Perfect. Thank you so much, Selena. So, without further ado, we're going to leave the discussion on physiology to the end. We're going to go now to the second part of the webinar, and we're going to ask Dr. Jackie Thames-Holland from Mount Sinai Morningside, co-chair of these guidelines, to talk about culprit versus non-culprit interventionist stemming. Thank you, Jackie. Thank you, Mauricio, and thank you, JP, for inviting me. I'm really excited that gang's all back, and I love being with my group of members of the writing committee. So, I've been tasked with talking to you about STEMI and how we approach the infarct artery, as well as how we approach the non-infarct artery. I don't have any disclosures. So, with respect to STEMI, first of all, I think it's important to recognize that our guidelines really focus on the patient, and sort of the focus is on the patient with a condition and not, and revascularization in general. And since our guidelines combine both PCI and CABG, our recommendations combine it because they're really looking at the best mode of revascularization. And of course, in patients with STEMI, generally PCI is the best mode of revascularization, but we do include some recommendations for CABG as well. With respect to reperfusion of the infarct artery in STEMI, there's really hasn't been a whole lot of change in the recommendations or in, and that's because there hasn't been a whole lot of new data in terms of how we approach the infarct artery in STEMI. So, much of this is based on very old data from years ago, but generally speaking, we know that in patients with STEMI, that PCI is the way to go if they're presenting with symptoms for less than 12 hours since symptom onset. We also know that in patients with STEMI, and we have a recommendation for cardiogenic shock or hemodynamic instability, that regardless of the time from when they presented with their infarct, that PCI should be performed, or CABG in the situations where PCI is not feasible. We haven't upgraded the recommendation for how we handle patients with failed reperfusion. So, prior studies showed that there's a benefit to proceeding with cardiac cath with the intent of doing PCI in patients who have evidence for failed reperfusion after fibrinolytic therapy. These studies did have an increased rate of bleeding, increased rate of stroke, and procedural complications. So, there was an improvement in MACE, but at the cost of bleeding. And so, in prior iterations of the guidelines, it was a 2A to proceed with invasive therapy with the intent to perform PCI in patients with failed fibrinolysis. Now, there really isn't any change, and I just sort of want to point out why this recommendation became a class one. There's no new change in the data, but what we do see is that we do know that the risk of bleeding has decreased over time, particularly with Sunil and everybody doing with the radial artery improvement in antithrombotic therapies and antiplatelet therapies, and we really don't use too much GPIs. So, the balance between a benefit from proceeding with invasive therapy in a patient after fibrinolytic who has failed PCI, who has failed fibrinolysis, is now in favor of proceeding because the risks are much lower, and that's why it's a class one recommendation now. It's also, as was before, a class 2A recommendation to proceed with angiography after fibrinolytic therapy within 3 to 24 hours, even in stable patients. This was based on older data, and nothing has changed since the last iteration of the guidelines. In patients presenting with 12 to 24 hours, it's a 2A recommendation, and in patients who are presenting with STEMI that's complicated by ongoing ischemia, severe heart failure, or life-threatening arrhythmias, it's a 2A recommendation to proceed with PCI, irrespective of the time of the MI onset. So, you know, we summarize this with a nice summary of how we approach the infarct arteries. So, we have patients on the left with ischemic symptoms within 12 hours, and we have that if PCI is feasible, of course, primary PCI should be the way to go. Now, on the right, if you have ischemic symptoms for more than 12 hours, then you really need to consider the clinical context. So, if you have cardiogenic shock, you're going to proceed with PCI, irrespective of the time delay. If you have ongoing ischemia or symptom onsets between 12 and 24 hours, you're going to proceed with PCI. But if you have no other abnormalities, you're stable, you have no ongoing symptoms, and you have no electrical instability or shock, then PCI beyond 24 hours of a totally occluded infarct artery is a class 3. And again, this is based on older data, but it's just a summary of the information. Now, we're going to get to the meat of the RE-VASC guidelines with respect to STEMI. There's been a lot of new data over the years looking at how we manage the non-infarct artery in STEMI. And so, for this reason, we have a whole section on this in the guidelines. So, we now have a class 1 level of evidence A recommendation saying that in selected patients, if PCI is feasible and appropriate, then stage PCI of the non-infarct artery is a class 1 and appropriate, then stage PCI of the non-infarct artery is recommended. And this is based on several studies, but in particular, based on the COMPLETE trial, which was a trial of over 4,000 patients. And unlike other trials, this primary endpoint was a little bit more of a hard primary endpoint. There were two co-primary endpoints. One was cardiovascular death or MI, and you saw about a 25% reduction in this co-primary endpoint with COMPLETE stage PCI of the non-infarct arteries. And the other one was about a 50% reduction in overall MACE with COMPLETE stage PCI compared to culprit-only PCI. And this is why it's a class 1 recommendation. Now, when you look at the trials overall, you can see that there are