In this Cardiovascular Medicine webinar, Mayo Clinic cardiology experts David R. Holmes Jr. M.D., and
Mandeep Singh, M.D., discuss evaluation of patients with an acute ischemic syndrome as well as more-common atherosclerotic coronary artery disease and some less common etiologies. Early coronary angiography plays an important role in identifying specific mechanisms of the clinical presentation.
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Mayo Clinic Medical Professionals — Cardiovascular Diseases. welcome. My name is Mandy passing and I'm the director for the mayor Foundation and on behalf of the cardiovascular department at Mayo clinic Rochester arrival time y'all and I hope you're staying safe during this pandemic. It gives me a very distinct and a personal actually pleasure to invite Professor David Holmes who not only is a dear friend and a colleague but by my my mentor um For the last 25 years I was a student. I then became a colleague and a dear friend. Um some background on on David. Uh first off he was reading his tv, I couldn't finish it. It's like 156 pages long. So Uh H factories through the roof. He has more than 1000 publications. Um he has so many patents that he has not even numbered those patterns. So it's just amazing. He went to Princeton when I was born. You know, it's he's a legend. It's he's just an awesome guy. He's done everything from E. P. Transition transitioning to The interventional. When I joined 25 years ago he was my Catholic director. Um And he's guided me mentored me all the way to um that I am at the stage where I am now introducing him to um to give this talk on a few corners syndrome. And he's going to be talking on updates in classification, some newer mechanisms and then roll of early in geography. David. It's a distinguished and deep. It's great to be here with you in this audience and this virtual time and space mandy. But I do go back a long way. The very first time I met Man Deep, I was doing micro balloon valvular pastor. So this is a long time ago and we were then figuring out that chart in terms of what different balloon sizes to use. It was going to be a single balloon or a double balloon. And so we had a chart on the wall and I had turned away from the patient's table to study the wall chart and so I thought to myself and said to the people in the room, we're going to use these two device sizes because that's what the chart said, this person who I had just barely met at that point in time said no, that's wrong. You shouldn't do that if you do that, it will be a mistake. I looked at him and I said, oh really? And he said this is what you should use, I have done Maybe 1000 of these and this is what we should use in this particular case and that's what we used and it worked brilliantly well. And at that point in time I realized that this was a guy who had been around the block in terms of catheterization techniques and he is still going around the block and it's a bigger and bigger block to go around and so it's great to be introduced by Man Deep who then was introducing me in the past to how to do procedures. So we're going to then talk about updates on classification mechanisms and the role of early angiography. What are the learning objectives? What we want to identify the most recent classification of non stem me terribly important. Look at the evaluation of a throw throw embody IQ mechanisms of non stem E. As well as to me. And then look at the role of early and geography in patients with non steamy. And we will then talk about some specific examples as we think about acute coronary syndromes. It's an umbrella. Some people have called it a waste basket. Well I prefer to think of it as an umbrella under which we can see there is unstable angina. There is the wonderful word of trope anemia and then there are non stem ease type one and type two. And then there are stem ease type one and type two. But it is an umbrella that continues to shelter underneath it. Different groups of patients that we will have to become familiar with how to approach them. We know that the definition of my cardio infarction continues to change for those of you that worked in the 1950s, there was the first wh o. Definition And that was about 1955 and then that lasted until 19 60. And then we got to another definition in 1970 then we have continued iteration of the definition to sfc that W. H. O. Definition in 1980 and then the Monica definition in 1990 And then that was based upon epidemiology and then we've gone to clinical approaches in terms of the definition of my cardio infarction. In 2000 we had the E. S. C. A. C. C. Redefinition and then we had the you'd me definition and then we had the third. You'd me universal definition of myocardial infarction 2010. And we're now to the fourth and soon to be the fifth at some point in time definition of acute myocardial infarction. What do we know about this? 4th? Universal definition of acute myocardial infarction. This is incredibly important because we will base strategies of care depending upon the definition that is used. If we were to start at the top we could say it's a cute my cardio injury. The evidence is a rise and fall of proponent But it had to include at least one value above the 99th percentile of the upper limited. No but it had to include an evidence of acute myocardial ischemia. Whether that be symptoms of myocardial ischemia. Whether that be new scheme mickey CG changes whether that be pathologic Q waves, whether it be imaging evidence of new regional wall motion, abnormalities of loss of my cardi. Um or whether it be identification at the very end of the day of coronary thrombosis an angiography or autopsy? And so man deep we then struggle with these sort of definitions and say where does trope anemia