Chapters Transcript Video Revascularization for Left Main Coronary Artery Disease Brian Bergmark, MD, discusses left main coronary artery disease and optimal revascularization strategies. Thank you dr Canada I really appreciate it and I'm grateful for the opportunity to be here And so as noted. We're talking today about revascularization for left main coronary artery disease. I believe you'll have access to my disclosures. Have to talk about them if there are any questions if you don't have access to them. So for the talk today well I'll start with some brief points about left main coronary artery disease. Then we'll get into the trials of P. C. I. With drug eluting stents versus cabbage. Those are the syntax pre combat Noble and Excel trials. And then we'll touch on the controversy surrounding the interpretation of these trials that led to an individual patient data that analysis which we'll talk about and then some concluding thoughts. So left main coronary artery disease. I want to show you three very brief cases and I'd like for you to think about whether you would feel comfortable randomizing any of these three patients or which of them to a trial comparing P. C. I. First cabbage. And the point here is to think about who actually ends up in a randomized trial of this nature. And also to point out that we talk about left main disease as if it were a single entity. But it is of course not. There are diverse coronary anatomies, diverse patient substrates and clinical scenarios. So this first patient is a 59 year old with stable angina type two diabetes and ef of 45% and no major comorbidities. As you can see there is a short left main with severe disease at the distal vessel extending into the osteo led answer complex, heavily calcified. The second case is an 88 year old woman with an insta me, no diabetes, reduced ejection fraction kidney disease and severe COPD, severe distal left mainly Asian as well as you can see some disease here in the circum flex as well. The third case here is a 70 year old woman with an in stemming no diabetes normally f mild COPD and in Austell left language. So it's been known or observed for quite some time. That left main disease is of significant clinical importance. This is a description from 1912 of acute coronary obstruction from from this. And dr Herrick actually describes a 55 year old who had chest discomfort, epic gastric discomfort, you can see in the underlying portion right? His physician was called and found him to be called nauseated and with a small rapid pulse which is quite apt description of cardiogenic shock, which we're all familiar. This patient passed away and in the autopsy description underlined in the second portion, a short distance from its origin, the left coronary artery was completely obliterated by a red thrombosis that had formed at a point great narrowly and he concluded death is the result in nearly all of these cases. And on the left is the modern day correlate. This is a recent patient and the cath lab had with an obstruction of his left main present to mine. And so so what do we do about this? Going back to the early studies of revascularization. This is from the V a cooperative study. The trial enrolled 686 men with coronary disease. They were randomized to bypass surgery versus medical therapy in a subgroup of them, 91 had left main disease and that was defined as a stenosis of at least 50%. And as you can see in the panel on the right side of the screen, those who were revascularization with cabbage had a significantly improved survival over 3.5 years compared to those who were managed medically. Of course, noting that medical management at the time was limited. There were early observational data as well. This is a dupe retrospective cohort of 3200 patients who had an angiogram showing coronary disease. And these patients were categorized by whether they were treated medically versus surgically. And so of course that takes into account many confounding issues about who was chosen to be operated on. But nonetheless, after adjusting, you can see graded association here between revascularization and survival most pronounced among those with left main disease. There's also a meta analysis published in the mid 19 nineties of seven randomized trials in aggregate, 2600 patients who were randomized to cabbage versus medical therapy with varying degrees of coronary artery disease highlighted in red at the bottom or those with left main coronary artery disease. And there was a significant survival advantage to revascularization cabbage in terms of five year mortality. So cabbage was the early standard of care for left main coronary artery disease. Per catania's angioplasty developed in the late 19 seventies. And there were some early small randomized trials of bare metal stents versus cabbage which favored cabbage, lower rates of revascularization and my possibly a mortality benefit. But there were small studies stent technology improved by the early two thousand's which led to the question what about a drug eluting stent versus cabbage. So that brings us to the trials of P. C. I. With drug eluting stents versus cabbage. I'm gonna go through each of these chronologically. Just to give a brief reminder, I'm sure they're familiar to you on some level. Starting with the syntax trial. This was published in 2009. These patients had left main disease or three vessel disease. In a moment we'll get simply into the left main cohort. But looking at the overall trial either three vessels are left main and these patients had to be considered equivalently revascularization by cabbage or PC. I. That's true of all the trials we'll talk about today and it's really a critical point. There were 1800 patients left main disease was defined as a stenosis of at least 50% or medina. 