Evolving approaches to diagnose coronary artery disease | Professor Leslee J. Shaw

Aug 18, 2023

Evolving approaches to diagnose coronary artery disease | Professor Leslee J. Shaw

This keynote was filmed at Metabolism Day on March 14, 2023 at the University of Copenhagen. Metabolism Day is a conference about energy control and metabolism, and is hosted by the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR). For more information please visit: http://cbmr.ku.dk

Leslee Shaw, PhD is a leading outcomes researcher whose major focus is cardiovascular clinical diagnosis of ischemic heart disease. Dr. Shaw has published more than 800 publications and presented more than 400 abstracts in major scientific meetings in the United States, Europe, Asia, and South America. She has been ranked as one of the top 1% of clinical researchers with the most highly cited publications (awarded by Thomson Reuters), with an H-index over 150.

Based on her scientific contributions, in 2009, Dr. Shaw was recognized with the Simon Dack Award for academic excellence from the American College of Cardiology and, in 2013, the Coalition to Reduce Disparities in Cardiovascular Disease Outcomes Award for her research contributions in racial and ethnic differences in cardiovascular disease. In 2013, she received the Women’s Day Red Dress Award for her scientific contributions to women’s health. In 2017, she presented the Mario Verani Lecture at the American Society of Nuclear Cardiology. In 2018, she was awarded the Gold Medal from the Society of Cardiovascular Computed Tomography and, from the North American Society of Cardiovascular Imaging, gave the Paulin Keynote Lecture. In 2020, she was awarded the Bernadine Healy Leadership Award in Women’s Cardiovascular Disease from the American College of Cardiology. Also, in 2020, she received the Nanette Wenger Award from the American Society of Preventive Cardiology and, from the Academy for Radiology and Biomedical Imaging Research, she received the Distinguished Investigator Award.

She has served as an Associated Editor for several journals and now serves as Executive Editor for the Journal of the American College of Cardiology: Cardiovascular Imaging, with the highest rated impact factor for imaging journals (2020 Impact Factor: 14.8). She is also an editorial consultant for the Journal of the American College of Cardiology and Circulation. Dr. Shaw is a Past-President of the American Society of Nuclear Cardiology and the Society for Cardiovascular Computed Tomography. The only individual having served as president of two medical societies within cardiovascular medicine.

Content

1.001 -> NOTE: The captions are AI generated and may contain errors

9.39 -> So welcome back. I'm Martha Guasch. I'm a group leader here

12.51 -> at CBMR. And it's my great pleasure to introduce our next

16.05 -> speaker, Dr. Leslie Shaw. She's a professor of medicine and

20.43 -> cardiology at the Icahn School of Medicine at Mount Sinai. And

24.99 -> her work has been focused on cardiovascular clinical

29.01 -> diagnosis of ischemic heart disease. She has more than 800

32.58 -> publications on this topic. She has been awarded with several

36.48 -> awards, including the Bernadine Healey award in woman's

39.54 -> cardiovascular disease from the American College of Cardiology,

42.66 -> in 2020. She is the editor of several impactful journals in

47.55 -> the field of cardiology, including the Journal of the

49.77 -> American College of Cardiology, cardiovascular imaging, and she

53.67 -> will be talking to us about evolving approaches to diagnose

58.32 -> coronary artery disease. So it's a great honour to have you here

61.62 -> lately. And please, the floor is yours.

65.099 -> All right. Everybody has their lunch and they're ready to go.

70.679 -> I'm a cardiology, cardiovascular researcher. I'm a clinical

74.909 -> researcher, you know what the worst thing to do and for a

78.269 -> clinical researcher, is to speak to an audience of mostly basic

81.659 -> scientists. So I'm going to do my best I hope you'll, you'll be

85.409 -> gracious with me. And but let's importantly, let's have fun, I'm

90.089 -> going to keep you awake for the rest of the afternoon. So here

93.839 -> we go. Just some relevant support disclosures, mostly from

98.579 -> rich people, which is important places in the United States. So

104.639 -> I don't have to tell this audience you may not know

106.559 -> anything about atherosclerotic cardiovascular disease, nothing,

110.729 -> you know the term you've heard it, you know, it has to do with

113.369 -> the heart and the vascular system, that's all you know, but

117.149 -> you likely most of you know that it increases the diabetes

121.409 -> increases the risk prevalence of atherosclerotic cardiovascular

125.249 -> disease, at least to fold and more in higher risk patient

128.699 -> populations. So I'm not going to spend a lot of time on this

131.789 -> slide. It's all forms of atherosclerotic cardiovascular

134.999 -> disease, I'd rather talk to you about some evolving approaches

138.929 -> to diagnosing atherosclerosis, which is really exciting. At

142.949 -> least it is to me, so the best thing in the world is to find

145.889 -> something you're passionate about. So since the late 50s,

149.249 -> early 60s, this was our approach to diagnosing coronary disease.

153.389 -> The whole goal around it was to detect an obstructive stenosis,

158.639 -> a blockage in a coronary artery, because you had to actually then

162.839 -> go in and intervene on that. So that was our whole approach.

167.009 -> Guess what it actually affected such a small percentage of

170.909 -> patients. And and it resulted in treatment decisions that had to

175.499 -> do with largely with the treatment of coronary

178.739 -> recruitment with coronary revascularization either

182.069 -> coronary bypass surgery, or percutaneous coronary

184.979 -> intervention. And it didn't really optimise and emphasise

188.909 -> the use of medical management, which is highly important for

191.699 -> preventive care, which I've heard a lot of about today, in

195.299 -> 2021, this is all changed. But also, I would have to tell you

200.339 -> that these newer guidelines were led initially by a really,

205.349 -> really provocative guideline from from Denmark as one of the

209.219 -> first national guidelines to adopt this novel approach to

213.239 -> diagnosing coronary disease. So that's kind of cool, right. And

216.839 -> it also was followed by UK and now you know, the Americans are

219.539 -> a little slow. So we were the last in the group. All of you

222.509 -> would probably agree with me in this in this was the American

225.659 -> Heart Association, American College of Cardiology, and you

228.059 -> can see a whole array of other organisations involved in this.

