MANDEEP SINGH: Welcome. My name is Mandeep Singh, and I'm the ACS Director for the Mayo Foundation, and on behalf of the Cardiovascular Department at Mayo Clinic Rochester, I welcome you 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 my mentor. For the last 25 years, I was his student. I then became a colleague and a dear friend.
Some background on David. First off, I was reading his CV. I couldn't finish it. It's like 156 pages long. So H factor is through the roof. He has more than thousand publications. He has so many patents that he has not even numbered those patents. So it just amazing.
He went to Princeton when I was born. He's a legend. He's just an awesome guy. He's done everything from EP to transitioning to interventional. When I joined 25 years ago, he was my cath lab director. And he's guided me, mentored me all the way through, that I am at a stage where I am now introducing him to give this talk on acute coronary syndrome, and he's going to be talking on updates in classification, some newer mechanisms, and then role of early angiography. David, it's a distinct pleasure.
DAVID HOLMES: Mandeep, it's great to be here with you in this audience in this virtual time and space. Mandeep and I do go back a long way. The very first time I met Mandeep, I was doing mitral balloon valvuloplasty. So this is a long time ago. And we were then figuring out the 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 a thousand 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 Mandeep, 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? Well, we want to identify the most recent classification of non-STEMI. Terribly important. Look at evaluation of atherothrombotic mechanisms of non-STEMI, as well as STEMI, and then look at the role of early angiography in patients with non-STEMI, 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 wastebasket. 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 troponinemia. And then there are non-STEMIs, Type 1, and Type 2. And then there are STEMIs, Type 1, and Type 2. 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 myocardial infarction continues to change. For those of you that worked in the 1950s, there was the first WHO definition. That was about 1955. And then that lasted until 1960. And then we got to another definition in 1970. And then we have continued iteration of the definition through ISFC, that WHO 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 myocardial infarction. In 2000, we had the ESC ACC redefinition. And then, we had the UDMI definition, and then we had the third UDMI, 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 fourth 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 acute myocardial injury. The evidence is a rise and fall of troponin. But it had to include at least one value above the 99th percentile of the upper limit of normal.
But it had to include an evidence of acute myocardial ischemia. Whether that be symptoms of myocardial ischemia, whether that be new ischemic ECG changes, whether that be pathologic Q waves, whether it be imaging evidence of new regional wall motion abnormalities or loss of myocardium. Or whether it be identification at the very end of the day of coronary thrombus and angiography or autopsy. And so Mandeep, we then struggle with these sort of definitions and say, where does troponinemia by itself fit in the definition of myocardial infarction?
MANDEEP SINGH: Yeah, I think the issue I always struggle with is how to distinguish the myocardium injury from acute myocardial infarction. Is it just the-- so the situation I present to you, for example, I'm on consult service. I see this patient with shortness of breath post-op, did draw troponin as the troponin peaked. 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 MI that needs further attention, including taking this patient to the cath lab?
DAVID HOLMES: 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 fourth universal definition, the subclassification type 1, that would be the typical STEMI that we've had in the past. Primary coronary event, whether it would be plaque erosion or plaque rupture or a fissure.
There's type 2, then, as Mandeep has talked about, whether it's ischemia due to increased oxygen demand, or decreased supply. For example, anemia, arrhythmia, or hypotension, and that's going to be terribly important as we go forward and talk about some of the information. Type 3 would be sudden unexpected cardiac death. Type 4A would be myocardial infarction due to PCI. That's a different kettle of fish.
Type 4B is myocardial infarctions associated with stent thrombosis. Or type 5 is myocardial 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 2 myocardial infarction and Mandeep then sketched out a scenario. Type 2 myocardial infarction occurs because of an acute imbalance in myocardial oxygen supply and demand in the absence of an acute atherothrombotic 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 a myocardial infarction or what.
