 So today we're going to talk about structural heart interventions on structural heart diseases, some of the lessons learned from recent trials. So the need and some of the caveats of structural heart intervention. Let's discuss them first. So basically, some of the population based analysis revealed that the prevalence of moderate to severe mitral and tricuspid valve diseases is very high in the elderly population mitral valve disease almost is at 10% and the tricuspid valve diseases and the elderly exceeds prevalence of 4%. Only a small number of patients enrolled in many of these studies and trials. You know, the limit the data that's available to understand the real world clinical impact. And so the ability to verify the impact of these limited number of patient studies is very challenging. Further, there is limited randomized data that is available to compare these transcatheter therapies with optimal gold record medical therapies. And so what we've learned from our experience is that what's key to structural heart interventions is with quality imaging, optimal patient selection, timing of the intervention and appropriate device selection. A lot of these factors are controlled for in a lot of the studies and trials that we're going to discuss here after. But in the real world is easy to forget that you have to have all these ingredients to have the perfect recipe. So patient selection, ensuring that the quality of the images good timing the intervention and device selection again is is critical. And this usually involves multidisciplinary planning. So we'll start with some of the mitral valve interventions. Trans catheter edge to edge repair also called tier is now the standard of care for patients with symptomatic functional mitral regurgitation or FMR. Those who have MR, despite guideline directed medical suggested a class to a recommendation for select primary MR. While the 2021 European Society of cardiology and cardiac surgery gave a class to be recommendation for use of tier and primary MR. Further a new class to a indication has been recommended by both ACCH and the European guidelines for functional MR patients. So more than 33,000 patients have received a tier for the mitral valve disease now that's using the mitral clip. And with continuously improving 30 day mortality which is now less than 5% and a surprising average length of stay of just about one day. Now, the Abbott mitral clip is the first trans catheter technology with the CE mark and FD approval for treatment of both primary and secondary MR since its first implantation in 2003, over 100,000 procedures have been performed worldwide. The co-app study that randomized patients with heart failure and moderate to severe or severe functional MR, who remain symptomatic on gold retinal therapy came out with three or outcomes last year. It showed a sustained through your improvement in my favorite station severity, quality of life and functional capacity. The analyze heart failure hospitalization rates in these patients remain low at 35% compared to 69% of gold retinal therapy and the mortality was also low at 42% compared to 55%. So it just highlights the significance of this procedure compared to guidelines and medical therapy. Now, the patients that had crossed over from the medical therapy arm to the tier group also actually had improved both mortality and heart failure hospitalization, which is very significant. Now, again, the key here is patient selection, the difference between the co-app and the mitra FR trial that had come out. It basically assisted us in development of a new physiologic concept of proportional versus this proportional mitral regurgitation. And the concept is based on the fact that the effective regurgitant orifice area or the EROA depends on a lot of factors such as the LDM diastolic volume, the ejection fraction, the regurgitant fraction, and the velocity time integral of the mitral regurgitation. Now, one of the largest contemporary real world study of mitra flip called the mitral mitra flip expand study came out as well. This shows effectiveness of the mitra clip and the MR reduction in almost about 90% of patients at one year and a significantly reduced reduction in heart failure hospitalizations at one year as well with excellent safety profile. So this is one of the largest real world studies that we have looking at the mitra clip. Now from other studies we have also learned a little bit about some predictors of mitra flip outcome, primarily aged less than 75 years, lower serum creatinine, low LV and diastolic volume and the absence of diabetes hemodynamic instability and atrial fibrillation and COPD are associated with good outcome. Other sub studies of the co-op have also shown that a residual MR greater than three plus is associated with worsened mortality at 30 days and also at two years. And we also understood that gender specific impact of tear in heart failure hospitalization treatment, the benefit was less pronounced in women when compared to men beyond the first year after treatment. Further, the role of tear compared to surgical mitral valve replacement in post MI was also evaluated in another retrospective study of about 500 patients. These patients had at least moderate to severe MR following myocardial infarction. The immediate procedural success did not differ in the two groups, however the in hospital and the one year mortality rates were significantly higher in the surgical mitral valve replacement rather than repair replacement rather than the tear groups. The tear came out a little bit better in overall mortality in these patients. But definitely if the mitral clip fails, and the patients need surgery, there is this small outlook, the cutting edge registry of about 300 patients looked at mitral valve surgery needed. If, if the edge to edge repair