011 meaning osteo led answer complex disease or three vessel disease. They were randomized 1 to 1 at P. C. I. Or cabbage, P. C. I. Was with the first generation drug eluting stent. The primary endpoint was a composite of death stroke and my or repeat revascularization at one year. And so these are the primary results for the overall trial. That includes patients with three vessel disease. As you can see in panel a no significant difference at one year in all cause mortality in panel B. A composite of death stroke or am I no difference? Excuse me, repeat revascularization significantly higher after PC. I. In panel C. So if you add the repeat revascularization and see to the composite from D. You get their primary composite significantly higher after PC. I. At one year one of the central observations was from this trial was the importance of the syntax score. Um And so I'm sure this group is aware. The syntax score is a system where lesions are graded given points for characteristics that contribute to complexity, bifurcation, calcification, tortuous city, etcetera. And so this score was simply intended as a tool to force the sites enrolling patients to systematically review the angiogram of potential subjects. But the importance has been far beyond that. And so one of the key early observations is that there was an interaction between coronary anatomical complexity as defined by the Syntex score and the randomized treatment effect And so on. The right here, patients with a low syntax score 0-22 you can see there was no difference in one year. For the primary endpoint for an intermediate syntax score 23-32. No statistically significant difference. But I think a reasonable person would wonder where those curves are headed uh beyond one year. And then for those with a high syntax score at least 33. A clear advantage with bypass surgery. So what about patients who had left main disease? There were 705 you can see in panel a no significant difference in the primary endpoint at one year. No difference in death and panel B. Myocardial infarction in panel C stroke. Lower with P. C. I. And panel D repeat revascularization and E. Is higher with P. C. I. And then the composite of death stroke and my no difference. So that then brings us to the pre combat trial published in 2011. These patients had left main disease defined as a stenosis of at least 50%. And now we start to uh also get into limiting the degree of coronary complexity allowed. Which we'll see in the other trials here. There could be no plan to treat more than one C. T. Oh there's also no ef less than 30% allowed. There were 600 patients randomized 1212 P. C. I. With the first generation drug eluting stent versus cabbage. It's important to note that there was planned and geographic follow up in the pc Ir in 8 to 10 months And the primary endpoint was death stroke and my or ischemia driven target vessel re basket one year. So here are the primary findings out to two years. The event rate was 12.2% in the PC. I arm as compared to 8.1%. And the cabbage arm was not statistically significantly different in this sample size. And you can see there was a large uptick in the PC I arm during that 8 to 10 month. And geographic follow up driven by revascularization, you'll get just death stroke or am I on the right side? No difference at two years. And the hazard ratio for death was 0.69 with 95% confidence in the role of 0.6 to 6 to 1.82. And so the 2014 european guidelines reflected these two trials and I mentioned these guidelines because then we will see their update in 2018 and also become a focus for the conversation and controversy within the last couple of years. So 2014 this notion of categorizing patients by the Syntex score is reflected in the guidelines for cabbage Class one recommendation across the range of coronary complexity level of evidence be and then for pc I the class of recommendation depended on the Syntex score as you can see also level of evidence. The so that brings us to the two newer trials, Noble and Excel. So for noble 1201 patients left main disease was defined as a stenosis of at least 50% or an F. F. R. Of less than or equal to 500.8. They also had to have three or few other complex lesions meaning a. C. T. O. Bifurcation or calcified or tortuous vessel randomized 1212 Pcr cabbage. The primary endpoint five years was death stroke? Non procedural M. I. Or repeat revascularization. So I'll emphasize there. They specifically chosen not to look at procedural M. Eyes which would become another topic of conversation here. These are only the spontaneous events As you can see here in their primary findings out through five years significantly higher after P. C. I. A benefit to cabbage appearing to manifest after about one year has a ratio of 1.46. Looking at the individual components, no difference in death through five years. Non procedural M. I significantly higher after PC. I. As well as repeat revascularization. Uh No statistically significant difference in stroke. And also a finding here. That's been the challenge to explain beyond chance. Which is that during the first year which is when I think somebody might expect a difference between treatment strategies to manifest. There's appears to be a lower rate after Pc. I. There was then uh increase in stroke after one P. C. I. R. Red line in the bottom right. And then the Excel trial. So this is the most recently published results. This is 2016 and also the largest 1905 patients here. There was a bit more nuance to the definition of left main disease. So the lesion had to be at least 70% and geographically or 50 to 70% with evidence of ischemia which could be noninvasive or invasive with this or FFR. And then a local syntax for less than or equal to 32. So specifically looking at patients with a low to intermediate syntax for they were randomized 1212 P. C. I. With a later generation drug extent versus cabbage. And the primary endpoint was death stroke or am I at three years. So you can see the primary endpoint in panel. A no difference between the arms. A higher initial event rate in blue. That's the cabbage. Lower after P. C. I. A procedural period and then a flatter curve for cabbage after that initial period, procedural period. Uh And a steeper curve for Pc. I. And that three years about exactly the same as a ratio of 1.0 if you look at death from any cause no statistically significant difference. But America was higher after T. C. I threw three. Looking at stroke. There was no difference and then myocardial infarction has a pattern that mirrors the overall primary endpoint results initially higher after cabbage lower after P. C. I. And they met at three years. And so