Chapters Transcript Video Use of MCS for High Risk PCI Dr. Krishnan delivers an overview of the clinical need for mechanical circulatory support for high-risk PCI. Thanks for giving me the opportunity to talk. Uh, this is, uh, as a fellow, this was one of the most interesting aspects in every single case that I took part in, uh, but you know, when, when I was preparing this, this talk, I actually, um, led to asking more questions of myself than answers we have available. So hopefully, um, I can over the next 40 minutes or or so shed some light on, uh, the data that we have available to us, um, in the same. I have no relevant disclosures for the talk. I'm gonna start off with a case that I saw at the Beach Hospital. Uh 70 year old female with significant peripheral arterial disease, recent angiogram and digit amputation before Christmas, uh, came in from a rehab facility complaining of intermittent chest pain and shortness of breath. Her labs were concerning, uh, for. A non-stemy as well as significant heart failure with uh an AKI as well. She was a little old lady with a baseline of 0.7 and a sodium of 129. EKG showed sinus rhythm with left bundle branch block that was uh chronic and her comorbidities included type 2 diabetes and hyperlipidemia. This was an echocardiogram, and even for someone who doesn't treat echocardiograms, you can tell that what's supposed to be squeezing well isn't and the EF uh detection fraction was 15 or 20% global hypokinesis, uh, the RV function was also mildly reduced. Um, she had elevated LV filling pressures based on eco parameters as well as elevated right-sided pressures, uh, based on the dilated IVC and thankfully she did not have any evidence of an LV thrombus. So she goes to the table of truth after diuresis for 72 hours and um for the non-interventionist in the room, essentially this is an angiogram, we have a catheter via her wrist. We're looking at the left sided system. And there is a tight blockage um in her left maine right from the osteum all the way into the trifurcation of the left anterior descending artery, the left circumflex artery, and the reus intermedius. uh, there's also a presence of heavy angiographic calcification. She also has proximal to mid RCA 90% stenosis and her EDP was 15, uh, but as you can see, her blood pressure was not the most robust. So let's pause on the case one, and this is another case that I did last week. Um, this was a patient who came in with um an acute MI. This is one done by one of our partners overnight in the early AM 51 year old male past medical issue of hypertension, type 2 diabetes, acute infralateral MI, um, had a, um. Residual stenosis, as you can note in the proximal RCN he had a 100% occluded proximal left circumflex, uh, for which he got a drug eluting stent after aspiration thrombectomy done. um, it was a challenging procedure, uh, but they got an excellent result. Uh, labs were consistent with, uh, a sodium of 132 as well as a creatinine of 0.9. Um, anti-Pro BNP was, uh, 4:15. I'm trying to get that video to play again, but essentially he was, he also had, uh, mid LAD stenosis, um. Which and also had evidence of mid LAD myocardial bridging distal to the stenosis, um, which was interesting and I can show that in a second it should play down there. So they got a good result in the circumflex you can tell that the flow is not as robust even post stent, um, which could be in the setting of some myocardial edema, um, and you should be able to, I can point out the LED stenosis in a little bit so right there there is um a little bit of haziness in the in that LAD, um, and there is an evidence of mid mid LAD myocardial bridging. This is his echocardiogram. He did have an EF of 40 to 45%, regional wall motion abnormality with some hypokinesis in the area of the infarct also had elevated LV filling pressures based on echo parameters. However, normal right sided filling pressures in terms of his IVC and PA systolic pressures, and there was no evidence of LV thrombus. So after seeing the couple of two cases, what I want you guys to think about is are both patients equal uh PCI risk? Is there a way to optimize risk prior to PCI if we were to take them for percutaneous coronary intervention? And what are the factors to consider while assessing risk in such patients? And which of these two will likely need MCS supported PCI? Um, and looking back, when you look at the guidelines both in the United States and Europe, we don't have robust guidelines. They're both, uh, the US guidelines from 2021 revascularization state that in selected high risk patients, elective insertion of an appropriate hemodynamic support device as an adjunct PCI may be reasonable, uh, to the level of evidence B. In selected patients with heart failure with reduced EF undergoing high risk PCI for complex CAD, use of a micro axial flow pump may be considered at experience centers. That's what the European 2024 guidelines state with again a level of evidence to be Class C. So you can see that the evidence is not