In this Cardiovascular Medicine webinar, Mayo Clinic cardiology experts
Bernard J. Gersh, M.B., Ch.B., D.Phil., and Mandeep Singh, M.D., focus on several issues regarding coronary revascularization in patients with coronary artery disease (CAD) and severe LV dysfunction and chronic heart failure (CHF). The concept of a paradox in which revascularization is associated with an increased early hazard but a greater long-term benefit is discussed, followed by the results of the STICH randomized trial and the myocardial viability substudy. Viability testing remains controversial and is discussed from the standpoint of pathophysiology and natural history, diagnostic modalities, the importance of quantification, and the interaction between viable myocardium, the extent of scarring and ventricular remodeling and its impact on the results of revascularization. Drs. Gersh and Singh also provide a clinical approach to the use of viability testing and coronary revascularization in specific patient subsets.
For more information or to refer a patient, visit
Mayo Clinic Medical Professionals — Cardiovascular Diseases. hi everyone who have joined us virtually in this ongoing quarterly webinar series. I am your host and moderator Amandeep Singh. I'm a professor and coming live to you from Mayo clinic in Rochester, the department of cardiovascular disease. And I have a distinct pleasure and honor to introduce actually reintroduce my teacher, my friend and colleague Dr Bernard Gersh, people who had joined before had enjoyed his talk on farm ago invasive therapy. All these topics that we do on a webinar are archived and recorded so you can enjoy them later. But today he will be speaking on coronary revascularization in patients with severe left ventricular dysfunction and mainly talking about the status of viability testing. Dr Gersh is well known to all of us as The last I checked was 1300 publications. His H Index is through the roof. He is very well known in the academic circle and he has been the editor co editor reviewer in almost all the journals in the world. It is my distinct pleasure to introduce Professor Gersh who will be talking on this topic. Dr Gersh welcome, thank you very much men deep for that. Nice introduction and as was pointed out I'm going to really talk about two aspects of revascularization. One is the results of coronary revascularization in patients with severe LV dysfunction. Uh and then the second is really to take a look at the role of viability testing. And is it still viable? The prognosis of patients with lv dysfunction and coronary disease is really illustrated in this slide. The major determinant of mortality in patients with coronary disease is the severity of LV dysfunction and in patients with LV dysfunction, the major determinant of prognosis is the severity of coronary artery disease. Excuse me. And esky mia can the results of revascularization or in some ways a paradox. There is an increased peri procedural risk but that is counter balanced by the potential to reduce late mortality. So a little bit the greater the risk, the greater the reward. And to really understand that one needs to realize that if you have severe LV dysfunction, clearly it will increase peri procedural risk. If there are any complications from the procedure, they will be magnified. On the other hand, because we are addressing as a target the severity of schema and coronary artery disease. If one can correct that, that may have an effect on reducing late mortality somewhat greater effect than in patients. Many patients with normal LV function and this has been documented in the original case study of coronary artery bypass surgery and medical therapy Uh published in the very early 1980s, overall trial results for neutral. This was a neutral trial. But if you look at the subset of patients within an ejection fraction between 35 and 50 those with multi vessel disease and LV dysfunction had a distinct survival advantage with coronary bypass surgery. And really I think another example of um the potential benefits of correcting a scheme area in patients with left ventricular dysfunction. It's been shown more recently in the ischemia trial that was published last year. Now in the ischemia trial, There was a small subset of patients, about 7.7 you had heart failure with reduced ejection fraction, heart failure with preserved ejection fraction. And then a group with reduced ejection fraction but no heart failure. And if one looks at the results again, should emphasis the ischemia trial was a neutral trial for these endpoints CV death, non fatal M. I. Hospitalization for unstable engine a or heart failure resuscitated cardiac arrest. The yellow dots are the conservative arm and the orange dots are the invasive arm in this trial and these are patients who had heart failure and LV dysfunction. So it's this to group of patients here and amongst these there is a distinct benefit for the revascularization strategy in these sicker patients with heart failure and LV dysfunction. In a trial which overall was neutral. And then if you look at those who had no heart failure with LV dysfunction shown in the solid lines, there's no difference at all in outcomes And the interaction was almost significant .55. And if one looks at the primary endpoint, which is this endpoint all cause mortality and cV mortality. In patients with prior heart failure, dotted arm is conservative. The dotted line is conservative therapy. The orange is invasive. And if one looks at an ejection fraction of somewhere around 55-60%. What you see is um a benefit with the curves crossover with a lower mortality in the invasive bomb. Uh and the lower CV mortality and a lower primary endpoint. The stitch trial was the first trial however, to address this perspectively and this was a trial confined to patients With an ejection fraction of 35% or less. Unlike what I've just shown you in the previous fight, which was a subset analysis from a trial of patients who by and large had no heart by and large had normal LV function, the median In a schema. I think the media an ejection fraction was 60%. 