Our speaker is Dr. Yousif Ahmad from Yale University School of Medicine. Dr. Ahmad will be speaking about the role for revascularization in patients with heart failure reduced ejection fraction. Dr. Ahmad did his PhD and Medical training in England before coming to the US for his interventional training. This is a topic that we clinically deal with on a regular basis, yet the data has been somewhat mixed. Will certainly be interesting to hear his approach to the overlap of CAD and HFrEF.
I don't know. What's the, now, this is great. You know, this has always been such a fascinating topic for me and I'm an eventual cardiologist. But, um, also I've, I've always had an interest sort of in heart failure and kind of the, the two fields between C and heart failure. Yeah, it's getting a little bit is a topic. Yeah, we, we, we struggle and discuss all the time. Yeah, I honestly think it's getting more confusing. Not less. All right, good morning. We'll give everybody another, uh, another couple minutes here to log on and then get started. All right, good morning, everybody. Um, welcome to cardiology grand rounds today. I apologize if multiple versions of me are popping up, but I'm not sure what happened, but the last uh, session as well, it looked like some non, non pen people were somehow getting into our grand rounds. Um, so we'll have to look into that but welcome. Uh, everybody. Today's CMV code is 89782. Again, it's 89782 and we'll be sure to put that in the chat um box as well. So it's my pleasure to introduce our speaker today. It's Doctor Yusuf Ahmed who joins us from Yale University. Doctor Ahmad is from the UK where he did his medical and phd training. He was a fellow at the Imperial College of London and Cardiology. Before coming back to the US, he trained at Columbia in Cedar Sinai in complex coronary and structural heart disease and is now an assistant professor of medicine at Yale and the director of their complex high Risk PC I program and associate program director for their Interventional fellowship, Yusuf uh was recently awarded the Sky 30 in their thirties award, the AC C Young Author Achievement Award and the C RT Young Leadership Awards. He's really become a leader and is part of multiple trials that study interventional therapies and heart failure, structural heart and refractory angina. So this is uh a topic that I know we all face quite commonly is the overlap between coronary disease and heart failure with reduced ejection fraction. You know, I've personally seen a number of patients that we revascularize and their LVEF improves. And I've seen quite a few that we revascularize in their LVEF does not improve and it's trying to sort through the risks and benefits of this and how to best identify and select these patients. So I know it's a uh a topic that clinically uh almost on a daily basis we're discussing and talking about. And so with that, I'm gonna turn it over to doctor Ahmad to give us his insight on this important clinical topic. Thank you very much. Um Thanks for that very kind introduction and for having me today. So I am gonna speak on coronary revascularization and systolic heart failure. Um These are my disclosures and I guess my main disclosure as Samir said is that I am an interventional cardiologist who has interest in sort of complex and high risk coronary revascularization. So I really do spend quite a lot of time thinking about, you know, the best way to sort of manage these patients. You know, what um is the evidence that we have at the moment? How best to apply it and what are the ongoing sort of evidence gaps that we need to address in the coming years? So we'll try and talk a little bit about um the indications um the evidence base, as I said, that exists at the moment and persisting evidence gaps and there will be more of a focus on percutaneous revascularization. Um This is I think getting a little bit more confusing and challenging um to think about when we should offer it. And then when we do offer it, what are the sort of overall considerations that we have when treating these patients? So I guess the first question is, should we offer revascularization and systolic heart failure at all? And this is a big scale problem. It's not sort of a small niche area. Um despite, you know, sort of advances in prevention and medical therapy. Ischemic heart disease is still the leading cause of death worldwide. And it's also the commonest cause of left ventricular systolic dysfunction and clinical heart failure. Um We know that patients who have heart failure from underlying coronary disease have a worse prognosis than those who have it from other etiologies. And I think everyone is familiar with these couple of meer plots now from the stitch trial. So the one I'm showing now is from the index publication in the New England journal in 2011. It's for the primary outcome of all caused death. So it all cause mortality. And you can see at the follow up of almost six years, the hazard ratio is 0.86 but the confidence intervals cross unity, the upper confidence interval is 1.04. So no statistically significant benefit at this time point, the P value is 0.12. Um but the curves are interesting. So the thicker line here is the bypass line and you can see there's clearly an excess hazard of mortality initially and that persists up until around this two year mark and then the curves cross and then they continue to diverge. Um and this uh other Kommas from the 2016 publication, what is the technically the stitches studies of the Stitch Extension? ST it's really just the long term follow up of the same trial. And you can see that with follow up now, out beyond 10 years, the curves continue to diverge, you know, to a certain extent. And now the hazard ratio is 0.84. But importantly, the confidence intervals do not cross unity. And so now this is a statistically significant benefit. So how do we explain these findings? I mean, honestly, the most important explanation is just a crawl of events which gives you more power and increases the precision around the point estimates. If we go back here, there's really not a material difference between these two results. In terms of the point estimates, a hazard ratio of 0.86 and a hazard ratio of 0.84. It's just that the confidences intervals are narrow. So we have increased precision, it no, no longer crosses unity and it's so statistically significant. But we also have that phenomenon that we see that the overall number of deaths is greater in the bypass surgery arm in the first two years. And those curves don't actually cross until after two years of follow up and two years is honestly quite a long time. And if you look at even shorter time periods, uh bypass surgery at 30 days is associated with a threefold increase in mortality compared to medical therapy. So I think this is the way we can reconcile, um, the discrepancy in the findings of the initial follow up and the subsequent publication. And how does that translate through to how our patients get treated. You know, we have evidence now that bypass surgeries uh leads to a reduction in all cause mortality, but it's really seldom used. So there's a study from Dan Doshi and Jack in 2016, which shows that just over 1% of hospitalized heart failure patients only give bypass surgery within 90 days. And in that same study, the rates of coronary angiography and then