STEMI part 1: focus on reperfusion- Elias Hanna

So, I will talk today about STEMI management, and I will focus on reperfusion. Hopefully, I will be able to give you more talks about STEMI. I'm not someone who likes to give a quick overview; I like to dissect every topic at a time. I will particularly focus on the perfusion timelines, when to use thrombolytics, and transfer patients that we get called about from non-PCI hospitals and how to combine PCI and thrombolytics. Uh, I want you to know the data beyond the guidelines so you can make quick and smart decisions.

This slide summarizes the timelines of STEMI. So, the first hour is what we call the golden hour, where most myocardium can be saved with reperfusion. That's why no delays into perfusion should be allowed in that first hour. Thrombolysis is very effective for fresh thrombus in that first hour. Now, one to three hours, the second landmark timeline, it's still a great time zone where a lot of the myocardium can be saved, and thrombolysis is still quite effective.

Three to 12 hours: most necrosis has already occurred by three hours. Thrombolysis remains effective, less so than in the first three hours, but PCI is much more effective than thrombolysis in that time zone. Thrombolysis and PCI may be close to equally effective in the first hour and in one to three hours, but PCI becomes much more effective than thrombolysis between three to 12 hours. Now, since most necrosis has already occurred, reperfusion is still very valuable because it streets very infrared ischemia and, most importantly, it reduces adverse left ventricular remodeling, improves the scar strength, and reduces mortality in this zone. You may still save some myocardium; it's not all necrotic, mainly if one of those three: if you have pre-infarct ischemia, or if the artery partially recanalized already (even one percent recanalization), or if you have collaterals.

And here is an important keyword: pre-infarct ischemia. Pre-infarct/preconditioning ischemia are actually great in a STEMI patient; they do reduce the eventual size of the infarct via two processes. Those who have pre-infarct ischemia develop collaterals—that's one. Two: there is a cellular process called the pre-ischemic conditioning that allows the myocardium that has been ischemic to tolerate future ischemia better and be less likely to infarct. So, pre-infarct ischemia is a great thing for STEMI patients, and it will reduce the size of the infarct and allow you to save some myocardium even at a later time. So, any of those three allow you to save myocardium late.

So, between the fourth landmark timeline is 12 to 24 hours or 48 hours. In the European guidelines, they use a 48-hour cutoff. So, most necrosis has occurred; thrombolysis is ineffective; you should not use thrombolysis beyond 12 hours. PCI remains somewhat effective between 12 to 24 or 48 hours and has given class 2A in ACC and ESC guidelines. Again, you can still save some muscle in that time zone if you have any of those three features here: pre-infarct ischemia, spontaneous partial recanalization, or collaterals. So, this is an idea of how reperfusion can work even in late patients.

Let's say this patient had an infarct of this territory; 20% of his myocardium is necrotic. If you don't reperfuse, this is what happens: that scar will become thin and extend, and it will exert tension—wall tension—surrounding myocardium, which will start to also expand, and you will end up with a vicious cycle of adverse remodeling and progressive dilatation for the very same area of infarction. Conversely, you reperfuse; that scar remains tight; you keep the wall stress and tension good at the edges, and so you end up with a better EF despite and lower LV volume despite the same area of MI. Also, medications do the same thing, but that's why reperfusion works late and still reduces mortality rate. Those are important ideas to know. I think most doctors don't know those.

Spontaneous recanalization, which is a great prognostic phenomena, if it happens: 15% of acutely occluded arteries in STEMI partially recanalized by four hours, and that gives you more time to save myocardium; 35% of acutely occluded arteries partially recanalized by 24 hours, and that will allow myocardial saving in those time zones. Another idea here that I noticed a lot of fellows don't know: 50% of acute MI develop collateral flow in the first six hours. So, yes, you develop collaterals very quickly. Most of those collaterals would be what we call a grade one; we have grades zero to three. So, most of them will be weak, grade one; they don't fill the uh vessel that is occluded, but they—you get a fan filling of the branches enough to potentially save myocardium. So, 50% develop collateral in the first six hours, and most, if not all, patients develop collaterals within one to a few days after an MI, and the robustness of those collaterals depends on pre-infarct ischemia. So, some patients already have good collaterals in the first few hours or day of an MI if they've had pre-infarct ischemia. Even a small percent will have a grade three collateral by 24 hours; a grade six usually takes two weeks at least to develop. So, those are patients who've had like a 90% stenosis for several weeks; now they develop an MI; they are more likely to have developed collaterals, but all patients will develop some collaterals—almost all—within one to several days.

So, I'll move to another idea about, you know, our mentions thrombolysis. You need to know those numbers. I always quiz fellows, and very few of them know those numbers. When you give thrombolytics, what's the efficacy? Thrombolytics open the artery with a TIMI two or three flow and about—if you want to remember a number—70%, likely much more so in that first golden hour, 90%; they establish TIMI three flow in 60%. So, you know, you need to know those two numbers: 70% TIMI two or three, meaning opening the artery with flow; 60% with good flow. TIMI two means you open the artery and you have a flow all the way distally, but it's a sluggish flow; TIMI three flow means you open it all the way, and it's good flow. So, 70% and 60%. You get intracranial hemorrhage on average 1%, but I will describe high-risk subgroups where the risk is much higher than that.

The superiority of PCI over fibrinolysis widens as the presentation is more delayed—over three hours. So, in the first three hours, primary PCI and fibrinolytics, like I said, are almost equally effective; primary PCI is a little bit better—not dramatically better—but the difference widens beyond three hours. Beyond three hours, fibrinolytics efficacy, in terms of not just recanalization but mortality benefit, drops sharply, whereas the primary PCI benefit drops much more slowly; the slope is much more slow, and so that's why the gap between them widens beyond three hours, and that's why delays in door-to-balloon beyond three hours may still not trump the superiority of PCI over fibrinolytics, as I will explain in a little bit.

So, here I will provide you a general overview of reperfusion and timing in the guidelines, in my own summarized way. So, emergency perfusion with primary PCI or fibrinolytics is recommended if the presentation is within 12 hours of symptom onset for fibrinolytics and up to 24 hours for PCI, and you still have persistent ST elevation beyond cut points in at least two contiguous leads. So, class one recommendation for PCI or lytics at less than 12 hours and class 2A for PCI at 12 to 24 hours. Like I said, 12 to 24 hours, do not give lytics. There is only one isolated ST depression that qualifies as STEMI—qualifies for primary PCI or fibrinolytics as a STEMI—it's isolated ST depression that is isolated or most prominent in leads V1 to V3, which is equivalent to a posterior STEMI. So, keep that—there is one isolated ST depression that qualifies for emergent reperfusion as a STEMI. So, those recommendations apply even if chest pain has resolved, as long as ST elevation is persistent above cut points and the onset of pain is less than 24 hours. We see sometimes this patient where chest pain is—chest pain has—it is all but his ST elevation is still pronounced; this patient still qualifies for emergency perfusion, even emergent lytics if you cannot do a timely PCI.