the 2018 European Society of Cardiology and Association of Cardiothoracic surgeons revascularization guidelines now then reflected uh these two new trials as well. Noble and Excel. The class of recommendation is the same across as they were in 2014. But the level of evidence has increased to level of evidence a saved for those with high sent explorers and PC. I still level of evidence. So that's where things stood until the controversy which we will now get into uh uh and move on into the meta analysis. So this really opened up in 2019. Uh Pretty much exactly three years ago we just had the T. C. T. Conference this past weekend in boston. This was T. C. T. In 2019. And the five year follow up data for Excel were presented. You can see the primary endpoint shown in panel a no statistically significant difference. Uh And then the endpoint plus primary endpoint plus a schema driven revascularization on the right significantly higher. And noted at the bottom. There was a higher rate of death after PCI odds ratio of 1.38 95% confidence interval 1.03-1.85. There was a swift and unusually uh sort of personal attack uh sort of trading of interpersonal attacks that occurred here and this spilled out the social media. And then the mainstream media bombing the BBC. And this really brought this area to a halt. And so what was this about? And we'll get into some of these. Um one of the major issues raised was the interpretation of the mortality difference in the five year results. So concerns were raised that this mortality difference favoring cabbage was not emphasized adequately in the presentation of the data or in the paper in the new England Journal Medicine on the part of the trial team. The response was that this was a secondary and point in an overall neutral trial one among many. And that to emphasize this particular secondary endpoint in the neutral trial would be statistically inappropriate. Uh And of course the counter was that that may be true statistically, but nonetheless this is the most important end point mortality. This also that relates to the primary choice of the primary composite. Uh and and what went into it and discussion of whether the trial would have been neutral with a different definition. And so that that involves procedural. My accusations that the definition was chosen that favors PC. I. And that rates of procedural and I defined differently according to the universal definition of M. I had not been reporting talk about this in a moment. And then the choice of the primary composite endpoint. Uh The on the one hand, people saying, well if revascularization for example have been included in the primary composite then it would have been a positive trial favorite cabbage. The counter on the trial team being that revascularization is not clinically equivalent to death stroke or am I and that smaller studies have included it simply for power but this being the largest did not require the inclusion of that. And so much of this came down to um uh questions of intent, there was a breakdown of trust here and what was intended interpretations of intended intent from the trial team and and others. And so in the end this this term which was new to me, trended on social media called the chocolate trial Excuse me. Which is a trial which has been designed to achieve the results desired by the trial team. And so that was the summit of accusation. So to get into this we have to talk about procedural and I and this is a rabbit hole. We could spend all day talking about procedural mind. We have no further clarity than we have now. And so I'm going to go through it briefly but just to highlight the major points that are central here and so this, this is an issue that is everywhere on the left or the primary results from excel. But numerous other trials are impacted by decisions on how procedural and eyes are defined. So on the right is the ischemia trial and you can see the same pattern. There's an initial high early event in one arm in this case the invasive strategy followed by a shallower slope than the blue arm and how we define that initial event rate is going to have a major impact on our overall conclusions. So from ischemia, if you look at procedural am I on the left that is obviously higher in the group of people who get procedures. If you disaggregate that from total M. I. And then look only at spontaneous M. I. On the right, you can see that that's lower with an invasive strategy. Um And so how we define procedural is going to determine how we what we conclude about overall and I. And so this is actually shown in the ski mia trial and their supplement. The initial primary results is relatively high bio market threshold on the left. If all you do is shift to a lower bio market threshold to define a procedure like mine, you can see on the right the overall primary endpoint for the entire trial looks worse for for an invasive strategy. And so this is of course true in Excel as well. And so the fourth universal definition of M. I. Is shown in the top box. Um It favors troponin, oversee can be Troponin is more sensitive for these procedural um eyes than the sea can be. The fourth universal definition of my uses different bio market thresholds for Pc I versus cabbage. So there's a lower threshold to call it an M. I. After a Pc. I then after a cabbage and then E. C. G imaging or and geographic findings are also required. Sky has a clinically relevant. Am I after a vascular ization definition which favors ck MB. So it's more specific. There's an equivalent high standalone bio market threshold for Pc. I. And cabbage doesn't matter which modality it's the same threshold and there's also a lower bio market threshold paired with E. K. G. Changes. And so this is a paper from circulation in 2018 simply looking among a cohort of patients undergoing PCR cabbage. What would you conclude about the rates of procedural? AM I using different definitions? You can see among the 2nd 3rd universal definition of different rates overall. Higher with Pc I. Sky definition higher with cabbage. The Excel trial definition is uh similar to the sky definition. And so without getting into the nitty gritty there are reasonable uh approaches a person might take in arguments for for