percutaneous revascularization are also very low. And there's also general data showing that patients who present with clinical heart failure are amongst the least likely to be offered revascularization, probably due to, you know, underlying risk and comorbid conditions. So we know that bypass surgery and the s you know, stitch extension study reduces all called mortality. But we know that patients with heart failure rarely get it. And you know, we have to try and understand why that's the case um to try and move the field, you know, a little further forward. The first reason is, you know, it's a reflection of a randomized trial versus real world clinical practice. You know, by definition, every patient who's in the stitch trial was felt to be an acceptable candidate for bypass surgery, both by their, you know, treating clinicians who are willing to enter them into the trial. And then the research team that assessed their eligibility. And importantly, all of these patients were willing to undergo bypass surgery, you wouldn't be in the trial. Otherwise I think that, uh, hazard, um, is an important reason why patients don't end up getting bypass surgery. Patient may be fearful of the upfront complications. The referring, you know, clinician or cardiologist may also be wary of it. If you look in a more detailed stitch, 25% of patients developed a serious complication early after bypass surgery and those, um, early serious complications were associated with subsequent mortality. We all, you know, if you, again, if you look at some subsequent publications, the benefit of bypass surgery diminishes with advancing age. And I think that for a lot of us, um a lot of the patients we're seeing, you know, on service and in the clinics with coronary disease and advanced ventricular dysfunction are relatively elderly. Um And there is a signal that or a sign that the benefit diminishes with time and many patients simply cannot undergo surgery due to comorbid conditions or will not undergo surgery. I will tell you that the latter, the sort of unwillingness to undergo surgery having trained in the UK and then moved over to the US is certainly more of an American phenomenon than it is. I think in um, in the NHS, if you tell a patient that they should get surgery, they, they'll just say yes and have it done. And you know, the concept of, you know, while patient centered care is very important, we want to tailor to patient, you know, values and preferences. That's something that I see much, much more often over here than I did in my training in the UK. And I think that this summarizes it best. This is from the New England Journal editorial uh for the subsequent publication, the 2016 paper. Um and it states that there's an appropriate tension between the durable long term benefit of bypass surgery and the early mortality associated with the intervention. And I think that this is what, you know, we wrestle with all the time is uh is that upfront procedural risk gonna be worth it to this individual patient that we're treating in, in front of us? Um And are we gonna be able to persuade them to accept that upfront hazard is a for the long term benefit. And again, that depends on individual patient factors, comorbid conditions, life expectancies and the patient's individual sort of values and preferences. And so we know that, you know, ischemic systolic heart failure is highly preven prevalent, it's lethal and you know, it has a major burden to healthcare systems. Globally, we have an effective treatment strategy which is, you know, proven with randomized control trial, evidence of the reduced mortality, but it's clearly underutilized across the population. And I think if you look at those factors together, that really is an unmet clinical need, you know, we need to try and offer patients something that is gonna help reduce the burden of both to individual patients and the healthcare systems of, you know, ischemic systolic heart failure. And I think that up until recently and probably honestly, even until now, this is the kind of what I call the natural rhythm of these ischemic heart failure patients. They get a new diagnosis of heart failure. Hopefully they get some type of ischemic evaluation. Let's say coronary angiogram, they get multi vessel or severe coronary disease demonstrated on the co coronary angiogram and get appropriately evaluated for bypass surgery. Um because we know that that reduces mortality, but then something in the testing shows that they're not a candidate, too high risk or the patient doesn't want to undergo bypass surgery. And I think that would trigger an immediate referral for PC I. And I think this is the kind of pattern that we see in clinical practice all the time. And I think that, um you know, we'll talk now a little bit about the revived trial. But I think that even since revive has been published, I haven't seen a huge change in this sort of natural sort of chain of events that you know, you go down this cascade and it it ends always with a referral for PC I and these high risk patients. So the revived trial was really trying to find evidence of benefit of PC I. And it's predicated on essentially what the stitch trial showed, which is a long term benefit in patients revascularized with bypass surgery, but a short term procedural um hazard and an increased mortality. And so if we can revascularize these patients in a way that is not associated with that upfront risk, are we gonna get that long-term benefit without the trade off upfront? So that's the premise of the trial. Um They enrolled patients with extensive coronary disease and they judged it by something called the sort of beis jeopardy score. Uh The ejection fraction was 35% or less. And we'll talk about that a little bit later that both trials, you know, really had a fairly, you know, advanced ventricular dysfunction in terms of the patients studied and they had to have viable myocardium. The principle behind that being, they were trying to select the patients they thought would benefit most from revascularization. Now, uh viability was not mandated in stitch in the patients that in which it was done, it wasn't shown to sort of predict benefit with bypass surgery. But nevertheless, this was the way the trial was designed and the idea behind that was to sort of enrich the trial population with the patients that the investigators felt were most likely to benefit from revascularization. And the primary end point was a composite of all cause death and heart failure hospitalization. And there are around, you know, 700 patients total stitch was around 1200. So a much, much smaller trial, but this is the k of my plot for that um combined primary end point, which is again, all cause death or halfway to hospitalization and it's really identical. So the hazard ratio is 0.99 the number of events is almost identical. And there's, although, you know, median follow up, I think is 3.4 years. And people have said, you know, we need to follow these patients up longer which we do um to see what happens to them, particularly informed by what happened in stitch. But there's no real crossing of the curves or a hint that if we follow these patients up, that all of a sudden, we're gonna see a mortality benefit um emerge with PC I. And if you look at the early portion of the Kaplan my curves, there's also not that upfront hazard in the