by itself fit in the definition of my carry on function. Yeah, I think the issue I always struggle with is how to distinguish the myocardial injury from acute my cardio in function. Is it just the so the situation I present to you for example, I'm on console service. I see this patient with shortness of breath post op they draw troponin has the troponin peak and they ask us to see this patient who just underwent a non cardiac surgery. Now would you then qualify this patient as having just a demand ischemia from this recent surgery Or has this patient had an acute M. E. That needs further attention? Including taking this patient to the cath lab. I think that is really the background of the decision making. That is sometimes difficult in these patients now that we have more information based upon the frequent troponin measurements. If we were to use this 4th universal definition With sub classification Type one that would be the typical stem E that we've had in the past, primary corny event. Whether it would be plaque erosion or plaque rupture or a fisher, which type two then as Mandy Pez talked about whether it's ischemia due to increased oxygen demand or decreased supply, for example, anemia arrhythmia or hypertension and that's going to be terribly important as we go forward and talk about some of the information that three would be sudden unexpected cardiac death. Type four A would be my cardio infarction due to PC that's a different kettle of fish four B. Is my cardio infarction associated with stent thrombosis. Or take five is my cardio infarction due to coronary bypass graft surgery. If we were to then measure cardiac enzymes following coronary bypass graft surgery, there's going to be different definitions of what is abnormal and what is normal. Let's talk a little bit about Type two. My cardio infarction and man deep thing sketched out a scenario typed. My cardio function occurs because of an acute imbalance in my cardio oxygen supply and demand in the absence of an acute Jethro dramatic event. And that was the situation that he sketched out for us a person. Post procedure, post surgical procedure. And you have to then decide whether it's my cardio infarction or what. And then we have to try to distinguish between my cardio injury versus a Type two. My cardio infarction, Type two. My cardio infarction can relate to anemia can be seen or arrhythmia or heart failure or chronic kidney disease or hypertension shock or hypoxia me in all of those Then could result in a type two. My cardio infarction that would result in elevated proponent, but also could be seen with abnormal electrocardiograph IQ changes. As Dr Singh has talked about. Let's then talk about some cases. First case 76 year old man with acute onset of chest pain. It had symptom onset four hours before the time that he arrived in the catheterization laboratory. So as you look at this, you look at it is abnormal. Obviously there is an inter ventricular conduction defect. That is true. There is S. T. Segment elevation. And so this is a person that had symptom onset of acute chest pain four hours before. And we're going to then decide whether this is a type one Stem Me. It's an traumatic event, whether it's a plaque rupture or whether it's a plaque hemorrhage or whether it's a black fisher or a plaque erosion. Okay. And so we're going to take him to the catheterization laboratory. And this is what we're going to see. As we look at this, we thought that the inferior changes on the electrocardiogram looked more ominous. And so the first picture of the right corner B. Dr Singh, what about this huge traumatic burden? And how would you How would you then think of this being a Type 1? My cardio infarction from a a throat robotic event. Yeah, if you just go by statistics, I think uh plaque rupture remains the number one cause for M. I. Uh and more. So if you then add some cardiovascular risk factors. Um there is uh stenosis just before the large body of trauma is seen as a filling defect. Um but certainly if you just have this thomas and no skin, no sis as you as you as you have shown um certainly can point to a plaque erosion, especially in younger patients without cardiovascular respect. Good. So we're going to then say this is a steamy with large dramas type. So Timmy two floats downstream. What are you going to do about this? You're going to have to decide in terms of management of this and other cases that we'll talk about. We're going to say, are we going to do from beck to me and this person with a very large promise. We used to do a lot of thrown back to me. We don't do as much anymore because the at least Swedish information would say maybe we don't need to or maybe it's harmful. Are you going to dilate it? Are you going to medicate it and wait his head's ongoing pain. It's just been within four hours. And so you're going to have to then decide in your management of this patient. We can see that downstream. There is also this stenosis immediately before the crux, immediately before the take off of a smallish poster descendant. And so we then pass the wire through and maybe do a little bit of stuff and then all of a sudden the patient's chest pain gets worse and Izzy CGs changes also get worse. And we can see that what had been there has moved around. And so that was a large promise that you have moved more distantly and you now have a complete occlusion downstream from that. So at this point in time we have a couple of strategies, we can say, let us trap that promise with a potentially a long stint or if you lived in europe, you could use an instant that's a covered stent or you can just have a go at it and see how things look. The problem is that you have. Now this complete filling defect occlusion down here where the dramas