And then, we have to try to distinguish between myocardial injury versus a type 2 myocardial infarction. Type 2 myocardial infarction can relate to anemia, can be seen, or arrhythmia, or heart failure, or chronic kidney disease, or hypotension shock, or hypoxemia. And all of those then could result in a type 2 myocardial infarction. That would result in elevated troponin, but also could be seen with abnormal electrocardiogram changes, as Doctor Singh has talked about.
Let's then talk about some cases. First case, 76-year-old man with acute onset of chest pain. He 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 interventricular conduction defect. That is true. There is ST-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 1 STEMI, so an atherothrombotic event, whether it's a plaque rupture, or whether it's a plaque hemorrhage, or whether it's a plaque fissure, or a plaque erosion. 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 coronary artery, Dr. Singh, what about this huge thrombotic burden, and how would you how would you then think of this being a type 1 myocardial infarction, from an atherothrombotic event?
MANDEEP SINGH: Yeah, if you just go by statistics, I think plaque rupture remains the number one cause for MI. And more, so if you then add some cardiovascular risk factors. There is a stenosis just before the large body of thrombus seen as a filling defect. But certainly, if you just have this thrombus, and no stenosis, as you have shown, certainly can point to a plaque erosion, especially in younger patients without cardiovascular risk factors.
DAVID HOLMES: Good. So we're going to then say this is a STEMI with a large thrombus type. So TIMI 2 flow. It's 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 thrombectomy in this person with a very large thrombus?
We used to do a lot of thrombectomy. 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? He has 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 posterior descending. And so we then pass a wire through, and maybe do a little bit of stuff. And then, all of a sudden, the patient's chest pain gets worse. And his ECG changes also get worse.
And we can see that what had been there has moved around. And so that was a large thrombus that you have moved more distally. 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 thrombus with potentially a long stent. Or if you lived in Europe you could use an M stent. 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 thrombus 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 patients. And this is an option that people might not consider. You could potentially bathe that thrombus in lytic therapy. We don't usually do that. We would use a 2B3 agent downstream or something.
But another strategy that can be used can be to take a guide liner down it and wedge it in the stenosis. That has blocked flow down. And you could then move further downstream, and you could put in a 2.5 millimeter balloon and block outlet. And so you could use this as a strategy to bathe that whole segment of the artery that you have embolized thrombus into.
And so in this setting, it is already occluded. That is true. He's going to have chest pain. That is true. You'll have to watch for rhythm disturbances. All those things are true. But you can then instill TPA. You have a guide liner 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 thrombotic burden in this type 1 STEMI.
And then you can aspirate it. So you've put in the TPA. You've let it sit there for a bit. You still have your 2.5 millimeter balloon up. But you can take the guide liner and then aspirate that whole column, that whole column from where it was wedged down to where the balloon is occluded.
And then you can see, gosh, you've been able to take out most of the [INAUDIBLE] stuff that's there. And you have restored pretty good flow down there. Mandeep, what do you think about a strategy like that? And what would you do next?
MANDEEP SINGH: Yeah, this has worked wonderfully. But I think it is very under-utilized strategy as one of the options when you have a large body of angiographic thrombus. Typically, what I do is some kind of thrombectomy. But with high rates of stroke, I think people have shied away from using this routinely. But in this patient, at least, if not a thrombectomy, either rheolytic thrombectomy or aspiration thrombectomy, this is a beautiful strategy, and it worked beautifully.
DAVID HOLMES: So then, you have the situation that you can then stent it. So you've gotten rid of this thrombus. You have done what is called a lytic marinade. Isn't that a great term? A lytic marinade. As another treatment option for heavy thrombus burden. 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 thrombotic burden.
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 have seen him. He was a smoker. He'd had a one-month history of exertional chest discomfort, radiated jaw, and arms, and his back. And so he presented to an outside hospital for evaluation, had a troponin I of greater than 5, and a D dimer of 0.32, and he had a CRP that was extraordinarily high, at 17.5.
This was his electrocardiogram. And what would we 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 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 coronary artery, we can see that in this 39-year-old smoker, there's probably some tubular disease in the LAD, but main looks OK.
