Originally broadcast March 31, 2021
A case-based overview of contemporary treatment approaches in acute coronary syndromes.
Drs. Darshan Doshi, Sandeep Nathan and Steven Yakubov discuss contemporary treatment approaches in acute coronary syndromes.
Mhm. Hello and welcome to our session on acute coronary syndromes which is supported by by electronic. My name is Doris Window, she um an interventionist at the massachusetts General Hospital as well as on the faculty of Harvard Medical School. Now tonight is the first of many sessions in the bio emerge series of talks. So for those of you that may not be familiar with uh this bio merge series consists of cases based lectures that aimed to highlight the evidence based for the most contemporary practices as well as the best practices within interventional cardiology. Now, these sessions will focus on some hot button topics within our field and we also anticipate a significant amount of debate between our panelists. Now these sessions are geared more towards early to mid career faculty and will be led by some of the premier interventionist here in the US. Now, with that being said, let me introduce the two other interventionist on the panel today. Um frankly they don't actually need any introduction, but I'm gonna do it anyway. So first up is Doctor Sandy Nathan Nathan from the University of Chicago. Um He is co director of the Cath Lab there as well as the director of their interventional cardiology fellowship program. He's also medical director of the I. C. U. There. Um the cardiac ICU. Um as if that wasn't enough um you know, David holds multiple hats uh and is also a pioneer when it comes to research within the field. Next is dr steve Yacouba, who is from the Ohio Health and Vasko Physicians group where he is the System wide medical chief of structural interventions. He was also their former head of their catholic. He's also the medical director of the research institute. So thank you both for joining me today. Um and you know I anticipate this being a great session. So without further ado let's get started with the first presentation by Sandeep. Gosh, thank you so much. It's great to be with both of you, Darshan steve and really looking forward to this. Big thanks to uh to buy a tronic for supporting this educational endeavor. And uh for all of you for for joining us this evening I'm going to start us off with a discussion on the essentials of stem e intervention. Uh And then uh dr Doshi will continue with acute coronary syndromes and and we'll try to keep this lively and interactive. Here are my disclosures. Okay so this is what the path of a typical stem E patient looks like going from pre hospital and E. M. S. Care to the emergency department. Early Cath lab course where we're focused on D. Two B. And P. C. I. The culprit vessel later Cath lab course uh inclusive of uh sort of bailout therapies and some adjunctive maneuvers. And then I see you care where we have to ensure that this patient does well in the post procedural period as well. Some of the common clinical challenges that we encountered in primary PC. I. Are shown here, the clinical issue shown here on the left, the potential consequence on the right rush vascular access and increased risk of access site bleeding, vascular complications, all of the attendant risk associated with intensified anti thrombin, arctic therapies dealing with rhombus bearing lesions. There's a lot of pitfalls and booby traps there. Poor visualization of the vessel can sometimes lead you astray poor uh adapt loading or adapt exposure inadequate uh due to the timing of the P. C. I. Or a co administration of opioids can result in stent thrombosis and then finally failure to recognize that the patient is sort of sliding into shock. Can get you into a deep waters later on. So let me sort of kick this off with a clinical case. This is a case that I think is fairly uh topical. Uh and you'll see why here in just one slide, this is a 36 year old covid positive male who presents late for a variety of reasons to an outside hospital with crushing back pain and chest pain. His E C. G reveals 8 to 10 millimeters of S. T. Elevations. I won't bore you with all of the reasons why he was a delayed presentation, but his ischemic time at this point is already four hours or more numerous calls are made to outside hospitals, but transfer wasn't possible because of ongoing riots, racial tensions and the George Floyd riots and so forth, had had resulted in uh basically police lines everywhere. And so this patient has initially given aspirin and clopidogrel as they're trying to transfer this uh this gentleman, um ultimately, the transferring hospital uh kind of gave up on uh door to balloon and and just gave him T. P. A. And in oxytocin, which perhaps wasn't my choice, but, but that's what they gave. His chest pain and shortness of breath are unchanged. Eventually, we're actually able to get him over. Uh and uh, we went from a right radio approach in what you see here in a normal tense of patient who's actually recently, well compensated given the massive amount of territory that's in jeopardy here is a very large thrombosis lady. I can't figure out when he got his knots apparent or his clopidogrel. So we decided to load him with tie casual or 180 mg, uh and get to work on the, on the L. A. D. We chose a universal guide. We crossed pretty easily with a run through in a Caravel micro catheter. We gave a pretty large gentleman. We gave up to 10,000 units of heparin to get an A. C. T. Of 300. And at that point, given the excessive rhombus burden, we also gave ivy, kangaroo lore uh to uh to see what we can do in terms of breaking up the clot. Well, you know, we certainly got a balloon in there pretty easily but it really didn't have any meaningful effect on the vessel. We escalated to aspiration thrown back to me and then realistic thrown back to me. Um And then finally we put a micro capital all the way down the vessel and gave pulse spray vaso dilator, a dentist in sodium nitro cross side. Um to try to determine where this vessel was. And you can see that you kind of see and lady that is largely free of any branches. Unfortunately, all these branches have been snow plowed shut with clots. You can already see filling defects as the lady feels backwards. Uh And so we get to work ballooning and stenting. This is kind of a remarkable case for a lot of different reasons, not the least of which is uh the very long scented lengthen this vessel. We ultimately ended up putting about 110 millimeters of overlapping or Ciro stent in this vessel. And then optimizing with uh with IV's as best as we could. At the, the end of the case, we've got a vessel. It's uh, you know, largely devoid of any branches, unfortunately. But we do have trickle flow to me to flow all the way down into the optical segment of the L. A. D. And after some more pulse spray, uh Dennis zine and uh nitrile cross side. Uh This is what we, what we end up with remarkably he is still hemo dynamically stable throughout the flow is just sort of waxing and waning. The right coronary artery looks pretty good. Uh And in total the patient received aspirin and clopidogrel. 