robust, however, This is a recent paper uh by uh Doctor uh Zaitoi et al which which looked at trends in prophylactic MCS support in elective PCI and you can see that there has been a significant trend up in in patients with uh multi vessels stable CAD requiring PCI. Um, and there has been an increase in MCS support other than balloon pump. Uh, again, the data is not classic. So going back to, uh, medical school, uh, the mechanics of a single heartbeat. Um, as you can see that every single heartbeat, um, has certain physiological background, and I wanted to use the next couple of minutes to kind of go over this. When you look at a pressure volume loop, um, and this is based on, um, a cystole and diastole, um, the four corners of this quadrilateral are essentially the mitral valve closing and opening and the aortic valve closing and opening. And when you look at the pressure curves, you see systolic blood pressure at the peak there and then the diastolic blood pressure, um, at a point, um, essentially if you start from uh clockwise at point A, um, the, the change in the volume is essentially the stroke volume and this curve is limited by two points at the slope of the first one, where the arterial elastin is, is essentially, um, a degree of contractility in the heart. Um, the end-diastolic pressure volume, um, ratio, the relationship is essentially what the preload is, and the slope of these two points, the ESPVR and the EDPVR, is essentially the afterload. And this is what happens in every single heartbeat, um, the stroke volume multiplied by the heart rate is what gives the cardiac output. On the other hand, what happens in someone with severe LV dysfunction is that the contractility drops off, the end-diastolic, the LV EDP rises, so the curve essentially shifts to the right, um, and as a result, the stroke volume drops and the stroke work reduces while there is an increase in the in the afterload and essentially there is loss of pulsatility and over time if this were to progress with organ dysfunction is what leads to cardiogenic shock. And these are some of the MCS devices that we have and hemodynamically speaking, this is what each of them is going to do. Uh, the first, the first curve on the left is essentially what a balloon pump does and what it does is it doesn't change contractility as much, but it reduces the afterload, hence increasing the area under the curve and allowing the heart to to pump against the lower load. Um, in the middle is what you would is what an impella or a micro axial continuous flow pump would do because there is complete LVAO uncoupling and uh because the Arctic valve opening and closing is kind of taken out of the picture, the shape changes into sort of a triangle. On the far right is what ECMO would do. uh, there's continuous support, however, it would significantly increase the native LV's work by increasing the afterload. So looking at the trials, um, the first trial that I could look at, uh, was the balloon pumps assisted coronary intervention trial. It was the first RCT of safety and efficacy during high risk PCI. They had about 300 patients which were randomized in a 1 to 1 with reduced EF of approximately 30%, extensive myocardial risk, and they described this as a BCIS1 jeopardy score of 8 out of 12 or greater, and over 40% myocardium risk otherwise or if they had left main disease were enrolled across centers in the UK. Uh, they did have a. Exclusion criteria in terms of patients who had cardiogenic shock were within 48 hours of an MI or any contraindication to IABP as well as a planned staged procedure within 28 days. Bailout IABP was allowed and this was in the era of, uh, pretty robust, uh, 2B3A inhibitor use, um, which I've highlighted because it does play a role in the bleeding risk going forward. And when you look at it, this, the primary endpoint of the trial was essentially a composite of major adverse cardiac events, which was defined as death, MI cerebrovascular, or further revascularization by PCI capped at 28 days. And the secondary endpoints were a 6 month. All cause mortality or major procedural complications, uh, which included prolonged hypertension, VT or VF requiring defibrillation, or CPR requiring defibrillation in addition to a composite of other end points such as bleeding complications, a site complications, TIA, and duration of hospital stay. So the primary endpoint was actually negative, um, in this trial, um, there was 15% versus 16% um. 12% required bailout a balloon pump, um, and, uh, when you look at predefined procedural complications they were higher in the unplanned IABP group, um, as you can see, bleeding uh was also higher in the unplanned IABP group, um, but this was in the era before we used syntax scoring to look at the the you know the complexity of coronary artery disease, um. And essentially what they said was the most common common of these complications was prolonged procedural hypertension, which occurred in approximately 13 patients in the group with no planned IABP and 