In this Cardiovascular Medicine webinar, Reperfusion therapy for ST-elevated myocardial infarction (STEMI): A case for the pharmacoinvasive approach even in the USA, Mayo Clinic cardiology experts
Bernard J. Gersh, M.B., Ch.B., D.Phil., and Mandeep Singh, M.D., focus on the impact of early reperfusion on infarct size and outcomes with an emphasis on a systems approach in communities that do not have a percutaneous coronary intervention (PCI)-capable catheterization laboratory and consequently rely on rapid transport to a referral hospital with the requisite facilities. The advantages and disadvantages of thrombolysis followed by transport (the "drip and ship" or pharmacoinvasive approach) are discussed, as are barriers to optimizing this therapeutic strategy.
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Mayo Clinic Medical Professionals — Cardiovascular Diseases. Good morning everyone and welcome to the webcast on a Q corner syndrome. My name is Mandy passing and I'm the professor and director of acute coronary syndrome for me a foundation and on behalf of the cardiovascular department at Mayo Clinic. It is my distinct honor and privilege to welcome and Professor Bernard Gersh who is uh my teacher and mentor. Um and we are so lucky to have him. He um just to give him give the audience a brief introduction about him. He's a professor at our department of Cardiovascular diseases. Um He received his doctorate from philosophy from Oxford University where he was the Rhodes scholar as well. He has authored co authored more than 1200 publications. He sits on the editorial board of more than 27 journals. He has been nominated teacher of the year multiple times, has visited almost every country in the world as a visiting professor. He has received a distinguished achievement awards both from American College American Heart Association, from University of London. Uh He has been the most cited author From 2000 to 2 2012 And most recently in 2020 and has received a distinguished scientist awards and I don't think he needs more introduction. So we are so lucky to have him and I welcome him and he's going to speak on re perfusion therapy and stem e case he's going to make for far Mayko invasive approach even in the USA Professor Gosh, welcome. Thank you very much indeed. It's a great pleasure to be here and two be part of this webinar. Today, I'm going to talk about restitution therapy for stem E. That really make the case for the pharma co invasive approach. Even in the United States, there's no question that in many parts of the world the pharma co invasive approach is the only realistic option. But I really want to point out that that applies to the US as well. So the learning objectives are to emphasize the relationship between time and muscle in terms of re perfusion therapy. To identify the rationale and the pitfalls of a systems approach to re perfusion therapy in the community and to identify situations in which a pharmacologic invasive approach may be superior. Two primary pc. I think we all agree that primary P. C. I. Has the bear stop, but it may not be that may not apply to every part of the country or other countries. Uh And um in a community setting, I want to talk about where the role is of primary PC. I versus the farmer co invasive approach. Now, when we talk about time is muscle. We go back to the classic Experiments of Reimer in Jennings 1979. Really heralded the reaper fusion era and what they showed in dogs with coronary occlusion is progression of necrosis with time. Uh 40 minutes after occlusion, 64% of the ischemic myocardial is viable. The gray here reflects democratic transmittal in function and the red and honor scheme. After three hours of inclusion. You can see that the wave front of necrosis has expanded And now only 11 of the ischemic marco diem is viable and after 96 hours, Only 9% of the ischemic myocardial as well. So this really provided the rational and the impetus for the re profusion era. With the understanding that if you could open an art art an artery and restore blood flow within a certain time window, you could salvage my accordion. Well, it's important to realize that there are marked species differences uh in in this relationship. And I ask you the question here, why does the guinea pig when the rat race of life compared to the domestic pig? Well, the guinea pig has a very, very extensive collateral circulation and the domestic pig has a very poor collateral circulation and humans probably in terms of collaterals. As a species, we tend to be closer to the domestic pig than to the guinea pig, which means that the window of opportunity is much narrower than in many other experimental animal species. Now, the impact of time delays after primary pc was a recently shown in this very comprehensive and nice study from Redford Redford and dr Greg Stone Published in circulation intervention 2021, 3000 patients from 10 randomized trials and in fact size was looked at by suspect in three studies and Seymour in seven studies and in fact size was measured within a month of the timing of the initial in front. They stratified patients according to the symptoms to balloon time Short, less than two hours intermediate 2-4 hours and long greater than four hours. And my daughter balloon time, which door being presentation too. The hospital with a catholic Short, less than 45 minutes. Intermediate 45-90 minutes and long, greater than 90 minutes. And if you look at infarct size stratified by short balloon time, symptoms to balloon time and door to balloon time, what you can see if you just focus here on long. You see that people with a long presentation time had a much larger influx on it. And really what I want to emphasize with this slide is probably the period where we can modify time delay is the greatest is from the presentation from the onset of symptoms to seeking care in the hospital. That's