had started here and has moved down to the white arrow and you've not done him any favors. What are the options that you have? Well, this is an interesting option that can be used and we need to be thinking about different strategies of care in these patience and this is an option that people might not consider. You could potentially bathe that thomas in little therapy. We don't usually do that. We would use a two B 3 agent downstream or something. But another strategy that can be used can be to take a guideline er down it and wedge in the stenosis that has blocked flow down and you could then move further downstream. And you could put in a 2.5 millimeter bloom and block outlets. And so you could use this as a strategy to bathe that whole segment of the artery that you have symbolized dramas into. And so in this setting it is already included. That is true. He's going to have chest pain. That is true. You will have to watch for rhythm disturbances. All those things are true, but you can then instill T. P. A. You have a guideline er there, You have a 2.5 balloon there And then you can instill this and see whether you can dissolve some of that very large robotic burden in this type one semi and then you can aspirate it. So you've put in the ke pa you've let it sit there for a bit. You still have your 2.5 MB balloon up. But you can take the guideline er and then aspirate that whole column, that whole column from where it was wedged down to where the balloon is included. And then you can see gosh you have been able to take out most of the gross stuff that's there and you have restored pretty good flow down there. And what do you think about a strategy like that? And what would you do next? Yeah this has worked wonderfully. But I think it is very underutilized strategy uh as one of the options when you have a large body of an geographic traumas. Typically what I do is some kind of throwback to me but with high rates of stroke, I think people have shied away from using this routinely but in this patient at least if not uh come back to me either realistic comeback mere aspiration to come back to me. This is a beautiful strategy and it worked beautifully. So then you have the situation that you can then standard. So you've gotten rid of this dramas. You have than what is called elliptic marinade. Isn't that a great term of living marinade as another treatment option for every traumas murder. And you can treat it there you can decide whether you're going to treat this or not. But you have taken care of this robotic burden. So that's the first case. Let's talk about a second case that presents some other important things to think about. He's a 39 year old man. I had seen him. It was a smoker. It had a one month history of exertion, all chest discomfort, radiating jaw and arms and his back. And so he presented to an outside hospital for evaluation Editor opponent. I have greater than five and a D. Diamond of 032 and S. C. R. P. That was extraordinarily high at 17 point fine. This was his electrocardiogram. And what would you see in this electrocardiogram? Sinus rhythm, relatively narrow QRS complex as you looked at it. And as we looked at it there were these changes in the inferior leads and then some changes in the lateral leads. And so it would point us towards being something in the right coronary artery. in this 39 year old smoker that has had pain for a while intermittently. So as would typically to be the case in these cases we would do the non infarct related artery. First we thought this was going to be the right coronary artery as we look at the left corner artery. We can see that in this 39 year old smoker. There's probably some tubular disease in the lady that main looks okay. An important thing to note is that there aren't any left to right collaterals. We always look at that so that we can see what the distal right coronary might have looked like had it been included? So we do another picture of it. Again we can see that there is mild disease here. We know that atherosclerosis doesn't usually just have one specific point of entry into the body. That there is oftentimes more mild disease. And that's true there. I wouldn't have done anything with that. Nor would I have been terribly concerned about that. Other than we would go the route of intensive secondary prevention. Another view of the same vessel. Again, looking for any collaterals. And now at this point in time you begin to see perhaps some collaterals right down here and anybody you think about that it looks like down there. You can see some visualization. Yeah. I think this uh uh Mario criminal shot definitely uh gives you an indication that one the the R. C. Is included um into the collaterals to the right P. D. A faintly filling from the septal and destroy reality. Okay so we then position that we had trouble position in the catheter. And so while we don't typically use amplats catheters. We did it in this particular case. And so we see the injections. It's a deep engagement. That is true. Um Could it be better than that? It could have been better than that for sure. But we now see a filling defect in the distal right coronary artery. Now you're going to say well that's a throw sclerotic disease I guess because there's a large filling defect here. And as we can see it involves then the poster or lateral at least a little bit. And we can see where the collaterals from left to right would have filled part of the posterior descending. And so we put a wire down and the wire. I'm not sure the wire zipped right along through that. And so now we're faced with maybe it was just a ruptured plaque and a clock on top of that. And maybe there's not much disease there. It's unclear whatever it was. It did move down and we then chased it down into