Hi, I'm Steve Hollenberg and it's a pleasure to be here, if only virtually. I have no disclosures with respect to this talk. So I'm going to tell you all about acute coronary syndromes, ST-elevation and non-ST-elevation all in one talk. And although the boards lag a little behind the most current knowledge, I'm going to try to give you an up-to-date look at the current spectrum of acute coronary syndromes. We'll talk about the pathophysiologic underpinnings, which don't really change that much, although they do evolve. And then we'll talk about therapies, reperfusion, and adjunctive therapies. And finally, we'll talk about complications of acute MI. These are in fact getting less common over time. However, they are not getting less common on the boards, and so we'll spend some time talking about them. This is the current spectrum of acute coronary syndromes. As you can see, they are divided by EKG into those with ST-segment elevation and those without. And then they are further divided by biochemical markers. Patients with ST-elevation have ST-elevation myocardial infarctions. Those without ST-elevation but with positive markers are called non-ST-elevation acute coronary syndromes. And those without EKG changes and without biochemical markers fall into the category of unstable angina. This shows the epidemiology of mortality in ST-elevation myocardial infarction from the Sweetheart Registry in Sweden, dating from the late 90s up until 2014 or so. And what you can see, although overall population mortality in the orange on the bottom hasn't changed very much, the incidence of death and cardiovascular death at one year from ST-elevation MI have been decreasing, a testament to successes in prevention and also in therapy. The serum markers in myocardial infarction are shown on this slide. We used to talk about CPK and Bs and sometimes even about LDHs, but in fact now everything is about troponin. You can see both troponin T and troponin I peak early and stay elevated for 6 to 10 hours and these are now the gold standard of biochemical markers in myocardial infarction. The development of coronary atherosclerosis is in part a story for another day, but you can sort of see on this slide how you start from intimal thickening, you develop cholesterol in the plaques and then you develop calcium in the plaques. And on the right you see the so-called thin cap atheroma. As we will hear, these are the plaques that are vulnerable to rupture and they have both calcium and cholesterol inside the plaques and the inflammatory process is thinning the cap and decreasing its tensile strength. So which plaques rupture? Here's a chart from the late 80s, actually early 90s, looking at patients who had previous angiograms and what their stenosis had looked like within 6 months of a subsequent plaque rupture. And what you see is that most of the plaques were not in fact angiographically stenotic before the rupture. As a matter of fact, two-thirds of plaque ruptures occurred in lesions that are without flow-limiting stenosis. And this poses limitations for detection of plaques that are about to rupture by something like stress testing, which is only positive in the presence of a hemodynamically significant lesion. And so the thoughts about pathophysiology of atherosclerosis began to go toward vulnerable plaques. And here's a graph of so-called vulnerable plaques. And as you can see, they have a large plaque volume, but they also, that may or may not be impinging on the lumen, but they have a thin cap that is vulnerable to rupture. And the current holy grail of research is to try to identify vulnerable atherosclerotic plaques before they rupture. We're not quite there yet with that. So we'll move on to therapy. And this is a slide of the therapy over time. So in the pre-CCU era, we're talking before the late 60s, there wasn't really very much to do. You put people at rest. You gave them oxygen. You gave them morphine for the pain. And you kind of waited it out. The mortality was about 30%. Then in the CCU era, we're talking late 60s into the 70s, defibrillators became available to prevent death from ventricular tachycardia, certain degree of hemodynamic monitoring for patients with heart failure, allowing for diuresis was available, and beta blockers came into use. And the mortality was about half to about 15%. We're now in the reperfusion era, dual antiplatelet therapy, fibrinolytic therapy, percutaneous coronary intervention, stents, and all that. And now the mortality is down around, in hospital mortality, 3% or 4%. And it gets harder and harder to show improvements on that with adjunctive therapy. And as such, the trials get bigger and bigger. So the first question is, should we give thrombolytic therapy or primary PCI? This is a meta-analysis out in the early 2000s of 7,700 patients enrolled in 23 trials of lytic therapy. The stent era actually was only at the tail end of this study. And what it shows is that for all comers, PCI is probably