the period that accounts for the longest period of delay and it's probably the most amenable two measures to shorten that period. If you look at microvascular obstruction again, those with a long symptom to balloon time and a much greater degree of microvascular obstruction. Symptom to balloon time carries greater weight than daughter bill in time and then ejection fraction here, those with a long symptom to balloon time, had a marked reduction in ejection fraction or significant reduction and also those with a long door to balloon time had a lower rejection fraction. Now the relationship in turn between infarct size and mortality is shown here. Another study from Dr Stone's Group 10 trials, 2400 patients. MRI in fox size assessment In 72% inspect in 28%. And if you look at the core titles of infarct size, the yellow being one to less than 8% and blue being greater than 29.8%. You can see a very striking effect on mortality within the first year ranging from almost 9% Down to 1.2%. So really this again is the rationale for re perfusion therapy that if you can salvage Marcotti um and reduce infarct size, you will have a major impact on mortality. Now this is a study that's impressed And there's a rather sad story attached to it in that it's a prospective registry of 55 interventional centers in mainly in europe and the UK. Of patients with COVID-19 positive or high index of clinical suspicion who presented with an acute colony syndrome. Now, the individual who put this registry together was Tony gersh lit from the United Kingdom. And sadly he died of Covid. Uh He was one of the real pioneers of interventional cardiology in the United Kingdom and I was fortunate to be able to work with him on this registry. And again, somewhat sadly the last time we spoke was in regard to this paper that we were submitting to Jack. And this paper really emphasizes time is muscle. I want you to look at the stem E sub group 145 patients. Pre covid uh The pre covid data came from two large UK databases That were established in the year before COVID-19. If you look at symptom to admission time, it was previously About 179 minutes. About three hours during covid. It went out to over five hours. People were scared to come to the hospital. They were nervous about coming to the hospital door to balloon time. Very short in the year before COVID 37 minutes now doubles. And what impact did that have on mortality and the development of cardiogenic shock. And these results are quite shocking really in hospital mortality totally was about 5% in the year before Went up to 23% with steamy cardiogenic shock. Uh more than doubled from 8.7% to 20%. So this is really um, you know, time is muscled on steroids, so to speak. Uh really striking in a tragic example of what delays can do and affect how they can affect outcome. No, I don't care if we, we know what to do. We know primary pc is the best form of therapy and I don't think there's any argument about that but there are a number of constraints. It may impact the efficacy or primary pc. Geography, distance, whether Mode of presentation, whether it's 911 or hospital coordination of services. Both at an institutional level and a regional level and the allocation and availability of resources. So we know what to do. The question is, how well can we deliver? Okay, this is a Homestead County Mayo clinic is here in southeast Minnesota, we don't have traffic is in, you've got 232 helicopters in the field, one based at Samaria Hospital in rock and Rochester. But what we do have is with it and this is a winter storm and this is a storm in the summer. And when you start seeing red and orange, this means a tornado watch and if you, I don't know exactly what it was last year. But uh most years, uh the helicopter and air transport is grounded For about 40 to 50 days of the year for at least part of the day. So you need to have a system that it can account for that and when you have these delays, that's when you need alternatives to primary PC. I Now this is from a paper that are published in Jama In 2005 and this is a hypothetical construct of the relationship between mortality reduction and extent of salvage and the other authors were my colleague David Holmes Dr Greg stone and dr hardy White in from new Zealand has played a big role in the re perfusion era and what this slide shows is on this axis is the duration of the ski mia. Prior to re perfusion on this axis. Black line, thick black line is the mortality reduction in percent. Everything under this black line reflects the extent of salvage as a percentage of the area at risk. And this is the impact of treatment delay. And what one can see highlighted here is early on in the 1st 1 to 3 hours time to treatment is critical time is muscle thereafter. Um When you get out onto the flat part of the curve, it really doesn't matter whether you open the artery here. We're here. Well we're here. Oh yeah. What is important is that you open the artery and the infarct related artery and in this part of the curb PC will always be more effective than from politics. But here is the window of opportunity and the question and the entire rationale of the pharma co invasive therapy is this if you have a patient that presents to a community hospital without a catholic after 50 minutes of symptoms and it's going to take you an hour transport that patient to an institution with a catholic and you're on this part of the curve. How much delay is acceptable to get the better therapy which is primary PC. I as opposed to getting analytics and transferring the patient for primary pcR. And that's the key question. And then there are all these modifying factors. I mean this is this was a hypothetical construct. But in fact the subsequent data produced by stone and others really showed that by and large we got it right but modifying factors collaterals. Ischemic preconditioning. Myocardial