1200 patients, coronary artery disease, multi vessel coronary disease EF less than 35% or 35% or less. A very difficult trial to do. And a lot of credit goes to the investigators And if one looks at death from any cause as the primary outcome. Initially, the trial was a trial over 3-5 years. But subsequently there have been The follow up has gone out to 10 years And if you look at death from any cause, which is the primary outcome at 3-5 years. There was a difference in favor of bypass surgery That was magnified when you get out to 10 years and the 10 years The hazard ratio .84 A 16% reduction in mortality P .02. And what I really want to point out again is this paradox very early on. There actually was a higher mortality in the bypass on not significant the trending that way. And then after two years, the curves diverge in the other direction with a benefit for revascularization number needed to treat us surprisingly small. Only 14 patients death from cardiovascular causes, Hazard ratio .79 same thing slightly higher cardiovascular mortality early on in orange. And then a distinct benefit for bypass surgery P equals point 006. And if you look at All cause death and cardiovascular hospitalization is a 28 reduction in favor of bypass surgery Again took a period of time. But the benefit really only became clear 1-2 years after the initial operation p less than .001. This is a subset analysis from the stage trial that makes and I think an important clinical point and that is if one looks at all cause mortality, cardiovascular mortality and all cause mortality and CB hospitalization and on this axis is age. And this is the hazard ratio. You see a very distinct benefit and quite a large benefit All cause mortality early on in younger patients under the age of 50, Both with CB mortality and all the endpoints. Now, this doesn't mean that there's no reduction in mortality in older patients. But basically once you get over 65, the risk is greater their stories a benefit and cardiovascular mortality. There still is a benefit on mortality and cV hospitalization, but the benefits are smaller and really emphasizes that when one deals with revascularization in sick patients with LV dysfunction and heart failure. You have to look at the entire patient very carefully because the benefits and the risks obviously go up with age and that does not mean that older patients may not benefit. But patients selection needs to be very stringent and careful. Now. The mechanisms have improved prognosis following revascularization, potential benefits. I mean the obvious one is an improvement in resting ejection fraction, a recovery and regional function and this is why people benefit and this may apply in some patients. But there are other explanations. We May one of one benefit from revascularization is to reduce induce a ble ischemia and repetitive stunning, which is a phenomenon. People will be dysfunction and currently disease that in turn could improve diastolic function. In turn, it could also improve ventricular remodeling and the symptoms of heart failure and improve the prognosis through those mechanisms. The other is when I've always believed that ischemia is a cause of malignant ventricular arrhythmias, that acute ischemia or even chronic ischemia can cause sudden cardiac death and prevention of ventricular arrhythmias. Maybe another potential benefit from revascularization and the one that is gaining attention now is uh the concept that the benefits of opening an artery may have effects that are independent of the schema and viability. But what they do is prevent recurrent events and in particular recurrent myocardial infarction from other vessels that are not obstructed but will be obstructed in the future. And that I think is a very plausible hypothesis that has recently been floated in the literature. And this is an interesting analysis from dr Julio Penza. Uh based on on the 10 year follow up of the stitch trial. If you look at the change in ejection fraction on this axis with medical treatment alone and bypass surgery plus medical treatment. Now the numbers are small and I accept that and this is in patients without viable Marcotti. Um there's no effect really at all on ejection fraction if they had viable maya Cody. Um Both medical therapy and bypass surgery improve ejection fraction. And this has been a well documented that medical therapy with peter blockers and other drugs may really improve the ventricular function. Um In patients with bible myocardial, but here's the catch, there was no association at all between these changes in ejection fraction and subsequent mortality. So it's complex. There's no doubt that revascularization has been a bit beneficial. I believe that the as stitch trials showed that, but the mechanisms are multifactorial and less easily understood. Hibernating mike. Autumn is a concept that was proposed by the latest tiburon tula who died