better. They have lower death as seen on the left, lower incidence of MI, lower incidence of the classic cardiovascular combined endpoint, death, MI, and stroke, and actually even a little bit lower incidence of stroke. So primary PCI is preferable, but it also depends on timing. This is a slide titled, Time is Outcome. And what you see on the y-axis is the absolute benefit per 1,000 treated patients of lytic therapy compared against time to treatment. Now classically, this was depicted as a linear relationship. But actually, a more accurate relationship is a curvilinear relationship. As you can see, there's a great benefit if you get in there with this in the first hour. And maybe in lytic therapy and reperfusion, there is a golden hour. And that has come forward to today. So this slide is lytic therapy from trials. This slide is mid-90s from the lytic trials. But the same is true among patients treated with primary percutaneous coronary intervention with ST-elevation MI. However, this is data from the DANIMY trial in Denmark. And this actually doesn't look at door-to-balloon time. It looks at system delay, which is the time from when the system was activated. And what it shows is that every hour of time to delay was an independent predictor of death. So we want to talk about the barriers to timely reperfusion for acute coronary syndromes. As you can see, there's an increasing loss of myocytes with time. And we have focused a lot on the emergency department and the cath lab because those are things that are under the control of the hospital physicians. However, we need to start thinking a little bit earlier. We need to start thinking about EMS. And we need to start thinking about raising awareness of acute coronary syndromes because the system isn't going to be activated until somebody begins to call. So really, we should start talking about systems of care. We should talk about, and this is the so-called five R's. We should talk about relationships between EMS services and hospitals and patients and how they get to the hospital. Half of the patients that come to a hospital with acute coronary syndrome come through EMS. Half of them get there some other way. We need to focus on better recognition of acute coronary syndromes with perhaps atypical presentations classically in the elderly. We need to talk about reperfusing earlier. And we want to collect data about how we're doing in real time so that we can reassess and refine. And what is happening now is people are moving toward quality over quantity and bundled payments for ST-elevation MI are coming down the pike. So we need to think about optimizing the entire system and not just little pieces of it. So one of the ways to do that is to try to optimize the flow of patients into the system. And this is a graph. This is actually a graph from the European guidelines. The American guidelines are similar, but I don't like the graph as much. And it talks about the total ischemic time. It talks about patient delay, EMS delay, and then system delay as we referred to. So down on the bottom, if you come to a PCI center, you make the diagnosis and the goal is to get to primary PCI and reperfusion within 60 minutes. If you're not at a PCI center and you make the diagnosis, then you have to think about the time to PCI and you want to ask if you can get to PCI within 120 minutes. Then you ought to have a primary PCI strategy, even if that means transfer to a PCI center. But if you don't think you can do that, then Lytic's therapy is probably preferred. The 90-minute number, as opposed to the 60-minute number for transfers, recognizes that there's a little time allowed for transfer, and Lytic therapy should be done within 10 minutes. So systems that think about bypassing, you probably should try, instead of driving 10 minutes in the wrong direction, maybe you should think about driving 15 minutes in the right direction, because if you drive 10 minutes in the wrong direction, you might then have to drive 25 minutes in the other direction. So now let's rethink the basics a little bit. On the left, what you see is an angiogram. What you see here is a thrombus, a little hazy here, a little hazy there. This turns out to be a circumflex coronary artery, and it's totally occluded. We've sort of talked about plaque rupture and the fact that many of the lesions are not fully stenotic, so maybe this is a 40% lesion with a plaque rupture and mostly thrombus, in which case the therapy is going to think about antiplatelet and anticoagulation, PCI of the culprit lesion. Maybe we'll suck the clot out, and we'll prevent recurrence by modifying the vulnerable plaques. If we can figure out how to do that, we'll figure out. We'll talk about that later. But maybe this really isn't. This is what happens in this patient when you actually, before they put the wire in, after they did the initial angiogram, the thrombus went away, and what you actually have here is a 90% lesion with plaque rupture. And now, prehospital