PC I so PC I seems safe, but despite not causing this upfront procedural hazard that bypass surgery does just because it's a less invasive therapy that didn't translate to sort of a benefit in long term outcomes. Um These are some of the secondary end points, you know, ejection fraction um didn't significantly improve. There was some benefit in symptom um profile for the patients as assessed by the KCCQ score. Um That benefit um was more pronounced at six months, still present at 12 months. It is attenuated at 24 months. Um Couple of things to say about that is that obviously, um after randomization, patients in the medical therapy are more able to be revascularized at some point and 10% were that may explain some of this attenuation of benefit. And I know the investigators are looking a little bit more in detail at this sort of quality of life endpoint. Um, and it's also an unblinded trial. So it's, uh, you know, in the wake of Orbiter and other trials, you know, I think assessing symptoms in an unblinded trial is challenging and maybe that upfront placebo effect explains some of the benefit and symptoms early. Um can't say exactly with the data. Um but there was a, you know, some benefit in terms of um quality of life, some caveats, you know, revived, excluded patients with acute coronary syndromes. I think that's important to remember a lot of the time we're assessing these patients, they are admitted with an acute coronary syndrome, they're decompensated, they're hospitalized and they're not necessarily the patient population that was studied in revive. If you look at um the symptom profile, actually the vast majority, if you just initially look at heart failure symptoms, nyh a functional class, the vast majority um were asymptomatic or mildly symptomatic. So in class one or two, and if you look at Angina, the vast majority of patients had no angina and I think unacceptable Angina was a exclusion criteria, but near, you know, hardly any patients had clued through a worse angina. So this, you know, trial doesn't really apply to patients with significant angina. Some people have felt that maybe these patients weren't ischemic. Maybe they had coronary disease and systolic dysfunction. Although viability testing was mandated, ischemia testing was not. And um you know, some people feel that maybe an absence of angina is a surrogate that these patients weren't actively ischemic. I don't know, can't tell from the data that's available to date. But what we do know is that these patients did not have significant angina. There was less unplanned revascularization in the PC I arm, which was statistically significant. Overall, myocardial infarction rates were not different, but there was less spontaneous M I in the PC I, if you look at overall M I rates including per procedural M I, um that's why it was neutral because obviously you can only have per procedural mm I in the arm that has a procedure um but spontaneous M I was significantly reduced with PC I. So in the wake of sort of these two trials and you know, the natural sequence of events and those natural rhythms that I showed you before. The question is, who should we now offer percutaneous revascularization to um I think acute Coronary syndromes, there's good evidence in patients with and without LV, dysfunction that you improve harder end points of death, cardiac death and M I revascularizing with PC I patients who have angina and unacceptable angina. Despite medical therapy, I think that's still a very, very strong indication to offer percutaneous revascularization. I will say that I'm more inclined to offer it to younger patients. Now, this is not necessarily evidence based, but I do feel that um that might be a patient population that is more likely to benefit and the risk benefit calculus becomes very, very important. I think almost by definition, patients who are referred for percutaneous revascularization in the context of ischemic heart failure are not surgical candidates because you know, surgery is generally considered the first choice. And so these patients have comorbid conditions, the coronary anatomy may be adverse and you really have to do an important risk benefit analysis and decide, you know, when you might want to proceed. And so what I would say that is that now in the wake of revived, we should have a natural pause before I think, you know, immediately pursuing PC I for the majority of patients, I don't think it should be an automatic trigger. That patient is not a candidate for bypass surgery and they should immediately be referred for for PC I. You know, our approach and my approach here is, you know, true, true multidisciplinary assessment. It's very important to engage in the cardiologist who's looking after the patient, uh the advanced heart failure physicians and the cardiac surgeons. And you know, we will nearly always see these patients at the bedside together and get together with the surgeons and decide what the right approach is. And a lot of patients are referred for PC I by cardiac surgeons. And there are a lot of patients that we're asked to revascular percutaneously that, you know, we sit together and we think, you know, we think surgery is the best choice. So there's really no competition between the surgeons and the interventionists. And it really, really is a multidisciplinary assessment. And I do think that when you take the time to have that multidisciplinary assessment that it leads to better outcomes and we have honest discussions with the patients about the available trial data and what we're hoping to achieve with revascularization. And you know, I'll be honest with them that we have a trial that will show that, you know, your rates of death and, and heart failure, hospitalization weren't shown to be reduced. The procedure was it was safe, you're less likely to need further procedures, maybe less likely to have big spontaneous myocardial infarctions and some evidence that you'll feel better for at least a year and for a lot of patients that's important. And a lot of patients don't necessarily have horizons of, you know, multiple, multiple years of, you know, thinking of how they're feeling they wanna get out of the hospital, get stabilized, feel better. And I think, you know, in certain cases with judicious sort of case selection, we can achieve that for them. I do think in the absence of A CS, there is no rush to immediately perform revascularization for most of these patients. Now, obviously, there are exceptions based on, you know, individual patients and you know, we have to be clinicians first and foremost and understand when it's urgent when it's not. But for the vast majority of ischemic heart failure patients, if they haven't had an ischemic, an acute Coronary syndrome, and they don't have very, very high risk coronary anatomy. The data tells us there's no rush, we can treat them medically, we can see how they're doing in the outpatient clinic and then we can decide at that time if they need to be revascularized. So what is in the wake of, you know, the data that we've looked at what is, you know, a contemporary way and to sort of think about these patients and you know, when they get referred for PC I I think the clinical presentation is important, you know, there's a vast spectrum of ways that patients with ischemic heart failure can present and they can be ambulatory and