100 mg of T. P. A. A milligram per kilogram of N. Ox apparent I. V. Heparin, pyo taek a girl or an ivy candler. And uh I'm delighted to say that he actually made a complete recovery, although his L. B. Is is still sort of limping along at about 30%. But he came into clinic about a week 10 days later with With class zero symptoms, both heart failure as well as Angina. And so I think this case raises a lot of the hot button issues and controversies in primary pc. I personally, some of them have highlighted here access and anti coagulation, radio versus federal choice and loading of oral P two Y 12 inhibitor G. P. I. Vs. Kangol or use of thrown back to me stent choice delivery opposition. The issue of complete versus culprit, revascularization and use of mechanical circulatory support. So first the controversy of translated trans radio versus trans femoral in my mind. This is not much of a controversy but it continues to be a bit of a controversy in the United States. This is an updated men analysis that was presented at A. C. C. Last year showing a 29% reduction in all cause mortality, 41% reduction in major bleeding, 58% reduction in major vascular complications with trans radio versus transfer Meral in stemming intervention. So I think this should be a radio first approach if possible. And if everyone is comfortable with what's going on, vascular ultrasound is your friend, irrespective of whether you're going radio versus federal. Uh in terms of allowing real time guidance and avoiding complications. And even in very small caliber vessels, the case can be done pretty quickly and expeditiously. Um Use of universal guide catheters is the standard in our lab. Uh is certainly not a mandate, but there may be some time savings if your facile with use of universal guide catheters, you can kind of get in at least for native anatomy. Just get in and get everything done with a single catheter. What about the distal trans radio for primary Pc? I over the past couple of years, distal radio, particularly L. D. T. R. A. Has gained some popularity in the United States and more popularity in the East. Specifically in uh in japan Korea and china. If you're going this route, this should not be your first case. Your primary pc. I should not be your, your entry into the world of digital radio. Um do have some ultrasound skills and, and a reasonable pulse to hit and know the anatomy of the snuff box before you do it because there are some unique challenges, positioning of the arm may not be familiar to all staff members. The entry angle is often a bit steeper, the skin over the snuff boxes, a little bit tougher sometimes to get through. Uh and you may encounter some tortuous city. But if everything lines up a typical trans radio primary Pc, it kind of looks like this. I actually had my fellow just scribble a timeline of what we were doing in real time just to see, you know, how, how much time it took to get from point A to point Z. Um and as you can see here, the door to balloon here was 33 minutes. And uh we really got in and out pretty quickly for a different stemming. Not this one, this one took some time, but for a different uh inferior wall stem me door to balloon was 33 minutes and the patient was out of the room in uh under under 45 minutes. Adjunctive pharmacology and steady. This is this is sort of a simplified diagram plotting out the coagulation and platelet cascades and cardiovascular disease and I won't be labor this other than to say that there are many opportunities for pharmacologic intervention. The key crossover point between the coagulation and the platelet activation sequences is the generation of thrombin and it's a bidirectional relationship and that thrombin is the most potent endogenous activator for platelets. And uh in return the surface of the activated platelets serves as the platform for assembly of the pro thrombin is complex on the platelets side. You can see that there are many different classes of agents that we have and this is sort of where it fits in in terms of sight of action of the oral and parental anti platelet agents. The one point that I want to make on the slide is that generally clopidogrel and glycoprotein inhibitors go together and can galore and Taicang griller go together because of the binding site location of clopidogrel. If you have candler onboard the file metabolite metabolite of clopidogrel is unable to bind the P two Y 12 receptor. And so those two don't go hand in hand. If you're picking clopidogrel, consider glycoprotein inhibitors. If you have to escalate, if you're picking taika galore pick angle or if you have to escalate. And this is sort of a selective escalation strategy are routine based on the available data, is to use Taicang galore or prasugrel in in patients who are uh eligible for that and otherwise don't have any contraindications before going to the Cath lab and in the capital, based on procedural considerations, consider the use of candler or like a protein inhibitor primarily as a short infusion. Uh to cover that patient. If pio dual anti platelet therapy hasn't been given, hasn't been absorbed or there's a very short loading time appeal in the patient's stomach uh is not equal to pre loading of uh dual anti platelet therapy. And certainly there is a large the rhombus burden as there was in the in the case that I presented. So what about choice of stent in primary pc. I for first Emmy, this is sort of an interesting area because I think that we all sort of think about stents, drug eluting stents as a commoditized market. We've got a number of excellent choices and and that's the good news. Um but really it's sort of it falls on local contracting and personal preference rather than data. Um And so general concepts, I think we all agree that D. S. Second generation D. S versus Bms decreased restenosis, decreased T. L. R. T. V. R. There's no clear reduction in mortality and a possible increase in stent thrombosis in some series with respect to DS versus BMS and stem E. D. S. Houston Steamy has generated controversy for quite a while ever since DS entered the US market in 2000 and three. Um and clinical trials and registries early on showed no difference in death or recurrent empire. Perhaps even restenosis in some registries. Um and there is the specter of a numerically higher rate of stent thrombosis. This is a publication about 12 years old from the mass stack registry published by Laura Murray and colleagues, 77,000 patients. And all from this registry, looking at the two year rate of risk adjusted mortality in patients receiving D. S. Versus BMS. Uh in the context of myocardial infarction and in all comers, all my cardio infarction, there seems to be a reduction in mortality in patients receiving drug eluting stents. Um and that's recapitulated in the steamy subset of this registry data. Now, the problem, of course, is that we're selecting people for de es versus BMS. So there's a heavy degree of selection bias in this type of data and it becomes a little bit difficult to understand. Is that the stent or is it the patient that was chosen to receive a drug eluting stent? More recently, ST paul dangler and uh and colleagues present uh published this mixed treatment comparison analysis from randomized controlled trials, making a number of very important comparisons between D. E. S. And different uh BMS and different DGS platforms. And then further between the different types of DS platforms. They concluded that in patients with stem E. Ds versus BMS was associated with a substantial decrease in TvR. I think we can all agree upon that without any compromise on safety, but further that E. S. That have a role in this eluting stents have the added advantage of a reduction in the stent thrombosis. Um There's more recent data still with the use of contemporary DS platforms incorporating buyer is horrible polymers and ultra thin uh struck designs. Uh and this is uh the or zero bios to me data. Uh 1300 patients in all, investigator initiated superiority trial design, 1 to 1 RCT of Arciero versus science in stem e patients with the primary endpoint of target lesion failure. At 12 months. The two year analysis of this study was just presented and simultaneously published in Jack interventions, was presented at CRT 21 virtual just a couple of weeks ago. Uh And this is what it looks like. The comparison I've already mentioned is between the or zero by reasonable polymer Sarona saluting stent ultra thin design versus the market leader, which is science durable polymer aerolineas, eluting stent 1 to 1 randomization and 1300 patients. There was a historical cohort from bioscience uh from the bioscience trial that was also incorporated into this analysis using Bayesian analysis techniques. Uh and there was a one year primary endpoint of tLF and the two year