the tear failed the mortality rate remained high at about 24% at one year, and 30% over 30% at three years after the mitral valve surgery. What's also interesting is that there was a very low rate of mitral valve repair possibility in these patients just about just about under 10%. Further, to retrospective studies also suggest that this procedure of end to end repair can be safely performed with moderate sedation, just, you know, a promising evolution of where these procedures are headed. We're going to discuss the Edward Pascal system that also gained CE mark in 2009, February for the treatment of both primary and secondary MR and the class study also came out with this two year outcomes recently. Now again to remember this is an observational study of about over 100 patients, and the results show sustained favorable, favorable outcomes with a very high survival rate of about 72% for for functional MR and over 90% for primary MR and high freedom from heart failure hospitalization rates as well. The Pascal device as of a month ago at the TCT was given FD approval for regenerative mitral rigor agitation. Now, let's discuss transcatheter mitral valve replacements or TM VR compared to tear or edge to edge repair. The field of TM VR is still pretty much in its infancy. And this is mainly limited by high rates of screening failure due to unsuitable anatomy. Our study will discuss that came out is a 10 dine the Abbott's 10 dine valve as shown in the image came up with this two year outcomes that showed an all cause mortality of 39% sounds high. It is a very sick population it was about 43% at 90 days, but 90% of these patients that survived did not have MR and they also showed decrease in heart failure hospitalization hospitalization so that's promising. Several other other devices are currently being evaluated for TM VR such as the the intrepid bimetronic for which favorable results have been reported and pivotal study but there's no big study that has really been revealed. Next, we'll look at the TM VR or TM VI for valve valve valve and ring and valve and mac cases. The one year outcome of a small study called mitral trial came out which looked at mitral valve valve with safety in three and high risk patients with 100% success rate and a low complication rate and a low mortality as well. A larger study looking at valve and valve and valve and ring almost 1000 patients collective followed these patients up for over a year median age of time for follow was about 500 days. Again, primarily these procedures were performed trans apically which is 62% and now we're actually seeing this trend reverse over the last few years we're doing a lot more procedures transvenous and transseptly. This looked at overall technical success rate which was very high and a low risk a low rate of residual MR and a high four year survival and the survival was higher in the valve and valve patients compared to the valve and ring patient which is not a surprise. Also the residual mean gradient greater than five was still very high in these patients at about 60%. The overall risk of LVOT obstruction or mispositioning was extremely low under 3%. Similar to this study, another large study looked at three different settings of about 500 patients and this is also looking at patients with valve and mac. Trans apical was again the preferred axis again you're seeing reversal of this trend and see more trans femoral use the valve and valve patients actually had a very low 30 day and one year mortality and a very low adverse event rate just about 23%. Compared to that the valve and ring patients had a slightly higher 30 day and one year mortality. But the worst were the valve and mac patients, these patients had a high 35% 30 day mortality and pardon that a 62% one year mortality. Also the rate of residual MR and valve embolization was also high, but what's key here is the LVOT obstruction almost at 40%, which basically drove most of these of the morbidity in these patients. Now better result for power in the Mac category came out from this global registry study in which the LVOT obstruction was just about 11%. So this kind of also explains that as we are progressively learning more about the procedure and you know we're using more advanced imaging technologies and you know using CT and AI based systems to predict LVOT obstruction some of these will eventually complication rates will eventually come down. Let's quickly discuss tricuspid valve interventions. So tricuspid valve interventions is very interesting it is estimated that over a million people in United States have functional tricuspid regurgitation the prevalence is very high so there's definitely need to understand and learn more about these interventions. Now the tricuspid valve has some anatomic challenges, it may seem like it's a, it's the most easily accessible valve. You know, you don't have to do arterial access, nor you have to do septal crossing, but it has its own set of unique challenges. And the first one is anatomically it has a lot of complex subvalverate components. There are simple cordate tendinane and papillary muscles which really increases the risk of entrapment and hindering device maneuverability under the valve. And it is a less understood D shaped analyst valve which is very dynamic both during the cardiac cycle, and also changes significantly with disease progression. It has a closed anatomic relationship with the septal tricuspid analyst and the AV node and his system so the risk of nuance at a worsening conduction abnormalities is high. Also the role of optimal medical therapy again is not really addressed by any of the guidelines so while the diuretics and ACE inhibitors they do provide some symptomatic relief. We haven't really shown any prognostic benefit in right heart disease so comparison to interventions, you