referred into the outpatient clinic and walk in or they can be, you know, in cardiogenic shock and on the other end of the spectrum, and you know, that clinical presentation is obviously very important both in terms of what you can offer, how quickly and other factors that you might want to take into account such as, you know, hemodynamic support, et cetera. What is the coronary anatomy? You know, it's um there are certain anatomies that are very favorable for PC I, there are certain anatomies that you really think there's a clear link between the coronary disease and the systolic dysfunction. And you feel confident that revascularizing them might improve the ejection fraction. And there's some that isn't, you know, you can have three vessel disease that is, you know, focal lesions and the distal vasculature that really isn't gonna improve someone with an ejection fraction of 20%. So you need to have a detailed analysis of the coronary angiogram, try and link it to the ventricular function, any other data you have available? And that ventricular function is important in terms of when we're offering, thinking about offering PC I because there's a big difference between a patient with an ejection fraction of 35% and a patient with an ejection fraction of 10%. We do try and get invasive hemodynamics really in nearly all of these patients, at least the LVDP for nearly all the right heart catheterization age is important both in terms of um how ambitious you want to be with revascularization and also the patient's ability to tolerate, you know, invasive procedures, which might be extensive ability of a patient to tolerate a complication should one occur. And these are the other sort of comorbid things that we think of frailty renal function, the bleeding risk. What's the peripheral vasculature? You know, how are we gonna get to the coronary? Do we have access to support devices and bailout options? Which I think is very, very important to both think about and have a clear discussion with the patient, the family and other stakeholders. I do think, you know, we have these concepts of risk and complexity that I do think get um tangled together and it is important actually to disentangle them. And a patient really doesn't care if they're disease is complex for us to treat. It's not patients fault that they have severe calcification of chronic total occlusions and technical complexity in and of itself should not be a barrier to offering rev vascularization. Now, complexity tracks with risk often but they're not the same, but procedural risk is much, much more important to me. And it's something that, you know, I'll have an honest conversation with every patient about what I think they procedural risk, it's a major adverse complication. Um and for some patients that it's not, they're not willing to accept that degree of risk, which is fine, but you have to have an honest conversation with them about what that risk is. And as I said, I think risk is a much more important determining factor for me in terms of revascularization and complexity alone. So I try and only start these cases when the patient is relatively optimized unless there is some, you know, urgency to the situation. Um You know, the interventional fellows are always very disappointed when you know, a patient comes down to the lab and they're scheduled for, you know, impeller and atherectomy and a left main PC I and they end up just getting a right heart cath. And that's it because if the patient isn't optimized, if their, you know, wedge pressure is 35 it's, you know, you really do not want to be undertaking a long complex procedure with high potential for hemodynamic, you know, instability, periprocedural ischemia, et cetera. So unless it's really, really urgent, I try not to start these cases until the patient is optimized. And we do rely on the invasive hemodynamics a lot and you have to act on that data. You can't just put the right heart cath in and forget about it. You know, you need to speak to whoever is in the CC US managing the patient, follow the patient up on subsequent days and make sure they're making progress. So you can bring them back in a more optimized state. If there's an obvious culprit lesion, particularly in the context of an acute coronary syndrome, I will treat that initially. If there are chronic total occlusions, I will essentially always treat the non chronic total occlusion lesions. Initially, I think that that will make subsequent procedures safer. I do think patients with ventricular dysfunction, it is um important and this is in the absence of good data to support it, but I do feel myself that it's important to try and get complete revascularization. Now, I say reasonably complete revascularization because you want to look at the risk of getting complete revascularization. Um And you want to look at, you know, the subtended myocardial territories, it com getting complete revascularization doesn't need mean you need to stent, you know, every juice marginal and diagonal branch. But I think that in these patients with, you know, ventricular dysfunction, if you can get the major territories adequately revascularized safely, that that will be beneficial. But this is often in stage procedures and you know, what we want to do is do as much as is safe in one go. But certainly we don't want to cause too much ischemia, too much human dynamic deterioration. And if we can re give them a portion of revascularization helps the patient get stabilized, get off the IC U, get out of the hospital when they come back for a subsequent procedure. It's nearly always safer when you've perfused the other territories. Already. I have a relatively high threshold for LV support. Honestly, we don't use um a huge amount and we'll talk uh briefly about some of the criteria. And as I mentioned earlier, the bailout options I think are very important to think about and define and discuss ahead of time. What you don't want to be doing is be two or three hours into a complex high risk intervention and then things aren't going well. And you're trying to, you have a million other things on your mind. You're trying to make a calculus of, you know, should we put this patient on ECMO? Is this patient a candidate for advanced therapies? Is this procedure, sort of the last shot. You want to have those conversations upfront and there are certain patients that will bring to the Cath Lab and the patient and the family will know we're gonna try Coron review revascularization. And what we're gonna do in the Cath Lab is the ceiling of care and we're not gonna escalate beyond that for certain reasons. And there are some patients that we say ahead of time. You know, if things don't go well, um we're gonna try and get them on, you know, advanced mechanical support, explore advanced therapies and then you wanna speak to everybody, the advanced heart failure team, the C IC U, the CT IC U all ahead of time. So as I said LV support is, you know, I if uh you know, I generally have a pretty high threshold, again, ejection fraction is a spectrum, you know, a patient with an ejection fraction of 35% compared to 10%. There's a big difference. Uh What's the RV function? What are the filling pressures? The P A saturation? Are we gonna need to use Atherectomy which can lead to more ischemia during the procedure? What is the um coronary anatomy? Are we