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 artery might have looked like had it been occluded. 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.
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. Mandeep, what do you think about that? Looks like down there you can see some visualization.
MANDEEP SINGH: Yeah. I think this artery cranial shot definitely gives you an indication that, one, the RCA is occluded. And two, the collaterals to the right PDA are faintly filling from the septal and distal LAD.
DAVID HOLMES: OK. So we then position, that we had trouble positioning a catheter. And so while we don't typically use Amplatz catheters, we did it in this particular case. So we see the injection. It's a deep engagement. That is true. 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 atherosclerotic disease, I guess, because there's a large filling defect here. And as we can see, it involves then the posterior 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. 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 clot 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 posterolateral segment with a little balloon.
And while there's certainly some distal embolization, the patient is asymptomatic. But we but we haven't done anything where the thrombus was. That was where the thrombus was, at least based upon the angiogram. So Mandeep, what do we do with that place where the thrombus was? Should we treat that, or--
MANDEEP SINGH: This is a case where I think it certainly can be applied erosion too. OCT or some kind of imaging would be very essential, just to look at the underlying mechanism. You can see the distal portion of the right posterior lateral branch. It's pretty stenotic.
But I think, as one can imagine, the thrombus is the most potent vasoconstrictor. It just must have constricted the vessel distally. So herein I would not just put stents and stuff, but just give some vasodilators through the posterior lateral branch, and see whether it can open up or not.
DAVID HOLMES: OK. So we then did some of those things, and it began to open up. We gave nitrates, and gave some time. And our decision at that point in time was to say, well, what indeed could be the underlying pathophysiology 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 Mandeep, so this is down in the region. What do you think? It's a pull back. That's the region where the thrombus was.
MANDEEP SINGH: I don't see a rupture plaque, and I don't see a whole body of plaque.
DAVID HOLMES: Right. So we were then faced with a 39-year-old guy that we can only presume had a ruptured plaque that we can't see. But in terms of finding a lot of atherosclerosis, we didn't in this 39-year-old smoker.
And so when we play it again, if we can do that again. Or maybe not. This was OCT-- this was using IVUS 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.
And so we're going to then say it was a ruptured plaque. Had we used OCT, we might have seen it better. This was conventional IVUS. But we're then left with a man that had a ruptured plaque. He does not have a significant stenosis there. And your options are, at that point in time, are you going to stent it anyway, because it had a ruptured plaque before. And so let's go on to the next picture. Can we advance that?
So those are the questions. What next? You've found you've got some atherosclerosis there. But it's not severe. Are you going to consider that this was an embolic thing? Or are you going to say it was a ruptured plaque? Are you going to stent it anyway, because it was vulnerable at one point in time? Or are you going to leave it alone to heal?
These were his demographics. You can see he's somewhat bigger than he might be. We then found this right coronary thrombus, and we said, gosh, maybe there's an embolic source. So we did an Adult TEE to look to see.
We didn't find any intracardiac mass. The left atrial appendage was free of clot. It was normal size and contractile. There wasn't any shunt 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 thrombus that could have been an embolus from someplace else. And so we then could say, this is probably a ruptured plaque. It wasn't an embolic occlusion. It was a ruptured plaque, and there's no significance stenosis. And we said, we're not going to stent you.
We send him to rehabilitation and secondary prevention, and had him stop smoking. Or at least, we encouraged him 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 there an embolic occlusion? Is there underlying atherosclerosis? Is it 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 FFR with CT FFR. Let's go to the next case.
It's a 39-year-old woman, another young patient that was on service. She had presented with a cardiac arrest. She had one round of CPR, and then ROSC. The report from EMS said she had torsade. 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 cerebellar infarct, a history of a small PFO, and no antidepressant medications. But it was a cardiac arrest that required CPR and then ROSC. So this was a electrocardiogram. This was at 9:13 in the morning. Mandeep, what do you think? She's now in the emergency room. She's recovered consciousness. Sinus rhythm. It's got some ST-segment elevation, I guess.