2 patients in the group with elective IIBP. Um, so essentially what this trial, uh, said was that we could use MCS support devices, um, and then came the Protect 2 trial which was using, um, the first generation of the Impela, which was a 2.5 L floor device. It was. Prospective randomized trial conducted in 100/100 sites in North America and Europe, non-emergent PCI of the unprotected left main or last patent vessel with an EF under 35% or multi-vessel disease with an EF under 30%. Um, they did have about 20% of their patients were female. The mean ejection fraction in this trial was 24%, uh, and they did have exclusion criteria which included recent MIs, LV thrombus, uh, low platelet count, and an inability to place a 12 French sheets, um, and, and this was an IABP versus impeller trial, um, they still. They use a significant amount of GP2B3A inhibitors, um, and, um, one of the key caveats of the trial was they did check hemodynamics every 15 minutes in these patients. um, again some of the salient points have been highlighted a mean syntax score of 30, uh, which is, which is extremely high, um, um, you know, 2/3 of these patients were inoperable, um, they were on average approximately 3 lesions attempted with almost 12% requiring rotational latherectomy. Um, and even though the, the Impala's hemodynamics were better, the trial was terminated early due to, uh, DSMB determination of futility, so they, they actually didn't complete, uh, the whole trial. However, when you look at, um. Uh, the data, this is an intention to treat, um, analysis when they looked at the 90 day data, uh, there was a potential trend towards the Impala being better again, uh, statistically, um, it, it was a negative trial, um, then when you look at the per protocol analysis, um. And this was something that uh they show at pretty much every interventional conference uh and by per protocol there was um a difference at 90 days in the composite of um these uh 10 outcomes between Impala Impala 2.5 compared to the balloon pump, um. And when you and this is the Kaplan Meyer curve, the first one is an intention to treat analysis, while the second one is a per protocol analysis, uh, and, uh, when they looked at a subgroup which was not treated with arthectomy, which was approximately 90% of the group of 396, uh, they did not better outcomes with the Impala compared to the balloon pump and the residual risk reduction. This was only magnified when they looked at the protocol analysis, um. The conclusion of this trial was that the 90 day mortality was in line with the Stitch trial, which is a CT surgical cabbage trial, and this, you know, the takeaway is that high risk complex CAD can be revasculized with PCI in patients who were deemed surgically inoperable. And this was an interesting takeaway as well from the trial where the investigators concluded that in this population they needed to have a minimum of a 90 day follow up because curves not only in this trial compared to curves like the BCIS1 trial, um, as well as the stitch trial as well as the as well as the IBP shock trial started diverging after 30 days up to 6 months, um, so 28 days or 30 days would be too short a follow up. Um, moving forward, the Protect series that was next, the Protect 3, which was, uh, which was a prospective multi-center, uh, observational FDA audited post approval study, uh, where they, they aim to monitor postmarket safety and efficacy of the Impela 2.5 and the CP which uh had started coming out and becoming more common for high risk PCI in the United States. Um, and a total of approximately 1100 patients, uh, who are undergoing non-emergent PSI with Impela were enrolled over the course of 3 years in the Protect 3 study. Um, and, um, what they did, um, In another, in another study was that they looked at these patients in the PTE 3 study who actually met the inclusion and exclusion criteria for the PTE 2 trial and they were trying to compare these PE 2 like patients in the Protect 3 study with the PTE 2 outcomes to see if there was a different. Um, in both the outcomes as well as the baseline characteristics and what they found was that the patients were older, more anatomically complex, uh, they had more lesions treated a higher percentage of atherectomy, longer duration of impella support and more pronounced improvement in post PCI, um, um, major jeopardy score as well as syntax score, so more complete revascularization. Um, and additionally, in the Protect 3 trial, more patients had, uh, closure devices placed because the Protect 2 occurred at a time before, uh, the approval of the Perclose of the ProGlide. Um, so essentially, uh, this is what, uh, this is what a study, uh, did, uh, done by Doctor O'Neills, um, uh, out of, um, Detroit, uh, where they compared, uh, the patients in Protect 3 who were PTE 2 like to the Protect 3 patients, um, and interestingly, uh, when you look at the lesion characteristics, uh, yes, there was less GP2B3A inhibitor use, um. made sense because that was the evolution of the