antiplatelet therapy may not be enough, thrombectomy might not work, and if you have a bunch of already stenotic lesions, then maybe you need to manage the stenotic plaque burden, and maybe you ought to think about PCI of non-culprit lesions. I'm going to show you a little bit of data. There are a number of trials, but we're going to talk about the largest of those trials, the COMPLETE trial, published out in the New England Journal in 2019. They looked at two primary outcomes. They looked at death or new MI, and then they looked at death, MI, or ischemia-derived revascularization. Basically you got admitted to the hospital and needed an angioplasty, and what it showed, it looked at the difference between culprit-only revascularization, just doing the artery that you think is acutely occluded, or complete revascularization, doing every artery that you thought had a hemodynamically significant lesion. And what you see is that the hazard ratio is 0.74, with a 95% confidence interval that doesn't cross zero. There's about a 3% reduction in the cumulative incidence of death or MI, and an even larger reduction of 49% reduction in the combined endpoint. That includes revascularization, with complete revascularization as an initial strategy in ST-elevation MI without cardiogenic shock. Cardiogenic shock is different, and you'll hopefully hear about that at some other point. I'd also like to talk a little bit about procedural aspects. Radial access is probably preferable if your interventional cardiologist is good at it and can do it quickly. Here's a meta-analysis showing a decrease in all-cause mortality with radial access, and also a decrease, here is the components of that, all-cause death, major adverse cardiac events, and in particular, bleeding and vascular complications are much lower if you can do radial access for PCI, as opposed to femoral access. So, now we're going to move on to acute coronary syndromes and antiplatelet therapy. Here you see plaque rupture with a thrombus in a coronary artery, and here's a blow-up that shows the components of that thrombus. You see, depicted in colors, you see the red cells, you see the thrombin in brown, you see the platelets in white, and you see the green is supposed to represent a white cell caught up in this, so you'd like to address all of those with antiplatelet agents. Here is a summary of the available antithrombotic and antiplatelet therapies, and I won't go into the details because they're familiar to you, but I do want to talk about the distinction, at least in terms of terminology, between anticoagulant drugs, that is, heparin and oxaparin, fondoparanox, and in different contexts, direct-acting oral anticoagulants and warfarin, and antiplatelet drugs, aspirin, which inhibits thromboxane, the ADP P2Y12 inhibitors, clopidogrel and plazugrel, and ticagrelor, cangrelor is an intravenous version, and the glycoprotein 2B3A inhibitors, all of which are involved in the platelet component of the thrombus. So aspirin is the first therapy that we'll talk about, and so I want to talk about aspirin dosing in the context of the recent ADAPTABLE trial, if only to talk about the trial design. So they took 15,000 patients with known atherosclerotic disease and one enrichment factor that is something that gave them higher risk. They identified them, and they had electronic consent and self-randomization on a participant portal. They then were randomized to 81 milligrams or 325 milligrams of aspirin, obviously open label. And then they had electronic follow-up with data either from the electronic health record or the health plans or Medicare. And so this trial was very efficiently done at a relatively low cost. Primary endpoint, a composite of all-cause mortality, hospitalization for MI or hospitalization for stroke, and a safety outpoint was bleeding, and here are the results. You can see that there's no difference in the primary effectiveness endpoint, and as you might figure, a little more bleeding with the 325 dose than the 81 milligram dose. So this is what the AHA guidelines say about antiplatelet and anticoagulant therapy, and I want to introduce you to the way these guidelines work. So the strength of recommendation goes from one to three. One is usually shown in green, it means do it, three is shown in red, it means don't do it, 2A in yellow, probably do it, 2B in orange, maybe there's a little bit of data that supports it in the level of evidence, A, B, and C, A, more than one large randomized trial and or meta-analysis, B, one large randomized trial, and C is less evidence than that. So I used to show the data on the dual antiplatelet trials against aspirin and clopidogrel and all. I don't really have time to do that, we're going to talk about other things. So we'll just get to the bottom line. It's reasonable to choose Ticagrelor over clopidogrel for as a P2Y12 inhibitor based on the TRITON trial. It's reasonable to choose Prasugrel over clopidogrel in patients who are not