MANDEEP SINGH: Yeah. And then some depression in the--
DAVID HOLMES: Some depression.
MANDEEP SINGH: [INAUDIBLE] leads to [INAUDIBLE].
DAVID HOLMES: So people were uncertain 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 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 coronary angiogram. This was a patient had been in the emergency room. She had had a CPR, and then after one episode had ROSC. So we then thought, well let's take a look. So we brought her to the catheterization laboratory.
This is, remember, of 39-year-old woman with protein S deficiency, alcohol, and other abuse things. And a smoker. Coronary 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's the story? This is a cardiac arrest. Could it be cocaine or something awful like that? And so people then looked at that and said, wow, we're feeling pretty good about this 39-year-old woman. And we then looked for SCAD. Could it be SCAD? That's always the one thing that we consider. Could it be SCAD?
But if we don't find SCAD, then? But we continued to look at it, looked for some details. And as we looked for some details, all of a sudden, it doesn't look quite as normal as we thought it looked. Mandeep?
MANDEEP SINGH: Yeah, I think the most distal portion of the LAD looks a little suspicious. It looks like maybe an abrupt cut off. And then looks like the middle portion of the LAD looks a little tinted.
DAVID HOLMES: So indeed--
MANDEEP SINGH: I don't see anything else.
DAVID HOLMES: --we thought that this was an embolic occlusion that had started up high. The thrombus started up high, and then moved down at the time of the arrest, and moved down, and then occluded the distal LAD.
So this was then a distal LAD, a distal LAD occlusion. And you can see it better here. It's an abrupt cut off here. And the things that we look for in terms of SCAD, in terms of other things, you had to look for another abnormality. And we found it. And it was an embolic occlusion of the very distal LAD that probably started proximally, and then worked its way down.
And so we then said, well let's do a transesophageal echo without complications in that patent foramen ovale, and a left-to-right shunt at rest, and then a right-to-left shunt at rest. And with release of Valsalva, a large right-to-left shunt. She had no intracardiac mass or thrombus. She only had trivial immobile atherosclerosis.
And this was her TEE. It's a big PFO. And that was the source of an embolic occlusion of the very distal tip of the LAD in somebody that had presented with a cardiac arrest.
Final piece of information. We'll talk about this different case, 82-year-old woman with dyspnea atrial fibrillation going fast at 140, ST segment depression. Troponin 0.08 and 0.09. And Mandeep, does this fall under the category of a type 2? She's going fast. She has coronary disease. What do you think?
MANDEEP SINGH: Yeah. I mean, if she's occluding, this looks an aerial cranial view. And where the pointer is looks like the LAD is missing beyond that point, or unless the LAD is going up. If the LAD is occluded, 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 with the sum of information that I have, I will lean more towards type 2 than type 1.
DAVID HOLMES: Perfect and this was a very old occlusion of the LAD. So she had a type 2 myocardial infarction related to demand ischemia. Supply-demand mismatch.
So let's now begin to talk about some of the issues. We've talked about type 2 versus myocardial injury. Type 2 is supply-demand mismatch. It must have symptoms. And she did. And she had evidence of ischemia. Myocardial injury might be sepsis or renal dysfunction. But without symptoms or evidence of ischemia.
So this is troponinemia. It's myocardial injury. That is true. But it's not a type 2 myocardial infarction. So there are knowledge gaps in the epidemiology of type 2 myocardial infarction. What are the pieces of information that we don't know?
I think that discriminating between type 2 MI and type 1 MI and type 2 MI and myocardial 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 Mandeep sees patients, he puzzles about it, because each individual case requires careful review by cardiologists.
And so what do we know then about type 2 myocardial infarction? It's understudied. It's difficult to study. But it's understudied. We don't really have any good evidence base 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 in our institution working with the cath lab looked at the Rochester Epidemiology Project. If you live in a county like Olmsted 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 Olmsted Medical Center. And they're isolated from other providers of medical care.
