the overall design of clinical trials and then also on patient care.
Dr. Gaudino: Well, whatever the result will be, both trials will provide very important information to, to treat,
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patients with coronary artery disease, and in particular women and, uh, and, underrepresented minorities. I would be very proud if after those studies have completed, a physician could finally have some guidance on how to treat those patients. And more broadly, if we, if recharge can, and Roma women can change the way trial are designed. Well. That would be really even more important because it would affect potentially patients with a variety of disease, not only coronary artery disease wise, so it's all very exciting.
Catherine: I mean, it is really exciting to hear about because what I'm hearing you saying is that it's not just that you're doing much needed studies on populations that have not traditionally been represented in studies, but you're actually potentially transforming the way that trials are designed in general because you are focusing on outcomes that matter to patients
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which makes so much sense and is so important. So, you know, thank you so much for making the time to speak with me today and more broadly for all the work that you're doing. It is just so needed and I for one truly appreciate it.
Dr. Gaudino: Thank you very much, my pleasure to be here.
Catherine: Huge thanks to Dr. Mario Gaudino for all the work hes doing to improve coronary bypass care and quality of life for women and people of color.
I’m Catherine Price.
Advances in Care is a production of NewYork-Presbyterian Hospital. As a reminder, the views shared on this podcast solely reflect the expertise and experience of our guests. To listen to more episodes of Advances in Care, be sure to follow and subscribe on Apple Podcasts, Spotify, or wherever you get your podcasts. And to find out more amazing stories about the pioneering physicians at New York Presbyterian, go to nyp dot org slash advances.
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