230.699 -> So I'm going to focus in on that. So historically, that

233.519 -> approach was to induce ischemia, looking for lack of blood flow,

238.259 -> which impacts either perfusion into the myocardium, or it

241.799 -> impacts wall motion. And I'll show you some examples of that.

245.159 -> This evolving approach now looks at focusing on non invasive, the

249.959 -> use of non invasive CT a CAT scan to actually look at

253.859 -> atherosclerotic plaque. So there is this conflict between the

257.399 -> two. And although I could talk about risk stratification, in

262.619 -> diabetics, looking at this is looking at myocardial perfusion

266.639 -> SPECT. And you can actually see some varying ad abnormalities,

272.849 -> you know, depending on the coronary artery that you can

275.069 -> actually visit a lot visualise. And then you can look at you can

278.069 -> obviously look at particular function. And on the figure on

281.489 -> the right, you can actually see a whole array of different risk

284.159 -> subsets based upon the percent of the myocardium. That's

286.859 -> ischemic, or has reduced flow in that including diabetic and non

291.929 -> diabetic populations. But that's not as exciting as what I'd like

295.919 -> to talk about and there are also other methodologies and looking

299.549 -> solely Get wall motion. And you could see this grainy image here

303.239 -> on the top, I'm being critical and we shouldn't diss other

306.509 -> modalities that are that are to not high as higher resolution.

310.499 -> And we can actually stratify diabetics, that's great on a lot

314.519 -> of the state is 20 years old. And you all mostly are young,

318.449 -> and we want to focus on cutting edge state of the art imaging.

322.979 -> But also, I'm a clinical scientist. And part of those, my

326.999 -> publications focus, not just on developmental work, but on

330.539 -> clinical trial work. And this is not my clinical trials. But this

333.479 -> is some recent clinical trials, which have shown that if you

337.589 -> understand the anatomy of a patient, you understand the

341.219 -> burden of atherosclerosis, you can do a much better job of

345.089 -> identifying risk in that patient patient population. And that's

347.999 -> what this promise trial data shows. You can actually see in

353.399 -> CT looking at coronary CT angiography, I always put the

356.729 -> abbreviations at the bottom for the most part unless I forgot.

360.149 -> So you can give you in case you don't know the abbreviations,

362.699 -> you can see a nice ability to risk stratify correct, you can

366.179 -> guys can see normal to markedly abnormal, but not so much here

370.289 -> on the stress testing can't necessarily differentiate the

373.649 -> normal from mildly abnormal, because not every stenosis, not

378.479 -> every atherosclerotic lesion actually induces ischemia. You

383.069 -> can form collaterals, around the blockage, and things like that.

386.879 -> So it's not as good a tool stress testing patients are

391.469 -> problematic. They don't like to exercise, particularly

394.019 -> Americans. So they don't do well on stress tests. And so, but

399.419 -> looking sitting under a CAT scan for a few minutes, seems to do

402.749 -> the trick. And I'm gonna get into a little bit more detail.

405.359 -> But this has led to a lot of guidelines. And here's one from

408.149 -> the the American Heart Association, very recently, in

411.929 -> type two diabetes, which is a physician statements that showed

416.189 -> an ad supported that coronary CT angiography has an advantage,

420.449 -> particularly in the patient who is at high risk for

422.999 -> atherosclerosis, the type two diabetic patients and patients

426.239 -> overall, with stable angina. So we're starting to get more and

429.719 -> more guidelines support for this, as you can see, and but

433.799 -> the biggest piece of information that I think should solidify,

437.999 -> that looking at atherosclerosis should be our primary target has

442.199 -> to do with a couple of clinical trials, which republished just

445.139 -> in the last few years. This is the promise trial, again,

448.769 -> overall primary trial, this is a $70 million trial, sponsored by

454.079 -> NIH NHLBI Heartland Blood Institute. So what you see is no

458.279 -> difference in randomization of 10,000 patients to a CTA

462.599 -> approach versus a functional testing or stress testing

465.149 -> approach. But in a pre specified endpoints looking at a subgroup

470.039 -> with diabetes. And again, another specialty, we're not

472.859 -> really good at giving you more phenotyping around diabetes,

475.949 -> that's typical in medicine. You can see that on the top.

481.14 -> Here, you can see here on the and I'm like challenged with

484.65 -> this pointer, as you can see that you get a hazard ratio of

488.94 -> point three, eight, okay, so clinical trials, 1011 minus the

493.08 -> hazard ratio gives you the relative risk reduction. So what

496.53 -> a 62% relative risk reduction if you're a diabetic, and if you

501.18 -> have a coronary CTA as the initial diagnostic strategy to

506.01 -> guide clinical management. So CTA guided strategy, that same

510.57 -> benefit did not was not manifest in the non diabetics.

514.29 -> Interesting. Why is that more prevalent atherosclerosis, more

518.64 -> high risk, and therefore detection of atherosclerosis, in

522.42 -> treatments initiated by the presence and severity of

525.96 -> atherosclerosis is going to initiate improvement in outcome.