Now, when you decide PCI versus lytics, evidently, overall PCI is preferred. Now, PCI is preferred if door-to-balloon time is less than 90 minutes in patients presenting to PCI hospitals, like our hospital, and less than 120 minutes in patients transferred from non-PCI to PCI hospitals. Those are the ACC guidelines; you need to know those two cut points: 90 minutes in PCI hospital, 120 minutes. Door-to-balloon is accepted in transfer patients, and I'll elaborate a little more later. The European guidelines use different terminology and different timelines. Door-to-balloon means what? Is door time? Door time is the moment of the first medical encounter of the patient. For example, if EMS goes to the home of the patient to take him—the ambulance—that's door time. If the patient presents to the ED, the ED is the door time. A lot of the older studies used ED as door time, even in patients transported by ambulance, but it should be first contact of the medical personnel, not ED. So, that's door time to the time you open the artery and first re-establish flow—that's door-to-balloon. European uses STEMI diagnosis, which is a little bit more delayed, and door-to-wire crossing time, and they use 30 minutes less targets. So, in patients presenting to PCI centers, they shoot for less than 60 minutes; in patients transported by paramedics or presenting to non-PCI centers, they have 90 minutes—so 30 minutes less cut points. This is because—and those, I think, cut points should be particularly applied to those presenting in the first three hours where door-to-balloon time or STEMI-to-wire crossing time is critical, and that's why they want to improve on those times.

Another idea in those timelines: so I described the first 12 to 24 hours and the door-to-balloon times in ACC and European guidelines. Now, beyond the 24 hours after symptom onset, those patients do not have an indication for emergent PCI anymore—certainly in anthrombolytics—but no emergent PCI anymore. European guidelines—and there is—hearing conflict that you will see throughout those slides—they use 48 hours. So, the patient in the European guidelines still qualify for primary PCI 12 to 48 hours—not 24 hours—and this is based on a different interpretation of the TIMI trial. TIMI trial is a trial that has shown that there is no benefit of opening occluded artery beyond 24 to 48 hours after STEMI or Q-wave infarct. So, patients presenting more than 24 to 48 hours after symptom onset generally do not have an indication for emergent PCI based on the TIMI trial, which I will elaborate on on the next slide. However, emergent PCI is still—not lytics—but PCI is still selectively indicated in some of these patients, such as they have persistent ongoing chest pain, they have new heart failure, persistent chest pain, or they have cardiogenic shock, or they have an equivalent of cardiogenic shock, which is massive pulmonary edema. I'm not talking about mild pulmonary edema or the crackles and requiring requirement for diuretic; I'm talking about massive pulmonary edema, almost practically requiring intubation—the so-called Killip 3. Killip 2 is mild pulmonary edema; that's not equivalent to cardiogenic shock; Killip 3 is massive pulmonary edema, and that qualifies to be managed almost as a cardiogenic shock, and it is managed with emergent PCI. So, those are the two big ones where you can still do emergent PCI beyond 24 to 48 hours. The third one that I frequently use myself is: we don't always know when the onset of STEMI is. Sometimes they have a staggering unstable angina before they go into full-blown STEMI. So, I give patients the benefit of the doubt. So, when it is not clear—24, 48, 72—so in that one to three days, it's—if it is not clear to me, I consider it less than 24 to 48, and I take them emergently.

Another idea in that beyond 24 to 48: a non-urgent PCI. So, non-urgent, but they still qualify for PCI if they have recurrent chest pain at rest or mild activities. So, they don't have—they don't have ongoing pain; they don't need emergent PCI, but they have chest pain when they walk around; they have chest pain off and on. So, those patients will qualify for a non-urgent PCI, but they will qualify for PCI. Those were not included in the TIMI trial. Also, if they have severe ischemia on stress testing—preferably exercise, modified exercise Bruce protocol—mainly if they get chest pain or ST depression or large area of reversibility on stress testing. If you don't have pain, you can do that—modify the stress testing—and verify whether they will qualify for an elective PCI, especially that chest pain. You can see if you can elicit chest pain on exertion beyond 24 hours. Now, keep in mind here: non-urgent coronary angiography is different from non-urgent PCI. So, those late presenters who have symptoms—we do coronary—who have symptoms often on, we do coronary angiography non-urgently—next day—and for example, next day, and we do plan to do PCI if they are having often-on chest pain or ischemia on stress testing—chest pain or stress testing. However, if they are asymptomatic, they still qualify for coronary angiography. So, coronary angiography may be done in all patients, even those presenting late, even if symptomatic—asymptomatic at this point. However, do not do PCI of an occluded artery more than 24 to 48 hours. So, you can still do cath on those asymptomatic late patients and we should—with the class 2A recommendation—but do not open it if you find an occluded artery; you do not do PCI of this occluded artery if you don't have those two criteria as per TIMI trial.

So, the question is: if we're not going to perform a PCI in that last group that is asymptomatic, what's the point of doing coronary angiography beyond 24 hours? The point is what I explained a little earlier here—this point that 35% of acutely occluded arteries partially recanalized by 24 hours. So, if you do coronary angiogram at more than 24 hours and the artery is not 100% occluded, you will qualify for PCI. There's another type of trial called the BRAVE 2 trial and other trials that have shown that if the artery is not occluded even beyond 24 hours, you do derive a mortality benefit almost similar to the mortality benefit you would derive in patients undergoing PCI between 12 and 24 hours. Okay, so that's the point of doing that coronary angiography even in asymptomatic patients: is that if you find a non-occluded artery, you can revascularize it. It is occluded, then you have to seek—if he's not having chest pain—then you have to really prove ischemia on stress testing—whether chest pain, ST depression, or large area of reversibility within or around the infarctic territory.

Another reason to perform coronary angiography beyond 24 hours in an asymptomatic patient is to define the coronary anatomy. Keep in mind that up to 50% of STEMI patients have multi-vessel CAD. So, let's say a patient has inferior infarct; even if his RCA is totally occluded, we may find that he has severe left main or severe LAD disease, and we know that there is value in non-culprit revascularization electively in STEMI. So, this patient will require revascularization of his left main and of his LAD. I want to make another comment—a side note—about pain resolution after STEMI. Pain rarely fully resolves after STEMI. Imagine you have been punched in the chest, which is the STEMI pain; even after the punch is over, you are left with a mild bruising pain of one to two over ten. I don't call that persistent pain; I consider that very mild lingering bruising pain equivalent to the resolution of the STEMI and not an indicator of persistent ischemia and not an indicator of a need for late PCI. I don't call that bruising—mild pain—persistent pain.