don't really have much information in head on comparison with medical therapy. Overall, percutaneous tricuspid valve interventions so far have a really good procedural success rate over 90%. It is associated with good survival and reduce heart failure hospitalizations. There is a low complication risk in most of these procedures just about 2%, and the average 30 day mortality of about 5%. The other problem with a lot of these interventions is the definition of procedural success because the definition used in a lot of studies that we mentioned uses greater than one TR grade reduction as procedural success. And there's also a discrepancy in this reduction in TR or the correlation of tricuspid regurgitation with improvement in functional class. So although the TR may just reduce by one grade, the improvement in the patient's functional class is quite significant so we haven't quite gotten our head around this concept that you know how just reduction of TR grade by one is translated into clinical success or technical success. So let's discuss the TR technologies, edge to edge repair technology for the tricuspid valve. So there are no currently FD approved transcatheter modalities. The biggest one is the triclip, which is by Abbott the trilluminate study. And it was in September 2022 that part of their study outcomes came out. The one year outcomes and it found that the triclip was safe and effective in patients with moderate or greater TR 75% of the patients were in class three or four. So these are very sick patients, and they had a reduction in TR severity in about 90% of these patients. Most of these patients again 90% ended up in NYHG class one or two with significantly improved functional class and also reduced six minute walking distance. The event rate all caused mortality was low just about 7%. And the functional status improvement was quite significant in these patients. So we're again keeping those definitions of reduction in TR and improved functional class. The my triclip XTR was also studied in about 30 patients for the tricuspid region. And these patients of application gap is more than seven millimeters and about half of them. And this is significant because over time you realize that over seven millimeters and under 10 is kind of like the tricky area where it gets challenging to have technical success or significant reduction in tricuspid regurgitation. Over 10 millimeters is something that becomes very, very challenging and may need, you know, a revised thought process about valve replacement and sort of valve repair. The procedural success in the my triclip XTR was also high about 90%. And there was a high rate of single leaflet SLDA in in about 25% of the patients. Next we look at the class study, which is basically looking at the Pascal device for the tricuspid. Here we saw that the patients had a substantial reduction in TR functional class and quality of life with a very low event rate or need for intervention. This device has also been studied in the United States in a small compassionate use study, and again showed significant survival and reduction in functional class minimal complication. So the class TR second studies a bigger randomized study which is going to be looking at the Pascal device versus medical therapy alone. Now let's discuss some anaoplasty techniques for the tricuspid cardio band. The trial band was the biggest study that came out showed a low 30 day mortality and a high rate of bleeding events. So this was the challenge and cardio band bleeding rates, systemic bleeding rates were high, a majority of these patients experienced improved TR grade by at least one. And the six months data from early feasibility study showing high improvement and an alert dimension reduction. So basically what the device does is that it's a contraction wire and a polyester fabric that is since to reduce the AP and septolateral danglers. So you can look at those outcomes of 20% reduction in an alert dimension. So this is something that the edge to edge repair does not address. And also what's going to be important in the future is to identify patients that would probably benefit from an anal capacity in combination with an edge to edge repair. The trial line device is also undergoing a study named the scouts trial preliminary results came out looking at one to your great reduction, no high complication rate and a decent technical success rate in these patients as well. A trial replacement for the tricuspid. Again, there are quite a few devices that are on our market, the biggest one trial that came out last year was a tri-cent trial. This was about 100 patients in the six month follow up was available with high technical success rate, a higher TR reduction in 100% of these patients reduced to mild or less, and the improved functional quality of outcomes for very, very significant in these patients. Freedom from heart failure was also over 90, 95%. Now the tricent to randomized trial is underway and we are also enrolled here at Bethesda Leakness. These are some of the other orthotopic bioprocesses that are available. This is the, the evoke valve. This is a gate system. This is built by the Navigate company in California to self expanding bioprocesses. The Lux valve is actually from China is a tri leaflet bovine pericardium valve and is delivered through thoracotomy and now it's coming also through a trans atrial approach. This is a sapien valve that we know, and the trick in the tricent to our cable valves which we'll discuss. Heterotopic bioprocesses is cable implantation. Basically what it does it reduces heart failure symptoms and and volume overload specific anatomy is required to pass for a cable implantation for example if you try to put analysis too big. The annular dilation is too big for a TMDR or patient has pacemaker wire so you