Thank you so much. This was super, super, it was an excellent but very comprehensive lecture and I think you guided everybody through the algorithm. So our next speaker will address cardiogenic shock and address the issues of revascularization and mechanical support, Shripal Bangalore, who is at the NYU and he's been a very important member of this guidelines committee. He has a tremendous wealth of knowledge. Thank you very much and thanks for that generous introduction and great to be back on this panel and thank you everybody for joining us today. So I've been given the task of discussing about cardiogenic shock, revascularization, mechanical circulatory support. I don't have any relevant disclosure for this particular talk but in terms of cardiogenic shock, I mean we're going to discuss in the next nine minutes or so about emergency revascularization or initial medical therapy. So in other words, should we cool off these patients before we do anything? We'll then talk about, which Dr. Tam has already mentioned, culprit versus complete revascularization if you have multivessal disease. What do we do for management of CTOs in patients who have cardiogenic shock? If they have multivessal disease, should we be choosing PCI versus CABG in patients with AMI and shock? And finally, we'll briefly discuss about mechanical circulatory support. And in all of these, we'll weave in the 2021 guideline recommendations. So in terms of what to do for patients with AMI and shock, emergency revascularization versus initial medical therapy, nothing has changed. This is a shock trial from 1999 of patients with their AMI. The reason I want to just briefly go over this trial is it has implications on how we practice and it's also important today because many of the nuances sometimes get forgotten. So shock trial enrolled patients with AMI complicated by cardiogenic shock and this could be within 36 hours after an MI. And if the patient has a shock, they were randomized within 12 hours to either an emergent revascularization. And the key thing I want to emphasize here was that the emergent revascularization was performed within six hours after randomization or to initial medical therapy, immediate medical stabilization. These patients could get revascularized after 54 hours. So in this trial, 302 patients were randomized. And here, 86% of these patients had intra-aortic balloon pump use. This was back in the day when POBA and later stents were introduced. So stents was used only in around 36% of the patients. And it's also important to note that shock trial was not just a PCI trial. In a third of patients in the revascularization arm, they underwent coronary artery bypass graft surgery. So at 30 days, numerically significant higher survival with emergent revascularization compared to initial medical stabilization, but, and this reached statistical significance at six months. And that was persistent at 12 months and also up to six years of follow-up. So significant benefit of emergency revascularization compared to medical stabilization. The point I want to make from this is the fact that a third of these patients underwent bypass surgery and this bypass surgery is not saying, okay, we'll wait, cool off, give an antiplatelet, let's wait five days and then do bypass surgery. So this, in this trial, bypass surgery was done within six hours. In fact, the average time to bypass surgery was just around two and a half hours. So I think this is very important to recognize. And if you want to implement this, this is how it should be implemented in clinical practice, because the time to revascularization does matter. So this is data from the shock registry, looking at time to PCI in patients with cardiogenic shock. So the earlier you do revascularization, so if it is within six hours, the mortality is 40%. And the longer time to revascularization greater is your mortality rate. So important to make sure that PCI revascularization is done as soon as possible in patients who have cardiogenic shock. And also, it's also important to make sure that we get as optimal results as possible in the shock registry. If you have TME3 flow, the mortality is much lower than patients who had suboptimal PCI outcomes. And so just quickly going to the guidelines. So if you have acute MI and cardiogenic shock for culprit artery, it's a class one, both for STEMI and non-ST elevation AMI to do either PCI or CABG. CABG on PCI is not feasible. We'll come back to data supporting CABG use in cardiogenic shock patients. And this is class one to improve survival, irrespective of the time delay from MI onset. And this is also true for patients presenting with non-ST elevation ACS and cardiogenic shock. And as you can see here, nothing much has changed. In 2011, it was a class one. It's a class one now because there is no randomized trials saying otherwise. So this should be the standard of care for patients with AMI and shock. So how are we doing? This is data from the United States. So this is from the national patient sample, looking at over 60,000 patients with cardiogenic shock and over 11,000 patients who are older than 70 years, 75 years. And you can see over the period of time, the rates of this is CABG and the blue one is for PCI and the green is for CABG. The rates of PCI have increased from around 51% to 62%. The rates of CABG in acute MI cardiogenic shock patients have decreased from 26 to 17%. And if you look at early invasive management trends, and you can see that those rates have also improved with the PCI rates improving from around 86 to 89%. And also CABG within 48 hours, you can see half of the patients who underwent CABG undergo CABG within 48 hours. And similar to what we saw in randomized trials, in this registry analysis, we saw that patients who underwent invasive strategy did very well, reduced mortality, whether the patient is older or younger than 75 years, whether they presented with STEMI or NSTEMI. And again, if you were to conservatively manage for whatever reason, your mortality is very high, but if you manage them invasively, you can see the trends in mortality seems to be lower. But even this is back in 2011, the mortality, even with an invasive strategy was around 33%. So going back to our drawing board, acute MI cardiogenic shock, emergency revascularization, this was data from three decades ago, that's true even today. What about multivessel disease in patients with AMI and cardiogenic shock? One thing which is clear from many of these trials is there is a very high proportion of patients who have multivessel disease if they're present with AMI and shock. So here you see upwards of 50% in many trials, close to 80% of patients have multivessel coronary artery disease. So this question comes up repeatedly in clinical practice, what should we be doing for multivessel disease? Should we just treat the culprit vessel? Should we do complete revascularization? How do we approach this? This was answered in the culprit shock trial. So this was