And what did she found? She looked at the community based epidemiologic study of type 2 MI to look at the incidence, temporal trends, and outcomes of type 2 MI in this defined geographic population, and use type 1 MI as a comparator. And this is what she found. This is data from 2003 to 2012. It was 10-year data.
Looking at type 1 myocardial infarction in solid blue, and type 2 in lighter blue, we can see that both of them have declined somewhat from 2003. But type 1 myocardial 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 1 myocardial 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 2 myocardial infarction versus type 1 myocardial infarction? It's of interest in the past. A term that we used was non-ST 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 a more ominous predictor, because they had recurrences. If you look at this information and the incidence of all-cause mortality after type 2 versus type 1 myocardial infarction, you can see that the unadjusted incidence of mortality is higher with type 2 myocardial infarction than with type 1 myocardial infarction.
Type 1 myocardial infarction typically involves an isolated area, such as the very first case that we saw. You take care of that. They may have other co-morbidities. That is true, but we intensify our treatment of those. The type 2 myocardial 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 than the group of patients with type 1 myocardial infarction.
Let's look at the cause of death. This is really interesting. If you were to look at the type 2 myocardial infarction, non-cardiovascular death accounts for the increase in mortality. If you were to look at cardiovascular death alone, they are similar between type 2 and type 1, indicating the fact that these patients die of those comorbid conditions that caused them to have the oxygen supply-demand mismatch as a course of their acute coronary syndrome.
If you were to look at multivariable 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, more mortality. If you have renal disease, all these other things are associated with increased mortality.
If you look at those patients that have greater than 70% stenosis at the time of angiography, it was not statistically significantly different. And so what this says is the other things, the other company, the type 2 myocardial infarction runs around with. It 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 2 infarctions, that supply-demand mismatch. It can be anemia. It can be hypertension. It can be hypoxia. Those are the real big players. If you see someone who comes in with a hemoglobin of 7, you can take care of the STEMI, or the non-STEMI for a while, but it may be that they have an underlying malignancy.
If you come in with somebody who's severely hypotensive, they're going to have CNS damage related to that. If they have an arrhythmia, you can treat that. If they're a post-surgical case, like Mandeep 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 hypotension or severe hypoxemia, you may not be able to improve that as much, and reduce the provoking factor for their type 2 myocardial infarction.
So what then could we say going forward? We have talked about issues with myocardial infarction. It's an umbrella. Under that umbrella, we have different categories of myocardial infarction. We now have the fourth universal definitions that include type 1, like we've talked about in the past. And the first case looked at that. It's an atherothrombotic event. Ruptured plaque, plaque fissure, 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 1 myocardial infarction and type 2 myocardial infarction are identical, at least in our practice. And so that first case of atherothrombotic 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 embolic occlusion of the distal tip of the LAD, we need to look for things that we weren't used to looking for. We're used to looking for SCAD. We're used to looking for thrombotic occlusions. We may not be as observant about details as Mandeep picked up with the distal occlusion of the LAD
Or we can find a patient like we saw who was a smoking patient, who came in and he had a clot. And then when you looked 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 to the greatest extent that we possibly can a specific kind of myocardial infarction, and treat the specific underlying cause.
And if we identify provoking factors, we need to do the very best that we can to treat those provoking factors, because for type 2 myocardial infarction, their excess in 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, Mandeep.
MANDEEP SINGH: It is. It was just a phenomenal talk, David. Thank you for summarizing such a complex topic. And I hope the listeners and the audience benefited 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 helped you distinguish between type 1 versus type 2, thinking that if it's an occluded vessel, especially if it's an ST elevation, or even if it's a non-ST elevation, the magnitude of troponin is much higher, as compared to type 2.
DAVID HOLMES: That's an important-- that's a really important question that has multiple facets to that. And then we see patients that have marked elevation of troponin. They have more myocardial injury as part of that. And 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 troponins. And we struggle with that all the time. If there is a mild elevation of troponin that's a high sensitivity, we're more likely to say, well, indeed that is myocardial injury, but it may not be infarction.