the poster lateral segment with a little bloom. And while there is personal, certainly some distal embolization. The patient is asymptomatic. But but we haven't done anything where the promise was. That was where the thrombosis was at least based upon the angiogram. So mandy. But what do we do with that place where the thrombosis was treat that this is a case where I think it certainly can be a plaque erosion too. Um oh ct or some kind of imaging would be very essential just to look at the underlying mechanism. Uh You can see the distal portion of the right posterior lateral branches pretty static. But I think as as 11 can imagine that Krampus is the most important ways a constrictor. It just must have constricted the vessel distantly. So here and I would not just puts tents and stuff but just give some these are directors through the posterior lateral branch and see whether it can open up an art. Okay so we then did some of those things and it began to open up and we gave nitrates give some time. And our decision at that point in time was to say well what indeed could be the underlying half a physiology here we're going to go to the next slide. Let's see if I can move that forward. Can we advance that? We decided to do intravascular ultrasound. So man deep so this is down in the region. What do you think the pullback? That's the region where the rhombus was? I don't see a ruptured black and I don't see a whole body of plaque. Uh So we were then faced with a 39 year old guy that we can only presume how to a ruptured plaque that we can't see. But the but in terms of finding a lot of atherosclerosis we didn't In this 39 year old smoker. So when we play it again we can do that again. Or maybe not. This was O. C. T. And this was using avis to look at the wall with virtual histology And we're going to then say this is probably the plaque that we just couldn't see much. So we're going to then say it was a ruptured plaque. Had we used smoked we might have seen it better. This was conventional Ibis. But we're then left with a man that had a ruptured plaque. It does not have a significant stenosis there. And your options are at that point in time. Are you going to stand it anyway because it had a ruptured black before. And so let's go on to the next picture. We advance that. So those are the questions what next you sound you found you've got some atherosclerosis there but it's not severe. Are you gonna considered that this was an m bolic thing? Are you going to say it was a ruptured plaque? Are you going to stand it anyway because it it was vulnerable one point in time or you're going to leave it alone to heal. These were his demographics you can see is somewhat bigger than he might be. We then found this right coronary promise and me said gosh maybe there's an symbolic source. So we did an adult T. E. To look to see we didn't find any intra cardiac mass the left atrial appendage was free of Claude. It was normal size and contract. I'll there wasn't any shut at the atrial level. No atherosclerosis in the aorta estimated ejection fraction as you can see here, there was mild mitral regurgitation. But we didn't find a source for thrombosis that could have been an M bliss from someplace else. And so we then could say this is probably a ruptured plaque. It wasn't anim bolic conclusion. It was a ruptured plaque and there is no significant stenosis. And we said we're not going to stint you, we sent him to rehabilitation and we're secondary prevention and had him stopped smoking. At least we encourage them to stop smoking and he remains asymptomatic at this point in time. And so that patient is another kind of acute infarction where you have to decide is their anabolic inclusion, Is their underlying atherosclerosis, is a ruptured plaque or something else. That's the second case. And at follow up he continues to do well. And at follow up cT he did not have a positive fr with CTF of our let's go to the next case. Mhm. A 39 year old woman, another young patient, I was on service. She had presented with a cardiac arrest. She had one round of CpR and then rask. The report from ims said she had to assad she had a whole bunch of other things that were problematic that were things of concern, protein s deficiency, tobacco use, alcohol use and other potential use things. She had a history of old cerebellum, infarct, a history of a small pf Oh no antidepressant medications but it was a cardiac arrest that required cpr and then rask. So this was an electrocardiogram. This was at 9:13 in the morning mandy. How do you think she's now in the emergency room? She has recovered consciousness. Sinus rhythm. It's got some S. T. Segment elevation I guess. Yeah and then some depression in the cardio leads to right? So people weren't people were uncertain in the in the emergency room what to do? So they said let's get another electrocardiogram. She is just now a few hours from a cardiac arrest. And so at 12:50 then they did another electrocardiogram. Still some still some a little bit of elevation here. The lateral changes don't seem to be something that would have attracted much attention. But at that point in time the decision was made to proceed with the corner angiogram. This was the patient had been in the emergency room. She Had had a CPR and then after one episode head rask. So we then thought well let's take a look. So we brought her to the catheterization laboratory. This is a member of 39 year old woman with protein S deficiency alcohol and other abuse things. And a smoker corner arteries look pretty good. They look pretty great. So we took a picture of the left circulation and that looks pretty great too. People said gosh, what what's the story? This is a cardiac arrest, could it be cocaine or something awful like that? So