oxygen demands stuttering in function. And what I believe will be an absolute key in the next 5 to 10 years is understanding the impact of microvascular dysfunction. So re perfusion strategies to semi. What are shown here is a diagram from the guidelines One Steamy published 2017. U. S. A. A. C. Ch A guidelines are very similar. It's just that the most recent are the EC guidelines and they look at total ischemic time shown on this axis, patient delay. E. M. S delay and system delay. Uh And the first two scenarios are patients who are are transported by emergency medical systems services and patients who first medical contact is at a non PC. I. Center. So this supply is really to community approaches inpatient in patients presenting to a center that may not have a cath lab or alternatively who were transported by ambulance. And really they divide the system delay. That time delay is uh into two Time to P. Ci less than 120 minutes Time to PC greater than 120 minutes. Now if in fact you can transport a patient Within 120 minutes. That's 2 1st 1st two primary pc. I if you can do it within 100 and 20 minutes. In primary Pc I. Is the preferred strategy but they categorically state. If the whole process is going to take longer than two hours, then you need a fiber analytic strategy followed by transfer. On the other hand, if you have a patient who comes to a PC center, Then the only strategy that really you can justify is primary PC. But it needs to be done within 19 minutes. one of the areas of greatest delay is impatient presentation and in transport time. But the ec guidelines I think really lay down very clearly that if delays are greater than 120 minutes, you should be using fiber analytics, all things being equal. And by that I mean it depends on the risk of bleeding. And this is a study from the United States and illustrates driving times and distances to us hospitals with primary PC facilities. And what you can see. Um That in most of the country, The pre hospital time period to PC. Eye Hospital is less than 60 minutes shown in blue. And if you look at our metropolitan centers on the West coast and the East coast florida up here in near Seattle Chicago. Large metropolitan centers, there's no shortage of cath labs looking for business and it Pre hospital time period is less than 60 minutes. But look at other parts of the country. The Rocky mountain marriage parts of the midwest Where the pre hospital time period to PC hospital is greater than 60 minutes and 79% of um 79% Of patients live within 79 minutes, 79% of patients live within um 60 minutes of APC. I hospital. But let me turn it around 21% don't. And driving times from a non PC I two P Ci hospital or less than 30 minutes and 74% of patients, but not for 26%. So we need a system. Again, I emphasize, we all agree that primary PC if performed expeditiously is the best form of treatment. But we need, we need to account for this 2530% of patients where they cannot get to PC eye hospital in uh expeditiously in an appropriate time. You need re perfusion networks. And this in both guidelines is across one indication set up a network. The network needs to have clear, clearly understood and articulated goals based on evidence. And the objective is not to compete for patients. The objective is to enhance the speed and delivery of re perfusion therapy to all eligible patients in the community. It has to adjust to local conditions. Everybody needs to buy in, everybody involved needs to understand their role and buy into it. It needs to be simple to follow And it needs to function seven days a week, 24 hours a day. It needs to be continuously audited to monitor your performance and adapt to new knowledge and this is what we've done at Mayo. We have a network that covers 150 miles a network of hospitals within a 150 miles circumference and we stratified our patients according to the duration of symptoms. If their symptoms are relatively short and we can achieve Primary PC within 120 minutes, that's one pathway. If their symptoms are greater than two hours and we we will not achieve primary PC. I've and then within that time they have a different pathway ah in this group that um have a duration of symptoms relatively short and need to be transferred. I want to point out here again, this is in community hospital. If they come to ST mary's hospital in Rochester, they all get primary PC. But this is how we deal with patients who need to be transferred relatively short duration of symptoms, fiber analytics and then they transferred preferably by helicopter, depends on the weather and they will have a routine angiogram after about three hours after the onset of symptoms. That's the farmer co invasive strategy. If on admission to the PC. I. Capable hospital, they have persistent symptoms, about 30% of them will go to rescue P. C. I. If they have a long duration of symptoms and they're on the flat part of the curve. A Big one. And the number of clinical trials that at one stage advocated watchful waiting. But we don't do that in. They all go to a routine angiogram. Now, if they're on the flat part of the curtain Greater than 120 minutes now time is not of the essence. And what we do is transport them the best way we can and they will undergo routine angiography and PC. I after admission. Do we facilitate with fiber analytics in this case? No. This was a concept that was that uh proposed 5 to 10 years ago that all patients would have fiber analytics on route and we don't do that. Now the risk outweighs the benefit. We save the farm. Ako invasive approach for those patients with a relatively short duration of symptoms. And in those on the flat part of the curve, we believe that simply getting them to cath lab and not exposing them to the risk of bleeding with fiber analytics is preferable. So what are the results? This was from my colleague dr scientists published a few years ago, 