at risk for high bleeding, but there is a little bit more bleeding, and it's reasonable to give it like a protein 2B3A inhibitor in the cath lab. How long to give dual antiplatelet therapy? Well, our NOW guidelines, this is a nice article out, and this shows the current guideline recommendations, and I show this sort of not to deal with the top of this in stable coronary artery disease because that's complicated, but to show that it's relatively more straightforward in the patients with acute coronary syndromes. If you don't have a high bleeding risk, class one recommendation says you should give them for a year no matter whether you do angioplasty or not, and a 2B recommendation to continue out to 30 months, not really much data after that. If you are at high bleeding risk, the recommendations are now moving towards saying you can probably get away with six months of dual antiplatelet therapy, particularly if you've used one of the new fourth generation stents. How about anticoagulant therapy in acute coronary syndromes? Well, so this says level one, you should give an anticoagulant, intravenous unfractionated heparin is useful, bivalorudin is useful, and then there's some stuff about bivalorudin monotherapy and enoxaparin versus unfractionated heparin, which is also reasonable, and there's some data, but I really show this slide for the bottom. Fondoparanox should not be used as the sole anticoagulant in PCI. There were clots on the catheters that worried people about possible stroke. This is a class three harm recommendation with a level of evidence B. Why do I tell you this, particularly if you're an American and you're not using much Fondoparanox? Because board exams love to pick class three harm recommendations. You're supposed to know not to give Fondoparanox alone, so even if you don't necessarily need to do this in your practice, you should remember this should it come up on an examination. Regardless of what you do, you really have to worry about the dose. Here's data from the Crusade Registry looking at the percentage excess dosing of antiplatelet and antithrombin agents, failure to adjust for age and or body mass index and or renal function. 42% of patients got what would be considered an excess dose, particularly older patients less than 75, shown in green, so you really got to worry about the doses. But wait, there's more adjunctive therapy. We're going to go through them quickly because I'm guessing the data are pretty familiar to you. Here are the beta blocker data, the effects of on mortality in randomized trials, for acute treatment, for secondary prevention, and overall a robust reduction in mortality with beta blockers. And here's what the guidelines say about whether to give them. They say that you should start oral beta blockers in the first 24 hours if you don't have contraindications. If you do have a contraindication the first 24 hours, you can wait, but after that you should think again. If they had heart failure and you got them out of heart failure, you should think about whether you can start 24 hours out. And intravenous beta blockers at initial presentation are okay, particularly if you have hypertension or if you have ongoing ischemia and tachycardia, but you should certainly think twice about them in the following situations. Signs of heart failure, evidence of low output state, increased risk for cardiogenic shock. You don't want to put somebody who's tachycardic because their stroke volume is low into cardiogenic shock by slowing their heart rate down. If they have heart block or asthma, real asthma, steroid-dependent asthma, hospitalization asthma, then you ought to be careful with intravenous beta blockers and to some extent with oral beta blockers as well. The angiotensin system blocker data is shown here. Three different ACE inhibitors, captopril, tranolopril, and ramipril, all eligibility criteria with a low ejection fraction benefit of 20 to 40%. The Valsartan trial was a comparison of captopril and Valsartan that showed no difference between the ARB and the ACE inhibitor. And if you look at patients, so the majority of the benefit was shown in patients with low ejection fraction, but if you actually take all comers, you can see a benefit with renin-angiotensin system inhibitors, and that is reflected in the way the guidelines read. An ACE inhibitor should be administered within 24 hours with patients with an anti-RMI, heart failure, or an EF less than 40%. That follows the trials. If you can't give an ACE inhibitor, you should give an angiotensin receptor blocker. The Valiant trial is one trial, therefore a 1B recommendation from one trial, not two big ones. And ACE inhibitors are reasonable for all patients with no contraindications. That's based on the data that shows in all comers you can see a benefit. Mineralic corticone antagonists are useful in heart failure, and they turn out to be useful in acute coronary syndromes as well, at least in the following population. Patients