recently and was a friend of many of us at the mayo clinic. This was published in 1982 and this is a patient with single vessel disease and included lady Ejection fraction, 37 Dilated left ventricle and after nitroglycerin. The L. b. uh remodeled or the volumes were reduced and the ejection fraction went up to 51%. And after bypass surgery post operatively with a patent graph to the lady. If I'm not sure why it was 76 which is actually hyper dynamic but the L. V. N. Diastolic volume was much smaller than originally. So he proposed the concept that this was hibernating myocardial and that the my accordion hibernated to protect against the ischemia and prevent necrosis. And this was really his concept which I think still holds true today. Uh The definition of viable myocardial. When you look at the literature, one has to be careful. It's my cardi um that is dysfunctional addressed, it's not scarred and it has the potential for functional recovery after revascularization and in fact you can only diagnose hibernation after the fact. And that is it's a term that should be used retrospectively only to describe those segments which actually improve following revascularization. And this is important because often one sees the term viability used incorrectly and a number of studies now viability and prognosis in patients with LV dysfunction. There are a number of different substrates and some of these are still under investigation hibernation implies resting ischemia and it may be a protective phenomenon to prevent the ischemia causing necrosis, another form of hibernation may be repetitive stunning and that is that in an obstructive vessel there is recurrent ischemia which is induced herbal when the pulse rate goes up for instance, and repetitive stunning can cause uh LV dysfunction which is reversible. one needs to take into account not just the viable myocardial but the extent of scar, the amount of remodeling and the duration of hibernation. Because over time, if you make a diagnosis of viable myocardial, that may be hibernating. And you come back 69 months later that hibernation may have progressed to necrosis. And one of the questions that we really don't know is how much is enough. It's not an all or none issue. It's not enough just to say, viability or hibernation. How much viability And this is a question, We don't know. And really the question is, how much viability is there that if we correct that and re vascular eyes and improve the bible Marcotti, um it will have an effect on prognosis and future trials. I think we'll continue to address the clinical impact of multi modality imaging strategies in guiding treatments. Treatment in terms of outcomes. And what I really mean is we now have a number of sophisticated imaging techniques to try and get at this issue. How much is enough? When is it sufficient that we can justify a fairly risky procedure of revascularization. This is a matter analysis that It is now 11 years old but tried to actually answer this question. 29 studies, 4000 patients met analysis and on this axis is the amount of viable maya cardi. Um As a percentage of dysfunction in my accordion. So 50% of the ventricle is not working. What proportion of that and dysfunctional my cardi? Um do you need to have viability present to justify the improvement or to let me put it differently? How much viability does there need to be there to justify the risk of surgery? Or maybe pc with a view to improving prognosis With pet? About 26 Stress. Echo 36%. Spect almost 40%. So it's not enough to just report an imaging study and is a viable Mark Carney um is present. It's how much viability is key. Now the clinical indications you don't have to look for viability and patients with normal LV function. These are patients with coronary disease and severe LV dysfunction. My cut off would be an ejection fraction of 35% or less if they have severe coronary disease, they've never had a history of my. That should make you raise some questions about viability. No Q waves on the eeg if they have significant angina or stress induced ischemia, you should have viable micro medium to cause that if an angiography you see sub total inclusions with extensive collaterals and then the entity of flash pulmonary oedema with subsequent dramatic improvement. Typically this occurs in people with hypertension and heart failure with preserved ejection fraction. Occasionally one will see a patient with severe pulmonary oedema E. f. 35%. And you come back the next day and the ejection fraction is normal Or up in the 50s. And that should make you think of a large amount of ischemic. And um by definition viable myocardial and all of these should raise your clinical suspicions about viability testing. Well, we've all seen this. This is a patient before surgery. L. B. F. 26%. The orange reflects score the yellow areas of hypo kinesis which are reversible presumably After surgery. El the year 45 and much of the areas of so called scar tissue have in fact improved and we've all seen this clinically So and and again. And this is I think 14, 13 years old. A well known meta analysis of 14 non randomized studies showing that if viability was present, revascularization had a very large beneficial impact on mortality. A viability was absent. There was still a benefit from revascularization over medical therapy but it wasn't nearly as impressive but no randomized trends. And then in the stitch trial and what I want to emphasis this was a myocardial viability sub study, It was not a trial. It