Sentara cardiologists review a few key points from the late-breaking clinical trials and research presentations from American College of Cardiology 2025.
Alright, let's do it. Thank you, Amy, for getting this together and thank you everyone for attending. I know we've got people both live and virtual. This is Deepak Tara and I'm joining, uh, Doctors Amin Yeha and Doctor Anan Krishnan. To do a review of what we learned at the American College of Cardiology Scientific Sessions 2025, which was held March 29th through 31st in Chicago. ACC always to me is one of the interesting meetings because it's a very broad meeting that has a lot of different, different parts of cardiology, everything from general cardiology through imaging, interventional, structural, and so there's always a lot to learn. There's also some of the biggest late breaking trials across the country. So quick couple quick summaries. I'm trying to make it as if you were there with us. There's actually a number of members of our division there, including some of our trainees giving talks. On the upper left you see Dr. Brush, and below that Dr. Bassin. Next to that in the middle top is Dr. Yeha and a group on the session he was giving. And then below that is Dr. Krishnan and I, and then on the far right bottom is Dr. Benza, who's joining us as the academic chair for our fellowship program coming up. And those that attended our last all SES meeting know that Dr. Yehan and the team have been and Dr. Veer and the team have been working very hard to get that program online, and I'll ask him to make a few comments about that before he starts his slides. So each of us is going to take about 15 minutes and go through the presentations. It's always interesting for those of us that track ACC closely to see what's going on in the world at large, and this year's president for 2025 was Kathy Bega. Many of us know her and interacted closely with. Her during the last two decades, she was involved in med axiom and she does a lot of the practice negotiations and in fact helped us here to do a lot of the work that helped ultimately to create centero cardiology specialists and work with a number of groups in the community. She's, to my knowledge, one of the few non-cardiologists that's been president of the American College of Cardiology, and so that was an interesting change. Next year or the coming year or current year I should say, it'll be Dr. Christopher Kramer, who is an imaging physician at the University of Virginia. Many of us know and have interacted with him closely. He specializes in cardiac MRI and has done a tremendous amount of work in that and has actually partnered with us some in projects over the years. So it's exciting to see the next iteration of ACC with a Virginia president and hopefully we'll we'll all participate in that. Also, it's fun to see each of us evolve in our careers, and this is Dr. Krishnan, who I didn't know I was going to show this photo, but I managed to get a hold of it during his progression from being a member of the American College of Cardiology to being elected as a fellow of the American College of Cardiology. And it's nice to see a younger member of our division who receives this tremendous honor and joins us and will help support the American College of Cardiology going into the future. So amongst the few topics that caught my attention, I spent a lot of my time in the main session and then in the structural arena. In the main session, there was an interesting reference to a book of Factfulness, and we live in an era where, you know, regardless of where you are in the political spectrum or economic spectrum, there's a lot of, you know, concerns and questions about what does the future look like both in this country and other countries. And the message that this talk gave was that there really is some pretty amazing, great things happening in the world around us, and I thought this was neat. If you look at what's happened in this chart shows lifespan on the on the y axis and income on the X-axis, and we've seen tremendous progression in across the world in terms of increases in lifespan and health span even. There still are areas, especially underserved smaller areas, where that lifespan really needs to be improved, and so always room for improvement. But in general it's interesting to see some of the demographics around us, and I think that as intelligent consumers and healthcare providers we should know a little about what's going on in the world around us. They group the world into 4 income levels level 123, and 4 and you can't really differentiate these by country because these are 4 different countries shown. And in level 1, for instance, if you look at drinking water, there's very limited access, maybe at best a well far away. Level 2, there's better access where they have, you know, facilities to actually contain water and take it. Level 3 typically has running water, and Level 4 is what most of us are fortunate to enjoy, which is, you know, water coming directly to our home, sinks, faucets, etc. The same thing can be said of transportation. Level 1 is mainly walking and sometimes without. Shoes. Level 2 gets up to some sort of mechanical transport like bicycles. Level 3 gets you a little further to some machines, for example, motorcycles or other sort of transport that isn't necessarily the level we have, and level 4 would be cars. Same thing with cooking where you progress from, you know, basically using fires to some sort of natural gas or propane type given heating to the ovens we're used to level 5 eating. A level 1 through 4 eating and level 1 through 4 sleeping. And if you look at the, the population around the world, level 1, it's less than $2 of income a day. Level 4 is above $32 of income per day, and obviously there's a huge spectrum there, but you see, much of the population of the world lives in level 2, and the goal is we've been steadily escalating with people moving from 1 to 22 to 33 to 4, but level 4, which most of our country is, is still very fortunate and still in the minority. If you look at the population and region by region and by income, what you see is North America actually represents a fairly small segment of the population, and