working on the last remaining vessel? And every time we have a balloon inflated, the heart's gonna essentially be anaerobic or is there good backup perfusion from other territories? Um Again, per procedure with ischemia from balloon inflations or, you know, ref flow or interruptions of blood flow issues with side branches. And honestly, it's not one or two of these factors that will lead me to using a a hemodynamic support device, but you really need to have a lot of them. So if we're just doing atherectomy in a patient with a low ejection fraction, almost will never be a mechanical support case to me. But if I'm doing ar in the last remaining vessel and the ejection fraction is very low and the index and output are low, then yes, maybe in those cases, I will use hemodynamic support. Um This is an area that needs to get studied more. You know, we need data first to show if there's a benefit of using this these devices for high risk PC I. And then hopefully, if we can establish that data, we can try and figure out which of the patients that are really gonna benefit. And I obviously look at the peripheral vascular anatomy um and the bleeding risk to decide if we're gonna, you know, put a large ball device in. So these are a couple of, you know, quick case examples. We won't go into the technical aspects too much but really more about the decision making. This is a 46 year old male. He was known to have ischemic systolic car failure. He had a prior inferior myocardial infarction had multiple interventions to a right coronary artery. His ejection fraction was around 25% and importantly, he had angina as well as Disney and fatigue. He has um you know, a distal left main lesion which affects the tr education with a large ramus circumflex and significant proximal L ad disease. He has a chronic total inclusion in a stinted section of uh the right coronary artery and he is appropriately referred for bypass surgery, but the patient adamantly refuses bypass surgery. And if you actually look in the notes, then there's, you know, it's written that, you know, patient had lack of insight, et cetera and you know, is jeopardizing his, you know, health by refusing surgical intervention. But when you speak to the patient, he actually had a fairly sensible uh outlook and that he was 46 he'd done his research and he has read about the concept of graft failure and he was worried about what was gonna happen if he had bypass surgery at 46 and his vein grafts, you know, went down in 5 to 10 years and he's in his early fifties. So it wasn't, you know, he was appropriately referred for bypass surgery. I think that is the first choice for him. But his reasons for not wanting to undergo surgery were not, you know, insane at all. So he was referred for consideration of PC I. So when I met the patient and consented him, you know, I told him it was a higher risk procedure. Um, he had a left main lesion which was a trifurcation. He had low ejection fraction in a right coronary. CTO I think I told him that his risk of adverse procedural um events and complications would be in the order of 5% I thought, and that stage procedures were necessary that I wasn't gonna try and do everything in one go and that would be, you know, I thought that would put him in harm's way. And in this case, I decided to use LV support because his right coronary was occluded. And we were working in a left main which had three important sub tender branches and we were gonna frequently be interrupting blood flow while doing our balloon dilatations. Uh So we put an impala in, in this case, we didn't do the single axis technique because we wanted an A French guiding catheter with, you know, three branches. When we do these tr applications, I tend to pick two branches and do two stent techniques in those two branches and then just rescue the third with kissing balloon inflation. So that's what we did for him. And then we brought him back in a few weeks and did the right coronary CTO and he's done well. He's, you know, asymptomatic, I did that a couple of years ago, his ejection fraction improved to the forties. And you know, the most important thing for that I think was the um indication, you know, he did have Angina, he was young. Um He had a left main lesion and included, right? Coronary. So have high risk coronary anatomy. So I think warranted revascularization. And as I said, I think the referral for bypass surgery was completely the right thing to do, but you can't force patients to have, you know, interventions that they don't want to have. And I think in his case, PC I was certainly preferable to medical therapy. Second cases of 55 year old male, slightly different. He'd had prior bypass surgery had very, very severe LV, dysfunction with an ejection fraction between 10 or 15% depending on if it was by MRI or echo. And in May of 2022 he had an end stem at another hospital. Um His native coronary were all completely occluded. Um His vein grafts to the sec in the right coronary were completely occluded chronically and he had an acute thrombotic occlusion of his sinus vein graft to his L AD which was not intervened on for some reason, I don't know why he never had a, a mammy. Um And he was actually referred to our program for transplant assessment, but when he met with the transplant team, his predominant symptom, it was angina. So this is the Coron angiogram that he had with us, you know, chronic total occlusion of the circumflex, completely occluded led in the mid segment and then a completely included right Coronary in the mid segment two. And all of his bypass grafts were occluded. So this was a patient, as I said, referred by the advanced heart failure and transplant team. And rather than being what I called a high risk procedure, I told him this would be a very high risk procedure and that the chances of things going wrong. And at least in the index procedure were probably in the order of 20% all of his grafts were down, all of his natives were down. His ef was very, very low. Again, mandatory stage procedures. And this was another procedure that I felt at least initially we would do with hemodynamic support due to him not really having any patent coronary. And we had decided upfront that in a case of acute deterioration where if we couldn't wean him from the temporary M CS, we would proceed with full escalation of support. Um So this is the first procedure with an impeller uh dual injections and we were able to open the L led uh by an Antegrade approach uh and stent that for him. And he actually did well after that, um we were able to take the impeller out, I think the next day and he went home a couple of days after that, we then brought him back for the right coronary and retrograde on this case with the led being open, I didn't use uh hemodynamic support and we were able to get his right coronary opened in Stanford with a good result. Uh And this is his note from epic from the transplant team which is says spoke to Mr Blank. He reports drastic improvement in symptom profile after staged interventions reviewed decline for listing from heart transplant wait list due to improvement with alternative treatment modalities. So, you know, we can make a big difference for some of these patients with percutaneous revascularization. Um Again, his predominant symptom was Angina. Um I don't know if there is something there that you know is