was a sub study from a randomized trial. But in the viability testing sub study which was about 50% of the patients in the trial, you underwear inspect the very mean stress echo. If you look at mortality without viability versus with viability, the mortality without viability or at least the mortality in patients with viability who are revascularization, Hazard ratio .6436% reduction immortality in those with viability p .003. This is in people not just revascularization, this is in people revascularization and with medical therapy. So having viability is better than no viability and that may be because medical therapy also works in patients with viability. This was the surprise and in this viability sub study, if you look at the results of bypass surgery versus medical therapy With viability 14% reduction in mortality not significant without viability, 30% reduction in mortality also not significant. So these were trends, but this is really what came as an incredible surprise. If you look at this visually, you would say that the group that did better even though the numbers are fairly small. The group that did better with a group who had bypass surgery without medical without viability. And this was very difficult to understand and still is and did raise the question. The english physiologist, the whole concept of viability might be another beautiful hypothesis slain by ugly facts. Now, I have to tell you that almost overnight, at least in the United States testing for viability dropped by about 25 to 30% on the basis of this sub study. Well, there are other studies from this Mark cardio. Bye buddy. Sub study. And at the time I said to the investigators, I'm pretty sure that if you look at those patients who had induced herbal myocardial ischemia and viability. Those patients with induce a Beleskey mia would clearly have a benefit from revascularization. Well, if you look at mortality in patients with induce double myocardial ischemia, this is no ischemia and this is ischemia in the sub study. Uh no difference at all from bypass surgery and medical therapy. Another huge surprise and difficult to understand. And then this study in the importance of angina in patients with coronary disease heart failure and LV systolic dysfunction. Again said to the investigators, I think if you look at the group who have a significant engine in addition to heart failure, they will do much better with bypass surgery. Well, conclusions from this study where the presence of engine to did not confer a worse prognosis but neither did it demonstrate a benefit from rive ask a greater benefit from revascularization by bypass surgery, cabbage. Didn't it improved the symptoms of angina compared with medical therapy alone but had no effect on prognosis. So this again is very difficult to understand because I've always been brought up to believe you know you re vascular rise for ischemia. You re vascular rise angina and that will improve prognosis. And my colleague Jeff Boesky and I published this editorial for this paper angina in revascularization of the scheme, a cardio myopathy. The hole quilt or just a stitch. So to try and understand this because I don't know about you. I found this very confusing and if you're not confused by this, I think you're just not thinking clearly. So. And my colleague Ray Gibbons and Todd miller at the Mayo clinic also raised this question is a ski me a dead after stitch and my age number of points. The study was underpowered by today's standards. The use of the was very low. It was A single vessel disease and greater than 25%. And really maybe we have better ways of looking at viability and ischemia using Spectrum DSC. And their conclusions were that there still a role to identify patients with moderate to severe and severe ischemia, um significant coronary disease who are at relatively low risk for revascularization. And made the statement that the absence of evidence of benefit must not be interpreted as evidence of lack of benefit. I think a good editorial. So I think that there is a way to understand this. And I want to go back to this study from Cedars Sinai Medical Center. Not a trial, But a very large study of 14,000 patients who underwent to Dennis zine or exercise spect imaging on this axis is the total amount of myocardial that is esque Emmick. This is a long hazard ratio. The oranges revascularization and the yellow is medical therapy. And if you look at this point here once about 12.5-15% of the my Kardian became ischemic. you then see a higher log hazard ratio with medical therapy and a clear benefit from revascularization. But in a subsequent study from the same database, what was shown was that the role of ischemia, this powerful effective ischemia In patients who had a fixed myocardial defect or scar tissue greater than 10%. The role of the of Ischemia and particularly the percent of ischemic myocardial fell away. It lost its significance. And there was no interaction with medicine and medical therapy and revascularization. And so to translate that, what it means is that the role of ischemia on the benefit of revascularization was nullified by the presence of the extensive infarction or scar. And the patients in the sticks trial had very extensive scar and prior in folks. So is there a role for viability and ischemia testing? Is the concept still valid and rational? Well, I think if you go to the stitch trial, you have to say in stitch patients. No, there was no effect of viability induce a bill ischemia, an angina. On