we tend to be largely levels 3 and 4. China, India, and Southeast Asia tend to be the largest population. Right, this is, this is only going to grow, and we'll see that in the next slide, and they tend to be fairly more dispersed than anywhere else. And Africa, where the greatest future growth is projected, is actually in the position of being more level 1 and level 2 than any other demographic. What's interesting though is by 2040 on current trajectory trends we see the greatest population growth will be in China. India, Southeast Asia, that area, and in Africa, and we see that the projected greatest growth and movement will be in those countries as well in terms of moving up to Level 4. It is interesting. You'll see a slight increase in relative population in the in the US that's in that level 23 segment. And so we have work to do to get better across us. But if you really look at what the last 100 years has brought. There's a lot of positives. Average life expectancy over from 1800 to the 2000s has gone from 31 years in the world to 72 years. You see some down dips with epidemics and with world wars, but you see in general it's been a pretty upward progression which continues to escalate. It'll be interesting to see now. It's flattening out if there's technological innovation that will increase that further. Going to the right, literacy has dramatically improved across the world. This is the share of adults 15 or older with basic skills to read and write, and it's gone from 10% to nearly 90% across the world. Extreme poverty has decreased from 85% in 1800 to 2017. And the point was made that the average middle class US citizen right now lives at a level far in excess of where the greatest royalty would have lived in the 1800s. So that's a huge and positive move, and deaths from disaster have gone down remarkably even over the last really 50 to 100 years from 900 in the 1930s. And remember that's not wartime either down to where we are now at 72. So even though we worry about planes and trains and automobiles, things have gotten better. Four good things that are increasing is protected nature has increased quite dramatically, although we have a way to go still. Harvest yield of cereal has gone up considerably. Literacy, we already talked about and immunization has largely increased fairly dramatically, and that obviously has important, you know, lessons for what's to come for us. Four bad things that have actually gotten better. Childhood deaths have gone down tenfold. Oil spills have dramatically decreased even in really the last 2.5 decades. Plane crash deaths have really gone asymptotically down to virtually nothing compared to where it was even in the 1940s, 1950s, and the share of people who are undernourished has gone down. So the message of this session was that the world is in a good place. There's a lot of room for us to continue to improve, but if we're looking around us, we've achieved a lot of great things together. The next topic that I'll keep very brief is I went to a lot of the sessions on artificial intelligence, and it remains an interesting area in health care. It is interesting. My gross summary is the question they asked the audience in one of the big panel sessions was, when you hear AI, what do you think? Do you think the Terminator or B C-3PO and R2-D2 as friendlier robots? And it was interesting. It was kind of a 50/50 split when they surveyed surveyed the large audience. And we're now in the 3rd epoch of artificial intelligence and healthcare. We're using foundational models beyond just simple deep learning, which was innovative a decade ago. We're now generating new content, text, sound, and images and performing tasks without new data or retraining. We're creating models that really have advanced. And if you look at the healthcare spectrum, The current role in AI that this this session considered was voice to text to decrease documentation. Again, you think of what we have locally. We have pilots of DAX co-pilot, and so more and more of us are getting involved in that early detection and triage to appropriate care, optimizing EHR and hospital data, assessing populations to identify opportunities to improve and to optimize GDMT. And enabling enabling practice efficiency with personalized responses to common questions. We'll be starting those pilots later this year in concert with EPI and Chat GPT that'll allow us to help craft in basket messages to patients, although we'll ultimately still be the ones responsible. And the landscape has gotten incredibly complicated. This is one nice summary slide that depending on which area you're in, there's tremendous competition and innovation ongoing. I would say on a weekly basis our AI teams or our IT teams rather get approached by industry partners who are interested in partnering and, you know, looking at data and looking at ways to make us more efficient. The challenge, of course, is you can't implement all of this at once and in fact a lot of it is. Incompatible with each other and we only have so much build time and time to train all of us. So it's a complicated environment. It'll be interesting to see who emerges as the Amazons and eBays and Apples out of this group and obviously there's a lot of continuing ongoing innovation, but there are great sessions, and that reminds me to make mention that for anyone who's interested in hearing more of this. A subscription to ACC will give you access to pretty much all this online and you can earn 100 CME by watching videos in the background, and it's a pretty good educational session. Two trials I want to show quickly, and now I'm going to move at a really fast pace because in my 15 minutes I'm hoping to get through a bunch of trials. The stride trial looked at someagnotide and walking capacity in patients with symptomatic PAD and type 2 diabetes. This was a phase 3 double blind randomized placebo controlled trial, and for all these trials, I'll show the investigators slides. The idea was there's some, there's a huge burden of PAD, more than 230 millions individually. And most of those patients will die from cardiovascular disease, and a lot of it is a result of type 2 diabetes. We know that drugs like simaglotide, the GLP-1RAs, have