I received another question from the audience. So, the question: if somebody has Q waves and he has persistent elevation more than 24 hours after onset, then yes, even if the ST elevation is persistent, if it is more than 24 hours after pain onset and the patient is not having ongoing pain, he will fit within the TIMI trial and he would not qualify for emergency perfusion at this point. Now, I will give—on my next talk—I will elaborate more on those late presenters and how their EKGs look. It's not always very straightforward, but if the pain onset is over 24 hours ago and now he's not having ongoing pain, even if he has persistent ST elevation, you do not have an indication to undergo emergent PCI. Like I said, we have to individualize, and sometimes the STEMI is not clearly over 24 hours, and we may take them—and like I said, in that 24 to 72-hour time zone, we do tend to give patients the benefit of the doubt, and we keep a lower threshold to taking them. But if you want to get a definite answer, I would say no. There are some EKG features that suggest—even if you have persistent elevation—but you're having Q waves already that are very deep—it's fine to have Q waves; they still benefit from reperfusion in the acute setting, even if you develop Q waves—but if your Q waves are very profound and very deep—much deeper than the residual R wave—and the residual ST elevation—so we're having a Q of five, six, seven millimeters and you're having a tiny R and an ST elevation of about one and a half, two millimeters along with the history of his pain started 24 hours ago and now he's—it's resolved or almost resolved—I would consider that likely a late patient that will not benefit from emergency perfusion as per TIMI trial. Take this patient—if his pain has almost resolved and you suspect it's over 24 hours and he has this EKG—profound Q waves with very little residual ST elevation along with a proper story—unlikely to benefit; I would not treat him with a primary PCI unless he's having, again, a recurrent pain; that's a different story, but it will not be a primary PCI. Now, if you have that same EKG and he's coming in the first 24 hours, I will treat him with a primary PCI if the story suggests within 24 hours. So, you take into account the story—persistent pain—and you take into account the EKG features. Okay.

So, in terms of EKGs, I strongly recommend that you review my prior talks about ST elevation differential diagnosis, but briefly here: what degree of ST change defines the STEMI and qualifies the patient for emergent reperfusion? So, it's usually one millimeter in two contiguous chest or limb leads, except leads V2, V3, where the cut point is two millimeters in men and 1.5 millimeters in women, simply because normally we have a slight ST elevation in those leads; there is a normal variant—slight ST elevation—in those leads. Now, the most important thing is that it's not just the size; the shape has to be consistent with ischemic ST elevation. So, you may have a situation that is five millimeters related to left bundle branch block; that would not qualify for emergent primary PCI. So, you take into account ischemic ST elevation unlike—as the elevation secondary to LVH, left bundle branch block, early repolarization, or pericarditis, and I explained those in my other talks. And as I described, isolated or most prominent ST depression in leads V1 through V3—two of those leads—also qualifies as STEMI, and this ST depression will be reciprocal to ST elevation in V7, V9, and ST elevation in V7 would qualify you for also emergency perfusion. But keep in mind, if you do V7, V9, the ST elevation cutoff point is only 0.5 millimeters because V7, V9 are posterior leads, and they are far from the heart, which is an anterior structure, so lower cut point is considered significant. Interestingly, not all posterior STEMI will have ST elevation in V7, V9; that's why that isolated ST depression is important in the proper context to qualify for emergency perfusion. Now, lesser ST elevation—less than—less than those cut points—in the proper context with the proper morphology still implies injury and qualifies for emergency perfusion, but with PCI and lytics, you absolutely need to have those cut points to qualify for lytics, but to qualify with the proper morphology below those cut points for PCI.

Regarding a new left bundle branch block: a new left bundle branch block is overwhelmingly a sign of chronic cardiomyopathy—ischemic or non-ischemic—with a dilated or hypertrophied myocardium rather than an extensive acute infarction. So, when you—left bundle branch block is not a STEMI equivalent, contrary to the very old concept. In fact, STEMI rarely causes left bundle branch block, and among all comers of the new left bundle branch block, STEMI is a very unlikely diagnosis overall. That's why both ACC and ESC guidelines do not consider a new left bundle branch block as STEMI equivalent anymore. You can see the ESC guidelines; they say hemodynamically stable patients presenting with chest pain and left bundle branch block only have a slightly higher risk of having MI compared to patients without left bundle branch block, and in the STEMI guidelines, new—presumably new—left bundle branch block should not be considered diagnostic of acute myocardial infarction in isolation.

Now, when is left—a new left bundle branch block—an indicator of STEMI? Uh, in two circumstances: when you have what we call concordant ST changes, meaning you have ST elevation in a lead that has an upright QRS, where ST depression in a lead that has down QRS, or you have extreme discordance, meaning the ST elevation is opposite to QRS, but it's very high—more than 25% of the size of the QRS. This is what we call extreme discordance—relative extreme discordance.

Now, I will move to when to give fibrinolytics to STEMI patients presenting to non-PCI hospitals who are getting transferred to our PCI center. That's a frequent call we get when we are on a cath lab call. So, grossly, just primary PCI versus fibrinolytics: primary PCI is on average superior to fibrinolytics. I will use the term fibrinolytics or thrombolytics interchangeably; they mean the same thing. So, based on a meta-analysis of 23 randomized trials—PCI compared to fibrinolytics—it reduces absolute mortality by 2% and non-fatal MI by 4% and 1% reduction in hemorrhagic stroke, mainly, and this is—that—a meta-analysis. However, this—this depends on the expected door-to-balloon time. That superiority of primary PCI over lytics depends on the door-to-balloon time, and the door-to-balloon time that mitigates PCI benefit over fibrinolysis is 120 minutes. You need to know that number; they ask it sometimes on boards. It's called the equipoise point between PCI and lytics; it's 120 minutes. If you go beyond 120 minutes, you're losing that superiority of PCI over lytics. So, if you're coming to a non-PCI hospital and you expect the door-to-balloon to be less than 120 minutes, transfer them for PCI. Door-to-balloon over 120 minutes, the guidelines tell you give them fibrinolytics in the three to 12 hours timeline. However, don't just follow guidelines and algorithms blindly; make a more informed decision. So, when door-to-balloon is over 120 minutes, consider thrombolytics mainly if presentation is less than three hours from pain onset and account for three factors that argue against lytics: timing over three hours, lower-risk STEMI, and age over 75. If you have two of those three, even if the door-to-balloon is expected to be over 120 minutes, it's likely that PCI will remain superior to lytics. So, basically, even if door-to-balloon is over 120 minutes, if the patient is presenting over three hours, it's likely, based on a lot of data, that PCI is still preferred. And what do we call our system? High-risk system is anterior AMI, Killip class two or more, as I explained; Killip class two is heart failure; Killip class three is massive heart failure; plus four is cardiogenic shock. So, sinus rate over 100 and SBP less than 100, even if you're not in full-blown shock. So, those are high-risk features. If you have those and he's presenting over three hours but he is less than 75, I will favor giving this patient lytics. You have another important idea that comes up—comes up often: if you have subtle EKG—meaning subtle elevation of one millimeter—even if it's consistent with STEMI, I avoid thrombolytics; transfer for primary PCI. Why is that? Subtle EKG usually—when it's, you know, barely meeting the criteria—even if it is the morphology for STEMI, it usually means that either he recanalized and there is some flow or there are collaterals, as if the ST elevation was higher and now is improving. So, I try to avoid thrombolytics in those patients; it needs to be clear-cut ST elevation—not subtle—to give lytics.