field, um, they used these lesions were more complex. They used more uh calcium modification in terms of rotational latherectomy. Interestingly, the contrast volume use was lower uh they got more complete revascularization as witnessed by an improvement in the Jeopardy score as well as an improvement in the syntax score post-intervention compared to the original Protect 2 trial. And uh this trial, this looks at the outcomes as you can see there is a significant difference in the maze. However, this is driven predominantly by MI and this was because there was a difference um in um definitions between the two studies. So the, so the definition of periprocedural MI was different intE 2 versus the PTE3 study. However, despite accounting for that, what they did was they did a 72 hour landmark analysis and this, uh, to, to kind of negate that pretty procedural MI. However, despite that, uh, there was a significant difference in the, in the PTE 3 study among patients who were ProTE 2 like versus the Protect 2 study itself. There was a significant improvement, um, in the overall composite maze, uh, um, at 90 days. Um, and interestingly, the definitions for the MACE events, uh, although similar, the MI was different because they used, um, 8 times the upper limit of normal in the Protect 3 study versus 3 times the upper limit of normal, um, but despite that they did have better outcomes. So this is the evidence that we have for MCS uses in patients, uh, undergoing high risk, um, interventional procedures, um. And then the question then is what are the challenges of intervening in severe LV dysfunction. Um, there is, uh, some of the thoughts are that this leads to chronic LV remodeling, increase in wall stress, and elevated filling pressures, which then reduces the reserve of the heart. There is, uh, these patients are fully compensated at rest to maintain stroke volume and cardiac output and hence with um any ischemic times such as going up with a balloon or a shock wave or even as wiring a vessel leading to coronary spasm can tip them over. Um, and these patients often have other organ dysfunctions such as AKI, CKD, borderline respiratory status, as well as poor nutritional status. So knowing what we know, uh, looking at the ischemic effect of an unprotected heart, um, Every time we go up with a balloon, uh, in the left main or a single conduit artery, um, there is a drop in cardiac output. There's an increasing after load, and there's an increase in the LVEDP, and all of this leads to uh the patient decompensating and this occurs quicker and more likely in someone who has each of these high risk features. Um, the question then becomes what are those high risk features and what are the goals of MCS supported PCI. So the first goal would be to maintain adequate perfusion in a patient. To facilitate safe, complete, and optimal revascularization, as well as have an acceptable benefit to risk profile. And when we talk about risk, what is the risk we're trying to mitigate? These are some of the risk factors that um are considered every time there's a patient who needs one of these procedures. There are certain patient factors, um, uh, which are the common culprits. Uh, there is anatomical complexity which would include multi vessel disease, unprotected left main, last conduit vessels, severe calcification requiring calcium modification, uh, complex bifurcation, decreased TE3 flow, uh, or even heavy thrombus burden. And then the hemodynamics such as LVEF, are they on vasopressors inotropes, are they currently, um, in, uh, decompensated heart failure? Um, what is their RV function? And, um, there's actually data to say that LVEDV is a better predictor of risk than LVEDP uh, out of a small trial. And uh although there is not robust data, these are some of the algorithms that um um is in use. Uh, this is an algorithm out of the University of Washington and as you're reading this, just think back to the two patients that we had and see what their risk profile would be. Uh, so our first patient had an EF of 20 to 25%, so she gets a point for that. Um, she did have initial non-Stemi presentation. We were planning revascularization in more than 2 territories. Um, she had a significantly calcified left main and would likely need calcium modification, um, and she was in a decompensated state as well. So she is, according to this algorithm for all intents and purposes, both subjectively and objectively, she is someone who would need support. Um, our second patient, on the other hand, although, um, he did come in with heart failure, he was otherwise robust. There was a planned revascularization, yes, in two territories, the LAD and the RCA, um, it didn't appear to be significantly calcified, uh, so he didn't get a point for that. His EF was not under 25%, um, and his EDP was not over 20%, so in in him he's kind of borderline or unlikely to need support. And this is, uh, this algorithm is out of Dr. McCabe's group at the University of Washington. So back to patient one, she was transferred