one definition or another. And again, really what comes comes down to here or accusations of intent is this intended to favor P. C. I. And so that was one of the central issues. Uh And also that there was an accusation that procedural my rates as defined by the universal definition of M. I. Had been analyzed but we're not being presented publicly into the Excel team did present them publicly first in a letter to the journal. And then in this paper published in 2020 in jack. And so this table shows rates of the primary composite endpoint using different definitions of procedural and mine. And so you can see in the red box the first row, their protocol defined. Um I you can see the rates of the primary endpoint and the difference if that simple component of M. I. Procedural my is defined according to the protocol numerically higher with P. C. I 2.8%. But no statistically significant difference. If what you do in the next two rows is shift your definition of procedural am I to the universal definition of M. I. And and here they did it a couple of different ways using Ck MB or mixed troponin C can be you. Then your overall primary comparison composite is now statistically significantly higher after Pc I. So the entire result of the trial shifts based simply on largely what is a bio market threshold. So these are those major issues as I raised a lot hinging on the procedural M. I. And then these other interpretation issues as well. And so this led to calls for an independent transparent analysis of aggregate randomized trial data. And so this is what we did. There was a collaboration here among a group of independent investigators and it's important to note here is involved a statistician, noninvasive cardiologists and then a balanced number one interventional cardiologists and one cardiac surgeon. And then the principal investigators of the four trials, given the tenor of the conversation in the space. It's important to note that we as the independent investigators created the statistical analysis plan. We performed all analyses. We drafted the manuscript had complete control over the content and vouch for the integrity of the analyses and the findings. So what did we do? We used a one stage meta analytic approach on a combined data set of individual patient data supplied by each trial. The primary endpoint we selected was all cause mortality through five years. We chose this because it is clinically the most important endpoint and it is also unambiguous. There were five secondary endpoints, cardiovascular death, spontaneous semi procedural, my stroke and repeat coronary revascularization. We performed landmark analyses, supplemental analyses using 10 new mortality data which were available in syntax and pre combat as well as subgroup analyses. And we also perform Bayesian analyses to help quantify the probability and magnitude of any difference in mortality. So here are the based on the procedural characteristics. There were 4,394 patients. And again important to emphasize that these patients were judged by a multidisciplinary team to be equally suitable candidates for either approach. The median age was 66, 3 quarters for men, but one quarter had diabetes, minority had an EF less than 50%. The median syntax score was about 25. A small portion had left main disease only and about half had left main plus at least two vessel disease. The median number of stents or conduits was to ISIS was used in about two thirds of the P. C. I. S. A lima and nearly all of the cabbages and all arterial grafting in about one quarter of the surgeries. So here's the primary comparison mortality through five years. 11.2% after T. C. I. Excuse me. 10.2% after cabbage. Hazard ratio is 1.1095% confidence interval of 0.91- 1.32. The absolute risk difference was .9%. With a 95% confidence in the role of negative .9 to 2 Here is the basin analysis. So this is a probability density function. The vertical line at zero reflects no difference in mortality between pc and cabbage. Anything to the right indicates a higher mortality after P. C. I. So you can see that the curve is overall shifted to the right indicating most likely higher mortality after pcr to quantify that there was an 86% probability that mortality was greater with p Ci cabbage versus cabbage and that's any difference greater than zero. What about some more stringent thresholds? That might be of clinical importance. There was a 49% probability that there was a mortality difference between T. C. I. And cabbage of at least 1% over five years or 50.2% per year. And there was a 5% probability that the mortality difference was at least 2.5%. Which would have been .5% per year. So from this, we concluded that overall uh it was most likely that there was a mortality advantage to cabbage and that the absolute risk difference more likely than not was less than .2% per year. What about cardiovascular and non cardiovascular death? So you can see here on the table and neither one obviously statistically significant. And this is the incidents for cardiovascular mortality through five years, absolute difference of .4% not statistically significant should have been less than .1% for you Longer term has noted. We had 10 year follow up data for two trials, syntax and pre combat Mortality rate of 22.1% after cabbage, 21.6% after PCI hazard ratio of 0.96. And for subgroups, there are no statistically significant interactions across these major subgroups. We are looking into these more looking into diabetes versus no diabetes. One of other extending fellows just presented data on acute coronary syndromes at T. C. Thi this past weekend. And then we're looking more into the Syntex score and I do want to highlight this a little bit more. Obviously there's no statistically significant interaction here, but our a priori understanding of the importance of coronary anatomical complexity, paired with the fact that I think a reasonable person looking at these subgroups would say, you know, it does kind of look like there's something favoring cabbage there at the higher Syntex scores. You know, we thought we thought it was worth investigating a bit more. So here syntax scores modeled continuously on the X axis and then the hazard ratio for pcr versus