There's a phenomenon-- can I-- there's a phenomenally interesting study in that regard. It was a study that was in circulation about a year and a half ago that was a phenomenally interesting study. What they did was they took a balloon catheter. It was in a patient-- it was in at least one patient, and maybe it was a series of patients. I cannot remember that.
And 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 then maybe you would remember the length of time. It was several minutes.
MANDEEP SINGH: No.
DAVID HOLMES: Resulted in troponin elevation. Even though it wasn't sustained, and there wasn't any downstream effect of it. But the high sensitivity troponins are very, very sensitive for any little bit of ischemia. So that's just a really wonderfully interesting study that shows you how rapidly troponins go up, particularly to high sensitivity.
But back to the question, the higher the level of troponin, and the higher level that it stays makes you think more and more about more myocardial damage. More myocardial injury.
MANDEEP SINGH: The question I have from one of the participants is that, you described this lytic-- what did you say? Lytic what?
DAVID HOLMES: Marinade. It's such a great word.
MANDEEP SINGH: Right, right.
DAVID HOLMES: Lytic marinade.
MANDEEP SINGH: So how long do you give this marinade for to get the best result?
DAVID HOLMES: That was for about 10 minutes.
MANDEEP SINGH: 10 minutes, OK.
DAVID HOLMES: Now, obviously you're limited. If the vessel is occluded already, that's true. I mean, it's not as if you've taken a vessel that was patent, and made it occluded during the marinade process. So you would use that in a patient, such as the patient that we showed, that you've occluded it, or it has become occluded with a large thrombotic burden.
But the guideline or approach is a good one. Obviously, you 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.
MANDEEP SINGH: OK.
DAVID HOLMES: It's a great technique.
MANDEEP SINGH: Now, the example that you showed, there was a distal thrombus, and then with the wire, it went away, and conservative treatment. The question is, what do you do after, besides the cardiac rehab? In terms mainly focusing on antiplatelet and anticoagulant strategies. How do you treat those patients?
DAVID HOLMES: I think that we would treat those patients as an acute coronary syndrome, like we would do patients that would have a type 2 myocardial infarction. We would treat them with dual antiplatelet therapy. Now, if you were to say, well, 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 extraordinary piece of information from the type 2 literature on long-term treatments. And the audience might remember the ODYSSEY trial. The ODYSSEY was a 20,000 patient multinational trial that looked at patients coming in with acute myocardial and acute ischemic events.
There was a subset, a pre-specified subset of patients who were given either one of the PCSK9 inhibitors or standard conventional therapy. And it turned out in the subset, it was about 1,800 patients, that sort of range. In that subset of patients, after two years, or after one year, and out to two years, the patients with very intense lipid lowering therapy, despite the fact that they'd been on lipid lowering [INAUDIBLE] when they came in, did better. So I think there are some strategies going forward in terms of secondary prevention that we will continue to explore.
MANDEEP SINGH: Yeah. I think there was a randomized trial of about 30 some patients on patients confirmed to be having plaque erosion with the OCT. They did not stent it. Just the thrombectomy, and give them antiplatelet 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 plaque rupture, I think is the keys to manage the risk factors very aggressively.
DAVID HOLMES: But you have to-- that's not going to happen over the first month or three-- you're not going to get the benefit. They're going to need to be on longer term treatment, I think. Like [INAUDIBLE].
MANDEEP SINGH: That was a two-year study. But you're right. I mean, it has to be at least one, if not two years. Now, the next question is, would you then do a stress testing if you are managing these patients conservatively, depending upon the rise in troponin that you observed? If the patient is treated conservatively, and then you decide I'm not going to stent it. And then how do you follow in terms of stress testing?
DAVID HOLMES: 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, and I don't know that do we have really any answer on 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 ischemia producing lesion.
I don't know where that's going to play out. But I think that in those patients, at the time they finish the rehabilitation, before they go back to their regular activity, that a functional test is a really important one.