multiple benefits across the spectrum of cardio metabolic disease and is an increasing focus of, of the cardiovascular community. We're generating clinics to look at this for cardiovascular risk stratification, and obviously there's tremendous patient interest in weight loss, but in the PAD world, when patients are randomized 1 to 1, What we saw was an improvement in the primary outcome of baseline in maximum walking distance. So you see both groups improved with training, but the difference was significantly better in the group that received some magnetite, and that was statistically significant. If we look also at the composite of rescue initiation, a major adverse limb events, we always think of mace in the vascular disease trials, it's male and all cause death. We see a significantly better outcome in the group on simagnotide. And so that the conclusions of the investigators were that in addition to the other cardio metabolic benefits that someagnotide can help with PAD itself, reducing disease progression, improving ankle brachial index, improving symptoms, and meeting that composite endpoint, including very hard endpoints. Um, that's available in The Lancet. The next one in the same regimen was oral simagnotide for cardiovascular events in patients with type 2 diabetes and atherosclerotic cardiovascular and or chronic kidney disease. This is the sole trial, and in this trial, they looked at an oral formulation of imagnotide, randomized almost um 10,000 patients with the inclusions and exclusions seated here, they were adults with type 2 diabetes, A1C 6.5 to 10. With some sort of cardiovascular baseline disease, and in this registry they had nested hierarchical outcomes. Baseline characters who were very similar to the patients we see with about an average age of 66, an average A1C on entry of 8, and average BMI of 31, just in the obese range, with diabetes up to 15 years. And what they saw in this was again benefits in the 3 point mace composite with a 14% relative risk reduction. Very exciting, you know, we've been used to using subcutaneous injections, and of course those are still the mainstay, but this is an exciting event. Again, we looked at major adverse limb events and again see it takes a little bit longer. You see the curve start separating around 30 months, but again favoring the saggotide, so. Um, this is exciting GLP1RA that's oral now with proven CD benefits once again, again published on that topic of of drugs we typically think of for diabetes and their benefits. It was an interesting analysis as a structural guide that caught my attention. Um, DAA flows us in on trans catheter valve patients and patients were randomized post taver within that first two weeks, 1 to 1 to DAPA versus no DAPA, and interestingly enough, what was seen is if you look at the primary endpoint of cumulative incidence of worsening valve disease and all cause death, you see there's less heart failure in the group that is treated post tavern. This is not necessarily HPPA or he ref group. This is really a valve disease group that's been treated for that, and we see another extension. So something our structural team is thinking about. So among patients with aortic stenosis undergoing taver and at high risk for heart failure, this reduced all cause of death plus worsening heart failure compared to standard of care. Interesting, uh, change, and that was published in the New England Journal. Um, I had the honor of being on a panel presenting a couple things around some of the work we've done here locally. We looked at 5 year data from the evolute valves, and what we saw is in a population of about 1500 patients, we see that at 5 years when you compare the blue taver with evolute valve to the red surgical valve, and we saw earlier data in across platforms that similarly showed something impressive when we started the program in 2011, you know, we were only treating. Operable patients and we were considering ourselves successful if we got the patient off the table. Now we're seeing is data showing at 5 years that the taver valves compare very favorably, certainly not inferior to surgical valves, and that's kind of the dream of this, of this technology from many years ago is we wanted something that for the average patient who was able to undergo either Taver or SAR that we get results as good as surgical. And you know, some would point out the trend is even a little favorable on the taver side again. Um, at the end of the day, the message is non-inferiority continues out to 5 years. Cardiovascular mortality was also similarly very low, and again, about the delta of 2%, and that non-inferi is the end conclusion. It's really driven by cardiovascular mortality that we see that benefit. The non-cardiovascular mortality is about the same between both groups, and that makes sense. Since we're treating that, hemodynamics remained very favorable in this application. We see that the taver valves often end up with a greater effective orifice area and a lower gradient than equivalent surgical valves, and I would I would commend our surgical team. Our team has been truly fantastic about those patients undergoing surgery, doing more root enlargements than you see in most places in the country to make sure we have good surgical hemodynamics. So the results of the evolute 5 year data supports Taver as a safe, effective, and durable alternative to surgery in patients for severe aortic stenosis, regardless of their surgical risk, low risk, medium risk, or high risk included in this low risk trial. We also saw the first trial of head to head valves. This was a trial, the smart trial that we participated in. It looked at patients with smaller annuli, smaller body size, smaller valves typically, and we compared two valves that we use both of them that are both fantastic valves, the evolute and the sapien valves, and in this study of around 700+ patients which we participated in, what we saw is at the 2 year data now that. Um, one of the things we're following is what we call bioprosthetic valve deterioration or hemodynamic valve deterioration is another version, and we saw that the evolute valve, which sits superannular and in our coronary conference we just discussed access