people then looked at that and said, wow we're feeling pretty good about This 39 year old woman. We then looked for scared. Could it be scared? That's always the one thing that we consider. Could it be scared? But if we don't find scared then but we continue to look at it, look for some details and as we look for some details all of a sudden it doesn't look quite as normal. Well as we thought it looked mandy. Yeah. I think the most distal portion of the LED looks a little suspicious. It looks like maybe an abrupt cut off and then looks like the middle portion of the led looks a little tinted. Uh So indeed we thought that this was anabolic conclusion that it started up high. The drama started up high and then move down at the time of the arrest and move down and then occluded the distal L. A. D. So this was then distal distal led occlusion. And you can see it better here. It's an abrupt cut off hair. And the things that we look for in terms of scared in terms of other things, you had to look for another abnormality. And we found it. And it was anabolic conclusion of the very distal led that probably started approximately and then worked its way down. And so we then said, well let's do a trans esophageal echo without complications and Peyton firm in the valley and a left to right shunt at rest and then a right to left shunt at rest and with release of el salva a large right to left shunt. She had no inter cardiac master thrombosis. She only had trivial immobile atherosclerosis. And this was her T. It's a big P. Fo and that was the source of an M. Bolic occlusion of the very distal tip of the LED. And somebody that had presented with a cardiac arrest. Final piece of information, we'll talk about this different case. 82 year old woman with destiny april fibrillation going fast at 140 S. T. Segment. Depression proponent. 0.8 and 0.9. And mandy. Does this fall under the category of a type two? She's going fast. She has coronary disease. What do you think? Yeah. I mean if she's including this is the looks like an area of cranial view and where the point is. Looks like the LED is missing beyond that point. Or unless the LED is going up. If a lid is included, I definitely would see and expect much larger increase in troponin. But then you have an alternative explanation to account for the increase in troponin. It's a difficult case. But you know with the sum of information that I have, I will lean more towards Type two Than Type one. Perfect. And this was a very old occlusion of the led. So she had a type two. My cardio infarction related to demand ischemia supplied the man mismatch. So Let's now begin to talk about some of the issues we've talked about type two versus my cardio injury. Type to supply demand mismatch. They must have symptoms. And she did. And she had evidence of ischemia. My cardio injury might be sepsis or renal dysfunction but without symptoms or evidence of ischemia. So this is trope anemia my cardio injury. That is true. But it's not A Type two. My Cardio Infarction. So there are knowledge gaps in the epidemiology of type two. My cardio and fortune. What are the what are the pieces of information that we don't? No, I think that discriminating between type two AM I and type one am I. And type two am I. And my cardio injury is really hard. It is very hard to do that. It's one of those things that we puzzle about. And on the consult service when deep sees patients, he puzzle is about it because each individual case requires careful review by cardiologists. So what do we know that about two types? To my cardio infarction it's understudied. It's difficult to study but it's under understudied. We don't really have any good evidence based for treatment. We've had selected cohorts of registry studies or patients undergoing coronary or peripheral angiography or patients presenting to the emergency department claire Raphael. And our institution working with the cath lab looked at the Rochester epidemiology project if you live in a county like Homestead County, everybody goes to a medical center that's involved with Mayo in some way. And so we can look at this population of 149,226 patients. And we have every single patient in that County because all the medical records are linked since 1966 to either Mayo or Olmstead Medical Center and they're isolated from other providers of medical care. And what does she found? She looked at the A Community Based Epidemiologic Study of Type two. Am I to look at the incidents, temporal trends and outcomes of type two. Am I in this defined geographic population and use type one am I as a comparator or? And this is what she found. This is data from 2003 to 2012. It was 10 year data Looking at Type one. My cardio infarction in solid blue And type two and lighter blue. We can see that both of them have declined somewhat from 2003 But Type one, my cardio infarction has declined much more as we take care and improve habits of smoking And use statins and other pieces of information to improve care. But while both have declined type one My cardio infarction has declined substantially more over this 10 year period of time. But what happened in this group of patients if you were to look at all cause mortality. Did that change with type two. My cardio infarction versus type one. My cardio infarction. It's of interest in the past a term that we used was non S. T. Segment elevation Myocardial infarction. That's sort of a dinosaur term. Although we still occasionally use it and we used to think that that was more ominous predictor because they had recurrences. If you look at this information and the incidents of all cause mortality after type two versus type one, my cardio infarction, we can see that the unadjusted incidents of mortality is higher With Type two. My