528.78 -> This is a secondary analysis. So clinical trials, one to one

532.44 -> would still tell you, it's a secondary analysis, not the

535.65 -> primary aim. So it's important, but what you want to look at is

539.73 -> now patterns in the literature. And what we also saw from the

543.09 -> Scott Hart trial, this is a really interesting and accurate

545.94 -> acronym, Scottish study of the heart. Really, that's that's,

549.51 -> that's what the best they could come up with for an acronym. So

552.81 -> they also showed the same I mean, look at this, it's

554.97 -> amazing, this hazard ratio of point three, six, it's virtually

558.57 -> identical to the PROMIS trial. So now we're getting these

561.42 -> patterns in the literature, particularly in higher risk

564.21 -> patient populations, like those with diabetes, that having an

568.32 -> understanding, the coronary anatomy is fundamental to

572.76 -> guiding care, fundamental to intensification of preventive

577.29 -> care of cardiovascular disease. And so in the recent ACC AJ

582.93 -> guideline, this is one of the things you get to do when you're

585.96 -> old and been around a while. You get to interject a lot of things

589.65 -> in clinical practice guidelines that nobody agrees with, and

592.32 -> then you force it down their throat and then all of a sudden

594.3 -> it gets published. And everybody goes, Oh, that was a great idea

596.94 -> that I had, I'm like, Excuse me, but that's That's you. That's

600.69 -> called research and in a career, right, so CTA. So here we have

605.91 -> now I want to just illustrate this because this is fun. This

608.97 -> is, you know, all of these patients have plaque. So this,

612.51 -> this is a normal coronary, you guys see this little dark spot

615.48 -> here, or this white white spot, this is calcified plaque. And

619.62 -> this is non calcified, or lipid rich plaque. This, it's getting

622.92 -> increasingly worse, until all of a sudden it results in a

626.25 -> stenosis here. So this is our traditional definition, right?

631.02 -> It used to be way up here, look at all the plaque, we missed. My

634.74 -> gosh, this is 60% of a diagnostic population has

637.8 -> plaque. We were missing that plaque doesn't go away on its

642.96 -> own, it's only going to progress. Right? So if we don't

647.4 -> identify it, we're not going to treat it. And if we don't treat

650.16 -> it, you're gonna have the same outcomes you had a while ago. So

653.07 -> this is what I get passionate about. I know it's kind of

655.14 -> weird, right. But we've now you know, we've we've lowered that

659.64 -> threshold, way back here. So this is normal, everything else

663.45 -> is abnormal. And therefore, all of these patient populations to

668.25 -> the right are now all targeted for intensification and

671.91 -> intensified preventive therapies, which is really what

675.33 -> you're talking about why you want to do a better job of

677.79 -> identifying and understanding diabetes. And but after if you

682.29 -> look at a patient population, it's prevalent atherosclerotic

686.52 -> plaque is prevalent, you remember those white spots, I

689.07 -> don't know how well you can see this how well this projects,

691.68 -> this is just a cross section, a CT cross section of the heart.

695.46 -> And you can see, can you guys see these little arteries here,

697.95 -> they're all white, that's not, I'm not trying to identify that

701.49 -> that's a purely calcified lesion, it is so easy to image,

705.99 -> you don't have to be imaging expert, you can see calcified

709.65 -> plaque, because it's like bone, right, so you can see it. This

713.82 -> is just so simple. Coronary disease is simple, right? You

717.72 -> shouldn't have a should be nothing there. But what's nice

722.46 -> about about looking just at calcified plaque doesn't require

725.43 -> contrast, it's easy to image, it does require radiation exposure,

729.78 -> but a small amount, probably about the same amount as I had

733.14 -> from flying over the ocean. And it's generally low cost 50 to

737.76 -> $100 in the US, which is low cost. But you look at the

741.09 -> prevalence across patient populations across a whole array

745.56 -> of ages increases starts to increase in a woman somewhere

749.04 -> around age 45. Everybody knows what happens in that 40 to 50

752.82 -> year old range. It's called menopause. That actually is once

757.59 -> the protective effect of oestrogen is diminished, that

762.33 -> the incidence of cardiovascular disease increases dramatically.