Now, keep in mind those ideas: the first hour—what you call the golden hour—for lytics, you get a 50% mortality reduction and is 6.5% absolute mortality reduction. There are very few interventions that are in medicine that reduce mortality by 50%. One to three hours, you get a 30 to 40% mortality reduction in relative terms with lytics and 4% absolute reduction. And those numbers, by the way, are with the old streptokinase—with the modern lytics we use—you…

Add one percent in absolute for each one of those. So this is the data. There are multiple tries showing the great efficacy of lytics in those first two to three hours. You have these old trials, Track 2 and CAP team trials, and you have this modern STREAM trial, which took patients presented within three hours of onset of paying a randomizer to primary PCI versus lytics. Primary PCI was done within a reasonable time of door to balloon in 17 minutes—not ideal time, but reasonable time—and within those first three hours, primary PCI and lytics were equivalent in terms of mortality and hard outcomes. So that's why in the first three hours, you don't want to afford any door-to-balloon delays, and you want to give lytics. This study included inferior as well as anterior STEMI. However, as I said, the benefit from lytics strikingly drops beyond three hours, whereas PCI has a much less pronounced drop in benefit. So longer door-to-balloon—more than 120 minutes—may not and probably does not compromise the equipose with fibrinolytics in that 3- to 12-hour zone.

The superiority of PCI over fibrinolysis widens as the presentation is more delayed—more than three hours. And this is the data; several studies show that delays of door-to-balloon times more than 120 minutes do not worsen outcomes in patients presenting more than three hours, especially if they are older patients or if they have lower-risk STEMI, whether in comparison to lytics or in comparison to performing PCI at a shorter door-to-balloon. For example, here in comparison to lytics, if you have a patient presenting more than 120 minutes and he has a non-anterior AMI or he's over 65 years old, the equipose—the equipose delay between lytics and PCI—is very long. This will translate into door-to-balloon significantly more than 120 minutes. Same in those two; those are the two most important studies regarding this idea. This substudy of HORIZON and CADILLAC and another major registry have shown that delay in door-to-balloon more than 90 or 120 minutes worsens survival only in early presenters, mainly if they are also high-risk. In late STEMI, door-to-balloon delays less than 120 versus more than 120 do not—did not—worsen outcomes in those two studies, especially in late presenters who are also low-risk. So you got the idea here why door-to-balloon delays may not make that much of a difference. We are always obsessed with door-to-balloon, but really, door-to-balloon is so important in patients presenting in those first three hours. Beyond three hours, you're really working on LV remodeling, scar strength, peri-infarct ischemia, electrical stability, and so you afford longer door-to-balloon delays, and the equipose with lytics extends to longer door-to-balloon times.

To sum it up again: for patients presenting within three hours or high-risk more than three hours, do not accept any delay and keep in mind the effectiveness of lytics in this time window. Lytics are as effective as PCI in this time window. Give fibrinolytics and transfer immediately so that if the patient doesn't respond, it undergoes a rescue PCR; if he responds, he still undergoes cath within the first 24 hours, as I will explain. For presentation more than three hours and low-risk, especially if you have two of those three—more than three hours, lower risk, and age 75 over 75—two of those three, which includes to me even less than three hours but lower-risk STEMI and his old more than 75, I favor transfer without lytics. Some delay may be more acceptable in this setting; door-to-balloon is less important based on all the registry analysis I've shown. Elderly over 75: if you take the meta-analysis of all the old trials of lytics, all high-risk patients benefit the most. The only high-risk subgroup that doesn't benefit much from lytics was the elderly, partly because the elderly has high atheroma and clot burden for which lytics may not be very efficacious, but also because of their high hazard. And actually, if you do give lytics for patients over the age of 75, the ESC guidelines recommend half-dose tPA, and this is based on the STREAM trial, which recommended half-dose tPA to reduce the bleeding risk in those patients over the age of 75. Before making the amendment and the streams in the STREAM trial that I described earlier, the risk of intracranial hemorrhage in patients over the age of 75 was close to 8 percent. But like I said, the guidelines are more simple: you're within 12 hours; if door-to-balloon is expected more than 20 minutes, regardless of three—more than three hours—and time to reperfusion age, gives thrombolytics. The only thing they go by is contraindication to thrombolytics, and I want you to know those, so I see a lot of fellows not knowing those. So what are the contraindications of thrombolytics? I'll highlight the important ones.

Stroke—the biggest one is stroke. You have a stroke in the last three months? Absolutely not. A stroke over three months? Probably not; it's a strong relative contraindication. So that's one. Second big one: hypertension—acute hypertension over 180 over 110, 180 over 110. If you can drop it with an iPad or beta blocker, if you can drop it, then you can get lytics, but it's still relatively a contraindication. If you cannot drop it, 100% no. If you can drop it, probably no. Third big one is major surgery less than three weeks or recent internal bleeding; three weeks peptic ulcer, a major hematuria less than three weeks, and major surgery less than three weeks. So that's a third big contraindication. Fourth big contraindication today is oral anticoagulation—Warfarin or much more commonly today, Eliquis—that's a contraindication. So those are four big ones to remember. There are other ones, like if the patient has fallen and hit his head sometime in the last few weeks; if he has bruises on his head, definitely don't give fibrinolytics. Another one that they used to ask on board that I absolutely love because it's common: there is this combo of four; it doesn't fulfill any of those, but you have a small elderly lady over 70, 75—small elderly lady chronically hypertensive; she's not hypertensive over 180, but she has chronic hypertension—definitely avoid fibrinolytics; she has a high risk of intracranial hemorrhage. Okay. Another one that I like is chronic severe hypertension, even if it looks okay controlled now, so his pressure—the patient's pressure in the emergency room—is 151/60, but he's on four or five blood pressure meds and he's known to have chronic hypertension for a long time, uh, and maybe, you know, we have severe LVA; she has hypertensive nephropathy. I would be very careful giving this patient thrombolytics as well. Okay, so I use those in my decision-making beside those three important features that will get me away from lytics. Okay, again, I'm giving you ideas beyond guidelines; life is much more complex. We get called at 2 AM; we have to make quick decisions. There is a downside to thrombolytics when poorly applied.