cardio infarction then with type on my cardio infarction, Type one. My cardio in function typically involves an isolated area, such as the very first case that we saw you take care of that. They may have other comorbidities. That is true. But we intensify our treatment of those. The type to my cardio infarction patients have other causes that might be associated with mortality. If you were to adjust for age and sex, it doesn't matter. The group of patients adjusted for age and sex are still at risk for higher mortality. Then the group of patients with Type one myocardial infarction. Let's look at the cause of death. This is really interesting. If you would look at the type to my cardio infarction. Non cardiovascular death accounts for the increase in mortality. If you would look at cardiovascular death alone, They are similar between Type two and Type one indicating the fact that these patients die of those co morbid conditions that caused them to have the oxygen supply demand mismatch as of course of their acute coronary syndrome. If you look at marty multi variable analysis for all cause mortality. And when claire looked at this 10 year experience, you can see that all cause mortality if you're older, more mortality. If you have hypertension, more mortality. If you're a diabetic, more mortality. If you've had a prior stroke or mortality, if you have renal disease, all these other things are associated with increased mortality. If you would look at those patients that have greater than 70% stenosis at the time of angiography was not statistically significantly different. And so what this says it is the other things. The other company, the type two my cardio infarction runs around with that is the cause of that increase in mortality. Does it affect prognosis? And how does it affect prognosis? Well there can be different factors that provoke type two in functions that supply demand mismatch, it can be anemia can be hypertension and it can be hypoxia. Those are the real big players. If you see someone who comes in with a hemoglobin of seven, you can take care of the stem E or the non stem me for a while. But it may be that they have an underlying malignancy. If you come in with somebody who's severely hypertensive they're going to have cns damage related to that. If they have an arrhythmia you can treat that if there are post surgical case. Like Bandit talked about you can take care of that patient because they're having surgery to change things. But if you come in with severe anemia or severe hypertension or severe hypoxia you may not be able to improve that as much and reduce the provoking factor For their type two. My cardio function. So what then could we say? Going forward? We have talked about issues with my cardio infarction. It's an umbrella Under that umbrella. We have different categories of my cardio unfortunate. We now have the 4th universal definitions that include type one like we've talked about in the past and the first case. Look at that. It's an afro thermal up from biotic event, ruptured plaque, plaque, fisher or plaque ulceration and we can treat that it is declining in terms of frequency and indeed at the present time the frequency of type one, My cardio infarction and type two myocardial infarction are identical at least in our practice. And so that first case of a throw throw em Bostic disease we can treat them and the patients do well because we go through secondary prevention. If we were to then go to the next case of the symbolic conclusion of the distal tip of the L. A. D. We need to look for things that we were used to looking for. We're used to looking for scad look used to looking for from biotic inclusions. We may not be as observant about details as man dip picked up with the distal occlusion of the led or we can find a patient like we saw who was the smoking patient who came in and he had a clot. And then when you look for something, it was again a local event, a ruptured plaque. And so as we begin to wrap up, we need to make sure that we really understand the greatest extent that we possibly can. The specific kind of my cardio infarction and treat these specific underlying cause. And if we identify provoking factors, we need to do the very best that we can treat those provoking factors because for type two myocardial infarction, their excess and mortality is not related to the coronary disease, acute coronary syndrome? It's related to the other things that they come to the party with. That's really the background for this man. Deep. It is, it was just a phenomenal talk. David, thank you for summarizing such a such a complex topic and I hope the listeners and the audience benefited from, from your wisdom. There were some few questions rolling in and I will pass them on to you to get your response. So first is do you think that the magnitude of troponin elevation help you distinguish between Type one versus type two. Thinking that if it's an included vessel, especially if it's an S. T. Elevation or even if it's an honest the elevation, the magnitude of troponin is much higher As compared to Type two. That's an that's an important that's a really important question that has multiple facets to that. When we see patients that have marked elevation of troponin, they have more my cardio injury as part of that and when those, when that elevation has been factored in that is associated with increased mortality long term, I think that that becomes increasingly important as we use the higher sensitivity proponents and we struggle with that all the time. If there is a mild elevation of proponent that's a high sensitivity were more likely to say, well, indeed, that is my cardio injury, but it may not be unfortunate. There's a phenomenon. Can I? There's a phenomenally interesting