to heart hospital on the 11th of January. Uh, we got palliative care on board. Uh, CT surgery was also on board and she was known to be a poor candidate. This was the peripheral angiogram that she had done recently. Um, she had an abdominal aortic aneurysm and had some work done in her superficial femoral arteries as well, uh, significant peripheral arterial disease. Unfortunately she had a rapid response for chest pain and shortness of breath the day after she got here she was intubated. She had a balloon pump placed. Um, vascular surgery consult, uh, was to see if her anatomy would even accommodate um the sheet uh required for large board access for MCS placement prior to PCI. There was a family meeting with shared decision making, um, and they decided that, um, her quality of life, um, and her goals of care would necessitate that they did want us to continue with the procedure. And uh you know, the, the goal of this slide is to show the multidisciplinary input that we got for this patient before undergoing uh a high risk procedure as she would be a high risk at every single level of the procedure. And the procedure was finally planned for the 17th, um, so the procedure was done by Doctor Alomard. um, I, I had the opportunity to do the procedure with him, um, as you can see, we were, we were able to take the balloon pump out and put the impella in, um, and this is a single axis PCI, so we did not have to get contralateral access. Uh, initial ballooning, um, was done, uh, off the left main. Um, her initial EDP was 25 prior to MCS. Uh, we did, uh, we were, we were able to do IVIS after the NC ballooning, uh, to look at the morphology of the plaque. She had high grade calcium all the way from her proximity to the left main. Uh, shock wave lithotripsy was done. A total of 80 pulses were given 8 into 10 seconds each, and there was, she had loss of pulsatility, but she was completely dependent on the MCS device at the time. Uh, we implanted a single stent, uh, from the proximity to the left main. Uh, it was optimized by IWIS parameters as well. Um, finally, um, after which, um, we took a look at the, um, RCA. Um, that was the final result on the left main, um, and in the RCA, uh, we did a non-compliant balloon, um. The IVIS did not show any significant calcification at which, at which point a single stent was, uh, implanted, um, as well as optimized by IIS, and we were able to take the impala out at the end of the case. And we didn't have any residual dissection, perforation, or bleeding. So this is the 2nd patient who needed a staged revascularization. Uh, he underwent IV diuresis over 5 days. Uh, GDMT instilled included beta blocker and uh snolactone. Um, took him to the lab on the 5th day. I went radio, uh, initially his, his, interestingly, his EDP was 20, so it had gone up from 12, um, but otherwise he didn't have, uh, he was able to lay flat, it was well compensated, uh, got a single stent to the RCA which was optimized by IWIS did not need any calcium modification. Um, followed by which, uh, we decided to, uh, IFR the mid LAD stenosis, it was positive and, um, and after which he got a, uh, intervention done to the prox LED, uh, we were careful to not land the stent in the in the area where he was, he had the myocardial bridge, um. There was a place to wire in the cir for additional guide support, um, and at the end of it, uh, it was I was optimized um he did require IV Levofed during the procedure at up to 10 mics per minute, uh, during the LED intervention. However, uh, this was able to be weaned off at the end of the procedure. This was the final result, uh, optimized by IIS. And he was discharged the next day on GDMT. So at the end of these two cases, this is something to consider prior to each of these cases, and this is not just balancing one or two risk factors and benefits, but multiple of these. The goals of care of the patient were important in our first case, uh, vascularar access, LV versus BV support, cath lab staff, expertise, and overall a multidisciplinary, um, input from both Palmret, uh, colleagues, CT surgical colleagues, and vascular surgery. Um, is, is very important, uh, when we undertake such cases. And uh looking forward, what are some of the randomized control trials that are in the horizon? Protect 4 is one of them and um across in the UKIP BCIS 3 is another one, both of which are interesting, but essentially they're looking at, um, seeing if there is more robust evidence using uh more uh. Modern MCS support in such patients, um, the Protect 4 was enrolling patients with no, uh, with chronic cornea syndromes or non-STE LVF of, uh, under 40%, um, or acute STE over 24 hours with an LVF of under 30% requiring complex PCI. On the other hand, the, the, the CHI PCIS3 was, uh, is looking at patients with elevated jeopardy scores and an LVF of under 35% undergoing, uh, PCI. Um, and I think that Protect 4 is going to be negative. There is some data that came out of, uh, MedStar Washington, um, at the ACC conference, uh, where they did