surgical arc, there was improved remodeling, there was increased remodeling with non viability but no effect on surgical outcome. And remember this was a group of patients Ejection fraction 35% or less. But what about other patient subgroups? And I would argue that there is a very important role for assessing a schema and viability in other subgroups with severe LV dysfunction and in patients with LV dysfunction. And currently disease are the presence of viability induce double ischemia. An engine is still therapeutic targets. Fair question after stitch. But I would say yes. And the considerations are not just the presence and extent of viability and ischemia, but how much score is there? How much remodeling? Because with extensive scar and remodeling I showed you in the previous trial was not trial but study that the extent of scan remodeling could overwhelm the effects of viability and ischemia and when is the point of no return. And that's the question. So my conclusions are the viability testing may predict the response to revascularization. In selected patients with coronary disease and LV dysfunction, it's a marker of prognosis, it may influence the response to medical therapy. I think this gets underplayed viable. Myocardial responds to drugs. The impact of viability and residual ischemia may be overwhelmed by extensive scar and remodeling. If you have a ventricle that is already seven cm in diameter, perhaps that's people Point of no return ejection fraction less than 20%. Perhaps it should not be a routine determinant of the decision to re vascular rise. So in my practice, If a patient with LV Dysfunction. 30 35 if they have significant engine, good distal vessels, no Q waves, preserved voltage on the GBA important clinical science and there are reasonable surgical risk and I'll close with one or two comments about PC. I. In those patients I don't think it's necessary to get viability testing. But our patient population is sicker and older and has more comorbidities. In patients with severe LV. Dysfunction, extensive remodeling LV. End diastolic volume over six cm multiple comorbidities, incomplete revascularization is likely. Angina is less severe and under multiple comorbidities are will put advanced stage in this situation. I think I need all the help I can get in order to make a clinical decision as does the surgeon or the interventional cardiologist. And I think viability testing particularly with pet and MRI may be extremely helpful. Now again the negative I think impact of the state's sub sub study on viability testing has um had a number of I think unfortunate side of them most unfortunate so quickly. So this illustrates the utilization of testing for significant obstructive coronary disease among patients. Hospitalist with new onset heart failure. And I think that this is um a large study from boston missed opportunity. There is an administrative database, 67,000 patients um some of whom had no known coronary disease. Some had known baseline coronary disease. They presented with new onset heart failure. The only imaging tool really used was during index hospitalization within 90 days was the Echocardiogram, hardly anybody underwent a nuclear stress or a stress echo. If you look at the use of invasive testing During initial hospitalization. Very few underwent diagnostic coronary angiography 11% and within 90 days, only 16.5 Um underwent diagnostic angiography plus another 8.4% that also had right heart catheterization. So very underutilized given the fact that coronary disease is still probably the leading cause of heart failure. Now, if you just a few closing words about PC. I. This is a trial from the UK by Dr Pereira. This is a British cardiac interventional society trial. 700 patients PC for his scheming cardiomyopathy. This slide is out of date. They have completed enrollment E. F less than 35 extensive Currently disease using uh an interventional school, they had a viability study. They had to have at least four segments that could be full dysfunctional segments. That could be revascularization by PC. I. And if they're in that case they were randomized to OMT optimal medical therapy or PC and optimal medical therapy. Endpoint of all cause death. Well, excuse me for hospitalization for heart failure. I think We will have the results of this trial within the next 6-12 months. Very important trial, not much other data on PC in patients with severe LV dysfunction. This is a retrospective study from Ontario in Canada E. F. less than 35%. Why they left mean lady or multi vessel disease emergency revascularization excluded. Almost 5000 patients propensity matched if you look at death due to cardiovascular disease. Um Slightly higher with p. i. p .001. But the magnitude of the difference in favor of bypass surgery. Small. If you look at my Katelyn function at a high rate of Am I with PC. I did not perform as well as bypass surgery. But I suspect this full is a role for P. C. I. And that's where dr Pereira's trial will objectively. Um Tell us one way or another. Now this is the text of a cable sent by Mark Twain from London when he was having his breakfast at the London club and he read that his he read his obituary in the United States papers which had been mistakenly published and he sent back this telegram. The reports of my death were greatly exaggerated and I believe there's a great deal more. We need to know about the quantification of viability and specifically how much is enough to demonstrate a benefit. But I really