765.45 -> And you can see that really nicely illustrated here. And you

768.93 -> could see it in men about a decade earlier, so that by the

771.51 -> time you get a patient population, that is really kind

774.78 -> of seeing maybe a cardiologist or seeing a preventive medicine

778.02 -> specialist, at least half of them are going to have some form

781.77 -> of atherosclerosis. Just think about that you walk by a clinic,

785.7 -> and you look in and see people sitting there, least half of

789.03 -> those people have atherosclerosis. Now, I'm not

791.79 -> saying if you go by a paediatric clinic, just want to make sure,

794.07 -> just, but you know, it's really incredible how much we've

798.24 -> missed, and how much we haven't looked at this in the past few

801.87 -> years. Here's one paper from one of my colleagues, it's a very

806.13 -> complicated slide. So I'm not going to really go through it,

808.44 -> I'll give you the the cheat sheet on the right, you can look

811.32 -> across the the array of patients with type two diabetes, or no

816.45 -> type two diabetes across the ages and women and men. Bottom

820.14 -> line. If you you have calcified plaque at a rate that's fourfold

825.03 -> higher in diabetics, and it occurs at a younger age. So

829.53 -> they're going to have atherosclerosis longer than the

832.02 -> than a non diabetic patient, which is it's mine, it's mind

835.35 -> blowing, and what is going to happen with that diabetes. But

838.86 -> that atherosclerosis, it's going to accelerate faster, it's going

842.52 -> to lead to much more progressive and worsening disease states,

845.7 -> and therefore catching it early becomes fundamental to averting

849.18 -> risk, cardiovascular risk and a patient population. I'm just

852.72 -> going to throw at you a bunch of slides on looking at this simple

856.05 -> measure of calcified plaque. Here's two papers from some

859.98 -> colleagues of mine. Looking at this again, this corner account

863.73 -> or calcified plaque or coronary artery calcium. What we can see

867.42 -> in a type one diabetic population with a on average,

870.72 -> around 20 years of diabetes, this population risk based upon

875.55 -> a score, but what's really fascinating in this patient

878.97 -> population, so look at the top line, and you see in a patient

883.11 -> population 45 to 50 years old at about a decade, one in four of

887.16 -> them has cardiovascular disease one in four that's that's truly

892.77 -> truly amazing. In the same in the in the Mesa study, we were a

897.15 -> mesa site but you can look at diabetes metabolic syndrome and

900.81 -> people. And in every case, you'll see this gradation of

903.96 -> risk. This is just a pattern you see, in all of cardiovascular

907.71 -> medicine, there's an acceleration of risk

910.29 -> acceleration of atherosclerosis. If I say that like 10 times,

913.68 -> maybe we'll, we'll all remember it so and to get you through the

918.72 -> session after after lunch, now, this is where it gets a little

922.98 -> cardiovascular. So if you'll just let me walk you through

926.91 -> this. If you have an acute coronary syndrome, and you've

930.87 -> had a previous angiogram, that's it looking at the anatomy. acute

936 -> coronary syndrome would be a heart attack, myocardial

938.28 -> infarction, unstable angina hospitalisation, about two

942.45 -> thirds of the time, or 6060 plus percent of the time, you would

946.71 -> it would have occurred in a previously non obstructive

950.22 -> stenosis was not a significant stenosis. This is fundamental.

955.2 -> Because largely in the past, we ignored that, which was non

959.76 -> obstructive in many cases. In many cases, the cardiologists

964.08 -> would say, Oh, you, you're fine. You can go home, even if you had

966.69 -> a lot of plaque, even if it was diffuse and non obstructive.

970.23 -> They would say, No, no, you're good, you're good. But what I

973.32 -> really want to get you to appreciate because this is how

975.84 -> it's going to help in the field of diabetes, particularly, is if

980.37 -> you look at this cartoon here on the right, one from one of my

984.45 -> colleagues, Amir Ahmadi, this necrotic core is a lipid rich

988.89 -> plaque. It is the highest risk plaque, it's that which causes

993.09 -> an acute coronary syndrome. If you look at this, there are two

996.87 -> ways the plaque can go from there. And this is a 40%

1000.65 -> stenosis. This is cardiology 101 40% of the diameter is

1007.1 -> blocked, and it's a 40% stenosis, that gives you an

1010.37 -> idea. So stabilisation we can stabilise the artery, we can

1014.36 -> shrink the lipid rich component. Five years ago, if I sat up here

1019.01 -> and said, I would have got some booze, we now in the hole, we

1022.46 -> can shrink that plaque very easily we can stabilise that

1026.3 -> plaque, we can transition that plaque to be more calcified, so

1029.84 -> it's more stable. And I'll show you some examples of that. And

1032.63 -> here's what happens if it progresses, we can see that

1035.87 -> necrotic core gets bigger.

1038.749 -> But it also the artery starts to remodel and not necessarily into

1042.379 -> the lumen not necessarily where the blood flow, which is really

1045.439 -> scary because then it's not going to be detected by symptoms

1048.529 -> or other. So if it remodels outwardly, it can grow where you

1052.729 -> can't really actually get a manifested symptoms on it, which

1055.969 -> is really, it's not a good thing. But all the more reason

1060.379 -> for us to intervene before that patient has a heart attack and

1064.099 -> potential myocardial damage or death, which is really the goal

1069.469 -> of us in the goal of our research. And we know from

1073.549 -> pathologic This is from sudden death, that there are two

1076.609 -> components that we see in atherosclerotic plaque, we see a

1080.299 -> very strong inflammatory signal within the pathologic data. And

1086.299 -> we also see a huge bulky lipid rich, necrotic core and all

1091.939 -> kinds of lipid rich plaque much more than you see in non

1095.209 -> diabetic populations, which is fascinating, right, so both of

1099.769 -> those things, we can actually image and we can actually

1104.119 -> including inflammation, and we can actually shrink or alter

1108.649 -> that sequelae not for these folks, right? Because they're

1112.009 -> there already. And we have actually a large Sudden Death

1114.799 -> group as well, that we're just starting to explore, we're a

1118.279 -> little behind, that's research. So remember, two inflammatory

1121.819 -> components that are highly prevalent in in plaque and

1124.609 -> diabetics is inflammation, as well as non calcified plaque. We

1130.039 -> kind of don't like to call it lipid rich, because it's not

1132.379 -> always that but in terms of what we like to call it is non

1136.129 -> calcified plaque. So in on CT, here's one of one of my fellows

1142.099 -> papers, we can actually look at the density, you saw the

1145.189 -> calcified plaque, that big white thing there. And then I pointed

1148.609 -> to you when it was darker, that was non calcified plaque. So we

1152.209 -> these are a range across a range of CTE radio densities, or

1157.309 -> Hounsfield units, where we can actually measure across the

1161.449 -> range from a Hounsfield unit of negative 30 To 30 to 30, as well

1167.599 -> as all the way up to on the right, more than 1000. And you

1172.189 -> can see on the bottom of the slide, some interesting

1175.069 -> correlations between Hounsfield units and you know, but the

1179.929 -> bottom line is if you look at the blue line, everything to the

1183.559 -> right of that to the left of that centre line is non

1187.729 -> calcified plaque that's low density plaque or necrotic, core

1190.879 -> fibre fatty and fibrous plaque. And there's been all kinds of

1194.119 -> pathologic and invasive imaging correlations, and everything to

1198.859 -> the right is calcium FIDE plaque. And the more dense the

1203.089 -> calcified plaque gets, it gets more and more white on a CT

1207.139 -> scan. So you know, being a very visual person. I like the fact

1212.419 -> that everything's colour coded, um, kind of a simple, you know,

1215.299 -> so this is where it gets kind of fun for me. But what's

1218.689 -> interesting is there's plaque actually, that can be so

1221.749 -> calcified that it has the same density on a CT scan as bone. We

1228.829 -> can we can hit it that hard within our coronary arteries.