on ACE and beta blockers with an EF less than 40 or with an EF less than 40 and either heart failure or diabetes. And here's the Ephesus trial results showing a 18 percent, a 15 percent reduction in mortality, which was statistically significant. That's one trial, so this became a 1B recommendation. Probably the most important adjunctive therapy is from the Pruvit trial. And this is a trial that compared pravastatin at 40 milligrams with atorvastatin at 80 milligrams for a combined endpoint of all cause death or major cardiovascular events, showing a 4% reduction at 30 months with atorvastatin compared to pravastatin. And you can interpret this as atorvastatin is a better drug, 80 is better than 40 milligrams, but most people think that achieving a lower LDL is better. There was controversy over whether you should go better than good and that was tested in the Impruvit trial. These are patients who started 10 days out with an LDL between 50 and 175 and they were randomized to simvastatin at 40 or up titrated 80 or to the addition of ezetimide to simvastatin. And the duration was two and a half years with a primary endpoint of cardiovascular death, MI, hospital admission, coronary vascularization, or stroke. A relatively low risk population so one might not have expected a big change. Here's what happened to the LDL. You can see that you started an LDL of about 95 with simvastatin alone, went down to about 70 when you added ezetimide. It went down to about 55 and that resulted in a numerically small but statistically significant reduction, a 2% reduction in this combined endpoint of events with a 6% relative reduction at 7 years. So lower 55, lower at 55 was somewhat better than at 70 which was clearly better than 95. So here's a summary of the therapies. Proven effective in ST elevation MI, aspirin, dual antiplatelet therapy, early reperfusion, beta blockers, ACEs, ARBs, aldosterone antagonists, lipid lowering agents, IV nitrates and hepaner probably effective in the hospital. Nitrates particularly for people with ongoing pain and heart failure. Calcium channel blockers especially those of the negative inotropic effect are not effective and prophylactic lidocaine which used to be popular in the Dark Ages also not effective actually increases mortality. So let's move on and let's move on to non-ST elevation acute coronary syndromes which are usually identified by. So the term non-ST elevation MI or non-STEMI has now been replaced by the preferred term non-ST elevation acute coronary syndrome and the reason is that shown on this slide there are non-ACS causes of elevated troponin and the use of non-STEMI to refer to all that leads to confusion. So here are the causes on this slide. Heart failure, shock, aortic stenosis, injury, inflammation. There are pulmonary causes with release from the right ventricle and renal failure with lack of clearance. I think it's a little easier to think your way through this. You should know these causes and you probably do. It's a little easier to think your way through this to think about the new universal definition of MI and that's shown in this slide. So a type 1 MI is ischemic myocardial necrosis due to plaque rupture acute coronary syndrome and that divides into ST elevation MI and non-ST elevation acute coronary syndromes. Then type 2 is non-acute coronary syndrome ischemia. Ischemic myocardial necrosis not due to ACS. That is supply demand imbalance or if you want to use the term supply demand ischemia and there are coronary and non-coronary causes. So you could have increased demand either with or without coronary artery disease when the hemoglobin gets down to three. Even normal coronaries can get in trouble. Hypertensive emergency spasm embolism and then the non-coronary causes hypoxia. The blood is there but there's no oxygen in it. Hypoperfusion, tachycardia, aortic stenosis, increased demand, supply demand imbalance. Three or four are three is sudden cardiac death without an obvious cause but which was probably MI and type 4 and type 5 are PCI and CABG related and not really listed in this definition are the other non-ACS causes that we alluded to on the previous slide. Inflammation particularly sepsis, injury, pulmonary, renal and other sorts of things. So we're going to talk about non-ST elevation acute coronary syndromes and these differ from the STEMIs. There is no benefit from thrombolytic therapy in this syndrome that has been tried out. The TIMI trial was long ago showed that and risk stratification is the key. It has a multifaceted pathogenesis and so combination therapy to address all of those facets works best. It's a platelet-rich thrombogenic milieu and so anti-platelet therapy is indicated. There are vasoconstrictive substances released by those platelets and so anti-angio therapy is useful. Distal embolization from those platelets is occasionally occurs so anti-thrombotic therapy is added. There's a residual stenosis that can be addressed by mechanical therapy. So