final outcome of tlf. And so here's the randomization schema. Um there is a lot of detail on the statistical methodology for this trial, very robust uh that was published in the original Lancet publication in October of 2019. But essentially the superiority margin is charted out here based on this position credibility interval that was that was constructed from the bioscience data. And so here's the punchline target lesion failure of two years was statistically significantly lower for an ultra thin biodegradable polymer Ciroma, saluting stent or zero versus uh science. And you can see from the Kaplan Meier analysis that the curves continue to diverge for the duration of the follow up period. And so the conclusions by the authors at the CRT presentation, the final two year outcomes of bios to me demonstrate and uphold the superiority of the biodegradable polymer SCS versace's science with respect to tlf in steamy patients. Um And essentially it just represents a strengthening of the signal that was seen at the one year. Our endpoint with no difference in uh in patient oriented clinical outcomes. Moving on to the next controversy which is culprit versus complete revascularization, revascularization stemming all too often. This is what we're confronted with when we take somebody to the lab for a stem me, this is an inferior stem. It's actually stent thrombosis very late stent thrombosis of a first generation uh D. S. And the R. C. A. But there's also intermediate disease in the circum flex, which turns out to be FFR positive and hybrid lesion in the in the middle A. D. Um There have been a number of registries and trials that have looked at this and it's kind of yo yo back and forth. But in my mind the most contemporary and definitive peace in all of this is the complete trial. A randomized comparison of culprit only versus complete revascularization in patients presenting with S. T. Elevation. Myocardial infarction. Uh 4000 patients in all. As you can see here who had at least one additional non culprit lesion in a vessel measuring 2.5 millimeters in diameter with a greater than 70% visual stenosis. Or if they had intermediate disease. Uh FFR proven with an F. F. R. Value of less than 0.8 just like in the in the in the case that I showed you a couple of slides ago. Uh and the median follow up was three years. The co primary outcome shown here composite of cardiovascular death or my cardio infarction or cd death New M. I. And ischemia driven revascularization. So here are some of the procedural characteristics. The most important procedural characteristics that you should be aware of is that complete revascularization was actually achieved in 90% of non culprit lesion, Pc. I. Yielding a syntax score of zero. So really remarkable. And so the first primary endpoint here cardiovascular death or new myocardial infarction significantly lower in uh incomplete revascularization patients with an entity of of just 37 patients. And that signal strengthens if you include CB death, new myocardial infarction or ischemia driven Revascularization number needed to treat of only 13. Uh There's also been some controversy about when you actually complete the revascularization. Should you incarcerate the patient and get it done on the impatient side, should just send them home and bring them back uh incomplete In the complete trial. It really didn't seem to matter. You can see that there's parody of of outcomes whether they had it during the index hospitalization at one day or after hospital discharge On average, about three weeks later. Um, the next issue is thrombosis management in primary PC. I uh there's again been a lot of back and forth about this. Uh and the question is, does thrown back to me really have a role in contemporary primary Pc. I first Emmy, there's a lot of different straws on the market. Manual aspiration thrown back to be tools, uh, export, uh, pronto, uh, the Indigo system, all shown on here and then there's also realistic from back to me, uh, using the engine jet system. Um, I think the, the short answer to this is that uh, uh, routine use of thrown back to me probably is not supported by the data. I think we were all very enthusiastic. I think many of us were giddy with the tapas data suggesting that not only was there a benefit in terms of surrogate endpoints? Perhaps there's also a mortality benefit to be gained by use of a very simple technique to to aspirate clot from the vessel. Unfortunately, the subsequent trials failed to uphold that in fact, routine use of thrown back to me was associated with perhaps an increase risk in stroke when some of that clot gets dragged out of the vessel and is liberated in the central circulation. And so routine use of thrown back to me. And this meta analysis, inclusive of all these large trials failed to meet any statistical significance. However, in the cohort of patients who had large thrombosis burdens, uh, tv dramas, grades greater than three, greater than four. Perhaps there was some benefit or a signal of benefit in those patients. All of that said, you have to do what's right for the patient And you know, this is a case that I posted to twitter a couple of months ago, 39 year old gentleman. We tried everything we could to get out of uh from victimizing this vessel. And then ultimately, we made a couple of passes with a with an export catheter, got out that clot, which uh somehow came out exactly in the shape of a heart as you can see there. Um And uh and we had a great flow in the vessels and resolution of S. T. Elevations. I think the caveat, of course, is that you have to take extra precautions to avoid relocating that thrombosis into uh another vessel or even worse in the central circulation. Very rarely we pull out laser, but I think this is an underutilized tool for very resistant promise. You can see here in this bench experiment use of a laser at relatively low power settings uh vaporizes resistant rhombus pretty quickly and so more and more often than not. If the initial maneuvers have failed, we're thinking about pulling out a 0.9 fiber, Remember 0.9 and 1.4 will fit in through a A six French guide. If you want a 1.7, you're gonna have to step up to a seven French 7 French system. The last topic I want to talk about in the in the in the remaining couple of minutes is the use of mechanical circulatory support in uh in primary pc. I um hear the currently available uh mechanical search support platforms that are available in the U. S. Market with an estimated acquisition costs in us dollars at the bottom. There are pros and cons of using balloon pumps tandem as an L A F. A circuit via ECMO or direct lbd aortic actually pumping with various impeller devices. There are pros and cons of of all of this, and routine use is probably not appropriate yet in uh in steamy intervention will wait to see what, what the stem E. D. T. Data looks like. There's also big differences between these devices in terms of the estimated level of support and so, you know, balloon pumps, I think we can say has very limited value in stem e intervention. There have been a number of studies both in uh semi patients with shock and without shock, that have failed to show any significant benefit of balloon pumps. However, in beginning shock potentially in non A. C. S. Shock, there may be some value. There may be some value as part of an escalation plan or perhaps using it for venting a ventricle um that's been placed on vino arterial ECMO providing the aortic valve is actually opening. So it's a it's a pretty limited scope for use of balloon pumps, uh, in uh, in stemming intervention, in my opinion. On the other hand, um, in Pella may have some value across a broader uh segment of the spectrum, certainly in beginning shock uh, in steamy patients, classics shock, certainly a standalone therapy. And uh and there's value there as an escalation uh tool as well, uh, in deteriorating shock, maybe value a standalone therapy and certainly for venting somebody on via