1700 patients at that time related period. If you look at all cause 30 day mortality and all cause overall mortality. Actually the primary PC. I group have a higher mortality than the farmer Coene basis. But remember this is not a trial, this is these groups are different. So when we did a Multivariate analysis we actually show that the hazard ratio is not significantly different between the two groups. But what is reassuring about this is that the pharma co invasive strategy which is employed in a minority you can't who have short duration of symptoms but need to be transferred for for primary PC. I in that group. That minority of patients, what our data show is that the farmer co invasive strategy is not inferior and I think that that's encouraging this again is from dr gersh slick. And this is from the stream trial of the farmer co invasive strategy. And these are data on 30 day death, heart failure in shock. What you see, I beg your pardon? What you see is in patients who present early. If the PC related delay, in other words, if the delay involved in taking the patient to PC capable hospital, If the delay is less than 30, 40 50 minutes, primary PCI is does better. But when you look at the patients where the delay in transporting them Maybe 120 minutes or so, then the farmer co invasive strategy look better. Now this is a post hoc analysis but I think supports the theory. So to summarize if you have a relatively short duration of symptoms and time is muscle and you have a short delay in transfer. They should go to primary PC. But if in fact the delay is considerable in transferring them. They should have the pharma co invasive strategy depending upon the risk of bleeding. And I think that's borne out by this subset analysis. Now, a lot of work in this area has been carried out by doctors. Armstrong and welsh in Alberta Canada in Edmonton act. And this is their registry data. 3300 patients Pharma co invasive strategy. 55%. And I might point out that northern Alberta it's a bit like parts of the midwest, long distance, large distances and uncertain weather conditions. If you look at the farm. Ako invasive strategy and yellow and primary pc I. S. T. segment resolution of greater than 50%. Um, actually greater in the farmer Coinbase yvonne that suggests salvage. The rapidity of SD segment resolution is a surrogate for salvage. If you look at death, heart failure, shock and recurrent. Am I the farmer co invasive strategy actually did better. And if you look at major bleeding, there was no difference. Uh, in terms of intracranial hemorrhage. Not .6% vs not .6%. Why did network spell and their possible explanations there? Several. Because there are honest reports of networks that have failed. I've shown you networks that have worked, first of all, learning from others. Read history or relive it. You're going to set up a network talk to others failure to adapt to local regional circumstances, lack of universal by um, lack of resources and the commitment of dedicated individuals. A network involves flight nurses, flight dispatch people, communications people, physicians, referral physicians. A lot of people are involved and they all have to be first of all buy into it and be committed. And this is an example of what you don't want a lack of commitment, dedicated individuals. A college basketball coach talking to player? I told him some what is it with you? Is it ignorance or is it apathy? And he said coach And he and he said coach, I don't know and I don't care. Well I can tell you. I mean seeing the people involved in the mail and other networks. These are very committed dedicated individuals who do a great job in making the network work work. one size does not fit all. You have to work out what's best for you. Here is a cautionary tale and a reality check Saturday. The US National CV Data Registry of 22,000 patients. A good paid a very good paper from dr laura in the german internal medicine. And this is fiber any license use among patients requiring into hospital transfer. It's a complex slide and I want to take you through uh in this large database. This is the proportion of patients Who were able to have a drive time of less than 30 minutes and two from a community hospital to a hospital that could perform pcR And amongst these patients who had a drive time of less than 30 minutes. First door to balloon time Less than 120 minutes, 67 And only 6% had fiber under license. That's probably appropriate one would hope that it will be higher because you know, the guidelines state That if you longer than 120 minutes you really need to have fiber analytics. But what about the patients where the drive time was 31-45 minutes or 46-60 minutes Now. Only about 40 to 50 Had a daughter balloon time less than .120 minutes. And only 20 to 30% had five rental license. And if you look at those with a drive time of greater than one hour, only 30% had a door to balloon time less than 1 20 minutes and only 50% had fiber my license and I would argue that uh nearly all of them should have had fiber in ISIS providing there was no unacceptable risk for bleeding. And in fact the median estimated into hospital drive time in this U. S. National registry was about one hour. So you really have to ask yourself well are we adhering to the guidelines? And this is why I go back to the title of this presentation. Even in the USa we have no shortage of Catalan but with a large country in large distances, uncertain weather. And the question is how well do we do in terms of treating people within the guidelines? And I do think the guidelines again emphasize That if you're going to be greater than 120 minutes, you should consider the pharma co invasive strategy. Now this is from the race registry in north Carolina and paper by dr Jamie jones. And what they've done these are the five regions of north north Carolina and illustrate again, one size is not at