a trial where they looked at their own unprotected, uh, uh. Interventional patients who had met inclusion criteria for Protect 4, and they actually found out that their events were a lot less than what Protect 4 expects them to be and hence they they feel that the Protect 4 trial is going to be undercovered and is potentially going to be a negative trial, but that remains to be seen. On the other hand, the CHPPCIS 3 trial has an interesting outcomes and it makes a little bit more sense intuitively. Uh, their primary outcome is not a composite or a single outcome, but it's actually a hierarchical composite of all cause death, stroke, spontaneous MI, hospitalization, or per procedural MI using a win ratio, and it makes sense, um, because, uh, you know, with mortality would probably be the most important hard outcome. On the other hand, uh, perip procedural MI with a lack of universal definition available at this time would probably be not the most. Important outcome that you're looking at um and they're using a win ratio which would allow them to kind of determine multiple pairs um with a smaller overall sample size um and they have very clear separate definitions for perip procedural MI in patients whose troponin is elevated at baseline is not elevated at baseline, and is elevated at baseline and trending up, um, so I, I, I, you know, personally I feel that the BCIS3 trial is a more exciting trial and. Um, there's a couple of slides on how they, how they're going to do that. Um, they're going to randomize them to elective LB unloading versus standard of care. They're gonna follow them up for a minimum of 12 months and it's going to be a hierarchical composite outcome. Um, this is their, um. Inclusion criteria and just as an example to look at what their win ratio is going to be if you have a patient X in the interventional group and a patient Y in the non-interventional group, neither of them had death. Then you go to the next outcome, neither of them had a stroke, go to the next outcome, neither of them had a spontaneous MI, go to the next outcome, but patient X had two hospitalizations versus patient Y who had 3 hospitalizations and hence in that pair patient X1, and now you make each of these comparisons between. All of the all of the pairs that you can possibly make um in this trial. Um, looking towards other MCS options, um, I know that, um, we've done a few cases here at Centera, um. Um, with, uh, the Impala ECP, which is essentially a smaller device, uh, under 10 French, uh, which then unfurls into a larger device in the LV and then gives, uh, enough support which can then come out at the end of the procedure. Um, this is an option for patients who have uh significant peripheral arterial disease or smaller patients, uh, but there's other options, uh, which have undergone first inhuman, uh, studies recently the magenta elevate, uh. Martin Jack a couple of weeks ago this is again, I think it's about a 10 or 11 French catheter which then unfurls into a 30 French system providing complete support. They have two iterations of the model, the regular one and the high flow one. They looked at a first inhuman study in 14 patients and it showed the ability to give complete support in these patients with favorable hemodynamic parameters at the end of it. Um, the other trial, uh, which, uh, was presented by Dr. Laib, um, at TCT was the Supia system, which again is a 10 French system, um, has a low profile insertion, can provide over 5.5 L of flow. Um, the first inhuman trials for this device occurred in Paraguay, uh, for some reason. The previous trial occurred in Georgia. Um, but essentially they, they proved that this was feasible to place, feasible to take out and not didn't have any significant complications. Um, so, uh, the final take home points are a heart with severe LV dysfunction, although compensated is not the same as a normal heart. Patients with LV dysfunction often live on a thin line. Uh, with small insults often tipping them over, um, and this state of instability and stability is actually in flux and is a dynamic process. It it is best to be monitored with invasive femo dynamics. Uh, we need to factor in not only the risk of the procedure, the patient status, the vascular axis as well, and finally overall operator experience, um, you know, personal experiences. Someone who's fresh out of training, uh, doing complex cases, uh, you know, individually, uh, would, would not be the ideal way forward because these are real complications in these patients and ideally partnering, uh, with a more senior operator would be the best way forward is because personally I always end up learning a ton when I do that, um. Uh, but hopefully this kind of gives us, gives you all a little bit of an overview on, uh, what is the data and what is to come, and I'm uh happy to take any questions at this time. Published February 3, 2025 Created by Related Presenters Anand Muthu Krishnan, MD Cardiology View full profile
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