predicting benefit for these patients. Um And again, this was a true multidisciplinary collaborative approach, you know, referred by the transplant team. And you know, we all sit together and think about the best way to get the patients through and if things don't go well, what approach we're gonna take. So in the last uh few minutes, I want to talk about, you know, some of the evidence gaps we still have for these patients. And it's honestly a lot. Um you know, we have two randomized trials, but I think we have, you know, at least as many questions as answers at this point. Uh to my mind, there are four very important unanswered clinical questions for these patients, populations of coronary disease and heart failure. The first is have advances in contemporary medical therapy. Alter the value equation for either bypass surgery or PC I I think it comes up often. What would the result of stitch be if it was conducted today? What is the role of revascularization in patients with less severe forms of systolic dysfunction. Is there a potential for us to intervene upstream in the disease process that might give us more benefit rather than at the, you know, more extreme end of the spectrum with very low ejection fractions. What about patients with heart failure, clinical heart failure and preserved ejection fraction? Is there, is there a role for revascularization there? And what is the comparative efficacy of these two revascularization modalities for these patients? So in terms of, you know, whether this value equation of either bypass bypass or PC I has changed, you know, this needs new randomized evaluations of revascularization in the era of you know, device therapy, SGLT two inhibitors, et cetera. There is a trial which I think is being run out of Brazil which is completed enrollment uh 600 patients with um angina multi vessel disease and low ejection fractions. Well, they'll get randomized to bypass on medical therapy. I think it's taken a long time to enroll and you know all of these trials, if they take a long time to enroll, by the time the results come out, there's a risk of obsolescence if there have been even more advances in medical therapy, but we'll at least get an updated evaluation of bypass surgery hopefully soon. And as I said, is there a role for revascularization earlier stitch and revive both used ef up upward cut offs of 35%. There is a substudy from ischemia and ischemia was excluded patients with very severe systolic dysfunction. Um and this is a secondary analysis of uh overall neutro trt. So it, you know, couldn't be more caveat. But that substudy of patients with ejection fractions between 35 and 45% suggested invasive management. Remember, invasive management isn't revascularization per se, but invasive management was associated with better events, free survival um that was published in circulation. And if you look at the Captain Meer Curbs, you know, the, the group that is doing worse, this, you know, um dashed black line is conservative therapy with heart failure and LV dysfunction where they are, um event rate is very, very high. And if you have the same patients uh in terms of heart failure and LV dysfunction, but they manage invasively, the event rates are much lower and they're much closer to the patients who are um have no heart failure or LV dysfunction, whether they're treated invasively or medically. So, again, I don't know if there's something there. It's, you know, no firm conclusions can be drawn from something like this. But I wonder if there might be a role for trying to intervene a little earlier. And patients with preserved ef we know it's very common um to have obstructive coronary disease in patients with heart failure and preserved ejection fraction, we know those patients have worse prognosis. Obviously, that makes sense that that a group that has coronary disease versus no coronary disease. Is gonna have a worse prognosis. Um But it's a potential therapeutic target for a population that doesn't have many effective therapeutic targets. And I think it is worth being studied. And the last question is, what is the comparative efficacy and safety of PC I and bypass surgery? And we really can't make cross trial comparisons of A and PC I on the basis of stitch and revive, that's not possible to do for sort of myriad reasons. Um We can only understand their comparative effectiveness by performing head to head randomized comparisons. And there has been an international consortium established to try and answer this question. And the way this consortium is gonna work is that um investigators in all of these countries are seeking their own independent funding and performing their own independent trials with an agreement to at the end pull their data for the outcome of all cause mortality. Um And so the UK has got funding. I think Australia Canada Sweden have funding. Um We're trying to get funding in the US. Uh Another application is going in soon. Um But I think that would be very, very powerful data if you know all of these countries are able to run their individual trials and then we can pull them for the outcome of all cause mortality, comparing PC I and cabbage. Um that will be very valuable data. So I will start to wrap up. Um In conclusion, bypass surgery is associated with reductions in long term or cause mortality compared to medical therapy in patients with ischemic systolic heart failure. Despite that, it's seldom utilized, perhaps due to that upfront procedural hazard that we discussed PC I. When it was studied in its own randomized trial, the revived trial was not associated with that upfront procedural hazard, but there was also no beneficial effect on all cause death or heart failure, hospitalization. At 3.4 years of follow up, there were benefits, maybe I would say modest benefits in quality of life, less spontaneous M I less unplanned revascularization. PC I is almost always technically feasible in these heart failure, patients with advanced ventricular dysfunction. But that doesn't mean it should be offered to every patient. Appropriate patient selection is much more challenging than technically performing the procedures particularly in the wake of the revived trial. It's honestly, as I said, at the start, made things a little bit more confusing for us. I think a true multidisciplinary heart team evaluation is essential and that involves, as I said, the referring cardiologist, who knows the patient the best, the heart advanced heart failure team, cardiac surgery, uh and interventional cardiology. And I think it's so helpful when those discussions can we have sort of face to face together at the bedside with the patient, et cetera. And you know, having good collaboration between all those departments is essential to get good outcomes for these patients. And I do think that that is what leads to good outcomes is that really, you know, true multidisciplinary assessment. And despite these two trials, and despite, you know, our decades of clinical experience, there are still multiple persisting evidence gaps. And we really do need new randomized data to better inform therapeutic decision making for coronary revascularization and heart failure. So I thank you very much for your attention and that I hope um on time. All right, uh you said that that was perfect. Uh You're perfect on time. And once again, thank you for joining us. You