all. In some parts of the states of the state, they are transferred for PC. Others get fiber analysis, the farmer co invasive strategy and others have a mixed approach. One size does not fit all. And even in a diverse state like north Carolina, what works in some parts of north Carolina won't work on others where the distances and conditions are different. What about europe? This shows you primary Pc. I per year for a million inhabitants. In many parts of europe where distances are very small. It is easy to do. Primary pcr easy simple. Czech Republic, Holland. So 95% of patients get primary PC. In other parts of europe. It's more difficult in distances. Much wrong here and longer. And if you just look at countries in the european union, you see the great striking example of one size does not at all. This is the Czech Republic. Nearly all get primary Pc. I. And this is um this is Switzerland. The majority get primary PcR The UK has changed now. The majority do get primary PC but not at the time that this was published in 2009. Some of the best work in this area has been done by dr thomas, alexander in southern India. In the state of tom ahmadi and he really has illustrated hard systems of care can change the entire management of my partition function in a region of India of India. And he set up the hub and spoke system using the pharma co invasive strategy and in fact made a huge impact that came to the attention of the indian government at the federal and the state level. But as he said, he says on this editorial requires greater treatment and support in the coming years. You really need individuals but you need resources. And again what works in Tamil Nadu may not necessarily be optimum for a country like the Netherlands Australia. Wonderful place but does have its limitations. Once you get beyond the coastline you're dealing with huge distances and a very different system is in place using the flying doctor service an aircraft. So key messages, yeah delivery of care to patients presenting in non PC capable sentence. Again, I want to emphasize that if the patient arrives at the door of a PC capable hospital, No one will argue that the best treatment is primary PC. Timely transfer for primary PC is our biggest challenge. You know. Um Gosh 50% of patients or more greater than 50 Have a first daughter device time of greater than 120 minutes. And these people if we follow the guidelines should in the majority be treated with the farmer Coinbase a strategy uh unless the risk of bleeding is unacceptable and that's a clinical judgment. Emergency medical services taking patients to Amman PC center followed by ground transfer for primary PC. I. Is what I would call a system failure in large cities or areas where you have non PC capable hospitals Uh within 3-5 miles of APC. I capable hospital, you should transfer the patient for primary PC. I not to another hospital and then require another transplant. The major component of delay and transfer is what is called Dido Doren Dora. That is the time it takes from presentation to a non PC. I capable hospital to be transferred to the PC capable hospital. And the major delay in data is in obtaining transportation. Just think of that obtaining transportation. Do you have to call an ambulance from elsewhere? Do you have to call a helicopter from elsewhere or is it the helicopter in close proximity? If transportation times are generally are greater than 45 minutes. A general strategy should be lipsticks followed by immediate transfer. Now the patient is a 90 year old female, 50 kg body mass in the body weight. I would not give lyrics because the risk of bleeding is too high. You need to use clinical judgment. Even then, a plan for the most timely transport of lipstick ineligible patients not patterns is needed. And again, I want to emphasize this is the area where we can have the greatest impact one outcomes and that is shortening transport in times from non PC. I capable to PC. I capable centers and using the pharma combos of strategy. Yeah, there are unresolved unresolved issues. We still argue about the optimal fiber analytic dose with age, ethnicity, the royal attack Agra law versus clopidogrel, the optimal window for an invasive strategy. Um What do we do uh patients who have multi vessel disease? When do we treat the non culprit vessels at the same time or at a later stage? The whole issue of microvascular dysfunction is fascinating and needs, we need more to learn a great deal more about it, improving outcomes and cardiogenic shock. Think is a key. And I'm involved in a trial right now a pilot study in Germany, were we looking at many ways of improving myocardial salvage in mike and cardiogenic shock with remote ischemic preconditioning and pre hospital intervention strategies. So primary PC for all is a worthy goal. But for the majority of the world, the former co invasive strategy is the only feasible and logistical option and I would say for much of the United States, not the majority but for a substantial proportion in the United States. It also is a feasible and logistical option, Realistic goals or two repor fuse therapy reaper fused to as many and as quickly as possible. And in 2021 it's not just the nature of the therapy that the efficacy of its delivery and the key is to give it to as many eligible patients and as quickly as possible. I went to close with one other slide. This is from an article by dr tom Lucia in the european heart journal and really just shows 1950 45% mortality with stem E. And that was the introduction of the carny care unit in D. C. Defibrillators. And now in the modern era of re perfusion therapy We don't have an overall mortality of 10%. And that includes cardiogenic shock And then people without cardiogenic shock more like 4%. So what a wonderful 60 years if you think of it 70 years and the advances that we make from here on will be smaller. The