study in that regard. It was a study was in circulation about a year and a half ago. There was a phenomenally interesting study. What they did was they took a balloon Catherine. It was in a patient that was in at least one patient and maybe it was a series of patients. I cannot remember that. And they then they put the inflation balloon up in a normal artery over the first septal and they began to measure troponin over the next several minutes and they found that just elevation of a balloon catheter for a few minutes. And I can't remember that maybe you would remember the length of time, It was seven minutes resulted in troponin elevation, even even though it wasn't sustained and there wasn't any downstream effect of it. But the high sensitivity proponents are very, very sensitive for any little bit of ischemia. So that that's just a really wonderfully interesting study that shows you how rapidly proponents go up, particularly the high sensitivity. But back to the question, the higher the higher the level of proponent and the higher level that it stays makes you think more and more about more of my cardio damage. And I have from one of the participants is that you you describe this uh lyric, uh what did you say? Lady would marinade is such a great word. Right, Right. How long do you give this marinade for uh, to get the best results? That was for about 10 minutes. 10 minutes. Okay. Obviously you're limited, but the vessel is included already. That's that's true. I mean, it's not as if you've taken the vessel that was patent and made it included during the the um, during the marinade process. So you would use that in a patient such as the patient that we showed that that you've included it or it has become occluded with a large traumatic Burden. But the guideline. Our approach is a good one obviously have to make sure that you don't damage the vessel going down all of those things that we know about, but it was 10 minutes. Okay, now the the example that you showed that there was a distant traumas and then with the wire went away and conservative treatment. The question is, what do you do after besides the core degree have in terms mainly focusing on anti plated uh anticoagulants strategies. How do you how do you treat those patients? I think that we would treat those patients as as an acute coronary syndrome. Like we would do patients that would have a type and two. I carry on fortune, we would treat them with dual anti platelet therapy. Now if you were to say, well show me the, show me the data on that. I don't have any. I mean there's not a big data set on that. There is however, an extraordinarily piece of information from the type to literature on long term treatments. The audience might remember the odyssey trial. The odyssey was a A 20,000 patients multinational trial that looked at the patients coming in with a cute my cardio acute ischemic events. There was a subset a pre specified subset of patients who were given either one of the P two S K nine um inhibitors or a standard conventional therapy. And it turned out in the subset it was about 1800 patients that sort of range in that subset of patients out to two years or after one year and out to two years. The patients with very intense lipid lowering therapy despite the fact that they've been on lipid lowering therapy when they came in did better. So, I think there are some strategies going forward in terms of secondary prevention that that we will continue to explore. Yeah, I think there was a randomized trial of about 30 some patients on patients confirmed to be having black relation with the CT. They did not stand it just to come back to me and gave them manipulated anticoagulants for two years with no events. So, I think you're right. I think conservative treatment in a very select group of patients where you're not finding an obvious black rupture. I think it's the key keys to manage their risk factors very aggressively. But but you have to it's not going to happen over the first month or three. You're not gonna get the benefit. You're they're going to need to be on longer term treatment, I think. Yeah, that was a two year study. Uh Yeah, but you're right. I mean, it has to be at least one if not two years now. The next question is, uh would you then uh do a stress testing if you are managing these patients conservatively, depending upon the rising proponent that you observe. So, if patient is treated conservatively and then you decide, I'm not going to stand it. And then how do you follow in terms of stress testing? Sure. I think there are some important issues related to that. I think those patients after they get through with rehab before you then send them and they should all go to rehab initially. Then they need to have some sort of functional testing after that. The one that's interesting to consider is and I don't know that we have really any answer in that. So for example, in that The 39 year old, smoker the thought was that we would then do a CT FFR and that was normal in terms of no ischemia, no ischemic producing lesion. I don't know where that's going to play out. But I think that in those patients at the time they finished the rehabilitation before they go back to their regular activity, that a functional test is a really important one. Yeah, just for the audience, I think we'll have the next webinar is only on stress testing in the setting of VCS. Uh so we will have a full hour on that. The next question is very interesting. That would you treat type two differently as compared to type one in terms of medical management, including Heparin. So that is bitter blockers statins. Would you then you see in a consult with this patient as clearly a type to like your last patient. Would you treat her differently than a black