you want to look at high risk indicators of high risk and acute coronary syndrome and so here are up on top are the three that you can see at initial presentation. EKG findings, initial presentation with hemodynamic instability, heart failure or refractory symptoms and an elevated troponin IRT that shows increased risk. Now some of the other things do provide increased risk. Reduced LV function, complex lesions, reversible defects on stress testing, but those things only happen later. So most of the risk stratification has been focused early because that's when you need to decide whether you're going to go to the catheterization laboratory. So there are really two good scores to do risk stratification and non-ST elevation acute coronary syndrome. The TIMI risk score and the GRACE risk score. TIMI risk score is the factors you see on the right and the GRACE risk score has a bunch of factors and the score goes from 70 to 210. You would think this is complicated but you're going to do it on an app on your smartphone. You're going to put in the factors and you'll generate a number so it's pretty straightforward whichever one you use. And risk stratification can help select patients for cardiac catheterization. So here are the available strategies for cardiac catheterization in non-ST elevation MI. If your patient is hemodynamically unstable or has arrhythmias that won't go away or refractory angina symptoms, then you want to go to the cath lab right away. For patients with high risk features as listed, heart failure, anterior MI, and a high TIMI or GRACE risk score defined as a GRACE greater than 140, then an early invasive strategy is probably warranted. We'll talk a little bit about what that is in just a second. A delayed invasive strategy that is maybe not right now but within the next couple of days and patients with diabetes, reduced LV function, prior CABG or PCI, and an intermediate GRACE risk score. And if the patient is low risk or alternatively if the patient just doesn't want to do a catheterization or maybe the renal risk is higher, you do an ischemia guided strategy. If the patient doesn't have ischemia, you treat them medically. And if you do, you reconsider. So the data for invasive versus conservative strategies is sort of shown on this slide. And in general, the choice of an invasive versus conservative strategy depends on the risk. So a routine invasive strategy is in red and the selective invasive strategy is in blue and the percentage of adverse cardiac events is on the y-axis. So in patients at high risk, a routine invasive strategy is of reasonable benefit. And in patients of low risk, it probably doesn't make any difference. And as you might figure, the intermediate risk patients are in the middle. So you want to risk stratify. Patients at high risk should be considered for an early invasive strategy basically anytime within 6 and 24 hours of the presentation with non-acetylation acute coronary syndrome. So let's move on to the next section. We'll talk about complications. This is a television series I never saw, but it's apparently about a doc who has all sorts of trouble in his personal life. But we're going to talk about acute VSD, free wall rupture, acute MR, RV infarct, and end up with pump failure. Here are new data from a publication in circulation looking at the incidence and mortality of MI complications over time. And you sort of see the sort of eras I talked to before, pre-reprofusion, fibrinolytic, primary PCI era, and what they're calling modern now, systems of care for STEMI and shock era. And what you can see is that the incidence of complications has kind of gone down. It looks from 1.7% way back when now to somewhere around 0.3%, although the confidence intervals are reasonably high in the various studies. The mortality, however, hasn't really changed all that much. You know, maybe it's a little bit lower than the pre-reprofusion era, but you're still looking at a fair amount of mortality upwards of 30 to 50 percent of complications. So they are serious, and as I mentioned before, they also appear with disproportionate frequency on critical care examinations. Ventricular septal rupture presents with severe heart failure or cardiogenic shock with a pansystolic murmur. The pressure in the left ventricle is always higher than the right ventricle, and a parasternal thrill. It's a left-to-right intracardiac shunt, so oxygenated blood goes from the left ventricle to the right ventricle, so the saturation in the right ventricle is higher than the saturation in the right atrium, even though the blood hasn't gotten to the lungs yet. You want to stabilize medically and usually use mechanical circulatory support for heart failure and shock, and the earlier you get to repair this, the better the patient does. Free wall rupture happens in two flavors. Uncontained, all the way out into the chest, is a catastrophic event leading to electromechanical dissociation or asystole, and you're lucky if you can