Yeah. Now, once you have decided to get fibrinolytics because of expected delays, especially in the first three hours, when—when do you do PCI after fibrinolysis? There are two ways of doing it: one, you can do it in an emergent rescue fashion; two, you do it in a routine early fashion. I will describe those two. Rescue fashion: so I described about 70 percent of patients achieve TIMI 2 to 3 flow with fibrinolytics, so we have 30 percent who do not respond to fibrinolytics. Now, how do you know that? You assess the response to lytics at 60 to 90 minutes. I would go by 60 minutes using clinical and EKG features. If you ask persistent chest pain, regardless of the EKG, he hasn't responded. If he has persistent—much as pain—or the resolving EKG, I think we're good. So persistent chest pain, but particularly persistent severe chest pain—not one or two mild chest pains. Now, EKG: the EKG doesn't typically show full resolution of ST elevation; that's not what we seek. The response to thrombolytics is defined as improvement of ST elevation of more than 50 to 70 percent in the lead where you have the worst elevation. Let's say lead 2 had the highest elevation—had six-millimeter elevation—you want it to become three millimeters or less; that's what we call EKG response. I will say there is some caveat; a lot of data suggests 70 percent is a better endpoint, and a lot of data suggests using the sum of elevation using in all the leads that has ST elevation. For example, you have ST elevation 2, 3, aVF; make the sum and seek a reduction in that sum by more than 50 percent. Nonetheless, the guidelines want to use this: so more than 50% resolution in the lead with the worst ST elevation. A lack of that is considered not responsive to thrombolytics and will qualify you for rescue PCI. Also, if the patient has cardiogenic shock and is still in hemodynamic compromise, you need to take him regardless of EKG and chest pain resolution. Okay, so that's one, but we don't wait at the other hospital 60 minutes to see response. What we do, we tell them, okay, give lytics and just start transferring immediately, and we will assess when he arrives whether he needs a rescue PCI or elective cath and PCI. So the alternative to rescue PCI is if the patient arrives to us and his ST elevation has resolved and chest pain has resolved, we will still do cath. We do this—what we call routine early PCI after fibrinolytics—the so-called pharmaco-invasive strategy, which is even if you respond to lytics, we still do routine PCI 2 to 24 hours after lytics, regardless of lytics success. Multiple pharmaco-invasive studies—those are the two landmarks, TRANSFER-MI and CARESS-MI—and multiple registries have shown that a pharmaco-invasive strategy—meaning routine cath and PCI 2 to 24 hours after fibrinolytics with rescue less than two hours if needed—was associated with reduction recurrent MI, and that combination of lytics with a timely cath—whether rescue if needed or 2 to 24 hours routine cath—was associated with similar outcomes as if the patient arrived to a PCI center and underwent primary PCI.

Okay. Now, just here also a slight difference between ESC and ACC. Routine early PCI or pharmaco-invasive strategy is defined as PCI 2 to 24 hours after lytics per ESC and per data; however, ACC has a three-hour cutoff. I go by two hours; do not do routine PCI and cath within two hours of lytics. This is what is called facilitated PCR; just for you to be familiar with, sometimes we don't use that term anymore because we should not do it. Doing it within two hours has actually worsened outcomes; we only do it within two hours in a rescue fashion for those who did not respond to lytics; otherwise, you wait 2 to 24 hours. Now, some may ask why doing routine cath in somebody who already responded to lytics? How would routine cath and PCI help? So I want you to know this important idea: how does it help? Yes, thrombolysis re-establishes flow in those patients who responded by EKG and by symptoms; however, only 20 percent are left with another residual stenosis. So what you do, you recanalize the artery; thrombolytics—you open a channel; it could be a 5% channel, it could be a 20% channel, but they are still left with 70%, 80%, 90% stenosis. That's why there is a value in doing cath and doing PCI in the first 24 hours after lytics to reduce the chance of recurrent MI, recurrent ischemia after lytics.