believe that the role of viability testing is still alive and well and the subject of further investigation and continued investigation. Thank you for your attention. Thank you. Uh Dr Gersh I have a couple of questions for you just to open it up following this excellent presentation. Um First I think we made a lot of inroads in terms of medical management with a speed up lockers uh mineral receptor and Agnes in patients with heart failure. We have made lot of inroads with device therapies but somehow this revascularization component has lagged behind. Do you think in patients who have known LV dysfunction before we go for viability testing. Do you think all these patients should have their coronary anatomy defined as you pointed out in one of those studies where the testing and arrange a gram is dismally low in patients who present with acute heart failure man did you make? Thank you. You make 22 points. The first one is um I enjoy talking about clinical trials and I've always been very involved with the design and some of the statistical aspects of clinical trials and one of the points that I realized or make. But I think we all realized a long time ago all of these trials of revascularization which take 5 to 10 years to complete because you need at least five years of follow up in three years of enrollment because it's not easy to get the patients, they are all all obsolete by the time they finished I think in one of my slides I showed I. C. D. S were only used in 20% of the of the stitch population CRT was used in probably 15 to 20%. So in many ways This trial is obsolete is actually 12 years old already and that when you sit on a guideline committee there's nothing wrong with the trial. I mean trials get obsolete because technology changes and pharmacology changes and and techniques change. So when you sit in a guidelines committee you have to take this into account and you need to you don't dismiss the trial but you have to Understand that maybe what was across one indication based on this trial 10 years ago, maybe a to a indication 10 years later. So that's the first point. That second more important point that you raise, should you establish the presence or absence of coronary disease? I think in a patient with heart failure who could be a revascularization candidate in the future. I think you should establish the currently anatomy even before you reach the stage where you're going to re vascular eyes the patient. I think you need to know whether you're dealing with an honest chemical him up. They were in a scheme economy and I think there are other issues in that regard to because depending on the ejection fraction, whether it's ischemic or non ischemic, the indications for an ICD made different um the potential benefits from CRT may differ between people with ischemic and non ischemic etiology. Um I think back to the new OECD guidelines from the european society will probably not distinguish ischemic from non ischemic for the side. But in this country we do, I did think that what has changed our practice in people with chronic currently disease is the use of the cT angiogram. and if one looks at the 2019 EEC guidelines that I was involved with, we made a big point that in people with allowed to intermediate likelihood of coronary artery disease. A CT angiogram is probably the diagnostic modality of choice. If someone comes to you with heart failure and you feel there's a very high likelihood of coronary disease or you know, they have coronary disease there. You may go to a stress test to try and assess the degree of ischemia and various other factors. But I'd like to know whether I'm dealing with coronary disease is a cause of the patient's heart failure or some other ideology. And I think the sea to really has made our life much easier. Now I realize that sita is not helpful in assessing lesion complexity and severity in people who are undergoing revascularization, but it's negative predictive value is extremely good. I agree we have a question and I think I also wanted to ask you in terms of whatever studies you quoted. Plus, I I read about there is a distinct underutilization of pet. Um, maybe they do not want to compromise specificity over sensitivity. Maybe it's a it's not so much of a profusion metabolic ism issue. It is more about induce a bill ischemia issue. The stress echo respect is more prevalent in determining viability rather than pet. What is what is your take on which is which tests should be done to document and demonstrate viability and I think the reason for the only utilization of pet and the trial. It was very simple. Most people didn't have expertise or didn't even have it. And so they chose imaging modalities that were widely available, uh, in many parts of the world and in most hospitals in the United States. So I've always said, when people say, what what test do you think we should do? Does it do whatever you do well in your institution? So if you feel you have a very good nuclear program or echo program or both, then you choose between stress, echo respect. Uh, I think the ideal and we have that at Mayo is pet MRI in really difficult patients, I think using MRI to look at volumes and scar tissue and pet to local areas of mismatch, maybe the best combination available. But I say this with the full knowledge that not everybody has access to this. And even if they do, you have to have expertise and we have, you know, in my own a number of people who are particularly interested in this. So I think you've got