did a great job taking a very complex clinical um common problem that we face and, and helping us see your uh your approach to this. So I apologize my, my computer, of course, rebooted in the middle. So I, I lost some of the um some of the questions that were coming through, but Linda is helping me get these back in order here. So with our, with the next few minutes, um would like to walk through a couple of just getting your approach and, and questions here. So one has to do, I think with what I've always struggled is this idea that you've got a lot of patients with heart failure. You've got a lot of patients with coronary disease and, and where is the overlap in terms of causality? And it's very hard in a clinical trial because you're trying to make enrollment kind of broad enough to actually feasibly enroll in a study yet specific enough to answer the clinical question in need and just want to get your thoughts on that and, and do what do we do to tie those in together and better identify which patients truly have a cardiomyopathy because of coronary disease. Yeah, I think that's a great question. Um And I wish I had a great answer for it. I mean, the truth is there is no one test that is gonna tell us that the coronary disease is causing the systolic dysfunction. And I think that, you know, as clinicians, we are very good at um interpreting complex clinical data and assimilating it and making it, you know, judgment. But that is, as you say, very hard to replicate in a clinical trial. And that kind of detailed uh complicated clinical decision making is very, very difficult to do in a clinical trial. And if you look at a trial like revived, you know, a lot of the patients had two vessel disease and the mean ejection fraction was in the 20%. And so it's hard to believe that, you know, two vessel disease leads to very, very severe LV dysfunction like that. Um And to your point, if you're very strict in inclusion criteria trials are gonna enroll so slowly that they're gonna have no sort of um you know, clinical value. I do wonder in this population if angina might be an important determining factor and that patients who have Angina might be the ones who are gonna benefit from revascularization, not just on a symptom profile, but whether that Angina is a surrogate for really active ischemia and whether they're gonna benefit prognostically from revascularization um revived, as I said and had almost no Angina. We often put um you know, intrusive angina or unacceptable. Angina is an exclusion criterion in all of these trials because we revascular, these patients for symptomatic benefits. But we may be systematically excluding the very patients who will also get a prognostic benefit. How do you work in viability testing with your your decision algorithm? And do you have a preferred method of viability testing? Um I am honestly, I think so, the answer to that depends on your local expertise. I think that if you're in a program that does a lot of MRI and every, you know, your MRI department is um you know, strong and you know, there's a high volume going through, then that's great. If you're in an area where there's different types of expertise, I think it, it's important to tap into your local expertise. The truth is I don't do a lot of viability testing for these patients. A lot of them have had viability testing. By the time I've seen them, the reason being is um you know that when I show you those sort of natural rhythms of how patients get assessed, they'll get their angiogram, they'll have very severe coronary disease and severe LV, dysfunction, they'll be referred for bypass surgery. The surgeon will be uh for some reason, I keen on bypass surgery will ask for a viability test. And if there's no viability, they'll say they won't perform bypass surgery. So a lot of patients have had viability testing. Uh By the time I see them, I will say that if I'm um if patients are symptomatic that I will, um, revascularization is technically percutane revascularization is technically feasible, that I will offer it. Irrespective of um the viability testing. If there is no viability, let's say on the viability testing and the patient's not symptomatic, then I would endorse just continuing medical therapy for most of those patients. You know, when, when you look at the overlap of, of cardiomyopathy and, and coronary disease, we've, we've seen patients that we revascularize and, and they get better and they tolerate it and we've seen ones that we revascularize and they really struggle and, and I think we, we see that in some of the, the trial form from the cabbage side, I was a little surprised from the um on the PC I side that we didn't see some short uh sort of procedural related complications because, you know, I think we've all had patients where the revascularization go. It it's complicated but it goes very smoothly and yet we struggle with weaning off the, the support afterwards or, you know, over the subsequent 6 to 24 hours after the PC I, even though everything went great and you finish with Timmy three flow, they actually deteriorate and get worse. And again, picking the patient that, that will benefit. The greatest I think is still what we challenge with. And I was a little surprised in some of the trials that we didn't see more procedural related PC I complications. Yeah. And um you know, it provides as a UK trial. And so um hemodynamic support was used honestly very sparing impel is not, you know, uh widely available or utilized in the UK. I think that, you know, you're completely right that nearly always when we percutaneously vascularized, these sort of sick cardiomyopathy patients, even if things are perceived to go very smoothly in the Cath lab, we nearly always make them temporarily worse. So when we have the right heart cath in even if the case has gone very, very smoothly, the P A saturation is nearly always like 5 to 10% lower at the end. Um And I'm sure it's just to do with, you know, transient balloon occlusion and temporary ischemia. And you know, when we do that in a quote unquote normal patient who's got all the other coronary of patent and the LV is fine, they obviously sail through, but in these sicker patients, they don't tolerate it as well. I think part of the reason that revived had less per procedural complications than we expect is that these were predominantly ambulatory patients they weren't sort of decompensated, you know, patients coming down to the Cath Lab from the CCU these are patients seen in the outpatient clinic, you know, CCS class one, most of them ny A class 1 to 2. And I think that, you know, when I'm uh consenting patients, you know, the inpatient who have been admitted with the decompensation are the ones that I'm very, very nervous about and the ones that, you know, I'll tell the patient and the family that, you know, it's almost inevitable that will make you temporarily worse with what we do. Um That's why stage procedures also ends up being very, very important. I think, you know, particularly when you have a hemodynamic support device and the temptation can be due to do more and more and more. But there's always a, you know, cost to pay on the back end in terms of, you know, the the ischemia that we induce in multiple territories. Um but it's often better to set more um modest objectives for an index procedure, revascularize one