Okay, so this is the bottom line for patients presenting to non-PCI hospital. Again, this is another summary. The question is: how do you decide that the door-to-balloon is going to be less than 120 minutes? If you have a system of pre-established community transfer with a driving time less than 60 minutes—meaning the ED calls the cath lab staff directly and the patient gets transferred directly to the cath lab and the driving time is expected to be less than 60 minutes—which is usually rather than 50, 60 miles, or if it is more than that mileage, you expect helicopter transfer plus—so direct transfer to the lab, direct phone call, less than 60-minute drive plus—you expect the door-in-door-out—less than 30 minutes—that's another term, D-I-D-O—door-in-door-out—meaning from the time he hit their door to the time he leaves them, including the time it took them to call you, it will be less than 30 minutes. So we expect a very efficient turnover. If all those features are present, your door-to-balloon will often end up being less than 120 minutes, then transfer for primary PCI, regardless of when he's coming, whether it's one-hour presentation, two hours, or longer. Now, in the absence of those features, you expect delays, and here's a decision: if the patient is presenting less than three hours or he has high-risk features over three hours, then give fibrinolytics plus immediately transfer for either rescue PCI or early routine PCI. Now, if you have those three—presentation more than three hours or two of those three—or low risk or more than 75 years old, transfer immediately for PCI even if door-to-balloon is expected more than 120 minutes. That's not the guideline answer, but that's the practical, real-life answer. If you have contraindication to lytics, of course, immediately transfer, regardless of door-to-balloon. If you have uncertain EKG analytics—if you have a STEMI but, like I said, subtle ST elevation around one millimeter—I favor no lytics as well because I think the patient probably already slightly recanalized, maybe has a 1-5% channel or it has some collaterals which afford him to tolerate a longer door-to-balloon time. One question that arises here is: okay, I'm saying to do cath 2 to 24 hours after lytics—well, PCI so soon after lytics is safe with no increase in major or moderate bleeding risk in the pharmaco-invasive trial—how come? There are two ideas that explain that: one, the lytics we currently use have short pharmacokinetics. So we use two major ones: alteplase, which is rtPA; it's given as an infusion over 90 minutes and has a very short half-life of six minutes, meaning at the end of the infusion—by 10 minutes of the end of the infusion—most of the drug is already cleared, and you have very little effect of rtPA 30 minutes after the end of the infusion. Tenecteplase is given as a bolus; tenecteplase—it has a longer half-life, but it's a bolus; also, by two hours, almost all of its effect is gone. So far, short pharmacokinetics—that's one idea. The second idea is the short pharmacodynamic effect, and here's the thing: all those modern thrombolytics, they bind to clot-bound plasminogen—that's the key word, clot-bound plasminogen; they don't bind to systemic plasminogen. So they bind to clot-bound; they bind to clot-bound plasminogen, and they transform it into plasmin, which degrades fibrin. The—they do not bind to serum-free plasminogen. If they bound to the free plasminogen, they would destroy free fibrinogen, and they will affect the coagulation cascade, but they only bind to the plasminogen in the clot, and they only destroy fibrin in the clot, not the systemic free fibrinogen. Therefore, when they are out of your blood after their half-life is done, they are out of their effect as well. Do you understand? So short pharmacokinetics, but also short pharmacodynamic effect. All the streptokinase, which is not available in the U.S., used to have an effect for a day or two. Why? Because streptokinase binds to systemic plasminogen and systemic fibrinogen, so it destroys your fibrinogen, and it takes a while to rebuild that fibrinogen, so it will destroy your coagulation cascade for a day or two. We don't use it. So with the current lytics, it's safe to do PCI cath afterward. In fact, those pharmaco-invasive strategy trials use femoral access, not radial access, and there was no increase in major or moderate bleeding risk in those trials. Okay. And actually, if you check PTT half an hour after finishing your lytics—your current lytic—you'll see that you don't get much PTT effect. Okay. In fact, that's why when you're treating patients with lytics, you tell the outside doctor, okay, give the lytics, but make sure you give the patient heparin boluses up to 4,000 units and given infusion during and after tPA and tnk to prevent rethrombosis. They are—they have such short half-life that 10 to 20 minutes later, even if the artery canalizes, it will rethrombose, so you have to actually give heparin with those lytics when you're treating the patient with lytics. Another idea: what do you tell the doctor about what to give the patient before transfer? All patients beside lytics or those patients who receive lytics, they should also receive aspirin, clopidogrel. We give 300 milligrams if they are less than 75 and 75 milligrams over the age of 75 and heparin. Now, when they get to the lab, we give them all 300 milligrams; we make sure they all got 300 milligrams regardless of age. The idea here: do not use 600 milligrams per guidelines and data; do not use 600 milligrams of clopidogrel within 24 hours of lytics even if you do stenting and do not give prasugrel or ticagrelor within 24 hours of lytics. Now, in reality, I will say that I have used 600 milligrams when I stent after lytics, but by data and guidelines, 300 milligrams is enough and definitely no prasugrel or ticagrelor. You may use ticagrelor during—not upstream of your PCI—you may use it during PCI. We rarely used to use ticagrelor during a STEMI PCI these days, only around 20 percent of the time, but you may use it even if the patient has received lytics.

This is a board question, by the way, that 300 and the clopidogrel thing. I'll give you a case scenario here. This is a 61-year-old female, diabetic with end-stage renal disease. She presented to an outside ED with chest pain for two to three hours. She had a stroke six months prior. Her blood pressure is 126 over 78; no heart failure clinically. They called us for STEMI PCI transfer; expect delay over one to two hours. The weather was bad. Should you give fibrinolytics before transfer or not? Look at the EKG and try to tell me. The first question is: is this a STEMI? This patient has anterior and inferior ST elevation, somewhat diffuse elevation with ST depression in aVR. She has PR depression in lead 2, which you actually—be aware of that—you can see PR depression in STEMI, and you frequently do, so that doesn't make it pericarditis. But she has diffuse ST elevation with ST depression aVR, ST depression in lead 2. So it could be pericarditis. She doesn't have any definite STEMI feature. She has no Q waves; she has no bad T wave—whether bad inversion of the T or bad hyperacute waves—she does not have shrinking QRS yet. So this could be pericarditis; it could also be STEMI. Could you have STEMI without—with absolutely no reciprocal ST depression? Can you answer yes or no? STEMI with absolutely no reciprocal ST depression? The answer is yes. Anterior STEMI may look exactly like pericarditis, especially mid-led apical STEMI that looks toward all the leads, so you get the elevation in all the leads, no reciprocal change in 30 percent of anterior STEMI cases. So yes, absolutely. This EKG may be pericarditis; it is more likely—I think much more likely—to be an apical STEMI. However, you still don't have definite STEMI features. So how do you know how this side is a STEMI or not? There is one answer: repeat EKG 5 to 15 minutes later. And this is the repeat EKG in this patient. Look what you chose; this was about 20 minutes later, and look what it shows. This is definite STEMI, unquestionable, and look at the major change. I hope one of you can point out the main difference between those two. This is definite STEMI because of this shrinking QRS phenomenon. So in STEMI, before you have a Q wave, you get the shrinking of the QRS on your way to developing Q waves. So look at the QRS here in those leads before V5 and look at how it has become here; it's shrinking; she's about to form a Q wave within those leads before V5, but she's forming a QRS that is so small, so much so that the ST elevation is almost bigger than the QRS. When the elevation is close—like half, three-quarters—of the QRS, and your QRS is shrinking with an elevation rising, that's definite for STEMI, okay, especially you have it in two leads. So at this point, STEMI is definite. So should we give this patient lytics? She's presenting—it seems within two to three hours—a large anterior STEMI. I'll give you my answer here: no. Why? Because she has a bunch of relative contraindications for lytics. She's end-stage renal disease, meaning she likely has chronic severe hypertension and chronic microvascular brain damage even if the blood pressure is controlled now. Very importantly, she had a stroke—that's the biggest one, always number one in your mind: stroke and thrombolytics. She has two big contraindications in my mind. So we told the ED doctor, do not give her lytics. Unfortunately, they still gave her lytics. Now she arrived to us; her ST elevation had not improved at all. We did cath; she had mid-led occlusion—100% occlusion—as expected. We recanalized it; it went well. Unfortunately, the patient did develop intracranial hemorrhage, and she did eventually die. So beware of those risks of lytics; it's not just the absolute contraindication; it's getting the full picture.