1231.799 -> It's fascinating, right? Well, it is to me, you guys can just

1234.829 -> amuse me, right? So. But it's kind of fun. And so that you we

1239.569 -> can actually then this is some of my research, but it's some

1244.729 -> one, I tried to highlight the fellows work. And this is one of

1248.359 -> my fellows from, from the Netherlands who was with me for

1251.659 -> a couple of years. And Alex did this subsequent paper from the

1256.219 -> iconic registry, what we looked at in this registry, was to look

1259.939 -> at precursors of an acute coronary syndrome or acute

1262.489 -> myocardial infarction. And he looked at what was again, across

1267.409 -> the same array of subgroups with plaque. And all of you can see,

1272.209 -> you know, if you look at the necrotic core, that red stuff,

1274.879 -> that's not good stuff, and it gets more greenish, and then it

1279.349 -> gets darker green when it's fibrous, and then it gets more

1281.659 -> and more. So it's what we call one kg plaque, or 1000

1284.839 -> Hounsfield unit plaque, which is blue. And what is fascinating,

1289.339 -> if you look across a array of these different groups, you can

1293.329 -> see that as you get really dense calcified plaque, you're less

1298.999 -> likely to have an acute coronary syndrome, as when you have a lot

1303.919 -> of necrotic core. So by these subgroups, we can actually

1307.759 -> identify precursors precursor features in a patient that would

1312.919 -> lend themselves to being at risk for an acute coronary syndrome,

1316.339 -> we can also get an idea that if it calcifies, if it gets old

1321.289 -> enough, because that's what that's a marker of it's been

1323.389 -> around a while that it's calcifying and becoming more

1326.599 -> stable, then we know that patient's risk is less than it

1331.069 -> would be much less than it would be in the patient who has

1334.249 -> necrotic core fibrofatty plaque. There are other high risk plaque

1339.439 -> features which which is interesting as well. I talked

1342.829 -> about some of these in that little cartoon from my friend,

1346.279 -> Amir Ahmadi. So you see here again, the artery can do one of

1351.289 -> two ways of remodel remodels negatively or into the lumen

1355.009 -> blocking blood flow, or it can remodel outwardly. And it

1358.789 -> usually remodels outwardly first and then goes inward, it gets to

1362.269 -> a certain amount, and then it goes inward. So that's a high

1365.119 -> risk plaque feature. And low density plaque, we talked about

1369.499 -> this, there's another one called napkin ring Sinai, we don't see

1371.959 -> it that much. Some people see it a lot, I don't know where maybe

1374.269 -> we're just a little slow. In New York, we don't see it very much.

1378.229 -> But it is this kind of central area of low density that abuts

1382.279 -> the lumen. And that's the critical part. If you're going

1384.709 -> to look at plaque rupture, it's got to rupture so that it goes

1388.789 -> into the lumen, and therefore attracts a clot. And then all

1392.119 -> kinds of nasty things happen after that. But what's

1395.029 -> fascinating from this is that any of these high risk speech

1399.139 -> features will elevate risk, if it's just present any high risk

1403.309 -> plaque feature, if it's present, you can see an increased risk in

1406.819 -> as little as two to three years. Now in what I do for a living,

1410.779 -> that's a very short period of time. We actually then also

1414.709 -> published using the Scott heart data, we looked at this low

1418.789 -> density plaque here on the bottom, and we looked at the

1421.849 -> combination of patients. And so if a patient had non obstructive

1425.419 -> disease, again, we used to dismiss that. Now we understand

1428.749 -> the importance of this combined with a high risk plaque

1431.689 -> features, their risk of myocardial infarction was

1434.689 -> elevated almost seven fold over a very short period of time.

1439.97 -> That's a very, very high risk. So this is this one I'm like so

1444.8 -> fascinated by this is looking at para coronary fat, we actually

1450.32 -> see that there is fat around the coronary arteries as there is

1454.97 -> fat around almost every arterial bed. And you know, and what you

1459.68 -> see is that you can actually image this using radiomics,

1463.28 -> which is a form of kind of machine learning artificial

1465.65 -> intelligence, where we're looking at a textural analysis

1469.4 -> on the top upper left. This is from a group in Oxford that we

1474.2 -> work on work with. And here you can see an a culprit lesion.

1479.18 -> Look at the Can you guys see all that red, very high risk, very,

1483.2 -> again, Hounsfield units, all that red is high risk, very

1487.79 -> inflamed fat around the coronary artery, but look not so much

1491.18 -> over here. So there's all kinds of patterns we can see with

1494.78 -> this, which is kind of cool. I also tell you, that fat in other

1499.64 -> arteries can be problematic fat around the uterine artery during

1502.91 -> pregnancy leads to preeclampsia. So fat around arteries is just

1507.29 -> it's not not a good thing, it leads to vascular dysfunction.

1510.2 -> In this case, that we believe that the flat fat actually can,

1514.07 -> in an inflamed state will actually diffuse the the lipid

1518 -> rich plaque the fat into the coronary atherosclerosis and

1522.95 -> make it bigger until it actually results in an acute event. So we

1528.71 -> can image this again with CT using this Peri, Peri, coronary

1533.12 -> Peri vascular fat attenuation index that was in its this

1537.14 -> radiomics signal has been developed by these guys at

1540.11 -> Oxford, and it's highly predictive of coronary disease

1544.67 -> mortality and myocardial infarction. We have a large

1548.81 -> COVID grant from NHLBI where we're using looking at para

1553.43 -> coronary fat and so that we can actually see if that systemic

1559.46 -> infection will actually inflame the plaque and cause

1562.79 -> atherogenesis and marked progression of atherosclerosis.