ECMO, uh impel at 25 is is one of our go to moves and when you are confronted with with this. Uh, you know, before we started, Darsch was talking about a couple of cases that he had to deal with in the recent past that looks, I would imagine something like this. Um you know, this is the BCG that came through across the Life Net app. Um This is you know, kind of when you sprint out the door because you know what's about to hit the cath lab uh and predictably this is what hit the cath lab. Um It's kind of silly to talk about escalation in in this patient. You go on pump, you put in a paella, uh you get to work and uh and you pray a little bit um summary of device selection in these patients I've already sort of highlighted is very limited value of balloon pumps. More value for impel a tandem is useful if you've got a prosthetic aortic valve or some other reason why you can't get across the aortic valve uh in Pella in a number of patients. And I think it will be very intriguing to see what the stem E. D. T. You data looks like in non cardiogenic shock patients with interior stem stem ease. Uh and then finally be a ECMO for the worst of the worst. So the key takeaways from my segment before I turn it back over to my colleagues here in primary Pc. I personally consider using trans radio as your default if you and your lab are comfortable with this approach and set up available data support both thai category or procedural over clopidogrel in high risk asyst stem e patients available data support DS over BMS and steamy. And the newer data with biodegradable polymer D. S. May be associated with improved outcomes, particularly India in the semi cohort as well as a non stemming cohort. Uh complete revascularization trump's culprit only excluding uh cardiogenic shock patients vis a vis the culprit shock data which in the interest of brevity, I didn't cover um RCT data. Don't support the use of routine use of aspiration thrown back to me. But you know, you sort of have to make your own adventure depending on what's happening during your case. And then finally I would encourage everyone on the call to be fastened with M. C. S. And verification strategies in case your stem E. P. C. I turns into something a bit more complex than originally planned. I'll stop there and turn it back over to dr Doshi. Thank you guys for for your attention Sandeep. That was unbelievable. You give a whirlwind tour of everything that it takes about four years the fellowship to learn in about a half an hour. That was terrific. I do have a couple of questions if that's okay with you, Darsch. Um Yeah, you know, first of all, um when you talk about the very first case, you you had a, you started off with a terrible, terrible led uh total occlusion and you had some slow flow at the end of this person had already received lyrics and received an ox appearing and received kangaroo, received um oral uh anti platelet therapy and heparin. What left is there to try to do that? L. A. D. I mean, you've given an um there's a dilator, is a balloon pump ever helpful for flow. Do you go to super saturated oxygen? Um Can you afford to give any more T. P. A down that vessel? What were you thinking? Yeah, that's a great question. Steve. I mean, we were kind of scratching our heads and you know, we have our, you know, our our non dominant hand behind our back with our fingers crossed. Um you know that nothing bad would happen here with so much anti coagulation on board. I think, you know, there are a couple of things I think, you know, you you brought up the issue of SSO to we don't have that in our lab as yet, but I think there is some very interesting and provocative data on the use of SSO to in uh in large anterior stem is um you know, uh longer infusions of glycoprotein inhibitors, maybe. Um you know, we tried pulse spray, a dentist scene and basal dilator is down the vessel. I think at the end of the day we were left with a vessel that was, you know, thrombosis that was symbolized. And then, you know, you've got no re flow right, You've got uh you know, leukocyte adhesion, platelet plugging all of the release of radical oxygen species and free radical injury and so forth. Um I think at that point, and we're not here with the data yet, but you wonder whether unloading the ventricle, if you can't fix the supply, maybe you can decrease the demand and mitigate some of the injury to the ventricle. And so you know, I mentioned it a couple of times. The stem E. D. T. You pilot I think was encouraging enough to go forward with the large scale stem E. D. To trial. Um I think that you know, perhaps unloading the ventricles may benefit certainly in animal models that seems to have yielded benefits. Unfortunately the tri trial with tandem heart uh you know close because of poor enrollment but hopefully that won't be the case as more axial flow pumps start to come to the fore perhaps, you know that's a strategy for somebody like this. And to be very clear. He was never in shock, remarkably. He was never in shock. Uh you know, at any point in this hospital course. Uh, but I turn it back to you guys. What would you do, darcy? What would you do? Yeah, I mean, I think, you know, I would have done the same thing as Sandeep. I mean, it's a fairly young individual and I think that I know it took some delay to get him to where, Uh, he could actually undergo primary PC. I, but I would have done the same thing. I would have done everything I could in this 35 year old to open up his led. Uh, the one thing I may have done differently is instead of using Angio jet, maybe used the number of Qatar X system just because a little bit more familiarity with it. And I think that it emphasizes a little less, at least in my hands. Um, but but that is the only thing that I would have done differently. And even still, the outcome you got was a fantastic results in deep. And despite the fact that there was, You know, you have to put 110 extent. But ultimately he got a final outcome. That was fantastic. I mean, better than anything. I think anyone would have thought having seen that initial angiogram. Thank thank you for that. We have, we have pretty low, pretty low expectations going ahead. It was, it was outstanding. Cindy. But you brought up a couple of other things, you know, using ultrasound access, especially if somebody who's had so much anti coagulation, anti platelet therapy, etcetera on board. If you were going to do balloon pump or sso to therapy, you needed access site safety is really important. Before we move on to Darsch, I have one question for both of you, Sandy, if you presented terrific data on bios to me and you talk about or zero and it's a thinner strut, biodegradable uh stent with a different drug on anything that we have with science. I'd like to know from both of you. Which is it is it the thin strut that makes the difference? The polymer the drug? Is that all of them? What are your feelings? I know it's not a randomization, each individual thing, but you're both trialist. Tell me what you think is causing the difference in outcomes. That's a great question. I I mean, I think it's sort of the intersection of decreased inflammation and uh and decreased vascular injury. Um You know, if you sort of dig around in the pre clinical data, there was some very interesting data that preceded the design of the first generation drug eluting stents with with uh stent struck profiles that went from perfectly rounded and micro polished to aggressively made to be sharp. And there is a direct correlation between vascular injury and internal proliferation in in coronary arteries and and other in the periphery as well. Steve your big purple interventionists and and so you know the more you sort of uh you know torment that vessel. Um you know the more going to pay you back by by way of restenosis later on. And then I think you know preventing doing things uh to deliberately prevent inflammation in that vessel probably bears dividends as well. Dark. Do you do you agree with