techniques for this because one of the concerns is that it sits at a higher position. Could that ultimately make it more challenging in some cases to access the coronaries, and we've done quite well doing that. But one of the benefits is the hemodynamics seem to be sometimes in those Smaller patients, especially, um, very, very much more what we expect with a surgical valve, and what we saw is that 2 years there was no significant difference in the composite incomes of mortality, disabling, stroke, or heart failure rehospitalization between the two valves. So that's why we use both of them. But what we did see was uh the, the, um. The metronic valves, the evolute on the far left, you'll see the 1 year data, then the 2 year data have a slightly higher pacemaker rate that did not reach statistical significance, but it's about nationally a 15% pacemaker rate in the evolutes at 2 years and about an 11% rate at 2 years in the sapient valves for new pacemaker implants. And we saw a slight decrease which did touch statistical significance of subclinical valve thrombosis favoring the evolute group in that. And we saw that if you use the criterion of gradients across the valves, that's one of the reasons we choose evolutes in those smaller annuli patients is that the gradient tends to be a little bit lower and potentially that might ultimately result in some sort of long term benefit. Again, that remains to be seen and so that's why we choose each valve for each patient and we use all the available platforms the evolute by Medtronic, the Sapien by Edwards, and the Navior by Abbott and we individualize to each patient. The gradients though, as you see in the effective orifice areas tended to be favored in this small annuist group in the smart trial in that evolute trial. And there's some data when we asked, does this really translate into outcomes. It was pointed out, and I think this is interesting, the Australian National Ecor Registry and some other large data series show that it generally takes about 2 to 3 years for human dynamics to necessarily shape outcomes in some big registries. So we're going to be excited as we continue to participate in this trial to see what comes out in the future. Um, I'm going to be super brief. The last two minutes I have here. The Triuminate trial was a very interesting trial. Again, our team here, Matt has led, and Matt, Dave, Parth, and I have all done cases with this where we've looked at using tri-clips to decrease the amount of tricuspi regurgitation. The triuminate trial is the first randomized. trial again, the group here has been very active in participating in this space, and what we've seen is a significant impact in heart failure hospitalization, which was a pre-specified endpoint and an improvement in quality of life. So at 2 years there was a reduction in heart failure hospitalization in the device group with a statistically significant endpoint. And those are my slides. I know I've taken a little bit over the time I had meant to, but I'm going to hand the floor over now and stop sharing to Dr. Anand Krishnan to talk about. All right. Uh, so, uh, I'm just going to talk about three trials that, uh, from ACC that I felt would influence practice with a wide uh range of audience here. Uh, the first trial is, uh, a trial that compared Xarelto versus warfarin in patients with LV thrombi, um. You know, we think that the pathogenesis is uh consistent with Werhastra, which has been known for over 100 years now, uh, a combination of blood stasis, hypercoagulability, as well as endothelial dysfunction, all of which is commonly seen in patients who have a ST elevation MI. Um, and this is a slide that just showed the temporal trends of LV thrombi, as you can see that there has been a significant drop, uh, since the post primary PCI era, uh, the incidence dropping from 1/3 in all patients with stemmi to less than 1 in 10. Um, and a recent meta-analysis that used cardiac MRI, which is the most sensitive and specific test, uh, looking for LV thrombi, showed that the incidence rate is about 6% in all stems with that incidence rate increasing to double that in anterior MIs, uh, further increasing to almost 20% in anterior MI with patients with an LVF of under 50%. So essentially this was a well done trial. Uh, it was a, um, open label trial conducted at a single site in Pakistan which randomized 260 patients in a 2 to 1 ratio. Uh, average age was 5055, 80% of them being males, uh, with acute LV thrombite either Xarelto, uh, with an N of 171 and the rest, uh, undergoing warfarin for 3 months in the in the background of dual antiplatelet therapy, predominantly aspirin plus, uh, Plavix for the first. 4 weeks and then subsequently switching to the Plavix, uh, plus the uh the anticoagulant, um, and, uh, of the patients over 90% of them had a Stemi 85% of them underwent primary PCI, and, um, and most of them had an LVF of under 35% and over, you know, 94% of these patients, um, and, uh, at the four week follow up, uh, about 20% of them had. resolution in the Xarelto group versus about 8% in the Coumadin group and then subsequently at 12 week um and they checked these patients with echocardiogram with contrast use, uh, over 95% in both arms had thrombus resolution. So my key takeaways from this trial are that primary PCI has drastically improved LV thrombus rates. Interventionists are doing a fantastic job overall. Uh, however, there exist a risk of LV thromma, and we really want to be thinking about this in patients in the higher risk group, which include anterior stemmis, EFs under 35%. So you want to have a lower threshold to look for LV thrombi, and most LV thrombi happen within the first two weeks. So even if they may not have an LV thrombi in the echo immediately post, uh, presentation, uh, we should have a lower threshold to look for it. And if we were to find it, um, you know, this kind of. Uh, reinforces the fact that we can use Doax in these patients and most of the thrombo uh resolve at 3 months. Um, the signal from the study was also that there was no evidence of excess harm in terms of mortality, ischemic stroke, or major bleeding in the rivaroxaban group versus the Coumadin group. Um, the second trial that I found very