impact will be smaller in magnitude. But this will come down further. I'm confident about that. Well thank you for the opportunity of being part of this webinar and look forward to questions. Thank you Bernie. This was wonderful. I just have a couple of questions on my own. So we recently changed a protocol for fast track and lacks the time from two hours to six hours for inclusion. As most patients were not able to present within the two hour window. My my question to you as we are looking at our own male health system sites that the bottleneck as you rightly pointed out is the lack of transport timely transport of these patients and most of these sites are not able to maintain the door in door out time and sequential delays in transport. It just leads onto delays and us not maintaining our door to balloon time for my health system sites to within two hours. So um So my question is one what is the equipoise between doing a primary pc given the delays that we see as you said, you know, you read history or relive it um or we just continue because transport things will not change that what we have unless we dramatically asked the ambulances to start driving these patients to obtain capable hospital or we change the strategy to farm ago invasive approach given uh the the higher timmy to three flow rates to about 80-90 reduce heart failure, shock, the adoption rate of political legible patients even in our own spoke sites has been very low because I think the the buy in from the stakeholders is either I can transport the patient With maybe 10 15, 20 minutes extra delay or I I take the task of giving little therapy which is more onerous to the Mayor health system sites for example. Well, I think that, I mean I think you really illustrate the one size does not feel you are absolutely right. The universal buy in is is critical but it's not easy to get the buy in for the farm account by his strategy. And the reason being uh it's not just the work involved, it's you have to give the lipstick and then you are actually responsible during that period of time. If the patient bleed now in parts of the world where they still use streptokinase giving strip to kinda is it's not easy, they get hypertension and it is just easier to put them in an ambulance and transfer them and then the patient is someone else's problem because they're on their route to the PC. I capable hospital. I still think that in many ways, I think the situation in Alberta from what I've seen and I've been up there, it's much more analogous to where we are in the midwestern mayor and they have been uh successful in having people adopt the former co invasive strategy and their results I think bear that out. So it may be that they can do that in Northern Alberta but we may not be able to do that in Minnesota. We have to have universal by and people are not going to buy into that. We have to do the best we can. I think it's I mean I think the whole issue of door in door out is the one area where one can improve and the outcomes of part of re perfusion therapy and in europe they have been able to do this in most countries pretty well but we're dealing with very different distances. Yeah. Yeah, no, thank you for that and whether I still think that and what but I hate to see is someone young anterior infarct The other class 2-3 not that well and they pitch up at one of our non PC capable hospitals at a time When the helicopters are grounded and it's up to 50 days of the year when they may be grounded for part of the time. Not for the whole day but all of them. And that patient. And we've all seen this. I've seen that patient then arrived 3-4 hours later without getting a fiber analytic. And I remember very well seeing a patient who um arrived at a a hospital outside our network that was not PC capable in exactly that situation was placed on a helicopter and then that helicopter was diverted because of weather and ended up somewhere else. And this Individual aged 40 to 43 I think Ultimately got primary PC. I 4-5 hours off the presentation. With a big anterior in part and in fact had all the complications of a big anterior infarct. Surely that patient should have had um the farmer Coene basic strategy um we have a question from dr Richard Mulvane and he's asking one, he said Great Presentation. But then he also asked you, can you uh tell the participants what is the difference between Farmiga invasive and facilitated PC. And then and the second part of the question is he says some people give half those, can you explain when do you give half to athletics in pharma? Go invisible. Right. two Very good questions and thank you for your comment. Mm. The bamako invasive. It's actually almost semantic. The farm worker invasive strategy was routine lipsticks and then transfer. A big big your pardon facilitated Pc. Was routine lyrics and everybody um prior to transfer and then immediate P. C. I. So you would have a patient who would present at an outside hospital. They would get full dose lyrics And they would be transferred and go straight to the Cath lab one hour later and that was abandoned. High rates of bleeding. Um And this was a strategy that was developed by the late dr allen ross and that was a band eventually I'm not sure if we did it now if we would have the same rate of bleeding. The form a cone baser is um fiber analytics followed by transfer and then delayed PC. In other words Um they wouldn't have immediate PC. I. The the guidelines say wait three hours and do an angiogram between three and 24 hours. So the difference is pretty nuanced. One is an immediate angiogram on arrival. The other is waiting up to three hours. With one exception. Um about 35% of our patients required rescue Pcr and that is they had the lyrics on arrival at Saint Mary's Hospital. They still had s. T. Elevation. They still had pain or some symptoms and they went straight to the cath lab