1566.96 -> So fascinating work, not just in the coronaries, but around the

1570.71 -> coronaries as well. Now, why do we want to do this? Here's the

1574.76 -> we have two goals. Now we've shifted away from our data goal.

1578.48 -> Our two goals are Can we look at Progressive worsening? Can you

1581.81 -> guys all see this as a CT scan is just a different software

1585.23 -> package. Not much here. But look what happens this is in a year.

1589.1 -> This isn't a patient with a high elevated lipoprotein A, which is

1593.54 -> you know, highly atherogenic Man, these people progress. This

1596.54 -> is incredible progression. You can see here. So this is not a

1601.04 -> good thing. We don't want patients to progress. So we

1603.35 -> again, we want to stabilise the plaque. But we can with

1606.92 -> treatment, we can take plaque that looks like this. This is a

1611.57 -> patient a real patient that has a tonne of plaque included,

1615.05 -> including that low density lip or necrotic core. And we can

1618.23 -> shrink it to this after 18 months of therapy on a highly

1623.57 -> enriched fish oil via SEPA or Aiko sipping alto. So this is

1628.16 -> where it gets exciting, right, we can actually then now start

1631.7 -> to talk about regressing coronary disease. There's

1634.73 -> actually not much data so I'm you're going to be so

1637.67 -> anticlimactic. Right? I had you built up into all of the thrills

1642.26 -> of looking at atherosclerosis. But now I can tell you that

1646.01 -> we're really on the cusp of the of now we know we can do it, we

1649.64 -> can reliably do it. And there's really only a couple of examples

1653.75 -> in the literature that I can bring out to you one again is is

1656.69 -> Matt Rudolph's evaporate trial, which was just published a few

1660.17 -> years ago, using this for SEPA. You could see this example, when

1664.58 -> in visarpa, is used to patients with elevated triglycerides,

1669.74 -> already taking a statin. So again, we're eliciting benefits

1673.82 -> on top of statin therapy, which is given for dyslipidemia. So

1678.53 -> the primary endpoint, as you can see, but look at all these

1681.26 -> reductions, again, just up until a few years ago, nobody thought

1684.8 -> we could regress this plaque, everybody thought once you had

1687.29 -> that footprint, that footprint would never change. Which is

1691.31 -> interesting, because we now we know that we can actually elicit

1693.74 -> that change. But what's super important is we don't just show

1697.13 -> you pretty little pictures that how the plaque shrinks. And all

1701.39 -> of that in, you know, we actually develop a prevention

1704.96 -> strategy that actually would improve outcomes, right? We want

1709.52 -> the patient, whoever they are, especially the patients with

1712.7 -> diabetes, not to have a fatal or non fatal cardiovascular event,

1717.77 -> particularly a fatal cardiovascular event. And so

1720.59 -> there is some some examples in the Scott heart trial, where

1724.76 -> they recommended for all patients with atherosclerosis,

1727.79 -> that they use a statin therapy, as well as aspirin, which is

1731.54 -> like minimal cardiovascular prevention. In this patient

1735.68 -> population, they tracked the use of statins throughout the trial.

1740.48 -> And were able to elicit not in the not in the primary trial.

1743.75 -> But this was in a pre specified follow up. There's all these

1746.84 -> rules to clinical trials. So basic scientists, you're really

1750.02 -> lucky, you don't have to do all this rules, it's important that

1753.44 -> we want to establish really important what the evidence

1755.72 -> means. We saw from Scott Hart, and after a five year when we

1760.16 -> moved from three years to five years, we actually then saw this

1763.79 -> benefit. So again, perhaps when we're just learning, you know,

1767.81 -> we're learning that we need a little bit longer period of time

1770.57 -> in order to elicit a therapeutic risk reduction. So fascinating

1774.5 -> data on on on the role of shifting away from older

1779.27 -> modalities to more conventional imaging with CT so we can image

1783.95 -> not only we can image the atherosclerotic plaque, we can

1787.16 -> actually look at subtypes, we can actually now get a better

1790.58 -> idea of ones that we can regress, and therefore then we

1794.06 -> can actually start to think more aggressively about clinical

1797.15 -> trials. So I said you probably get all dismal. because there's

1800.42 -> not many trials, there's a tonne of trials ongoing, because if

1803.57 -> any of the clinicians in the room know, we have a, I don't

1806.99 -> know, probably 10, whatever different trials, different

1811.13 -> substances being developed for different targets, particularly

1814.52 -> around lowering cholesterol, there's this focus in

1817.55 -> cardiovascular medicine about residual risk, we've been able

1821.15 -> to do relative risk reduction about a 30% relative risk

1824.33 -> reduction. But we have a huge problem with cardiovascular

1827.69 -> disease and residual risk beyond that with conventional therapies

1831.53 -> like statins. And so there's a lot of new drugs and they're

1835.7 -> also extremely expensive. In a lot of injectables, try to

1840.8 -> increase adherence and compliance with patients twice a

1844.52 -> month, give yourself a shot, or you go to the you go to your

1847.88 -> doctor to give you have them give you a shot, all kinds of

1851.03 -> ways where we can spend $250,000 a year in therapies, but that's

1856.19 -> another story. So this is why the the newer guidelines are

1860.03 -> gonna focus in on anybody who has atherosclerosis,

1864.02 -> intensifying preventive stress strategies, and not necessarily

1867.23 -> embarking on any other types of diagnostic approaches. Of

1870.44 -> course, we're not littering the littling, what we should do with

1873.95 -> the patient who has significant obstructive disease, those

1877.1 -> patients really are in that category, that really need

1881.93 -> intensification of guideline directed medical therapy.