interesting was the host BR trial. It was interesting because there's been a lot of background data going on as to what is really the optimal duration of that. And when you think about it, there's really two strata of patients that we want to think about. There's patients in the higher bleeding risk group and there's patients in the lower bleeding risk group, and this trial was the first round. trial to stratify patients who received PCI with drug eluting stents based on their bleeding criteria on the academic Research Consortium, which has some good data to suggest that this is, this is what we need to be used for patients to stratify them. This was a stratified randomized study that came out of a single center in South Korea. This trial investigative group has done a lot of work in dual antiplatelet therapy in the past as well, and they're very experienced with the same. So in the high bleeding risk stratum, the patients were randomized to either a 1 month dual antiplatelet therapy versus a 3 month dual antiplatelet therapy, and in the lower bleeding risk stratum, patients were randomized to 3 months of d versus 12 months of dap. Um, and, uh, you know, when you ask yourself as to what constitutes high bleeding risks, these are some of the factors that go into this. And as you can see, a lot of these factors are common in a majority of our patients who come in with, uh, uh, needing PCI, both ACS as well as non-ACS, and they really, uh, you know, um, defined high bleeding risk as uh an annual major bleeding risk of 4% or more, um. And the hypothesis was very simple. They had 3 co-primary endpoints. Um, the first one was net adverse clinical events, which was a combination of all cause death, MI, stent thrombosis, stroke, as well as major bleeding. Uh, the second was major adverse cardiac events, and the third being uh bleeding Academic Research Consortium, which is BAC of 23, and 5, which constitutes major bleeding at the 12 month mark. And the hypothesis was essentially within each stratum, that is the high bleeding risk as well as a low bleeding risk. The shorter adapt, uh, would be non-infeter to the longer adapt for the 1st and 2nd endpoints, uh, co-primary. And be superior uh for the third co primary endpoint, um, so very intuitively designed trial. Um, so if you focus, uh, you know, on the, on the top half, uh, overall in the high bleeding stratum, there were 800 patients in each group, um, over 98.5% in each group completed the follow up. Uh, 60% of these patients were ACS, however, only 5% were Stemis, which is important to keep in mind. And one third of the patients were women. um, the 90% of the strategy was aspirin plus Plavix. Um, in the lower bleeding, uh, stratum, they were, um, approximately 1700 in each group. Uh, again, the predominant strategy was. plus Plavix, 60% of the patients had ACS. However, only 10% had stemies and um uh 20% of the patients were women. There were some exclusion criteria, they excluded pregnant patients, they excluded patients with allergic reactions uh to the commonly used medications. Um, so I'm going to summarize this slide, um, uh, you know, there's a lot of numbers here, um, and there's a little bit of wordplay, but essentially, uh, when you look at the, uh, second column of the high bleeding risk, which is where most of the action in this trial happens, is that in patients with high bleeding risk, the 3 month apt reduced net. Adverse clinical events as well as major adverse cardiac events, uh, compared to patients who received 1 month of that at a trend of slightly higher bleeding rates. Uh, however, the bleeding rates themselves are non-significant, so the takeaway is that 3 months of that might be the sweet spot for these patients in the higher bleeding rate stratum. Uh, compared to the lower bleeding risk, uh, 3 month apt resulted in less bleeding and lower rates of net adverse clinical events, primarily driven by lower bleeding. However, uh, did not have any significant difference, um, in major adverse clinical events. Uh, however, both outcomes showed non-inferiority, meaning the 3 months again was non-inferior to the 12 month gap. Um, so you know, the key takeaways for me from this trial are. Results of the study essentially guide clinical practice in patients not only at the high bleeding risk, but also at the low bleeding risk, but mainly 3 months is probably, uh, you know, the Goldilocks spot for the shortest, safest duration of tap in patients with higher bleeding risk. Uh, however, it is important to note that the devil is in the details. These had a low percentage of STE patients. Uh, this is only 1 year follow-up data, the trial results are going to go up to 3 years looking at target vessel revasculization. Uh, which will be interesting. However, my sense is that given the newer generation stance, this is unlikely to be different from current results, however, it remains to be seen. Uh, the newest ACS guidelines which just got published a couple of months ago, uh, give a class one recommendation for Tyagolor and rare as the preferred uh uh P2Y2 receptors in ACS. However, this trial predominantly had aspirin plus Plavix, which is the predominant dap therapy in Southeast in Korea. However, multiple trials have shown efficacy using these agents, um, as well in the short term. Um, so you know, what could the new era of dap look like? Potentially 3 months of dA with aspirin, uh, plus, you know, Plavix or any other P2Y12 receptor antagonist, uh, or alternatively, 1 month of aspirin to uh Berlinta and then de-escalating to 60 days. Of aspirin plus Plavix and then aspirin alone, um, but this trial again adds to the data that we know from both Ultimate, uh, DAPT as well as Masterdapt about, uh, you know, how the stents are getting better and, uh, we need to shorten that and the dictum of 12 months of apt may be moving away. The last trial that I wanted to talk to you guys about and share some data is slightly controversial, but it is interesting. So it was the FAME 3 trial and they presented the 5 year data on it, um, and the background on it is that some, you know, previous studies have shown that 3 vessels CAD, uh, cabbage, uh, resulted in lower rates of a composite of dead stroke or. compared with