cannot implant a new valve, then this is one of the options so you can do. Most of the valves used here again are the sapien valves, and there are two trials that are underway the tricable and the hover trial, which is also looking at, you know, high success rate but the risk of valve dislocation is there and the tricable study the rate of valve dislocation was very high about 30%. So one in three valves is getting dislocated so it was DC the hover trial is still currently underway again these are for very high risk surgical patients only currently. So this you can see the spread of all the tricuspid interventions currently taking place two thirds are still triclip or the mitreclip, and only about 15% are getting and will pass you but as more and more of these devices come out, you might see it shift in the trends. So quickly the aortic valve interventions, the main study that came out was the partner three two year follow up grade primary endpoint reduction, and the initial difference of debt and stroke that was favoring the tabber is although reduced but it's still present. However, unfortunately also showed an increased risk of valve trombosis over two year period of time. Similar to the to the partner three tabber valve we have the two year follow up from the evolution lowest trial and the lowest patients. Again the primary outcome was favoring tabber compared to the surgical valve replacement, although this was not statistically significant, and the need for permanent pacemaker with the evolut was much higher is about 20% compared to 8% in the surgical valve. And finally the five year follow up of the cert have eval also came out this was the RCT of over 1600 patients intermediate risk patients again the first two years were the lowest cert have these intermediate risk patients. And here the rate of all cause mortality or deceiving stroke was no different between tower and server at five years the primary outcome that was no difference at five years. So it's a very interesting trend because you know, when you compare tower to server obviously you can see that most of the benefit and primary endpoint which is reduction in all cause mortality debt stroke is much that the difference is much higher earlier than 30 days in up to a year. And as you see more data come out, you know, over two, three, five years, you might start to see a decrease in the benefit over period of time. The avatar trial the big trial. And the interesting one is looked at early surgical aortic valve replacement versus conservative management showed a good primary composite endpoint of actually reduction in heart failure and all cause mortality both to improve outcomes and only driven by decreasing the heart failure hospitalizations. Next we look at TABR use and bicuspid aortic valves. These are low risk patients who have bicuspid aortic stenosis. TABR appear to be safe with short length of hospital say stay literally zero mortality no disabled in strokes. Another analysis of the approved of the approved trials off lowest patients with bicuspid AS also showed comparable results and safety in patients who have were using TABR. A partner three sub study also showed TABR outcome worse in atrial fibrillation so that again something to think about that patients who had atrial fibrillation had a high risk for composite outcome of debt stroke or hospitalization. To summarize, we had a sustained two year benefits and lower risk patients. We did have sustained fiber benefits for intermediate risk patients but again this benefit was much less compared to the first 30 to one year, and that effectiveness of TABR and bicuspid aortic valve is established for low risk patients. And finally we look at the left atrial appendage interventions. The amelot device basically got FD approved last year. This was followed by the amelot IDE trial which compared the amelot and watchman for non inferiority. Basically the primary safety endpoint was achieved in both, and it proved that the amelot device was, in fact, non inferior to watchman. The left atrial bleeding rate and very similar all cause mortality and the left atrial fusion rate was actually much better in the amelot compared to watchman. Procedural later complication was slightly higher in amelot compared to watchman, but again very similar so now we have another great device you know for left atrial appendage closure. The data analysis of 40 studies also showed that intracardiac echo guidance for implantation of these appendage closure devices is safe while it reduces exposure to general anesthesia and associated possible risks with that. The comparative studies also suggest that left atrial appendage closure can be performed with moderate conscious sedation with same day discharge. So we are seeing a trend in a lot of these appendage closures being done with 3D ice guidance as you probably experienced at most of your centers. There are also studies that are comparing patients who are getting the appendage closure at the same time as atrial fibrillation ablation, and they're getting good results with long term success rates almost 100% ceiling rate of the left atrial appendage and about 70% long term And lastly, the four year outcomes from the trial looking at the left atrial appendage closure versus oral anticoagulants came out which showed that the appendage closure was non inferior to oral anticoagulants. So we're seeing a lot more patients are going to be referred for these appendage closures. And finally, we are experiencing more of the flex device I think most institutions have almost 100% converted to the watchman flex device the pinnacle of flexibility that came out in the last two years showed a primary effectiveness in 100% of the patients and a very, very low complication rate. So all in all we're doing some really good work and structural