that? Yeah. I mean I think in my mind I think that the things uh nature is probably not what is responsible. I think it's actually the coding. So there's both a passive coding and active coding when it comes to the A. Zero. So the passive coding is the pro bio that they have a proprietary technology. Then there's an active coding which is the P. L. A. And so based on pre clinical data it has a lower inflammatory response. So I think that is probably I would expect the cause of why you know the tlf rates were lower Um with a zero compared designs. But it's it's impressive though. I mean you know that analysis was done um You know there's a primary analysis with the initial bio semi population. Then there was a basin analysis that included um uh patient from another trial and whether you included those patients were not the outcomes were similar and sort of held up. So again I think it goes to what Sandy brought up the fact that you know a lot of people think that we've matched up and what we can do with our stands. And clearly that's not the case, that there is an iterative aspect where we can continue to improve outcomes with our state designs. I agree. You know, we can go on and on with questions. Your your presentation is so good, Sandy. But there is a common in the in the chat about what do you believe is a better choice? I I know you stratified this by oral to be three uh, oral anti platelet therapy. But Do you see better outcomes with tire five enter Kangol? I know there's no head at trials, but what do you how do you use these drugs and which one do you choose? You know, they're they're they're very different drugs obviously and um uh, you know, the the interesting thing about glycoprotein inhibitors and you know, as I, as I sort of chat with the current generation of house staff, most of them have kind of lost touch with like a protein inhibitors. But um you know, the interesting thing about glycoprotein inhibitors unlike tangle or is that appropriately dosed? And there's a big asterisks next to that because the appropriate dose and kind of varies from uh depending on who you ask. Um but appropriately dosed all of the glycoprotein inhibitors have six map off the market now, empty fiber tight on the market and terrified and the world leader just not in the United States um have the unique ability to disaggregate aggregated platelets, meaning the affinity for the glycoprotein receptor is actually higher for any of these agents than it is for the two native binding configurations for fibrinogen. So the the binding coefficients for fiber engine both of them are weaker than uh than the binding coefficient for for these agents. So it is possible at least theoretically to disaggregate the rhombus with like a protein inhibitor, something that has not really been demonstrated on the bench with CANDLER and hasn't been studied clinically. I think the practical thought here is bleeding tolerance. Uh you know, with the tire five and or empty fiber type, you've got a 2 to 2.5 hour half life. And so if you put your foot into a trap in terms of bleeding, you're gonna be treading water for just a little while. On the other hand, can galore has, you know, a biological half life measured in minutes. Um and so if you do incur some bleeding, you can backpedal pretty quickly. Uh I just wanted to ask another question. Um do you guys stand if I know where you stand on this, but just in the conversation regarding federal versus radio access for steamy. So the majority of data that you know is in favor of radio access comes from to potentially three trials. So rival is one of them. Rifle S. T elevation CS is another. But those trials were done in 2015 or earlier. The most recent trial was the Safari steamy trial, which was published last year and it actually showed there was no difference in mortality or outcomes if you underwent ephemeral versus radio access. And the thought was that potentially now with federal, what we're doing is we're using ultrasound more. We're using micro puncture access and maybe that may obviate some of the differences that you have with the radio. So I know sanity is a strong component. What about you steve, what are your thoughts on this? Um you're absolutely right on your interpretation of the data. So now we now we just come back to our own personal experience. I think there is no question that you should go radio. I absolutely believe they're bleeding risks are mitigated and it does give me more freedom of what anti platelet therapy to to use. And I am a total believer that even though we can't show it in clinical trial data, I know for a fact that we have a whole lot less bleeding in our lab going from radio access. I mean, I would agree. I mean, for me, I think if you're faster with radio access and Radio Pc, I um like Sandeep is, I mean, I think for me it's a no brainer, you're able to do what you need to do and then afterwards you really don't have to worry about a bleeding complications. So even if I use a two B three inhibitor during the procedure, I can go home feel comfortable that, you know, there isn't gonna be a big human toma or a a large belief that I need to deal with afterwards. So I I agree. I mean, despite what the data shows, I'm a radio first sort of guy. Also for some awesome, you know, dark, we should probably move on to you. I mean, these are fascinating topics. We're gonna give you enough time to present your ideas too. And thanks again. Sandy Pure asked them. So I'm, my presentation dovetails nicely from Sandy presentation. So he dealt with stem me. I'm going to be talking about n steamy and unstable angina as the tree odd for acute coronary syndromes, these are disclosures. So I'm going to jump off with a case. This is a case of a 64 year old male with hypertension, Hyperloop academia presented with two days of intermittent chest discomfort. Um now he had 304 minute episodes of chest tightness that sort of built up and then sort of dropped off At one point it was eight out of 10 intensity along with somebody apheresis and it occurred with minimal exertion. Um and uh sort of a baited with rest. Um He has no significant past medical history to really discuss um and no smoking history or family history of C. A. D. Uh But due to the waxing and waning nature of his symptoms, he bought himself to the E. D. Be evaluated where he was slightly hypertensive. His physical example is unremarkable. With the exception of mild apheresis, his labs were unremarkable. His troponin Most notably was Negant Times two. Mhm. So this is his electrocardiogram and I think the only thing to really point out on the electrocardiogram is he has some T wave inversions um in the inferior elites. But apart from that nothing that really jumps out at us. So you know acute coronary syndromes. Obviously this is not necessary elevation at my it is a a non S. T. Elevation, A. C. S. Uh picture. And given the fact that the biomarkers are negative, this falls under unstable angina. So should we cap this patient or not? And you know there's some controversy that exists and obviously medicine is an art, there are many ways to sort of skin this cut. But would you take this person to the cath lab? So there are obvious advantages to invasive therapy. The first is the rapid and definitive nature of the evaluation. You know whether or not they actually have coronary blockage that could potentially be causing the symptoms and then you can also treat it. Um And then on top of that you, instead of going through additional work up, you can also facilitate their discharged worker. Now the other way to sort of approach this is to sort of wait and then undergoing ischemia guided strategy. And the strategy which you would do is you would basically stabilize with medical therapy and then re stratify with some form of non invasive testing based on symptons ecology, and then make a determination based on the stress tests whether or not to bring the patient to the cath lab. Now, what I want to talk about is