PCI at long term follow up and you know some of the landmark trials in cardiology kind of confirmed this, including syntax, freedom, etc. These trials, however, were conducted in an era prior to newer generation drug leading stents, improved PCI techniques which included physiology guided revascularization as well as uh intra coronary imaging guided revascularization. The fractional flow reserve versus angiography for multi vessel evaluation, which is the FA 3 trial, compared essentially FFR guided PCI using current generation drug looting stents with contemporary cabbage, uh, both in the conjunction of receiving excellent GDMT. Uh, the key point here is that at 1 year, PCI failed to meet the primary endpoint of non-inferiority compared with cabbage with respect to the composite of death, stroke, MI, or repeat revascularization. Um, Uh, this, uh, the fiber, uh, trial was essentially again, an investigator initiated multi-centered randomized control trial, all comers with three vessels CAD, not involving the left main. And otherwise not having a significantly low LDEF for randomized to FFR guided PCI versus uh uh cabbage, essentially 750 patients in each arm, over 90% follow up at 5 years. The primary endpoint for this pre-specified 5-year uh analysis was a composite of death, stroke, and MI. This was a secondary endpoint of the original FAME trial, which failed to meet the primary endpoint, uh, which again is important when you kind of think about how we interpret this trial. And uh looking at the Kael and Maya curves, the curve on your left is, uh, from 0 to 60 months. Uh, it resulted in essentially showing no difference between the two groups. Um, the second, uh, Kaplan-Meier curve is essentially a landmark analysis starting at the 12 month mark to the 60 month, um, which also did not show any. Significant difference between the groups. Um, looking at the secondary end points again, when you kind of delve a little bit closer, knowing that this primary trial failed to meet its end point and this was a pre-specified secondary endpoint analysis, when you kind of add in the revascularization, repeat revascularization, you see that cabbage does significantly better than PCI. Um, PCI did have higher repeat revascularization rates as well. Um, however, there was no significant differences in death or stroke individually, um, but the MI rate was higher in the PSI group than in the cabbage group, uh, as was repeat revascularization. Um, interestingly, they also presented data based on the syntax score, which is essentially a score that tells you how complex the disease is, um, uh, with the thought being a score of 0 to 22 is slightly lower complex compared to a score of greater than 32. Um, and in the patients with the lower syntax score, um, you know, the data kind of suggests that PCI may be equivalent to cabots. So this is important information that we can kind of share with our patients, um, uh, essentially saying that, you know, um, if to make shared decision making. Um, interestingly enough, the trial, uh, the, uh, you know, the person who, uh, presented the trial also kind of uh compared the trial to the syntax trial, which is again landmark analysis, and when you can see that is that on the left hand side, the baseline characteristics of the patients in both the trials were similar. However, the results could, you know, were different, um, and one of the hypotheses is that, uh, when you look at the composite of death stroke or MI, um. Both, uh, cabbage as well as PCI, uh, have become better, uh, but when you look at just death in of itself, uh, maybe the mortality rate from PCI has, has dropped quite a bit. So maybe that's where the differences are coming from again, using modern interventional techniques, uh, for PCI, um, and, uh, interestingly enough, uh, what we don't know is that, uh, is this, is this across the patient board, um, and again, um, you know, this trial did create a lot of, um. Um, a controversy, uh, but the data is what the data is. Uh, conclusion is fiber analysis of FAM 3 providing contemporary data on FFR guided PCI versus cabbage in non-left main multi vessel CAD, uh, affirmed the reduction in outcome differences between cabbage and PCI with the evolution of interventional techniques. and provided further evidence to support individualized patient-centered shared decision making around choice of revitalization strategy. This is, this was the conclusion that the trial uh coordinators came to, and the many decades-long PCR relationship, uh, uh, with, with cabbage remains a crucial and symbiotic one for optimal treatment of multi vessel CAD. Uh, but there are some limitations that we need to keep in mind. Again, the primary composite endpoint was powered only for one year outcomes and it failed to meet that. Um, repeat revascularization was excluded from the 5 year analysis. Uh, cabbage related clinically relevant end points such as post-op afib, bleeding and rehospitalization were not included. Uh, and you wonder how the, you know, the data might have been influenced by these, uh, important end points. Uh, there was a low rate of complete arterial revascularization and cabbage arm and a lower rate of intravascular imaging. Only 12% of patients underwent, uh, in coronary imaging optimized PCI. Which may underestimate the longer term durability of both these strategies. However, the trial, uh, uh, investigators defended this, uh, by saying that the real world out there, only 15 to 20% of patients are getting PCI anyway, so this is probably more uh closer to real world data. Uh, participation of a lower number of female and ethnic minority patients, which may reduce the external validity of the trial to these population groups remain to be seen. There's actually another trial that, uh, Greg Stone is running, um, called the retard trial looking at, uh, you know, women and other ethnic minorities comparing cabbage versus PCI. So it remains to be seen. Um, however, uh, it was interesting and hopefully, uh, this gave you guys some insight into some of the important trials. Thank you. Good job. And next we'll turn over the floor to Doctor Emineja. My slides will be pretty short and sweet, um, I think one of my uh presentations was given