really salvage somebody when that happens. However, pseudomaneurysm, when there's a little bit of leakage, there isn't a wall but it's leaking and there's thrombus, presents with transient hypotension, sometimes electromechanical dissociation, bradycardia, patients look gray and restless and they just look like something bad is about to happen because something bad just happened and something worse may be happening soon. An electrocardiogram showing a pericardial effusion, sometimes you can actually see the blood going in, is diagnostic. Mortality is very high, but if you recognize it early, support with mechanical support and go directly to the operating room salvage is possible. Papillary muscle rupture, you can see that in the picture there, that's an echo showing the papillary muscle at the end of a cord in the left atrium with a little arrow there, presents with the sudden onset of cardiogenic shock with hypotension and pulmonary edema. All the blood is coming from the ventricle to the atrium and unlike chronic mitral regurgitation, this happens suddenly with no chance for adaptation. The hole is so big that the flow may not be all that turbulent and beside the patient is in pulmonary edema. So the murmur may be softer and audible, that happens sometimes in the clinic and with also frequency on exams, that's a sort of they try to trick you, they don't give you the murmur, that would be too easy, they give you the rest and you're supposed to figure it out. It's most common with the inferior MI and the inferior MI may actually be small because there's a single blood supply to the post remedial papillary muscle. So if you just infarct that tiny area, you can wind up with papillary muscle rupture. You want to reduce afterload and you again usually need mechanical circulatory support and definitive therapy is surgical with valve replacement. Right ventricular infarction in patient occurs in conjunction with inferior infarction. The incidence is 30%. It's clinically significant in about 10%. The clinical findings, classic clinical findings, right-sided failure without left-sided failure, elevated neck veins with clear lung fields because the blood never gets to the left ventricle from the right ventricle. It's a reversible cause of cardiogenic shock. The treatment is careful volume expansion. Once you start pushing the septum the wrong way then volume expansion doesn't work anymore. Inotropic agents to try to help the right ventricle and sometimes mechanical support of the right ventricle. Here is a finding of hemodynamic, a chart of hemodynamic findings in MI complications. As you can see the forward cardiac output is decreased in all of these patients including cardiogenic shock which we're going to talk about in a second. The wedge pressure is high except in RV infarction. Remember the blood doesn't get to the left ventricle and the clinical findings, characteristic findings are listed here. Free wall rupture you can see pressure equalization due to tamponade if you have PA catheter although you usually make the diagnosis of echo. A thrill is characteristic of a VSD. The hole is a solid murmur in both VSD and papillary muscle muscle rupture but the thrill is more characteristic of the VSD and as I mentioned the murmur may be softer absence in papillary muscle rupture and then there's an oxygen step up so if you see saturations in the right atrium and the right ventricle on a patient with an MI you should think about VSD. There's a prominent V wave in papillary muscle rupture. Frankly there's one in acute VSD too for complicated reasons which is why they probably won't show it to you. In RV infarction the right atrial pressures are high and the ratio of right atrial to pulmonary wedge pressure can be high as well but again you usually make that diagnosis with echocardiogram. So we'll finish up with pump failure the most common complication and the most common cause of mortality inpatient mortality from myocardial infarction. This is a graphic of the pathophysiology of cardiogenic shock and what you can see is that it's really a vicious spiral going downwards. Systolic dysfunction decreases cardiac output and causes hypotension and decreases perfusion pressure causing ischemia. It decreases systemic perfusion causing myocardial dysfunction and shock and on the diastolic side left ventricular and diastolic pressure is high there's pulmonary congestion hypoxemia and even the blood that gets to the heart doesn't have much oxygen in it. So ischemia begets myocardial dysfunction which begets ischemia which begets progressive myocardial dysfunction and if you don't break that cycle you can lead to mortality. So the landmark study in this area is the shock trial. The shock trial looked at patients within 36 hours of acute myocardial infarction and they had shock due to pump failure. They excluded mechanical causes and they were on vasopressors or had a balloon pump and they were randomized within 12 hours to either a strategy of