1885.8 -> Importantly, now, there's this movement, and I think this is

1889.19 -> where it becomes important for all of us to understand is that

1893.63 -> these patient populations now should, particularly the

1896.84 -> nonobstructive, should not have primary prevention targets, they

1899.9 -> should have secondary prevention targets, that's a little bit

1903.17 -> much for the American cardiologists to swallow. So you

1907.4 -> all are a little bit more forward thinking. So maybe you

1909.86 -> can embrace that. And now say anybody with atherosclerosis

1912.68 -> should be in the category of getting secondary prevention. So

1918.77 -> very interesting work that's ongoing, at least it is for me

1921.8 -> on diagnosing coronary disease. And it highlights the role of

1925.58 -> the burden of atherosclerosis, high risk at a younger age, more

1929.3 -> atherosclerosis, more progression, much higher risk

1932.87 -> associated with that we've gotten a fair amount of data, I

1935.84 -> don't think we have data as well as you all of you would like. Of

1938.96 -> course, that's why they call it a career, I never have data as

1941.51 -> much as I would like. But it's important for us to see that if

1945.83 -> we can target the right abnormalities, if we can target

1950.15 -> the right disease markers, we can intensify care. And not

1953.78 -> we're not waiting for a preventive therapy, necessarily

1958.31 -> down the road, we do have both statins and angiotensin receptor

1963.14 -> blockers that actually can regress atherosclerosis and have

1967.25 -> proven clinical trials to do that, in the invit, mostly in

1971.33 -> the invasive literature. But I think it's a, it's a really cool

1974.36 -> time to be looking at atherosclerosis, in large part

1977.78 -> because we can shrink the plaque there all kinds of

1980.12 -> methodological considerations that we have to break through.

1985.19 -> But I just, you know, I think it's just a really an awesome

1988.13 -> time. For us. This is an example of why we want to really target

1992.27 -> this, this patient has a lot of plaque, you guys can see this as

1997.22 -> the lumen that line. And then you see the the vessel wall,

2000.79 -> everything in between is is plaque. And this patient, then

2006.34 -> two days later, had a myocardial infarction. So this risk can be

2011.59 -> very risky, this plaque can be very risky, and can result in

2015.43 -> the more plaque it is, the more non calcified is the more low

2018.7 -> density plaque. It's a near term risk, and not just necessarily a

2022.36 -> long term risk. So and I want to thank you from New York City,

2028.33 -> and let you see my group. So thank you so much.

2036.91 -> Thank you very much for this very nice talk. And now we have

2039.73 -> time for questions.

2043.96 -> Jonathan Medina, University of Copenhagen, thank you so much

2046.69 -> for a very impressive presentation on a very important

2049.84 -> topic, related to obesity, diabetes, cardiovascular risk

2053.8 -> prevention. So my question to you is whether what's the value

2058.84 -> of ultrasound assessment of carotid plaque and carotid

2063.91 -> intima media thickness, because as far as I know, all the data

2067.69 -> that you're presenting, it's based on CT scans. Those are

2070.75 -> some cow impassive, people tend to use older sounds to measure

2075.52 -> the breath to determine whether they're plugged or not, and the

2078.82 -> amount of lipid that it's infiltrated under the sub

2082.3 -> endothelial wall. And then the second question is whether we

2086.8 -> should also look at this intermediate phenotype, which is

2089.5 -> increased karate, karate, intermediate thickness without

2092.56 -> the presence of plaque, because plug it's not the answer. Now,

2095.44 -> it's like a atherosclerosis of progress that starts with

2098.53 -> endothelial dysfunction and then pro SS? So I wanted to know your

2101.59 -> opinion on that. That's a good

2103.21 -> question. You know, ultrasound imaging, the carotid is bigger

2108.07 -> artery, so it's easier to image, right? The challenge is the

2112.21 -> reproducibility of the carotid imaging is not where we want it

2115.69 -> for clinical application. So if there are some centres that use

2120.13 -> carotid imaging, and there's correlation, right, if you can

2124.06 -> predict one, you predict atherosclerosis in one arterial

2127.87 -> value, you'll likely, you know, have some overlap and other

2131.32 -> arterial beds. But it's it's not as reproducible as we would

2135.52 -> like, and particularly looking at intima media thickness, it's

2139.15 -> highly variable. And it depends if it's, if you're good at it,

2143.08 -> you're good at it, if we probably would get too much

2146.05 -> variability. And so it's generally not recommended, even

2150.28 -> though you think it could be. And it has to do with developing

2154.06 -> the evidence and really improving it. I don't know if

2156.4 -> anybody is working again on that, you know, with more AI

2160.81 -> based, there's a lot of ongoing activity in what I'm doing some

2164.47 -> of what I showed you was AI based to look at automated

2167.23 -> segmentation. And usually that can improve reproducibility,

2170.86 -> right? Let the computer make the mistake, and that makes it less

2173.41 -> than me. So but not as much as we would like, and therefore,

2178.21 -> and there aren't. There are clinical trials, particularly in

2182.65 -> the carotid intima media thickness space, but not as much

2186.52 -> as overwhelming and consistent the way we see, you know, as a

2189.85 -> researcher, you can't do all the evidence, I just look for

2192.25 -> patterns and consistency in the evidence, and then I latch on to

2196.24 -> it, but when there's inconsistency, it's much harder,

2198.7 -> and it has to do with reproducibility.

2203.35 -> Yeah, what is the name of the Danish guy you mentioned in the

2209.74 -> guideline? Yeah, no, you said

2212.8 -> that each person that you mentioned,

2215.469 -> the Danish guidelines that were published, apparently was a

2218.349 -> governmental guideline or or that was published about CT

2222.699 -> angiography? You know, I think this in Denmark, you have a lot

2226.689 -> of ongoing CT research. There's a big, large registry of CT

2232.539 -> across western Denmark Bjarni Norgaard, has led a lot of that

2238.419 -> a cardiologist here and they've done really some seminal work in

2242.289 -> this area.