by Doctor Tereja one of the trials, but, um, moving on, so these are my disclosures, um, for I would like to start first by um announcing I mean we talked about it during the cardioology uh old physicians meeting. Um, we get approved, ACG approved for, uh, cardiology fellowship. I got an email last Wednesday as the program director of the upcoming fellowship. Uh, so we're gonna start in Centera. We're approved for around 12, uh, total in 3 years, but we might start with 2 rather than 4 fellows, or we'll see how we determine that for cardiology fellowship, uh, programs. So this is gonna be a monumental change in you. Total mindset, different, uh, practice, um, in the sense that we're gonna have fellows with us, we're gonna be involved in. Shaping the future of cardiology, helping serve our patients, helping serve our region, uh, but we're gonna be involved in mentoring, educating, and helping advance the career for multiple and many, uh, future generation cardiologists through here at Centera. This program will be in combination, um, under ODU or the EVMS, uh, basically, uh, as the. Um, sponsoring institution, the fellows will be mainly rounding and rotating here at Centera Heart Hospital, um, and this is gonna be huge for our region. So this is, uh, been in the works. I've been working on it closely with, uh, the team, the leadership team at Centera and ODU and I've got it finally approved. So, um, and this is Doctor, uh, Benjamin Fried. He is the chairperson of the. Um, all program directors for cardiology fellowship, I had a meeting and a workshop with them as all, uh, program directors for cardiology fellowship pre-ACC, and this is our, uh, um. Picture here. So this is a new change happening and this is a great change, I think, because again, it will help us keep us educated, help us, uh, stay informed, help us, uh, stay up to date and also help shape the future, as I mentioned of, uh, cardiology and healthcare in the region in the Hampton Roads area. So, uh, one of my starting with little talks about the rezipetide, uh, most of you know about rezipetide as either Manjaro or zebound have been used before for weight loss, uh, mainly, uh, trazippatide is a dual glucose dependent insuotropic polypeptide and GLP1 receptor agonist. Um, the data on rezippatide before, uh, show that it reduces weight around 20%. Um, but not just that, there's also some data on rizipetide that showed in patients with heart failure and preserved ejection fraction. When patients take rizippaide, there is a significant reduction in cardiovascular outcomes, be it uh cardiovascular death and heart for hospitalization. Uh, the study that was presented at, uh, ACC meeting, they looked at, uh. Trizippatide, if um in patients with heart failure and preserved ejection fraction who are obese, um, treated by rezippatide, does GFR affect the outcomes of these patients? So, uh, it all comes out from the Summit trial which was published a year ago, um, or two and which involved around 731 patients with heart failure and preserved EF um and had a BMI of um. 30 or greater. 60% of these patients had chronic kidney disease, and as I mentioned before, around 30% of patients who receive traippatide, there is a reduction of cardiovascular death and worsening heart failure. And when they examined the outcomes based on GFR because again, uh they looked at patients um with lower GFR between I think 35 and 60 and 60 and above, but they had chronic kidney disease, um, there was. Definitely there were no significant difference in the benefit of traiptide among the different GFR uh groups among the chronic kidney disease and as we can see here, uh, when they looked at GFR or the chronic kidney disease based for GFR or cystatin C, um, all patients with different, uh. Chronic kidney disease statuses, they had benefit from zip zipatide. So again, this medicine not just can reduce weight but also can improve cardiovascular outcomes independent of your chronic kidney disease. The authors of this study, they found that initially at the beginning of the study, there is a little bit reduction in GFR. Um, but again, at 52 weeks actually, the GFR increases because as we know, the lower GFR we think that kidney disease is not doing well or there's a worsening of chronic kidney disease, but at 52 weeks, the GFR increased. So technically, again, the authors of this uh paper found not just only can make your heart failure better, not can only make you lose weight. But also can protect your kidneys as well. So again, uh, this medicine is kinda trifecta of kidney obesity and um uh heart failure preserved EF. So again, these medications are gonna be used more and more as we're gonna be seeing later in the future years. I gave a um a talk uh recently at uh the turning the tide on diabetes. About GLP one receptor agonists and uh basic GIP GLP one receptor agonist, probably I'll give the grand rounds on it next year, uh, but again, these medications have changed the whole, uh, you know. Medical uh management for patients who are diabetic or even ob obese patients. The other medicine, semaglutide, which you all probably know by Ozempic or Ragovi or rebelsis, um, again, uh, Ozempic is for patients have diabetes, uh Rogovi for weight loss without diabetes, and rebelsis is the oral formulation of the medicine. Doctor Treja talked about the stride trial, so which is the, uh, patients with peripheral arterial disease who are uh receive um some maglutide, and as he mentioned, uh, basically there's improvement in six minute walk and also there's reduction in the outcomes, uh, of, um, basically urgent taking them to the vascular lab for revascularization or cardiovascular death as well. So we're gonna skip that, uh, the one thing I wanna talk to you about, um, not sure if, uh, it's called the oral semaglutide. If you remember, uh, we have rebelsis, which is approved for patients with diabetes. Now they're looking at patients, uh, with diabetes and high risk for cardiovascular disease also, it's called the Sole trial. And these patients, which is the first, uh, study of the cardiovascular benefit of the oral formulation of GLPion receptor agonist, if you all recall, uh, people online or here two years ago during the American