emergency revascularization with either balloon pump or with with insertion of a balloon pump and either PCI or CABG or intensive medical stabilization. Most with most of the patients got lytics. They did get balloon pumps but they tried to wait on PCI or CABG for 54 hours. And here are the results. The initial trial was 30 days but the one-year survival results were published later in the New England Journal of Medicine and what you see is there is a 13% absolute reduction in mortality with with early revascularization compared to initial medical stabilization. So this is the landmark study that shows that you need to revascularize patients with cardiogenic shock. I just wanted to mention mechanical support devices since I've alluded to them in the talks about complications. You're going to hear more about the mechanical support devices in other talks but remember they're left ventricular and right ventricular. The balloon pump is pulsatile. There's an axial flow device otherwise known by the trade name impella. There are devices with continuous centrifugal flow with an external pump. The tandem heart device and the VA ECMO. And then for the right ventricle there's an axial flow device that goes the other way that's designed to support the right ventricle and you can put in an external pump tandem device with or without something called a Protec Duo catheter in the right ventricle. And lastly you can do extracorporeal membrane oxygenation. This is a graph that talks about the selection of mechanical support modes in patients with cardiogenic shock. I don't really want to go into it in much detail except to say that you want to characterize shock into an LV dominant, an RV dominant, or a biventricular form of shock. That is best done by invasive hemodynamic monitoring. Perhaps a story for another day although new data suggests that outcome is improved in cardiogenic shock at least when you do invasive hemodynamic monitoring. So if you have a left ventricular dominant form you want to support the left ventricle. You have a right ventricular dominant form you want to think about supporting the right ventricle either with inotropes or with mechanical support. And if you have biventricular form of shock you have to ask yourself whether the right ventricle will get better if you support the left ventricle or whether you have to support both ventricles. And as important as anything else I've told you in this talk is secondary prevention after myocardial infarction. You have the patient's attention. Now is the time to make sure they stop smoking if you can. You want to control their blood pressure. You want to get them back into physical activity. You want to manage their diabetes, control their weight, and vaccinate for influenza at least. And it's 2021. It's the summer so I thought I'd at least mention COVID and ACS if only briefly. So pre-hospital PCI activation during the worst of it was suspended for COVID testing because you had to test people and figure out where to put them. STEMI mimics were much more common. Not all of the ST elevation resulted from ST elevation MI. And the non-ACS troponin release was also much more common. Because of all these things total ischemic times were longer. This combination of delayed activation and EMS response overtaxed EMS and transfers from one hospital to the other. There was more fibrinolytic therapy especially at hospitals without PCI because there was no transferring somebody from one hospital to the other. More use of telemedicine for follow-up. And we've adapted to that. Things are getting back to where they were but it's important to continue to monitor the performance and outcomes in the COVID era with the hope that soon we will be out of the COVID era. So to wrap up, key points. Acute coronary syndrome results from atherosclerotic plaque rupture. The key metric is first medical contact to reperfusion. We should concentrate on regional systems of care to reduce this as low as we possibly can. Primary PCI is recommended for ST elevation MI when it can be performed with speed and skill. PCI is indicated in high-risk patients with non-ST elevation acute coronary syndromes. P2Y12 inhibitors should be loaded and continued for 12 months in acute coronary syndromes. Oral beta blockers should be started within 24 hours unless they're contraindicated. High-intensity statins. Left ventricular ejection fraction should be measured. And if it's low, renin-angiotensin-aldosterone inhibitors should be started. It's very important to adjust doses of adjunctive therapy according to age, weight, and renal function. For mechanical complications, hemodynamic assessment is vital to achieve the best outcomes and rehabilitation programs, particularly those including exercise, are recommended. Thank you very much.

acute coronary syndromes

ST-elevation myocardial infarction

non-ST-elevation acute coronary syndromes

unstable angina

reperfusion strategies

complications

secondary prevention

COVID-19