cabbages on the Y axis for cardiovascular death. Again, the interaction term is not statistically significant. But I I think a reasonable person would look at this and say that the risk here looks neutral is right at one until a syntax score really of almost exactly 33 there appears to be a benefit of cabbage. Obviously we're limited by the statistics here. Um and I don't want to over emphasize this point but this this is the relationship mm and repeat revascularization. So spontaneous. M I obviously here higher with pc. I hazard ratio of 2.35 number needed to treat with cabbage to prevent one spontaneous M. I 35 years is 29 And then repeat revascularization. Same story higher absolute event rates has a ratio of 1.78 number needed to treat cabbage of 14 to prevent one repeat revascularization, procedurally. My so on the left here are procedural my events. According to the protocol definition of each trial Perform ratio of 0.65 significantly lower after PC. I I haven't listed the protocol definitions for each individual trial but in general they tended to favor ck MB and higher symmetric uh bio market thresholds. And then we have universal definition of my data for syntax and excel and you can see here no statistically significant difference stroke, so no difference over five years. 3.1% after cabbage, 2.7% after Pc. I. There was a violation of the proportional hazards assumption, meaning that it's not appropriate to assume an equal risk relationship across this time frame. And we also know biologically that we expect there to be uh if there were different related to therapy most likely in the immediate period rather than out to five years. And so if we look in the first year, there's a significantly lower rate with PC. I absolute difference of 1% hazard ratio .37. And then if we look beyond the first year, there's no statistically significant difference in the incidence of stroke. So, to summarize the meta analysis findings comparing P. CI with drug eluting stents versus cabbage in patients with left main disease. A medium syntax score of 25 and deemed equally suitable candidates for either revascularization approach. There was no statistically significant difference in survival at five years. So true at 10 years, An amazing approach suggested a different favorite cabbage probably exists and more likely than not. It is less than .2% per year in magnitude. Additionally, a possible cardiovascular mortality benefit of cabbage appeared confined to patients with high Syntex scores, cabbage unequivocally reduces spontaneous M. I. And repeat revascularization and P. C. I reduced early stroke differences in the risk of procedural and I depended on the definition used. So these findings of course need to be taken into account in a broader context for each patient that takes into account coronary anatomy, the non coronary anatomy. They're calcified ascending aorta, for example, local expertise, patient preferences which we'll get to in a moment which are critically critical and central here. Co morbid conditions and clinical stability research, utilization costs. And so where do we go from here? So it's first important to emphasize that these findings apply to a subset of patients with left main disease. These are patients where equivalent revascularization was considered possible. They largely had low or intermediate anatomical complexity and they had limited comorbidities. So often a response to this as well. Um What we need is a larger trial and we need higher rates of coronary imaging use all arterial revascularization and certainly that that would be nice of course. Um But a couple of things. One it's difficult to achieve adequate power for the mortality difference. Not that it can't be done but this trial and its results would be a long way off. Uh And also there is tension between long term follow up in state of the art rebased. So certainly by the time that trial ended and we have five or 10 year following, certainly we would be on to the next latest and greatest. But I would actually say that while I think that's an obvious initial reaction. I think this is actually missing the point and that perhaps refining the mortality difference point estimate is not the major issue. And For anyone who has these conversations on a regular basis with patients and their families, I think it's clear that if you were able to say with more confidence to a patient, well the more vitality difference over five years is .15% per year versus .3% per year. That doesn't inform the conversation at all that patients, their families are bringing to these conversations, priorities and values that really are central for them and often for which we don't have data and it usually comes down to one variable for them. For instance, you know, the borderline renal function and they want the approach that's least likely to result in long term dialysis. Um and we just don't have great data for that. And so to me, the central question is how do we balance patient values and preferences with a small number of hard outcomes for which we have data. There's an additional question here this raised, which is is there a role for medical therapy in the modern era? All of this is based on the assumption that we should revascularization left main disease. Medical therapy has evolved enormously over the last 30 years and we simply we don't know, but I think we often come across in practice somebody healthy largely symptomatic normally, if you happen to see a 60% left. Main reason for whatever reason they were in the cath lab is that somebody who absolutely needs to be revascularization that's not known at present. So what about the guidelines that just came out at the end of 2021? So those that pertain to the left. Main this is in relationship to medical therapy in patients with stable ischemic heart disease and significant left main stenosis, cabbage is recommended to improve survival. So it's just mentioned. This is consistent with guidelines and current practice but we have no new randomized trial data with modern therapy. Uh Now talking about Pc versus cabbage and selected patients with stable ischemic heart disease and significant left main stenosis. Working Pc. I can provide equivalent revascularization. P. C. I. Is