MANDEEP SINGH: Yeah. Just for the audience, I think we'll have the next webinar is only on stress testing in the setting of ACS. So we will have a full hour on that. The next question is very interesting. That would you treat type 2 differently as compared to type 1, in terms of medical management, including heparin? So that is beta blockers, statins. Would you then-- you see in a consult, this patient is clearly a type 2, like your last patient. Would you treat her differently than a plaque rupture that you stent it?
DAVID HOLMES: It's a really important and good question. We don't have a lot of information on that in 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 2 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 their outcome longer term, just because you have treated more aggressively their comorbid conditions.
MANDEEP SINGH: That's absolutely true. I think the distinction would be, in my mind, as you talked about the type 2 relating to the cardiovascular risk factors, or risk factor profile being much higher in type 2 MIs, diabetics, hypertensives, stroke, COPD kind of deal. And most of the deaths that are happening are noncardiovascular deaths. That risk factor management has to be much more aggressive in those patients. Whereas if you have a type 1, definitely you add on to prevention of recurrent plaque rupture, which was the inciting event in type 1, as compared to type 2.
Now, the next question is, can you differentiate type 2 MI and myocardial injury clinically, without performing an angiogram?
DAVID HOLMES: I think that you can.
MANDEEP SINGH: Is it the symptoms, do you think?
DAVID HOLMES: It's based upon symptoms. So for example, somebody that comes in that has chronic renal disease, and has elevated troponin, 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 myocardial injury from a type 2.
MANDEEP SINGH: 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 a lesion, would you stent it? If your suspicion is the patient has type 2, versus a type 1 MI.
DAVID HOLMES: I think in that setting, we would do an IFR, 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 improved the outcome. So we would-- we would do IFR or FFR.
MANDEEP SINGH: I think it's extremely important for our audience to learn that as we age, the cardiovascular disease ages with us. So about 80% of us will have significant CAD when we turn 80. 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. And 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 stent it.
DAVID HOLMES: And I think we will see more widespread use of FFR CT, and seeing patients like that as outpatients. Although, as you mentioned, in the older patients, because of the calcium, 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.
MANDEEP SINGH: That's true. Now, is there any risk of what the marinade you described? I would think hemorrhage, not a solution of thrombus.
DAVID HOLMES: That's a good question. I don't know that there's a large enough series to know that. We do know that in the past, we used intracoronary lytic therapy, and we still use intracoronary lytic therapy in some patients with a very large thrombus burden.
So for example, in vein graft disease, or a 2B3 agent. So can any of those things promote intra-wall hemorrhage? They certainly can. But in general, but you are not putting it at any pressure, number one.
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 stent. 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 intra-plaque-- an intra-wall hematoma, that couldn't get worse.
That can get worse just with heparin or putting a catheter in. I think what you use is that technique in someone that you're already having trouble with. And then you use that to get out of trouble.
MANDEEP SINGH: So there are two related questions on anticoagulants in type 2 MI. Do you use heparin in these patients? And do you use DOACs, or dabigatran, for example? Do you have any experience in type 2 MIs using anticoagulation?
DAVID HOLMES: We typically don't specifically, for that reason that you're talking about. That wouldn't be typically part of our strategy. Well, no, we do have the information from randomized trials that long-term patients treated with low dose of DOAC and another agent do better. But we don't necessarily apply that in this case.
MANDEEP SINGH: And the last question I have for you, David, is does the pattern of rise and fall of troponin help you distinguish type 1 from type 2? Or they follow the same rise and fall pattern?
DAVID HOLMES: I think they follow the same rise and fall pattern.
MANDEEP SINGH: OK, OK. I just want to thank you from the bottom of my heart. And for the attendees, this webinar, as our previously archived webinars, are available from cveducation.mayo.edu. You can certainly forward it to your friends, and learn from it, later view the recording. And the next webinar, as I said, will be on stress testing. Thank you, David. Thank you so much for your time.
DAVID HOLMES: Thanks, Mandeep. Thanks to the audience.
MANDEEP SINGH: Yeah, thank you, audience. Bye-bye.