territory, hopefully don't cause too much ischemia. Let the patient recover. And then when you come back to do subsequent territories, they're nearly always better tolerated because you've secured perfusion in a remote territory, you've let the patient recover and they're starting from a much better starting point. Um But yeah, I think in revive probably the lack of complications is because these were stable, you know, ambulatory outpatients. Um but yeah, the ones that really worry me are those, um, de, acute decompensated patients that we nearly always make worse. And for those, um, even with the utilization of a support device, I try and not sort of bite off more than I can chew and do too much in one procedure such that they'll really, really struggle to recover. The next question has to do with proximal disease versus diffuse distal disease. And the question that came across it, it reads cabbage with LV, dysfunction and more distal disease seems counterintuitive, isn't the most benefit with left main and or proximal disease. I I would say yes, I think it depends on the severity of the distal disease. You know, the distal disease is very bad and it precludes um adequate targets for bypass surgery that really the hazard of bypass in those cases um might not be worth it. Now, at the same time, very diffuse distal disease is not um good for PC I. And we know that from non LV, uh dysfunction studies that um you know your in um you know, some of the physiology studies in Orbiter and some of the subs studies when you do a pressure wire pull back across the coronary tree and you see very diffuse disease versus very focal disease. In terms of the pressure drop, the patient with focal disease do much, much better. They have much better post PC I physiology. And they also have a lot less angina. And so I think that these patients with diffuse disease are a real challenge. And often these are patients with diabetes. And we immediately think, you know, diffuse multi vessel disease, diabetes, they should have bypass surgery. But you know, whoever's asking the question is completely right, that if they have a lot of diffuse disease, the benefit of bypass is gonna be less. But we also don't have good percutaneous revascularization. And, you know, we have for patients who have very advanced LV dysfunction and very diffused coronary disease, we have foregone revascularization and if they don't do well medically, we pursue advanced therapies for these patients. Next question is, how does renal function play a role in your decision making? Um, a lot to be honest. Um I would say that when I've looked um retrospectively at my own data, you know, case logs and case reports, the patients that have done very poorly and no one will be surprised to hear this, you know, advanced renal dysfunctional dialysis patients. And it really seems that no, you know, no matter what we do. Um in terms of revascularization, those patients prognosis is very, very poor. Um, it's hard not to offer them something. You know, these are very, very sick patients and with dialysis invariably, you know, are not candidates for bypass surgery or don't do well with bypass surgery. Often our surgeons have the same, you know, reaction that, you know, the benefit of surgery may be much, much less pronounced in these patients. Um, you know, we know from stitch that to get a real benefit for cabbage, we need to follow patients out to 10 years and, you know, for, for, for a lot of dialysis patients, their horizons, you know, aren't that long. Um, but I have been struck, um, looking at, you know, patients that we've revascularized as a group myself or the surgeons with very advanced renal dysfunction and with um particularly the ones that are already on in stage renal failure on dialysis, just haven't done well. In terms of, you know, technical considerations, you know, there are um you know, hemodynamics is very important if the patient isn't already on dialysis, um getting the filling pressures correct hydrating them correctly. And then we can use very, very little contrast for the vast majority of these cases. Now, these are almost always staged interventions, meaning that patients already had a diagnostic angiogram. And so, you know exactly what you need to treat and with the use of IVIS and other techniques, you can do it with very, very little contrast. Sometimes that gives you the added benefit that it stops you from trying to do too much revascularization in the procedure because you're cognizant of the renal function, you're cognizant of the contrast use. And the patient actually probably benefits on both counts both in terms of their cardiac function from you not causing too much ischemia. And also from their renal function with not using too much contrast, you know, in the last couple of minutes. Um I'm gonna ask you if outside of revascularization, um I know it's a whole separate talk but any if you have any quick thoughts or ideas on other percutaneous options for treating heart failure patients, um, outside of, of re vascularization. Yeah, I think it's um, it's a fertile area for sort of um research growth and there's a l you know, there's now almost a whole field of transcatheter therapies for heart failure. Um in terms of established therapies that we have that are proven to work, obviously, um transcatheter um edge to edge repair some mili. So if the pa if your patient has, you know, systolic heart failure and they have um moderate to severe micro regurgitation and you know, that is a therapy that has an RCT evidence of benefit. We've done some cases here of, you know, LV restoration and as part of the Kinch Aisin trial um that, you know, device I think was initially in for much for regurgitation. And now it's being used just for patients with, you know, LV, dysfunction. Um I think with all of these um novel devices, it's, you know, it's very interesting and exciting, but it's really a wait and see. Um we have to see, you know, if, you know, it takes a long time to get a new novel device therapy from the point where you're trying to do it in the Cath lab in the first couple of cases to the point where it might be routine clinical practice. Um We have to perfect techniques that technology has to iterate. Then you have to get to a point where you can do a randomized trial and then the randomized trial has to be, you know, beneficial. So, you know, I'm excited by a lot of them. But um you know, I've always have, you know, a note of caution because there are just so many steps you have to get through to get these types of therapies, you know, to be able to deliver them to patients on a routine basis. Well, with that, uh you know, I wanna thank you once again for joining us, um enjoyed your talk and I, and I think it really helps us, hopefully start to understand how we should approach these patients and hopefully help as a heart team. We do it very similarly, you know, where it's a heart failure, interventionalist and the surgeon working together to try to make these decisions that are often times, very challenging and difficult. But we all appreciate your insight. We appreciate you joining us here today and I thank you for your talk. Thank you so much for having me. I really appreciate it. All right. Have a great day, everybody. Thanks again, Yusuf for joining us. Thank you.
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