rupture that you spend it? They're really important and good question. We don't have a lot of information on that and randomized trials by any means. But those medications that you have talked about, we give for patients that have established coronary artery disease to try to improve their outcome. And so that falls under the category of trying to improve their outcome from underlying cardiovascular disease, not necessarily just because they had a Type two myocardial infarction. So I think they deserve the same sort of intensive therapy because it's the treatment of those things that can potentially improve there outcome longer term. Just because you have treated more aggressively their co morbid conditions. That's absolutely true. I think the distinction would be In my mind as you talked about the Type two relating to the cardiovascular risk factors or risk factor profile being much fire in Type two diabetics, hypertensive stroke COPD kinda deal and most of the deaths that are happening on non cardiovascular deaths That risk factor management has to be much more aggressive in those patients. Whereas if you have a type one definitely you add on to prevention of record and black rupture, Which was the inciting event in Taipan as compared to Type two. Um now the next question is, um can you differentiate Type 2? AM I and myocardial injury clinically without performing an angiogram. I think that I think that you can is it the symptoms and based upon symptoms. So for example, somebody that comes in that has chronic real disease and has elevated proponent that has absolutely no symptoms. We then may not. We might stress them to see if they have underlying coronary disease because they have chronic kidney disease. But we wouldn't necessarily take them to the catheterization laboratory just because they have a troponin elevation in the absence of any of the other criteria That separate out my cardio injury from a Type two. Yeah, I think that distinction is extremely important. So we have to be very judicious in taking these patients to the Cath lab. But once a patient reaches the cath lab you find the legion, Would you stand it if your if your suspicion is patient has type two versus the type one. And I think in that setting, um we would do an fr or we would test for ischemia and we would treat ischemia. That's not to say that we would hope that by treating the ischemia in that lesion that that would have also have improved the outcome. So we would we would do if our or ever are, I think it's extremely important for audience to learn that as we age, the cardiovascular disease ages with us. So about 80% of us will have significant CED when we turn 80. Uh and so it will be very common for us to find significant coronary artery disease which may not be relevant to the presentation if we take these patients to the Cath lab. So David's point is I think very well taken that we have to have some functional significance of that rather than just see a lesion and standard. And I think we will see more widespread use of FFR Ct in seeing patients like that as outpatients. Although as you mentioned in the older patients because of the calcium that may that may preclude good data. But I think that you're exactly right. We will see more and more patients and we're going to be more dealing with physiologic treatment based upon physiologic assessment of ischemia. That's true. Now. Um is there any risk of what the marinade you described? Uh I would think hemorrhage. Uh No that's a fusion of trump to. That's a good that's a good question. Um I don't know that there's a large enough series to know that we do know that in the past we used inter coronary lyric therapy and we still use inter coronary lyric therapy in some patients with a very large traumas burden. So for example in vein graft disease Or to be three Agent. So can any of those things promote um intra wall hemorrhage. They certainly can But in general but you're not putting it at any pressure. Number one. So And number two then you're just going to stent an area that is abnormal number three and you're going to then limit the length of that step. That's not to say that you couldn't have somebody that had a ruptured plaque that was deep within the wall or already an inter plaque an intra wall hematoma that that couldn't get worse. That can get worse just with heparin or putting a catheter in. I think what you uses that technique and someone that you're already having trouble with and then you use that to get out of trouble. Um so uh the two related questions on anticoagulants in Type two M I. Um do you use happen in these patients? And do you use do X or Navigator? And for example, Do you have any experience in type 2? MS using anti coagulation? We typically, we typically don't specifically for that reason that you're talking about, that wouldn't be typically part of our strategy. You know, we do have the information from randomized trial that long term patients treated with low dose of Novak and another agent do better, but we don't necessarily apply that in this case. And the last question I have for you, David, uh Is does the pattern of rise and fall of proponent help you distinguish type one from type two or they follow the same rise and fall pattern? I think they follow the same rise and fall better. Okay, okay. I I just want to thank you from the bottom of my heart and for the attendees uh this uh webinar as our previously archived webinars are available for, from cv education dot mayor dot e D U. You can certainly forward it to your friends and learn from it later view the recording and the next webinar, as I said, we'll be on stress testing. Thank you David, thank you so much for your time. Thanks Bendy thanks to the audience. Yeah. Thank you audience.