for rescue P. C. I. That figure of 35 has come up in other trials as well. So about a third of the time the lyrics maybe initially effective and then become ineffective or they re thrombosis And that's 37%. And in fact the culprit trial was at least the rescue trial was another trial of dr gersh licks showing that in people with persistent symptoms take them immediately to the catholic. So let me just quickly summarize facilitated latex transfer, immediate angiography. Um that's facilitated for Mako invasive lipsticks. Transfer rescue in a third. Otherwise a delayed angiogram After a minimum period of three hours. So if the patient comes in at five in the morning they're completely stable. Do you you can wait wait till eight o'clock, nine o'clock, 10 o'clock or whatever and do it collectively now the second part of it in terms of the half dose when they did the stream trial, which is the trial that run by dr armstrong in Alberta Canada but carried out around the world, there was an unacceptable rate of bleeding With TMK in patients over the age of 75. So at that time during the course of the trial it was half those uh I think it was half those tiene que And maybe in Oxford parent over the age of 70 575 um was it Hoffa's tiene que and Hog nosing up to bat. Yeah. Yeah. Yeah. You're right after Isabel. Yeah. And then they also did not give the bullets for the anti platelet therapy to I mean, that's the other question. I think that that may also come up but go ahead carol. So, I was just saying that, you know, elderly patients, they that is one subset where you will give half those lyrics in pharma co invasive approach. The other question I have from dr Murphy. He also compliments you for your great talk. His question is now you've shown this graph of time to salvage. And so if a patient presents more than 1 20 minutes to a non PC I hospital and has ongoing chest pain, what would you do? Would you give little X. And then transfer or would you send the patient again to a pC capable hospital for a primary PC? I am. I think I just want to be sure I understand the timing here. So patient comes, they have ongoing pain. They all The duration of symptoms is relatively short. Yeah. By 1:20 minutes. Well, you know, you're right on the threshold. I mean, basically the quick to simplify it. I would say this if I could get that patient um to a Catalan Within 120 minutes of of presentation and they've got a relatively short duration of symptoms and I would just send them straight to the cath lab. But if that patients got ongoing pain, they're already two hours out and it's going to be another two hours of transport. And I would give them the pharmakom basic. Now do you stratify or do you know any literature that stratify eyes patient based on their risk? For example there is very high thresher. Forgiving for example trauma politics in elderly or patients who have different kind of in fact for example low risk in fart. Like an inferior versus a large. In fact as you pointed out in your discretion like large. And here in fact do you have a a sense of or do you think it should be universal or do you think it should be stratified based on the risk? Yeah it's a good question. I mean there is a literature on that and I've I've heard the argument is it anterior is an inferior is it a low risk inferior without hot block and so on. But I think that just complicates them. I mean I think my my own clinical assessment would be the greater the risk of bleeding. The more that would dissuade me from jimmy. And the so if sometimes when I show a place and I show An 87 year old woman with a history of hypertension, low body mass index who presented to hospital about Hour or two away from mayor And she was killed plus three and they called me and I said well you know I think just transferred her. She's quite a high risk of bleeding because of the age history of hypertension though. B. M. B. M. R. And I said just transfer and don't give analytics And she was killed? Class three. Well that night there was a tornado watch and then 10 minutes later they called and said helicopters are grounded And it's going to be about four hours road transport. And I said, okay, well then give a realistic and she came and we took it to the lab. The vessel is occluded was opened and then she died the next morning of an intracranial hemorrhage. Now I show that case and I say I still would have done the same thing today because her risk of intracranial bleeding was about 6-7%, which the other way of looking at it is 93% likelihood that she wouldn't bleed. But she did leave. But she was killed of Class three. And we had to do something and it was going to be four hours before she got to move. So, you know, it's a, it's a judgment call. I do think that in general what I think is a reasonable approach is are you are you going to be able to get the patient to cath lab within two hours of present outdoor presentation and then you take into account the duration of symptoms. So if the patient has had four hours of symptoms, it's not really gonna matter Whether you get them to a cath lab within two hours or two hours, 10 minutes or two hours and 30 minutes. Just transport transport them. But when you have someone with a short duration of symptoms, Maybe 60 minutes of symptoms. And now are you looking at 2-3 hours transport terms to the catholic? Well then you've got to weigh up the risks and the benefits. And someone like that young low risk of bleeding six get up close to anterior in fact or complicated in theory. In fact They've only got 60 minutes of symptoms And you now go 2-3 hour transport time. I think the guidelines say former Coinbase. Mhm. No thank you. The only other question I have is now, as we move forward, you talked about microvascular dysfunction as one of the prime targets. Um Do you think we should complement the novel strategies such as microvascular dysfunction