to do and rely on what do you do at your institution? Well, so two other questions. I have. One is now, our department has done a yeoman's work in terms of using artificial intelligence, not only predicting every dysfunction, but also future. Every dysfunction based on just simple, easy. And you've been a big proponent of if the dog is normal, your ejection fraction is normal. Um, I I I was your student when you, when you used to teach that based on your knowledge and based on what yeah developments we have in artificial intelligence do you think that can be factored into the management of these patients? What a great question. And as you know, I've got a huge interest in in the AI program and we focused at the moment and mayor, the focus has really been on the E. G. To assess LV function and the G to assess atrial fibrillation. Um you're right. I have always said if you have a normal EKG, you're going to have normal ejection fraction. The actual paper was written by myself and it was written by our colleague. Mutual colleague checked re hole and myself and from a registry we looked at 20,000 patients and if they had a normal EKG, no history of infarction and a normal cardiac celebrate on a chest x ray. The likelihood that they would have an ejection fraction of greater than 45% I think Was about 98%. And where I found that very useful is when you asked to assess someone in the middle of the night, they want to go ahead and do an operation or a procedure on a patient and you don't have time to do an echo. And I've always found that clinically very useful. We now have a very good algorithm developed by paul Freedman and our institution and others that shows that using a I on an electrocardiogram um, you can predict. Uh they reduced ejection fraction with great accuracy and in fact in our clinical practice we have an Ai dashboard when I'm doing a consult particularly if it's a remote consult when I'm outside the clinic. Um I use that dashboard to see what the ejection fraction is And if it comes back there's a 98% likelihood it is normal. Well then you don't have to do an EcG on. Now. The next step is how are we going to use it in these patients with severe LV dysfunction and coronary disease. And this is a topic that I think would be very exciting to investigate. And the one thing I've learned without a. I. Experience and I think this is a word of caution for everyone. Just because you show in one group of patients that the algorithm will predict atrial fibrillation in people who are in sinus rhythm who had an episode of atrial fibrillation a month ago. That doesn't mean that it will apply to other patients with atrial fibrillation. You have to retest it it looks like it does work. But for instance we recently looked at our algorithm to see whether we could predict peri operative atrial fibrillation and we couldn't because it's a different mechanism. So when you think of the patients with currently disease a very abnormally cG severe LV dysfunction. The question we would like to ask is can you use ai to predict a good prognosis or salvage after revascularization. That's a wonderful study to do. I'm not sure how we would go about doing it. But that's one that's one to look at that would be very instructive and helpful but it may not be it may not be A. I. The G. And maybe ai of an echo A. I have some other imaging technique plus the G. I don't know. I don't think we know the answer. So the the only other question I have is um we have all traditionally labeled severity of LV dysfunction either in a binary or a polic ah thomas kind of terms less than 35 is like this the The number to go to go to number to say if it is less than 35 it is severe. It can notes a different prognostic value and meaning not only to the provider but to the patient as well. My my my question is now the benefit uh as you as you pointed out it's a high risk surgery or now maybe Petey the lower your ejection fraction more the reward in terms of improving your outcomes. But one can we just look at this paradigm in a continuous fashion. And two, What happens if my ejection fraction is 36 or I am in the mid range as the ski me a trial post talk analysis demonstrated. So in other words, when can we just you know, be a little more optimistic or pessimistic notwithstanding the nuances of scar and remodeling and other issues. Well I think I think the reason that we use under 3535-49 and then greater than 50 really goes back again to the original trials and that goes back To the very early 1980s and that and those that were the cut offs that we used And the and 35 at that time 1982. This sort of era people thought that, I think the general thinking was if your ejection fraction was under 35%, you were far too high risk to put into a trial. And therefore the first trial Of revascularization within a year for 35% or less was the stitch trial 12 years ago. But the first trial of coronary bypass surgery, we're over 30 years ago. And in fact a big important over 40 years ago. So it's an artificial categorization. Um but it's it's been clinically useful and hopefully, I mean I think this comes up, you know, should we look at it as a continuous variable? Yes. But to give you an idea of how artificial it is. If you look at the guidelines for defibrillators, It's 35 or below What? About 36. Now? I know and you not mandate That we can tell the difference between 35 and 36%. Not with an angiogram, not with a mugger and not with an echo. So if I really feel that the patient um Needs a defibrillator