Heart Association, um, uh, land, um, uh. Like basically the first opening session, there's the uh trial called Select trial which showed that patients uh who received GLP1 receptor agonist uh with cardiovascular risk factors, these patients have significant improvement in cardiovascular outcomes. It was the first trials was um like breaking the, uh, you know, uh, groundbreaking trial at that time. And again, semaglutide was subcutaneously given. Now we're looking at patients who have risk factors for cardiovascular disease, uh, they have either aspirotic heart disease or chronic kidney disease, and where they randomize them to oral semaglutide, which is rebelsis technically. To placebo again we saw that there is improvement in um outcomes as um previously noted and reduction in uh all adverse cardiovascular events and deaths from cardiovascular events. So for patients who before that uh had problems giving themselves their medications, now we have an oral formulation of medicine uh if they are diabetic. And have um risk factors uh for coronary artery disease or they have a coronary artery disease with kidney disease. These patients, again, there's significant improvement in outcomes and also as you can see here, there is significant reduction in hemoglobin A1C, there's also weight reduction. And the CRP, which is an inflammatory marker, which is also associated with uh poor cardiovascular outcomes. Again, these medications that in the past that as a cardiologist, we completely ignored and we kept ourselves in silos and didn't want to engage. In prescribing them because we don't feel comfortable with it. Now we are, you know, obliged for some of us to be part of it, not just, you know, because we want to improve patient outcomes and. Um, I'm a big advocate for these medications because I'm, you know, uh, and we have to be on it because again, at the end of the day, the patients are benefiting and we have to provide our patients with the best available options for care. So again, this, these medications are pretty important, um, one last trial I wanna talk about is that uh in heart failure, we always tell our patients we need to limit your fluid intake, um, and again. When they're in the hospital or outpatient, limit your fluid intake to around like 48 ounces or 64 ounces, uh, because again, we would tell what we put in it should come out or if you drink too much fluid, that will make you, you know, more uh short of breath, volume overloaded. Well, um, there's a trial that was presented at uh the American College of Cardiology and published in Nature Medicine. Uh, which was done around 500 patients in the different medical, um, centers in Netherlands, and they looked at patients who were, uh, randomized either to receive fluid restriction, which is around 1500 ccs, 48 ounces, another group of uh patients who were told to liberalize their fluid intake. So, um, most of these patients who had, uh, you know, NYA class 2, so they are kind of the more stable patients, outpatient setting, they're not pretty symptomatic, um, and these patients were taking the standard guideline directed medical therapy, and 51% of these patients were on loop diuretics. Again, these patients, again, outpatient setting with heart failure, randomized to fluid restriction versus liver fluid intake, and they wanted to see if there's any difference in outcomes. Technically this study again is published in Nature Medicine, a lot of ACC and those simultaneous publication. They found that there is no difference in the primary outcome, which was, uh, in the study used as KCCQ which is cancer uh uh city cardiomyopathy questionnaire, which is quality of life technically and how patients are functioning so there was no statistical difference in the primary endpoint. And when they looked at the secondary endpoints and. Sub-analysis, there is also there's no difference in mortality or heart for hospitalizations or the need for a diuretics or acute kidney injury at 6 months' time. So again, uh, the, I can't comment much about that part because again it's a like uh multiple centers in Denmark and um Netherlands. And uh sorry, and there are only 500 patients again and um the primary endpoint was not mortality or hard for hospitalization, it was the primary endpoint was KCCQ. So again, at least these patients, uh, did not feel worse, but the patients in the uh fluid restriction cohort, they had more thirst, as you can anticipate, but also if you look deep into a little bit deeper into this uh study. The fluid, uh, liberal fluid intake group at around 760 ccs, which is still not too bad. I mean, uh, we, you know, it's, you know, patients who drink more than 2 L of, uh, fluids, be it water, soda, soup, whatever it is, um, it's not usually advised, but again, even the liberal fluid, uh, group did not use or um have more intake than. That's not too too bad. So again, the thirsty stress was significantly higher in the restriction R and the fluid restriction R. Um, these are the three main trials I wanna talk about, but at the end of the day, again, the most important thing out of, um, not just me giving a talk at the ACC and invited to give that talk and, but also the highlight of my presentation for those here and out is that again, July 2026, we're gonna start our cardiology fellowship. I ask, um, all the cardiologists who want to be part of that, please feel free to reach out to me. We have identified a group of core faculty eventually, hopefully we're gonna transition to a teaching hospital. Well everybody gonna be involved in educating their fellows, um, but again, uh, if you wanna be more involved in the fellowship, more involved in, um, shaping the future of uh heart disease in the region. Uh, to be an educator, please feel free, uh, uh, to reach out to me because this is happening. It is, um, we're gonna start participating in the match process. We're gonna open in July, um, so all hands on deck we're gonna be having, um, a lot of works, um, to try to have a successful training program. Uh, so, um, more to come on that, but just wanna share it. On that note, uh, I think I'm done, and, um, if you have any questions, I'll be happy to answer.
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