some data regarding the use of early invasive versus ischemia guided strategy. So here is a meta analysis that was published in Jama and this basically shows a routine invasive strategy, exceeded a selective invasive strategy and reducing my severe angina and rehospitalization over the course of approximately 17 months or so. But routine intervention was associated with a higher earlier mortality and then a trend towards mortality reduction at follow up. And so again, this sort of argues that potentially there's a benefit for early invasive. Now another trial that is where I was talking about is the T max study. So the study randomized approximately 3000 patients with acute coronary syndrome to undergo either routine early intervention or delayed intervention and routine here. Early intervention was angiography within 24 hours uh randomization and the primary outcome was a composite of death, myocardial infarction and stroke at six months. There was a pre specified secondary outcome of death, myocardial infarction or refracting engine and six months. Um and what they found out that early intervention did not differ greatly from delayed intervention Okay. In preventing the primary outcome, but it did reduce the rate of the composite secondary outcome. Moreover, when you risk stratified patients according to their grace course to the GRE score is a global registry of acute coronary events and we'll touch upon what constitutes that you found out that in patients that had a great score that was higher than 140, that they actually benefited from an early intervention strategy, as opposed to a delayed intervention strategy. When the great score was low, there really wasn't a big difference. So how is the Great Score calculated? I think a lot of us know this, but just to remind us the great Score basically has eight different factors. It looks at their killer class, their blood pressure, their heart rate, their age, their granny level. And then whether or not there's a cardiac arrest and admission SD segment deviation or elevated biomarkers. Now, the grey score basically predicts six-month mortality in a log arrhythmic fashion, and the cut point really is around 140 points where the risk starts to go up fairly exponentially. Um So the other way to sort of re stratify. So the great score isn't, the only score is the timmy score. So the timmy score has seven different factors to look at and listed here and then it's in low intermediate and high groups. And based on that again, um you know, high to potentially intermediate patients, you're going to favor an early invasive strategy. There are other scores that are out there. The heart score is a different score that some workers, some investigators here at MGH have also developed, but either way, despite the scores that you use for the most part, the patient is in the lower risk score. So as a result we're going to do is not take them to the Cath lab. And most likely we're going to do some sort of investigation. And uh with an ischemia work up. So this patient underwent an exercise act. And what it did show, however, was a large area of ischemia in the inferior and inferior septum. Um, and so as a result of the degree of ischemia, the thought was to bring this patient to the Cath lab. Now, these are diagnostic images of the left coronary system. I think what you can appreciate is that they're, you know, there's my aluminum regularities on the left system, but you clearly see some collateral ization to the right sort of foreshadowing what we're going to see on the other side, your original projections. And then this is the right coronary. And clearly there seems to be a lesion that probably is the cause of the patient's symptom a tautology. So, given the stress test, along with the symptom ontology, we opted to perform Pc. I. And so this was fairly straightforward. We pre dilated with a to five balloon put in a 25 or zero that we post related to three. Um Ivy's showed great expansion opposition. Um a post procedural echo show that the EF was preserved no issues. He was discharged on all the appropriate medications. Um One of the things that Sandy and I really didn't spend a lot of time on was specifically on pharmacology as it pertains to a CS, there's actually a dedicated lecture as part of the bio murder series that's going to focus more on that. So we're not going to touch upon it extensively here. Now in comparison to that presentation, I want to present another case. So this is an 87 year old woman who presented to the E. D. With chest pain. She had bilateral arm pain for approximately week and then over the past day the pain now radiated to her back. When she arrived in the E. D. She was also on volume overload her proponents. This time instead of the troponin T. This was a high sensitivity. Troponin trended up from 1 63 to 3 35 and then um and then went down to 29. Her anti pro BMP was elevated over 5000. Her creatinine was also elevated at 1.5 with some chronic anemia with the hematocrit of 29.6. Her medication, her past medical history is notable for the fact that she is a diabetic. She is elderly and lives alone and is connected with elder services but really has limited social support. This is your E. K. G. And again not much going on, but there are T wave inversions and the lateral leads. So she underwent an echo in the emergency room where her ventricular function was found to be normal. But in addition to her exam, which demonstrated a murmur, she was found to have moderate Michaels michael stenosis with a mean of about 11 to 12 millimeters mercury into mild M. R. It would example, sticking without stenosis. And so on the basis of the fact that she had chest pain, that worse inequality, even the fact that she's elderly. When you calculate her grace score, it's definitively higher than 1 40. And so she was taken to the Cath Lab and as part of her heart failure syndrome as well as her shortness of breath. In addition to her chest pain, she underwent a right hard cast and write her cat. Her filling pressures are found to be elevated cardiac index was too, She was found to have a mean gradient of eight with a mitral valve area of one. And so this is some of the diagnosed diagnostic angiography in which you can sort of see is that the patient clearly has a lesion in the circle flex territory and the proximal portion maybe also has something in the L. M. Not as critical has led disease and diagonal disease and has collaterals to the right. And so this is a diagnostic angiography of the right and that shows that there's an osteopath stenosis as well as a total inclusion of the mid right coronary with bridging and so on the basis of this, what would one do? So we know from the freedom trial that in patients that are diabetic that have multi vessel disease, it's definitively in favor of uh of cabbage compared to PC. I. So the primary outcome of this trial was death. Myocardial infarction and stroke. And when you look at death from any cause, it was in favor of cabbage. If you looked at myocardial infarction was also in favor of cabbage. But the only thing that was in favor of PC. I. With stroke. So for patients that are diabetic based on this trial, which is the seminal trial, you would assume that the way to treat this would be potentially cabbage. Now it's interesting despite the fact that we have compelling data when you look at a pool analysis of individual patient level data. So this is a randomized Um this was a compilation of 11 randomized trials with over 11,500 patients. And yes it was in favor of cabbage compared to PC. I. For a cumulative mortality. But the interesting part is if you want a diabetic, so this shows if you are a diabetic then there was a difference. If you weren't a diabetic, then there was no difference. Regardless of what your syntax support was. The other difference was if you had left main disease, if you have left main disease, there was actually no difference in cumulative mortality. If you under one