2242.71 -> Do question is about alcohol. In no time, we learned that alcohol

2247.27 -> prevent atherosclerosis, it's bad for the liver and a lot of

2252.46 -> things, but red one, people are doing a lot of right, why not

2255.97 -> saying that it prevent these things? How's it today? What is

2259.9 -> your opinion?

2260.92 -> You know, it's consistent with meditate Mediterranean diet

2263.95 -> literature, right? And particularly red wine. There is

2267.43 -> a threshold though Canadian guidelines just recently came

2271.27 -> up. I mean, there's a cancer risk, you know, the everything

2273.64 -> you do in your life is a balance. The Canadian it was

2276.37 -> everybody was in a tizzy. Last weekend was the American College

2279.67 -> of Cardiology. And right before that, the Canadian guidelines

2283.78 -> came out and say, more than two glasses of wine a week increases

2288.25 -> your cancer risk. And we all went to oh my god, what am I

2290.77 -> gonna do? But you know, it's, there is but it's a focus really

2295.6 -> on Mediterranean diet that really gives you

2298.21 -> that proven to glue rose

2301.9 -> atherosclerosis Correct. a Mediterranean diet is the one

2304.6 -> that consistently comes across, you know, you guys can think of

2307.54 -> it fish grains, less processed foods, etc. And that is when you

2312.58 -> look at alcohol, you can't it's very hard for you to separate

2317.38 -> alcohol from diet, as well as other adverse behaviours like

2321.64 -> smoking, etc. So

2323.26 -> should you to not recommend it to your patient?

2326.739 -> No. You know, I think if you enjoy it, then, you know,

2330.669 -> moderation is key and most things in life right. Over here.

2336.939 -> Thanks. My

2337.57 -> name is Eric Richter. I'm from the University of Copenhagen. So

2340.63 -> you didn't mention much about exercise. And I was wondering

2346.45 -> the regression of the plaques that you see with statins and,

2350.86 -> and fish oil, are they Is there any evidence that increased

2356.26 -> physical activity also leads to regression of already

2360.25 -> established plaques?

2362.35 -> Well, first of all, I live in United States and not many

2364.63 -> people exercise.

2365.71 -> So there are still some.

2368.89 -> I live in New York, we have to walk everywhere. I don't know in

2370.99 -> a car. Yeah, no, it's it's a valid point. And I thought about

2375.01 -> mentioning but I was hoping somebody would ask me, so

2377.8 -> there's not a lot of data for it in contemporary patient

2380.95 -> populations. I think like anything, you know, like the

2384.31 -> statins are going to give you a more potent kick in terms of

2387.76 -> reducing cholesterol or via SEPA or any of the PSP CPSE off the

2394.15 -> injectables, sorry. You know, they they will give you a more

2398.02 -> potent kick. I would guess that If you had exercise, that you

2402.58 -> would have to have a sufficient intensity, you know, as well as,

2407.89 -> you know, number of frequency per week, and probably over a

2412.33 -> longer period of time. So those of you in the room don't know,

2417.07 -> me or a lot about cardiovascular disease. But I used to play

2422.35 -> field hockey with Dr. Julie Zira, 40 years ago. So that's,

2429.97 -> that's why I get the invite to go visit my friend, which is

2432.67 -> awesome. She she could run faster than me, though. True.

2437.59 -> True. You have to acknowledge when you're beaten? No, I'm

2440.83 -> making a joke. But no, you're absolutely right. It would be

2443.29 -> great if we could look at not only exercise, but other types

2447.52 -> of modifying behaviours that we can elicit, largely because that

2453.73 -> would have to be NHLBI, or NIH sponsored, not many

2457.6 -> pharmaceuticals would sponsored. And the average American where

2460.93 -> you take them probably isn't capable of doing sufficient

2464.92 -> exercise in order to elicit that regression. I would I'm going to

2469.09 -> put be out there. But certainly, there is hope that other types

2473.86 -> of dietary modifications of reductions in other types of

2478.54 -> behaviours would be important.

2481.39 -> Any other questions? We have time for? Maybe one brief

2485.05 -> question?

2485.679 -> Hi. I'm Stefan Johansson, also from University of Copenhagen.

2490.389 -> As I understand that, statins also increases the risk for type

2494.979 -> two diabetes. Could you comment on this relationship?

2500.05 -> Yeah, I mean, I think you just said it. I mean, that's a real

2502.78 -> concern. And that's why there's, there's there's monitoring if

2505.72 -> you're on statins, but you know, they are very potent in terms of

2508.63 -> a cardiovascular effect. You know, this is this is the

2512.29 -> challenge, right? It's everything in particularly in an

2516.34 -> adult population, everything's a balance, everything, you have to

2521.05 -> weigh those balances in terms of therapy, you know, in, we don't

2526.6 -> get patients to really do sufficient diet modification to

2529.6 -> lower their cholesterol to where it should be no, the targets

2532.57 -> right now, I don't know how many people know their LDL

2534.73 -> cholesterol. You guys, none of you know your Oh my god. The

2539.92 -> targets now are like under 70. Could you do that on diet? I

2546.76 -> mean, that's incredible. I mean, you have to be very strict with

2550.45 -> your diet. So if if we have to use pharmacologic intervention,

2554.98 -> and then watch for those side effects on the in the diabetes,

2558.04 -> that's usually that's how it's managed it The hope is with some

2561.67 -> of these newer targets, these newer drugs that are under

2564.1 -> development, targeting lipo, Protein A and other types of you

2569.11 -> know in glycerin and other types of drugs that are on the market

2571.81 -> are entering the marketplace, that we won't see that effect.

2576.25 -> But you know, it's an important consideration. Thanks for

2578.44 -> bringing that up.

2579.219 -> Thank you. I think in the interest of time, we would like

2581.619 -> to thank Leslie, thank you so much.

Source: https://www.youtube.com/watch?v=BFChudLBY7U