reasonable to improve survival. So I think this is logical. Um It's also I think consistent with the primary findings of the meta analysis we performed. I will say it does leave a major gap in clinical practices. This isn't a criticism the guidelines. It's just simply we lack data but very often when we perform T. C. I. And people with left main disease. It is because they have they are often older have important comorbidities and surgery is considered prohibitive. Often these patients also have quite complex coronary disease in our aim isn't actually to provide equivalent revascularization. We might be treating the left main leaving an R. C. A. C. T. O. And just trying to get them over the hump. Uh And so we aren't actually providing equivalent revascularization and and and how PC. I. Compares to optimal optimal medical therapy in that situation is has not been in patients who require revascularization for significant left main disease and high complexity coronary disease. It is recommended to use cabbage over P. C. I. To improve survival. And so I think this is very likely true. But I guess I would say that is also in some circumstances probably relevant to consider the magnitude of that difference. Um take that into account with the other clinical circumstances and the patient's priorities. And so the guidelines, you know, have this figure which I would say is the most visually appealing figure I've ever seen. But I think appropriately puts this patient and a multidisciplinary team at the center of this discussion and and highlights that this entire approach involves the shared decision making, pre revascularization period, procedurally and then post procedurally optimizing this patient's outcome after the revascularization. So so what about these three cases? So this first one is a 59 year old with a stable Angina diabetes DF, no major comorbidities. And and I would be surprised if somebody felt appropriate that it was appropriate to randomize this person pc versus cabbage, I think it's pretty clear this person should get a cabbage with a high syntax score, low surgical risk and he was sent for cabbage. And and he did well this is the other end of the spectrum. This is the type of patient who we often performed T. C. I. And this is the elderly patient with a low ef kidney disease, severe COPD. This person had a syntax scores 32 very high surgical risk. You know I had a conversation with the patient family and agreed to proceed with irish pc. I did a left main DK crush and the patient went home a couple of days later. And then finally of the three cases I think this is the one where a reasonable person or group might think about either approach equally. This is the seven year old and stem E. Just the osteo mainly asian, low syntax or low surgical risk. And so here's where the conversation uh you know really hinges on what the patient is coming from. And this particular patient, she had a brother who recently had bypass surgery had gone well and she just wanted to be done with this and have the lowest likelihood of coming back for further issues. And so cabbage was the clear choice here. So she went for cabbage did well and was discharged. So in conclusion left main coronary artery disease is associated with high mortality. Current revascularization recommendations are informed by four randomized controlled trials differences in endpoints and interpretation have led to a standstill in the field, an individual patient data meta analysis from the syntax pre combat noble and Excel trials. We found that mortality difference favoring cabbage probably exists, It is more likely than not less than .2% per year in magnitude and it's likely confined to high anatomical complexity. There are higher rates of M. I. And repeat revascularization after P. C. I. The higher rate of stroke in the first year after cabbage. Finally integrating these findings into patient centered decision making is the central challenge moving forward. So thank you. I will open it up now. I'm sure there are some comments about this topic and again I really appreciate the opportunity to be here today. What a fascinating wonderful review. Thank you so much. Um And your meta analysis is well it was certainly enlightening and your summary with approach to actually the complex problems we deal with every day making decisions on individual patients and I thought your three examples were wonderful. I just I'm gonna simplify and just ask a really basic question and approach should our if I were a patient and you said to me that the difference between P. C. I. When feasible versus cabbage was 0.2% and I'm 72 years old or whatever age I am per year. And you told me that I could have P. C. I. With similar minimal change, it would be pretty easy for me to make that decision and I don't think most people are begging for cabbage over pc. I so I guess my question is if someone is a Pc I not a PC candidate like case number one is pretty easy. There's no choice if there are reasonable Pc. I candidate should the stance be cabbage. If not a PC. I. Candidate for most patients with this kind of anatomy. Should that be the initial approach? Yeah. It's it's a great question. You know, I think there are a couple issues wound up in there. One is simply what theoretically should be done for these patients and there's also the other practically, what do you do? Uh you know, often, you know, in the capital, we are making the diagnosis and so if you were to feel that way, you might simply just proceed with P. C. I. You know, I think practically speaking virtually all of these patients unless they are an extremist shock etcetera. If there's left main disease, I virtually always stop and have a conversation about it. But what what the end point of that conversation should be. It's really tough. It's it's you know, Having now thought a lot about these specific endpoints, it's clear to me how limited they are. Like you said, even mortality, which of course we care about how do you how do you make sense of .2% per year? How do you actually internalize that? And what are the things that actually matter to a person? And like you said, getting out of the hospital is actually often the highest on somebody's list, at