This is another case: a 55-year-old man, no cardiac history. He presents to an outside ED with ongoing chest pain for two to three hours. We expect transfer delays of two to three hours. So what should we do with this patient? First, is the EKG STEMI? And to me, yes, this EKG is definitely consistent with STEMI. Now, if you look at the ST elevation, if you measure it in leads 2, 3, aVF, it's, you know, barely making it one millimeter; it is about one millimeter, but it's definitely STEMI. So even if it is barely one millimeter, it is a STEMI because the morphology is 100% consistent with STEMI. So one, you have Q waves already in all 2, 3, and aVF; they are wide and pathological even if they are not deep yet. Do you have reciprocal ST depression in the lateral leads? So it is a STEMI, but it's subtle ST elevation. Should you give him lytics before transfer? He's still having ongoing chest pain. My preferred answer here is no because it's a subtle EKG. As I said, in subtle EKG, I prefer no, why? Because subtle EKG suggests some recanalization of the infarcted artery; maybe it is 99%, 95% instead of 100 percent now, which allows that myocardium to tolerate slightly longer delays to the occlusion; maybe it's progressive, and he had already developed some good prior collaterals or three of the territories are small. So we recommended no lytics with a transfer. The patient did arrive, you know, close to three hours later; the RCA was 99% stenosis with TIMI 2 flow; we treated it. Interestingly, the troponin—high-sensitivity troponin—minimally increased to only 49, and he had no wall motion abnormality on his echo. So this was a form of self-aborted STEMI in terms of partial recanalization; this patient is as if he already got thrombolytics, and his ST elevation went from 3-4 millimeters to one millimeter.

I will just tell you the doses. I see also fellows don't have an idea about doses of thrombolytics. Look, the outside ED calls you; you need to be very knowledgeable about lytics. The two most commonly used in the U.S. are rtPA—alteplase—and tenecteplase. rtPA is an infusion; the total dose is 100 milligrams, which is similar to what is used in PE, but it's given differently: it's 15, 50, 30. So 15 boluses, 50 milligrams over 30 minutes, 30 milligrams over 60 minutes, and if the weight is less than 60 kilograms, you just dose 50 and 30, but most often 15, 50, and 30. Tenecteplase: the dose is 30 to 50 milligrams; it's a gross half the weight, rounded up to the next five, up until 50 milligrams. So if your weight is 85 kilograms, you end up giving 45 milligrams. So just know grossly the doses: 30 to 50 milligrams. I've had cases where they told me the wrong doses, and I corrected him because I had it in my mind, so you need to be able to have an idea about those. It's another important idea: transient ST elevation. So a patient presents with chest pain that lasted four hours previously and inferior ST elevation; both his chest pain and ST elevation resolve after aspirin and nitroglycerin administration. Is emergency perfusion mandatory at this point? And I will make it more practical: when you have a STEMI and chest pain with it, I would say practically I very rarely see the pain fully resolved; they will always tell you, I still have something; it's as if you've been hit by a great thump on your chest; you have pain during the thump, and afterward, you have an aftereffect, like a bruised type of pain. So it's very rare for somebody to tell you, I have zero pain; they often tell you, I have one to two very mild lingering pain. So let's say this is the case here: is ST elevation resolved? He has that very mild—the bruised type of pain.

Is emergency perfusion mandatory at this point? The answer is no. And here is the differential diagnosis.

The differential diagnosis: What happened first to this patient? He had spontaneous slices, or maybe lies us with the acute Heparin and aspirin, or resolution of coronary spasm. That's the less likely thing. The most likely: you have spontaneous slices. As I mentioned, 15 percent of patients recanalyzed within the first four hours, and 35 percent within 24 hours. So this is what we call self-aborted stemming. Emergent re-fusion may still be perfioned, but is no longer mandatory. If this patient is presenting at 2 pm, I would do it. If this was at 2 am, you may say, okay, I'm going to do it at 7:00 am. So you don't have to do it. I do favor doing it emergently, but it's not necessary anymore. You can do full ACS therapy: Heparin, aspirin, and early coronary angiography within the next day. This is based on a trial called the transient stemi.

So a trial called the transient stemi, which is another term for self-aborty stami, has shown that you can wait. Emergent PCR was not better than waiting 24 hours if preferred. Good. So I, I, somebody asked what about transient elevation post VT arrest? So VTRs is a different topic. For patients with VTRs who are comatose to qualify for emergent PCI, they need to have persistent St elevation. Another thing about V-fib: it's not uncommon in after we fit to have a celebration, even if sometimes the event is not an acute MI event, for a variety of reasons. They get electrolyte shifts, they get acidosis, they get potassium shifts. They get, also remember, especially if you had a prolonged cardiac arrest, you get ischemia from the arrest itself, and you may get transient as the elevation immediately after resuscitation. So you have to be careful. Those transient accelerations after we fibers, I would seek persistence acceleration even after we favor rest.

Another case scenario: A 66-year-old woman presents with anterior stemi. She receives the thrombolysis at a non-PCI hospital with a resolution of chest pain and more than 50 percent resolution of ST elevation. She had a mild degree of pulmonary edema on admission, which quickly responded to diuresis. Echo shows severe anterior hypokinesis with an EF of 35 percent. Three days after that stamina, she's able to ambulate without chest pain and with a mild degree of dyspnea. What is the next step? No, so one I want to comment here: this is not a contemporary case. Typically, this patient after receiving thrombolytics, she should have been transferred immediately, without even waiting to see whether she responded, and even if she responds, she should have undergone cath within 24 hours, as we discussed. Yet nonetheless, that may still happen at some rural hospital. They gave lyrics, they waited, the weather was bad, they kept her at their institution, and this is where we stand now, several days later. She's doing okay, asymptomatic, ambulating without chest pain. So what is the next step? A transfer for coronary angiography? Do an exercise modified Bruce protocol stress testing? Pharmacological stress testing? Or continue medical therapy without any further intervention? This question will come on board, by the way, even though it's not practical.

So there are two answers here: my answer and the logical answer based on the data, and the equivalent answer based on the ESC guideline is A. However, the ACC guideline answer and the board answer is B. Here's the explanation: 70 to 75 percent of patients achieve TIMI two three flow with thrombolysis, but only 24 percent achieve more complete reverse re-analyzation with less than 50 to 70 percent stenosis. Knowing the importance of PCI of even non-culprit asymptomatic stenosis more than 70 in stemi, coronary angiogram is the logical answer, followed by PCI if the culprit artery is not totally occluded. Since this patient responded to latex by EKG and clinically, it's likely that the artery is not occluded, and therefore she will likely undergo PCI. However, if you do coronary angiogram and you find that the artery is occluded, then you fit into that old trial, then you should not do PCI. So that's a logical answer to me. Okay, she's likely left with the residual stenosis, even if she's asymptomatic. We know the value of recanalyzing asymptomatic stenosis, even non-culprit stenosis in an ischemic setting. It makes sense to do coronary angiogram and open a residual stenosis. If you happen to find an occlusion, then you should not do PCI. Do stress tests. If you have extensive ischemia, then yes, you do PCI, bring her back and do PCI of total local artery. Data have shown that doing routine cath and PCI within 24 hours of tabletics improves outcomes. Well, it makes sense to me to extend that interval to beyond 24 hours. However, both the American and European guideline state the following for beyond the 24 hours: If PCI was not performed the first 24 hours, as in the pharmacoinvasive strategy, whether the patient received fibrinolytics or not, with or without success, if you receive fibrinolytics, stress testing becomes an alternative to coronary angiography in the absence of angina recurrence. ESC guidelines give equal weight to stress testing and coronary angiogram beyond 24 hours, whether you did or did not receive latex, with or without success. ACC guidelines give higher weight for stress testing, give class 1 for stress testing, class 2 for coronary angiogram beyond 24 hours, again with or without lytics, with or without response.