a trial which enrolled patients with acute MI, cardiogenic shock, multivessel disease, randomized to multivessel PCI at the time of culprit vessel revascularization or to culprit lesion only PCI. And the primary endpoint as can be seen on the slide, death or renal replacement therapy, significantly worse with multivessel PCI, P of 0.01. This was driven by increased risk of death and also numerically increase in the risk or need for renal replacement therapy. If you look at the data, this is now one year data, you can see that the increased worse outcomes multivessel PCI lasts even up to one year, but most of these hazard is driven by upfront hazard. And after 30 days that the two curves are superimposed, no significant difference between the two groups. One of the things that is important to emphasize for the culprit shock trial is nearly one in four patients have randomized participants in culprit shock at one or more CTOs. And the trial protocol mandated that in the multivessel PCI group, immediate recanalization of a CTO was indeed recommended. So I think this is something to keep in mind in clinical practice, even though, so they did a subgroup analysis based on whether patients are CTO or not. And you can see if a patient did have CTO, and if you try to open that, the mortality was really 52% when compared to culprit only, which was 35%. So it seems that much of the mortality differences seem to be driven by CTOs. And I think we should be extremely careful trying to open CTOs in a patient who is really sick. In culprit shock at one year, there was reduced risk of repeat revascularization. If you had multivessel PCI, there was also reduced risk of needing re-hospitalization for heart failure with multivessel PCI compared to culprit only PCI. Based on this data, I want to emphasize that the culprit shock trial included 50% of patients with NSTEMI. So it applies to both STEMI and NSTEMI. So for STEMI, for non-culprit revascularization, routine revascularization is a class 3. There was no specific recommendation in the prior guidelines. For NSTEMI, it's the same, but I want to emphasize that class 3 for harm is for routine multivessel PCI in the same setting. So all of these should be recognized that the recommendation we are making is for routine. In other words, doing it on all patients at the same setting. So it doesn't preclude you from doing it staged at a later period of time. Okay. So moving forward, what about PCI versus CABG and AMI shock patients? We looked at these trends that a trend in PCI is increasing in AMI shock patients, then patients with CABG is somewhat decreasing. What is the data for CABG in shock patients? If you look at the shock trial, a third of the patients in the emergent revascularization group underwent CABG. And if you look at the survival, I mean, this is non-randomized. If you look at the survival between CABG and PTCA, there was similar survival, despite the fact that there was more severe coronary artery disease and diabetes in the CABG cohort. In fact, the data from the shock trial and registry looked at patients with left main disease with acute AMI and cardiogenic shock. And in this again, observational analysis, CABG had better outcomes compared to PCI in patients who had left main disease and cardiogenic shock. So something to consider, but there is no head-to-head trials of PCI versus CABG and acute AMI cardiogenic shock. So we do need randomized trials to see if anything is, if one is superior or the other, but my take on this is do the revascularization modality that is readily available to you and as quickly as you can. Now in the last few minutes, let's quickly switch to mechanical circulatory support. If you look at the cardiogenic shock mortality, 1999 into shock trial, it was 44%. 2017 culprit shock trial is still 43%. So nearly one in two patients die from cardiogenic shock, despite the best available therapies so far. So there have been a number of mechanical circulatory support device for cardiogenic shock. So some support the right ventricle, some support the left ventricle and some support both. I won't go into the details of any of these MCS devices or their mechanism of action. So I just have it on these slides to review at a later point of time. But let's look into the data of some of these mechanical circulatory support devices from randomized trials. So if you look at acute AMI cardiogenic shock and the use of IABP, this was tested in the IABP shock one trial. It's a randomized trial of 40 patients, IABP medical therapy. If you look at the surrogate marker, hemodynamic marker, interestingly, no significant difference in improvement of the hemodynamic marker with IABP compared to medical therapy. What about clinical outcomes? This was tested in the IABP shock two trial, randomized trial of 600 patients, no significant difference in mortality between strategy of routine IABP compared to medical therapy alone. So IABP as a strategy for acute AMI cardiogenic shock has no data either for improvement of hemodynamics or for outcomes. What about other MCS? So if you compare again, so if you look at some of these randomized trials, so there are four randomized trials. These are very small randomized trials. The total patients in all of these randomized trials is just close to around 150 patients. If you look at the surrogate marker of increased improvement in MAP, there is a significant improvement in MAP with the mechanical circulatory support device, like an Impala compared to a balloon pump. This is also true for improvement in cardiac index and improvement in lactate. But there is a price you pay for, in terms of increasing the risk of bleeding and leg ischemia with the circulatory, with the support device, such as Impala compared to a balloon pump alone. So although the surrogate markers are improved, there is increased in safety outcomes. And if you look at mortality as an endpoint, there is no significant difference again, but these are very underpowered, only 150 patients from these randomized trials. So there are a number of trials looking at now ECMO and also Impala trying to figure out if a strategy of using these would improve clinical outcomes in patients with acute myocardiogenic shock. So just to summarize in patients with acute myocardiogenic shock, emergency revascularization is the way to go. And revascularization is the only therapy proven to save lives. In terms of culprit complete revascularization, culprit revascularization is superior and complete at the same setting should be avoided and especially avoid doing CTOs in that setting. No data to directly compare head-to-head PCI versus CABG. And in terms of mechanical circulatory support, other than IABP with Impala, for example, there is improvement in hemodynamics, but we do need randomized trial data to show that it routinely improves clinical outcomes. Thank you for your attention.

cardiogenic shock

revascularization

mechanical support

emergency revascularization

clinical outcomes