and I see a report of 36%. I actually call the lab and say don't you think to me it looks more like 34%,, 33 or 32. Are you really that confident that it's 36%? And that's where the guidelines I've always said. I mean they're doing the best they can. I mean guidelines are not easy to write, but it's very arbitrary. And so another example is the transverse school and I was on a another zoom conference a week ago on risk schools for april fibrillation. So you have a patient, it doesn't want to go on anticoagulants. And that patient is 74 years old. He's A Chad's Vasko of one. No hypertension, No other problems. Chairs basketball. Well if it's chad's vascular one, the guidelines say you should consider antico regulation. But it's it's not a class one indication, chad's vascular too. Everybody agrees should be anti coagulated if possible. Now let's say what the day you saw him? It was the day before his birthday. So he's a chance fast one. He said, I don't want to be on anti Copenhagen's. So you say, okay, well you don't have to be until tomorrow and then you're a trans vascular too. You know, because we have these arbitrary cutoffs but we also have a brain and we have to make clinical decisions. And this is this is why medicine is still fun because it's not doubt. You know, it's not just just down to an algorithm. You have to I think it was Voltaire, the french philosopher who said common sense is not that common and we have to use common sense. So what is your take on the remodeling in terms of how long does it take? So when I look at the stitch trial, They had to ask for additional funds to extend the observation from 5 to 10. Now we have these new trials coming up which then uh randomized patients p ci versus optimal medical therapy And the duration is two years. Do you do you think those will not be able to capture the endpoints so soon after? Well, yes and no, I think it depends on the patient population if it's a group with a high incidence of recurrence of scheme here. I think we will be able to Probably come to a conclusion after 2-3 years in, in in in a situation like the stage trial, the difference is at five years, I think it was, I can't remember there was 34 or five years, but the original trial, I think was five years, But the majority of patients had only been followed for three years somewhere around there and the differences which were becoming they were either significant but still quite small And I was one of many that argued for additional funding to go out to 10 years and really prove the case beyond all doubt. So that's in this particular patient population, I think in and others, you know, if you think of the trials have left main disease at three years there was a trend in favor of surgery that was not significant. And originally it was decided to follow the patients out to five years. The funding was there. And that trend became more obvious after five years but still not statistically significant. Well depending on which end point you look at and that's still controversial. The point being that when you start to see curves crossover, that's a trend and a sign that you need a longer follow up. The same with the ischemia trump. I mean the schema trial is neutral in five years. I suspected 10 years. We may see a difference in favor of revascularization or pc in terms of my Katelyn function. Now, just because it reaches a p value is not the end of the story because you then have to start looking at the magnitude of the difference. So it's not just people less than .05. How much of a difference is that? And I think we also need to realize that when we do these trials, all the patients in the surgical arm and all the patients in the pc. I arm were suitable candidates for either procedure, highly selected patients. And just because we do show a trend as we continue follower still only provide you half the answer to the question. But I do think that at least with the ischemia trial. I have lobbied as much as I can for funding From NH L. B. I. To continue follow up out to 10 years. So I think when you I don't mean a two year trial is useless. Not at all. It depends upon the endpoints that you're looking at and it depends upon the event rate. Mhm. You've got a very hard entrant maybe you'll get an answer in two years but these trials do take time and they difficult to do and they do take time. Very true. Very true. No I thank you uh dr gersh for again uh taking your time off your busy schedule and uh the topic was very nice and I had to honestly read myself refresh myself in what the literature says because it's such a topic where most of us don't even know about how to approach a patient who has these issues of severe lV dysfunction then and how to offer revascularization to them. So thank you again it's my great pleasure to be. I think the reason I got interested in this was exactly that I wasn't sure what to do with these people. Then along came the trial and then you know I always used to get viability testing and then along came to trial and it certainly took two or 3 years of of quite serious thought to try and understand the trial and the viability sub study and the implications and I know find I think I feel fairly comfortable in making a decision in these patients. But the sicker they are, the more difficult it is the more you need the hot team and the input of the surgeon and interventionist and and the input from the patient. Yeah, I I thank you for your time. Dr Gersh. Have a good afternoon pleasure. Thank you.