least in the short term. What about issues of coming back for new atrial fibrillation. What about kidney injury that maybe doesn't result in dialysis. But now it's an issue, your lab strong, all this matters to people. Uh, and and it's very hard to quantify. We have some data from Fame three that's not left main, but comparing pcr and cabbage and otherwise some of the patients, you know, these issues of rehospitalization, kidney injury, atrial fibrillation or higher after cabbage. How does that matter compared to mortality? Of what magnitude? It is very difficult. So I do find it quite hard to make a blanket statement. I do think in uh, in about 30 seconds and speaking with the patient, you can get a sense of, of kind of where they stand and uh, you know, if you kind of say we found this, there are two approaches. Here's kind of the broadly speaking tradeoffs here, lower initial hurdle to get over out of the hospital sooner. Probably more issues going forward versus bigger hurdle upfront, but less likely to come back for more procedures. People believe that an open ended way people start to really guide you. I think very quickly. That's really helpful. Yeah, I think there is some data from valve disease that patients typically don't look at the long term, they more often would prefer the shorter term, easy um, therapy and not worried about the five or 10 years so much anyway, there's one question, I thank you for that that response and obviously a you have a lot of experience talking to patients making these decisions on a daily basis. Um There's a question from one of our interventional people. What is or was the average use of ibis O. C. T. In the larger trials and how much mechanical circulatory support was used as well? And again I would add to that. Also. This whole issue of 50% left main between 50 and 70 I think the difference how do we should we really ever just go on angiography alone for 50% vs. 70. Or should they always be evaluated with more advanced techniques and what data is out there? Yeah. Yeah. Thank you. Great question. Yes. So I think it's completely inappropriate to send somebody for revascularization. The left main without some sort of evidence that a lesion is limiting outside of an an geographically extreme lesion. But anything in the moderate range I think needs investigation. And you know it's always struck me as strange this notion that all human beings should have the same minimal Luminal area in their left main. So I generally do some sort of physiologic assessment if there's an intermediate left main lesion. Yes so the I've issues in aggregate was about two thirds 68% of the pc. I was pretty consistent. I don't know if you just saw it just came out presented T. C. T. Tenure data from the best trial where they looked at the office some group. Uh Most patients actually did extraordinarily well compared to cabbage. Um One of the issues of course with intravascular imaging is you don't know how people are using it. Uh And so this is simply that it was documented that i this was used but whether they were actually using in a way to optimize the Pc. I effectively rather than interpreting images who knows And then low rates of mechanical support use Samir brian fantastic talk. And really did a nice job of walking through the controversy that surrounded the interventional and surgical community last few years. And I think sometimes when when these debates were ongoing at T. C. T. And other meetings we kind of got lost and in the nitty gritty details and sort of missed the bigger picture. And I'm glad you were able to really eloquently um go over that you know my approach isn't necessarily as a patient better served with P. C. I. Or cabbage but the fact that several years ago patients were deemed if there were not a cabbage candidate there was no other option. And and a lot of cardiologists and interventional ists felt that there was no Pc. I option either because of the risk associated with it. And at least now we have a leg to stand on for patients that we can really as a heart team discuss what's the optimal strategy and we've got data now to support that both are very good options and it's a matter of finding the right fit for the right person. So great job walking through a lot of controversy and and explaining that um I've got two questions for you and the first one is, what's the approach at Brigham, let's say today you're in the Cath lab and you kath and outpatient who's got left main disease, you know, and truly worsening angina. What's your approach is the conversation between you and the patient? When do you involve ct surgery? Do you have a formal consult with your surgeons? How do you guys go about it? Yeah, it's a good question because this is something that is a constant source of consternation because I think in an ideal world, you would have a system where you sit down and you systematically review the data together with a surgeon. And also, if there's a primary cardiologist or team involved, practically that's quite difficult. Uh you could set up a weekly meeting. But if somebody comes in, you know, the day after the meeting are not gonna wait around for a week to have a meeting about it. Um and so as I said in general and unless there is a clinical circumstance pressing immediate action in the Cath lab, we tend to stop and talk about it. And by virtue of the fact that I happen to be the person who's made this or recognize this clinical scenario. I'm usually the first person to have a conversation with the patient and the family and I generally try to keep that broad along the lines of kind of what I just mentioned that there are two approaches here, we're going to talk about them. And then once they're a bit more conscious, have a more in depth conversation. And I also always up front say, you know, I'm talking to you as a person who puts instance and uh, you know, I don't want there to be a perception that I'm pushing one thing or the other. And I also think it gives me credibility if I'm saying, you know, in this circumstance, I really think a bypass surgery is the better approach that they know that's coming from the person who does the other thing. Uh, and so we immediately, you know, call the surgeons and ask