but also focus more on symptom onset to presentation. In other words, educating the public more or have some resources because we've done everything to shorten the door to balloon time that died of times which are after the patient makes a contact with a medical facility. But we haven't spent so many resources towards educating the public towards early presentation to a medical facility. You're absolutely correct. Unfortunately. What little data we have. It's not very encouraging. They were several years ago. There are a number of studies Perform. one of them was in Gothenburg. Sweden and they had a massive public education campaign. You know present early, go straight call the er And so and so and what they found in the first three months was the er was flooded with non cardiac tests. and three months later after the campaign I down they had this media campaign a tv campaign. Three months later everything went back to where it was before. And that's been the experience of others at least the published published data. And that is that. Uh huh. Educating the public to seek medical attention earlier is incredibly logical. I believe it would make a huge difference but so far attempts to do that have failed and you know in the U. S. I don't know what the figure is but a large number of patients still drive themselves to hospital and don't call E. M. S. It's only about 50% thing called E. M. S. I'm not sure that of the exact number but um. Mhm. The other part of your comment about microvascular dysfunction right now, the only way I know to reduce microvascular dysfunction is to treat earlier. one of the early slides, one of the first few slides that I showed illustrated that if you had along symptoms to balloon time you had much more microvascular dysfunction than if you had a short symptom to balloon to all the other attempts to improve microvascular function with you know multiple different agents and drugs and approaches have so far been black and another thing um I mentioned a trial I'm involved in and that is the role of remote ischemic preconditioning in the ambulance and its effect on myocardial salvage and in turn microvascular dysfunction. But that microvascular dysfunction quote re perfusion injury is still the last frontier I think of re perfusion and after two decades of trials we still left with the fact that many things work in animals but they don't work in patients. And I think the reason is that that you know the long presentation times. I mean you know, most people that we see already two hours out. So I have one more question before we wind down this excellent presentation is the question is at what point in time would you not recommend a farm ago invasive approach in a patient who is presenting to a non PC facility with longer transport times. The participants is often it's difficult to obtain history of exact timing of onset. Maybe a poor historian. And then the other thing he or she is asking is what a gent of therapy would you recommend with trump politics such as heparin plots, et cetera. The the yeah. Just think about this. First of all, it's a very good question. How do you time the onset of my Colin pop And we've all been there. We just don't know, Patient wakes up at 1:00 AM. They've got pain. They're restless, They take something, go back to sleep, Wake up again at 4:00 AM with more pain and then eventually at seven o'clock, eight o'clock go to the emergency room. Did the in fact start at one in the morning or you know, we don't hurt. And I think in my graph that I showed of the curve, I mentioned that one of the variables is stuttering and fortune and I think what is important there is to realize that you may not be able to time the onset of myocardial infarction um precisely but and you may not be able to do it. But one thing that it's not that reliable but the presence of cure and they have shown in in the trial of the stream trial that in terms of outcomes if you have pathological Q waves at the time of presentation, the likelihood of salvage. Mhm. Of extensive salvage is much less. That's quite an important determinant. So I think you have a patient, you're not quite sure of the duration of the infant. It's a stuttering in fact and they don't have to waves, they've still got good voltage esti statements elevated. That means one thing. But if you have someone else, you know exactly sure of the duration of time but they have them low voltage established q waves, pain. You know, all of these patients, if you say to them do you have any discomfort, I think most patients actually describe chest discomfort that goes on for even into the next day. But when you look at those patients, they're very comfortable, they're reading the paper and they say yeah, yeah I've got a little discomfort. Maybe they have a little perricone artists and but they're comfortable but the patient who has an ongoing and function is not comfortable. They die of heretic. And I think it's I think and I think it's a clinical judgment. So if someone comes in and yeah they may have been farted 3 4 hours ago they've got q waves, they've got great pain, there is no urgency now just transfer the um and I think you have to make a clinical decision and you will not in many patients have an exact time. You know it's not necessarily 122 minutes. 118. And then the adjunctive therapy. So Plavix is that you go to drug that you give with trump politics. Yeah I think that one of the points I made is you know is there is there a benefit to Tiki Grill or we don't know in this I don't think in this situation. Re perfusion therapy that we have that data. No I I want to thank you Bernie for this excellent presentation on behalf of Dr Lloyd Panetta Gina and Jeff's in media and from our own department which you are part of uh we want to thank you for for being a part of this webinar thank you so much. Have a wonderful day. Pleasure thank you