Pc. I. Vs. Cabbage. But if you had multi vessel disease, there was a difference. And this is regardless of whether or not you are a diabetic. So this is the data right now point to the fact this is a diabetic patient with multi vessel disease and would probably benefit from cabbage. So in this patient you would assume the cabbage would be the right way to take care of. So we got a cardiac surgery console. She was more limited by angina and ischemia. But given the fact that she came in with heart failure, given the fact that she's elderly, given the fact that she has renal dysfunction, given the fact that she has concomitant valve disease, her SCS mortality was thought to be very high and the risk of needing hemodialysis post procedure was thought to be high. So they actually asked us to conceal palliative care and then consider PC. I. Leaving the modules analysis unaddressed. And so she got a palliative care console and they agreed that surgery would not be consistent but would likely be a minimal to PC. I. So that's what we did. We did a compassionate PC. I of her led answer complex. And so the way we did this again for the interest of time is that we did pre dilatation um with a 2.5 millimeter balloon. Um the lesion didn't expand as well as we had thought. Probably because one of the three causes of an acute coronary syndrome is either uh plaque, rupture plaque erosion or calcification module. And this is probably more of a catastrophic nodule. And so despite that we actually had to use a threat to me. Um And then after that we stinted the circle flex and then went on to the lady. But the interesting part is when we were done or at least we were thought we were done. We saw some haziness specifically in the area of where we had to intervene on the circum flex. So one of the things to note was that this patient actually check the A. C. T. It was 2 58. We did not pre load this patient. And so we had her on Heparin. Um And that was the only thing that was given. And the plan was to put her on cacador afterwards. But in preventing the initiation of the thai cac. She developed some thrombosis and so she started an I. V. Candle. Or we then did additional work we ballooned again. Um And then we put a second nurse here stand and ultimately either showed resolution of the tissue protrusion and throw on this. And so this was the final result that took place. Now there's another case. But I think for the interest of time I think we'll just stop here so that we can stop for case discussion. It's a dark terrific cases. Those are challenging cases I have to admit. Um I'm taken aback by the accumulation of data that you got before doing both cases. For instance the first case you went ahead with the with the nuclear study. I think a lot of places would not have done that. The second case really brought out the hard team approach and share decision making with the patient and I have to applaud you for doing that on both cases. Is that fairly routine at your institution? Yeah. So one of the things that I think in this post covid world is the way that we can now interface via telemedicine. So for our heart teams we have a day of heart team whenever we want essentially. Um there's an email that is sent out to our surgeons as well as for interventionists and whoever is available joints. And typically we have at least four or five of the surgeons joined in at least four or five of our interventionist joint. There's a form that we have filled out. So for the hard team meeting where the fellow will have it filled out and threw it when we go and not only have their sts score, we have their syntax one score their syntax to score, um and then any sort of adjunctive imaging modality or cardiac modalities that were utilized. And then we have a conversation based on what we believe is the best course of action. So um it used to be rare. We used to have a pre scheduled once a week and now in this post covid world um with telemedicine, it becomes markedly easier. So we'll just get on a zoom call just like this um and then um and then talk things through for the first patient, the patient, you know, again the proponents weren't elevated um wasn't an extremist. So we took our time. And so that's why there was time to do that with the second patient, she was elderly. And obviously the decision must move quickly. So everything that we did essentially from, you know, working her up to the echo and bring her to the Cath lab was under essentially done under a day. And so the decision was made fairly quickly. Um From the time she went to the Cath lab to went to bring her back for intervention. In the second case when you showed the hazy appearance of the stunt was that you just wish you to high risk to get oral plant uh anti platelet therapy ahead of time or we should, you know just that. I mean it wasn't uh you know again I think that uh based on the appearance, I thought there was a catastrophic nodule and so I thought that the likelihood of it really proceeding to you know the amount of strong backbone that we ultimately saw was low and so I didn't pre loader. Um Now routinely for most of my aunts demis. Um And my A. C. S. Is I'll just use can galore. And the reason for candle or is you know as Sandy polluted too. So one is very potent to there's a quick on and off and three if you want to bring the patient to uh surgery or kick a bitch it gives you that optionality as well without having to wait for it to wash out. And so you know in retrospect I do wish I preloaded and if I did it probably would have been cancelled. Yeah. You know um Sandeep talked earlier today about the complete trial and when you when you have patients that are coming to the lab that are acute and um that may be the time we revascularization isn't quite as important when you do it whether it's at the same time later what's what's your style of practice or complete? And then I'd like to do it. Sandy routinely does also. Yeah. So for for my patients I think one obviously you're going to take care of the culprit lesion. But then if there are lesions that you know are intermediate, I'll do some sort of physiologic assessment on the table. So let's just say there's an L. A. D. Stemming. But then you also see a stark search stenosis. I'll do my frd fr or some some other resting index. Um And then that will allow me to know whether or not to come back to take care of it. I usually only do the main lesion and then try to get the patient off the table. Um Sometimes you'll see that patients will develop stent thrombosis and if they develop san thrombosis of the culprit there then going to potentially become hypertensive and then also have stent thrombosis of the non culprit. And so for me, I think you need to really demonstrate that are stenting procedure went while you were able to tolerate it. And so I'll usually do it a few days out. Um I think for me I think if I can take care of all the lesions before the patient goes home, I think I can rest a little bit more comfortably um knowing that there really won't be any sort of chance of any ace guests in the future while we're waiting for the repeat re intervention. But that's not born out of data. That's just out of my personal uh practice patterns, Sandy. But what about you? Yeah, no, I I agree with that. I mean, I think really it goes to how well the patient is tolerating it, you know, one topic that we didn't touch upon which I think is critical across the spectrum of, you know, procedures that we do is avoidance of contrast the property. Now, you know, there is a growing contingent that has cast some dispersion on whether contrast is really the bad actor, but I think, you know, in 2021 we have to, you know, still be mindful of how much contrast we're using and how that relates to contrast the property. Um One of the big take homes from from culprit shock was that, you know, uh renal, the need for renal replacement therapy after attempting multi vessel revascularization. Somebody who's already limping along human