them to come by and then we find the time to talk about it very often just given the, our patient population really, what this hinges on is that there is some reason the surgeons don't want to operate. And, and so we, we do a lot of left main pc. I and a lot of old people with a lot of comorbidities. Um, and uh, and, and so really the heart team is, hey, we found this, Can you please come make sure you don't want to do it. And if you do sure, let's, we can talk about the trade offs if there's nuance here. But usually it's clear it's the anatomical scenario favors cabbage and it's just a question of is it a reasonable thing to put this thing person threw a cabbage? We're in the same boat. And uh the number of left main P. C. I. S. Um for us is has increased year after year. In large part because patients are getting older the more complex and we've got a lot of other medical issues. And this is where I think the data is nice. Whereas before we really didn't have a leg to stand on from the Pc I perspective at least now we've got randomized data that says P. C. I. Is an option for a lot of these patients. Yeah I agree. And particularly where so for mortality etcetera you look at the acute period and then particularly for these older patients you can say, yeah, sure, over five years they're more likely to need to reinvest. But that that's not relevant to this particular conversation. Exactly. My next question is um, didn't make it to E. S. C. I'm not sure if you did. But there was a lot of talk around this trial of patients with low ejection fraction and coronary disease and a group of those included Left Main. I'm just curious. I know that wasn't the focus of your talk but what are your thoughts on this entity? You know, low ef left Main disease. Yeah. Well, you know, I mean it's I think AJ curtain has a really good editorial on this. And and so this gets back to the question of how how are we defining left main disease to begin with? I think one of the central challenges of this trial is I'm sure. So I think there's some like 40 centers and it took them seven years from all these patients and we don't know a lot about the coronary complexity but it sounds like not a lot. And so I think one of the fundamental questions here is did these people even have coronary disease in as a general group that was causing the reduction and ejection fraction? Or was this simply people like we often see they've got a reduced ejection fraction. I don't know. You find a 60% p. d. a lesion an om lesion uh by chance. But of course fixing that's not going to result in a change in the big picture. And so I think we lack the detailed data at the moment to really understand. Is that the group or not? And if not you also wonder what these people have truly that ischemic heart disease. Why why are you randomizing the ministry? You know because you know like that first patient I showed there obviously his ejection fraction wasn't that well but of course that guy's gonna get revascularization. And so you're left with this group of people who the team feels potentially comfortable not revascularization. Um and we don't really know the detail on who that group is yet from the trial. But but then it is a large group of people with left main disease potentially. Um there's 91 patients. Um so if those people truly had that left main disease that would be informative. That would be interesting to compare to medical therapy alone. I think we just don't know yet. Um Last question for you brian to wrap things up here and then harvey has anymore but as an interventional ist your approach from a procedural standpoint. Um I know for us the use of mechanical support is has actually gone down over the years. We used to put it on everybody and now it's probably you know maybe 20% 25%. Um And your approach to kind of two step strategy do how do you deal with the bifurcation of the left main into the led Circum flex? Yeah. Yeah I saw a couple of things about M. C. S. I think our approach is similar to yours you know first of all why why should we not put an appellate in every human being becoming a little more restrained to say is this really necessary every single time? But I think you know they got an R. C. A. C. T. O. And you're gonna be rolling down the led and the cirque and they've got a low E. F. You know putting in Pella upfront. Um the bifurcation. you know, I I find the BBC main compared trial pretty compelling sort of this step provisional approach. Obviously there's bad disease in each vessel, fine, you're going to deal with it, you know, But if if one of the vessels, the proximal vessel looks pretty good. I like to just try to stay provisionally across it and see how things are going. If there's any question, I fr r fr whatever and do my best to put as little metal as possible. But you know, I was actually just doing this exact thing yesterday. Um, and you know, sent to the hostel cirque across the left name Osmium led looked pretty good, but you know, checked by far is 0.87 in the mid led and we should just finish the job here. Um, if I'm gonna do a two step approach, I pretty much always do DK crush, not because I find the trials all that compelling necessarily, but just like that, you always have a wire down and extended vessel, you don't have to work. You know, you just, there's no reason not to as far as I'm concerned. Uh, and then if, you know, you try provisional and now you're doing something else, obviously you need a different approach again, thanks so much brian, all that Samir some up, but great talking and I hope we all learned a lot from it. Thank you. Thank you. I really appreciate it. No great brian, thank you very much for for joining us this way. And we appreciate all the work you've done in this field and really helped get gain a deeper understanding of left main disease. And I think it's uh, an ongoing, important issue that that affects a lot of patients. And I think we'll see more and more of this as the population ages. But thank you very much. And I hope to see around uh, one of the interventional meetings. Great. Thank you guys have a good one. Thank you so much. Bye bye now. Published October 5, 2022 Created by
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