several trials looking at stage PCI, and these are just some of them, but when you, oh, it's stage PCI or PCI at the time of primary PCI, but when you look at these trials, you can see that these trials really included relatively non-complex non-infarct artery disease. The trials generally excluded patients with prior CABG or with a non-infarct artery involving a bypass graft. They generally excluded patients with CTOs or left main or left main equivalent. And the majority of patients enrolled in these trials had only a single non-infarct artery stenosis as opposed to multi-vessel complex disease. So for this reason, that class 1 recommendation that we mentioned really cannot be extrapolated to patients with complex non-infarct artery disease. And in that situation, you may want to consider PCI of those vessels, but we do sort of emphasize that you might want to consider, and it's reasonable to consider, elective CABG in these patients at a later date, and that's a 2A recommendation. Now, with respect to doing PCI at the time of primary PCI, it remains a 2B recommendation to do PCI at the time of primary PCI in patients with low complexity multi-vessel disease. And this is based on earlier trials, the primary trial, the culprit trial, and the compare acute trial, all trials in which multi-vessel PCI was performed at the time of the primary PCI. The primary endpoints were MACE, and there was about a 50% reduction in MACE across these trials, even larger with the primary trial. This MACE was predominantly driven by a lower rate of ischemia-driven revascularization, although in the primary trial, all of the components of the primary endpoint were in favor of multi-vessel PCI. With respect to STEMI and complicated bicardiogenic shock, well, this is the class three recommendation, and we're all familiar, and I think Dr. Bangalore will be speaking about this in a little while, but we're all familiar with the culprit shock trial, which showed a lower event rate when you performed culprit-only PCI at the time of primary PCI as compared to multi-vessel PCI, and this endpoint was the lower rate of death or need for renal replacement therapy. A similar endpoint was seen at one year as well, so definitely a benefit to doing culprit-only. This does not mean that you can't do stage PCI at a later date of the multi-vessel disease, but at the time of primary PCI, you should proceed with culprit-only. So, you know, I think what we really try to emphasize, and we hope that you all read the recommended supportive text and looked at the algorithm very closely, is that all of the way in which we treat this non-infarct artery, you really need to consider the clinical context and take every patient individually. You want to consider the patient's hemodynamic status, whether you had a successful PCI of the infarct artery, and the nature of the non-infarct artery. Is there an ulcerated plaque or TIMI2 flow of the non-infarct artery? What's the percent diameter stenosis? What's the vessel size? Does the patient have other comorbidities, and what's the complexity of the disease? So, these are the things we want you to consider before giving a blank statement that everybody should get stage PCI. So, when we created this algorithm, we really tried to give a lot of thought. We start by saying you have to have STEMI and a successful PCI of the infarct artery, and you have to have a stable-appearing non-culprit lesion. And if you do, then you go on to ask the other questions. So, if it's a low-risk patient and low complexity, you had a successful PCI and it's a low-complexity lesion, you might want to consider PCI of the non-culprit vessel. But for all other patients, you're going to go to the right side of this diagram, and then you're going to start to consider, is there a large area of myocardium at risk, and is there absence of multiple comorbidities? And if that is a no, then you really want to consider whether you should just continue with guideline-directed medical therapy. But on the left side, if that is a yes, then you want to consider how complex the disease is. If it's complex disease, you might want to have a heart team discussion. You can still go back to do a stage PCI, but we stand clear of providing a formal recommendation with that. If it's complex disease, you might want to consider CABG, and if it's not complex disease, you should do stage PCI. So, in summary, before I end, I just want to mention a couple of key unanswered questions. We sort of steered clear of discussing this, although some of this information is coming out in more recent clinical trials. So, what's the ideal timing for the non-infarct artery? We really don't know. We assume it's staged, but is it truly staged? Better, there's little data looking at staged versus doing it at the time of primary PCI, and whether you do it as staged during the hospital stay or at a later date, what is the best timing? Additionally, should we use FFR or IFR guidance? The FLOWER-AMI trial and the FRAME-AMI trial actually provide sort of conflicting results about whether FFR guidance should be performed on these patients to identify whether it's important lesion. And finally, does plaque characteristics make a difference? So, what's the nature of the non-infarct artery, and will the plaque characteristics determine whether we should be doing PCI? So, in summary, our revascularization guidelines hopefully emphasize the importance of individualizing care, and in both performing, whether you perform PCI of the infarct artery or PCI of the non-infarct artery, you really need to consider the patient's clinical features, their presentation, their hemodynamic statics, the lesion characteristics, and the patient's symptoms to help guide decision-making. Thank you.

ST-segment elevation myocardial infarction

PCI

revascularization

individualizing care

non-infarct artery