dynamically, you know, that's that's a big deal. And so I think there's a there's a lot more variables in the mix. Um I think if there is real doubt as to what is the culprit lesion if you have an infra lateral semi and you see, you know, an angry looking lesion in the search complex in addition to uh something in the R. C. A. You're you're sort of bound to fix both of them and then deal with the rest later for stuff that is sort of clear cut non culprit, good flow. Not no uh no high risk features. Those are lesions that I try to get done before we send the patient home. If there's some compelling personal or medical reason why they need to wait. Uh I'm okay with that. But it does become a little bit of a challenge to real those patients back in. You know they've had enough of the hospital for a little while and then you know there there is sort of this this tendency to kind of kick the can down the road a little bit and and delay it. So um I think I'm, my practice is similar to your star shy. I you know, I try to get this all done before they leave. And a technical question when you're using or cyril, whether it's in a steamy or an elective case and you have to go back and pre dilate or posted. Sorry, when you post dilates. Once in a while, there are some stencils you have a little bit of trouble re crossing, You worry about according to stents. Any issues with a thinner strata. Zero stone. I I personally have not had any issues with it. I think that if you run roughshod over any thin struck stent and you know, remember, you know, for many of the early career practitioners that are on the call, they don't remember how bulky a cipher was. Uh, you know, kind of like driving golf club down a vessel. Um, uh, you know, for anythin struck stent, longitudinal compression or deformation is a very real issue. The stent is under deployed to begin with. You're going to have problems irrespective of whether it's a a 60 microns strut or an 81 microns strut. So I personally have not had any issues that are unique to or zero. How about you guys? Yeah, I would agree. I mean, I think, you know, you pointed out the limitations of a thin stranded stent, right? I think it helps markedly with deliver ability. So particularly trying to go through distal vessels or through tortuous vessels. I think it does a fantastic job. Obviously the bios Demi data is fairly compelling and then also the date of the five years at the long term data from bio flow five also shows great outcomes as it pertains to tlf. Um, but like you said, anything straight extent is going to have a potential longitudinal deformation if you are not careful. So obviously you want to make sure that you're meticulous with your technique. But again I I really haven't had it. Um It is exceptionally rare and when it has happened it's because I or the fellow have been really running uh stent ragged and so it's exceptionally rare for that to happen. And then just to clean up the chat you know um you did talk about bringing an elective or a non stemming to the cath lab both of you. And um does everybody get, and I played with oral anti platelet therapy is loading ahead of time? Or are there some instances that you have consideration that maybe they need they may need surgeon. We're going to withhold the oral anti platelet therapy. Who do you load who do you not load dark? You know? Just go ahead. Yeah. Well I was just gonna say for us I mean and I think all our A. C. S. I think we've moved away from pre loading I think for the most part we use candle or um and you can and again the onset is fairly quick to be offset is also fairly quick. So I think that's a medication that has sort of changed the paradigm. Previously. We would pre load people and we would pre load them with thai cag across the grill. You know based on the way it was prescribed in triton. Um You basically had to you had to load after the anatomy was delineated. Um So you know we would use tai kok previously but now we have basically the I. V. Version of titanic which is quicker on set with candle or so that's what we use. Well you know I'm glad you said that because we're going to disagree on this, it wouldn't be it wouldn't be fun if we didn't disappear in a couple of points. So uh you know, we um you know, there's a science and then there's the practice, right? And so I think we're calibrated on the use of calla kangaroo laura and and all of the value that that brings. But you know, six or seven years ago we protocol ized the use of upfront anti platelet therapy. This is something that's been challenged in the europe recent european Society of Cardiology guideline update uh in terms of pre loading. And it was really just a practical thing because we would many times get all the way through the case. And the oral anti platelet therapy had never been given. Now the patient is sedated. Now, they're on their back, you're waiting for them to wake up and we, you know, at that time, in agreement with most of the published guidelines, we said, look, we're just gonna protocol is this and we're gonna put some boundaries in terms of who receives taika galore versus who receives Prasugrel, Excuse me. A clopidogrel. Clopidogrel is sort of the drug of exclusion at our institution and the vast majority of our A. CS and stemming patients, if they can tolerate morals, are getting taika galore upfront. Sometimes we end up shooting ourselves in the foot and having to, you know, having to wait and uh you know, undo what we just did before they go to surgery. But the I would say the majority of the patients that are institution uh come preloaded and really more in deference to just practical considerations of avoiding stent, thrombosis and ensuring that it's at least, you know, somewhere in their gi tract before we we go up with a balloon. Great comments, how we doing on time. Yeah, I think we've come to the end of our time here. So, you know, I just wanted to maybe pause and ask for some final comments. So Sandy, uh when we start with you first for any sort of final comments for our audience and then we'll follow with steve. Well, this was a great session. Thank you for having me and I learned a lot just listening to to both of you guys. Um you know, I think that um there is a lot of new data in all of the different areas, uh, infarct angioplasty, a CS care, um many of those areas I think we've sort of come to take for granted. Um I sort of alluded to uh you know, the commoditized stent market and use of anti platelet therapy. You know, there's a there's a lot left for for us to learn and I think that we can potentially improve outcomes for patients that were sort of beholden to best practices and uh and new data. So, you know, thank you both for your comments and for educating me. Um dark, thanks for having me tonight. I you know, I love listening to both of you guys and I think this really points out the fact that this this field, we just continue to evolve and learn continuously. And this is a great example of it. You know, there's lots of tips and tricks on how to do coronary intervention that are brought out tonight by both of you that are so important and it shows that we all have little differences in style of practice. And I know that my practice has been changed by the little nuances that you both have said tonight, that you probably didn't even think twice about that. So I'm looking forward to the rest of the bio emerged series as you give us more tips and tricks on technique, drugs, differences between stones. This is a great series, Darsch. All right, Thank you so much, guys. It's hard for me to follow both of you and say anything more substantial of. So I'm not gonna try. Uh, I do want to thank our sponsor bio tronic for supporting us today. Um, this content will be available on demand uh through the by emerged website. Um, we'll have the next installation of bio merge within a month. Um, and we look forward to all of you joining us. Well, thank you so much and have a great night. Yeah.