I can discuss that one last idea. If, if there are fellows left, multi-vessel CAD and stemi, should you treat non-culprit artery and when? So the large COMPLETE trial has shown that systematic PCI of non-culprit disease in patients with multi-vessel disease and stemi versus just treating the culprit, reduce MI risk, but non-culprit PCI was not performed in the same setting. So in that study, they did culprit PCI, then they brought the patient back before discharge or within six weeks of discharge, and they did non-culprit PCI. Then doing non-culprit PCI versus leaving the patient alone and reserving PCI only for severe angina, doing non-culprit PCI regardless of symptoms was associated with an improvement of the future risk of MI, mainly non-STEMI, in comparison to culprit-only PCI. There was no mortality benefit, but keep in mind they did not do it in the same setting; they did it in a second systematic setting, and no mortality benefit. Now another trial supported the dynamic pre-multi, also support PCI in a second setting before discharge versus no PCI, and this Strider was not even a reduction in MI; there was a reduction in the need for revascularization. Now PCI, non-culprit PCI may be done in the same acute procedure based on smaller study, primary and culprit study. There was no MI or mortality reduction in these studies. So that's why guidelines give class 1 recommendation to do non-culprit PCI within six weeks of culprit PCI in a stemi setting, and they give class 2B to do non-culprit PCI in the same setting, and they suggest what I do, which is take into account the complexity. If the non-culprit PCI is going to be a complex bifurcation, heavily calcified, I would do it in a second setting. If it is relatively straightforward and the patient's kidney function is normal, I would do it in the same setting, and this is what the guidelines suggest as well.

Now one idea here: What do we call significant non-culprit artery? That's sometimes a matter of debate between me and the interventional fellow. Use the criteria used in the COMPLETE trial: it's more than 70 percent, not 50 to 70 percent stenosis in a major artery supply and major territory, whether proximal or distal. So 70. COMPLETE trial allowed 50 to 69 percent, but you have to prove it by FFR. If you look, however, at their baseline characteristic, 99 percent of patients had more than 70 percent stenosis and were recruited based on 70 percent stenosis, not based on FFR. And actually, there is a post-hoc analysis that shows that the patients who benefit are those with the QCA, quantitative coronary angiography, stenosis more than 60 percent, which usually corresponds to more than 70 to 80 percent visually. In dynamic pre-multi, they use 50 percent stenosis with significant FFR, but the benefit was mainly seen if the non-culprit was more than 90. So the bottom bottom line: it has to be a major territory with over at least 70 percent stenosis, if not 90 percent. Do not chase moderate disease or tiny branches. And okay, I described a non-culprit PCI. Cardiogenic shock is different. In cardiogenic form, you should avoid non-culprit PCI. Definitely avoid non-culprit PCI in the same setting, based on that culprit shock trial where doing culprit and non-culprit in the same setting increase mortality. So absolutely avoid in the same setting. Why? In, in shock, the more unstable the patient, the quicker you have to be. So that's why in shock we try to keep the treat the culprit and get out. The more tenuous the patient, the quicker you have to be. Non-culprit PCI increases procedural time, supine time, and contrast load, leading to more LV volume overload and renal injury and is hazardous in the hemodynamically compromised patient. This is beside the hazardous effect of sedation. Now in culprit shock, you know they allow the staged PCI a few days later. So you can do it a few days later. However, this was rarely performed, the staged PCI in culprit shocks, only 17 percent. So the bottom line idea in cardiogenic shock: do your culprit, don't do the non-culprit in the same setting, and probably don't do it even in this, in a staged fashion in the same hospital stay. Stay away from non-culprit, even though it's allowed a few days later, probably stay away from it. The only caveat of culprit shock trial: they included non-STEMI; 38 percent of patients were non-STEMI, and it's amazing that they only stented the culprit in a non-STEMI, because we know in non-STEMI it's hard to define the culprit based on MRI studies. We misidentify the culprit in 30 percent of non-STEMI patients because your EKG doesn't localize ischemia in non-STEMI. So to me, if you have non-STEMI with massive acid depression and I'm attributing the shock to the non-STEMI, I may revascularize multiple lesions because it's not always easy to identify the culprit. But keep in mind in that trial they were able to identify the culprit, and they stuck to the culprit, and that included at times patients with an RCA culprit who had a non-culprit LAD, and they left those alone.

Uh, one final idea: How about CABG? Emergent CABG is rarely acutely required in STEMI. That's why I wonder. STEMI is definite. We feel free about giving Plavix and Plavix Grill even before the angiogram. Now if staged CABG is judged necessary for full revascularization, non-culprit artery after culprit PCI, it's preferred to wait at least 24 hours and preferably three to seven days. CABG mortality is increased in the first three days after a large MI. So I'll give you a scenario here: in a patient with RCA-related MI, inferior AMI, who also has, you find left main or three-vessel disease. You stent the RCA and you perform CABG one month later for the left main and three-vessel disease. However, let's say you stent that, uh, you treat that RCA, or the RCA is the culprit, but there is also critical left main stenosis; CABG is needed sooner. So in those cases, what you may do: you open the RCA with balloon angioplasty plus or minus 2b3a and you try to perform CABG sooner, one to seven days later, without giving any ADP receptor antagonists. However, if CAD is critical, you know you have left main disease, but the RCA you could not get a good result with just balloon and 2b3a, in those cases you need to stent the RCA acutely. So what you do in those cases: you stent the RCA, you still want to do your CABG soon, one to seven days later. So what you do: you stent the RCA, you give intravenous cangrelor, which is a quick turn-on, turn-off of potent antiplatelet effect, and you give IV cangrelor, then you do your CABG one to seven days later. The important idea here that I've discussed with fellows before: if you do CABG so soon, okay, you're giving cangrelor to prevent thrombosis before CABG, expect that fresh RCA stent to thrombose during or after CABG from the hypotension, the shock that is around CABG time, and from being off P2Y12 blockade. Hence what they do in those cases: they should typically bypass the right, even if you get good stent result, you know it is highly likely to thrombose, so you likely should bypass that RCA when you're doing CABG a few days later. Here you definitely bypass it too if you only did angioplasty.