hard. There's so many ongoing trials and I could barely cover probably you know half of all the things that have been going in the past two, three years, but I hope that the review was helpful for you to understand where we are some of the challenges and the caveats and what the and where we're going to be going to the future. All right. Thank you without taking more time I'll pass along back to us. Thank you for the opportunity. Thank you very much. Thank you all for that detailed review. Just a couple of questions. One is one of the issues that comes up often with a special heart disease interventions, this topic of indication creep that a lot of these devices were initially tested on pretty failed patients. And as the technical challenges got ironed out a bit as a operators got more trained. They started applying these to more and more patients were really out very much outside the demographic for which the trials were done. And then as sort of more evidence grows or maybe sort of a bit of stepping back at in your practice are you seeing much of a stepping stepping back with any of these devices based on newer evidence to kind of clarify exactly where the line is, or are you kind of continuing to see that patient population grow despite the in a way that's in commensurate with the evidence base. So I think it's a double that's forward because a lot of these studies have very stringent inclusion criteria. Right. So we be took patients that are very, very sick. We took patients that have, you know, no chance of getting a surgery, but at the same time be ensured that their imaging is perfect is pristine I mean we have, you know a panel sitting and discussing patient imaging whether these patients should be enrolled or not. So, when you take these very sick patients, but you know, you know line up perfect imaging perfect device selection. And you know, in, in high volume centers where most of these trials are conducted, you get a certain outcome. Now when you change. One thing also to remember is that they also have a very expert referral group, you know you have advanced heart failure practitioners that are, you know that are assessing these patients, making sure these patients are optimized on medical therapy before they're going for interventions. The real world population is much different. You know we are extending some of the uses, you know practically to maybe slightly lower as patients. So we are seeing increasing pool. We're also seeing patients that have that are not, you know, perfectly screened for imaging for again device selection. We're not, you know, doing panel discussions about, you know, who, who are we bringing in for this. So there's a, there's a, there's a difference in the population that was enrolled in these trials versus real world population. And you have to be careful about a lot of these outcomes, as I was showing that, you know, some of the real world data overlaps in for example the Mitra clip, but some don't like the complication rate maybe, maybe much low. So, depending on, you know, advanced referral group, the technical skills of the, of the group that's, that's performing the procedure, experience of the of both the interventionist and the imaging cardiographer. It's going to be, it's going to be interesting to see how, how, you know, more data comes out and how, how structural interventions evolve. And it challenges us to see whether enough effort and research are put towards analyzing that data, because we have a lot of patients who can have surgery open surgery safely. And it's not difficult to sell an interventional procedure to a patient because from their perspective it's obviously much easier and much quicker procedure. But we really don't have a lot of open questions about the long term outcomes. The watchmen devices that, you know, as you know, is pretty controversial whether the indications for which it's being applied are really valid and to have a new device then be compared to the watchmen for non inferiority. There's a lot of concerns about sort of where we're, where we're going with this. And Marcus, are there any other questions that you want to ask. I just wanted to ask a one question. I'll be you had mentioned that you are starting to be able to maybe do mitral clips or edge to edge repair under conscious sedation is that I'm assuming that's going to be done with ice or intracardiac echo as the main imaging modality. And has there been any comparison of ice versus T for for long term outcomes in terms of the repair quality. Yeah, there's no, I mean, again, ice use for any of these, you know, since the advent of 3D ice is literally in its infancy, you know, we're seeing, you know, some of the most advanced centers having six months or less experience with ice. And it's still requiring, you know, a lot of technical challenges. Basically, a couple of expert representatives from the company to come and guide, you know, knobs and imaging and you know, rotation and acquiring images. And we know that I from our experience, you know, I says, for, for, let's say a appendage closure, it's not, it's not perfect, you know, an eight to nine out of 10 cases you'll be able to achieve. But then even with your best maneuvering, you know, you may not be able to achieve the goal for something like intracural septal closure, it might be, you know, more technically apt to use ice than T. And most study really has looked at head to head comparison of T versus ice to answer your question. But I think again, most people haven't started using ice for these procedures so again I think that it's a matter of time, in my opinion, as ice gets better you know, our field resolution is still limited in ice it's it's not perfect. But as again, the technology advances with that, we might be, we might be headed in that direction. Thanks so much. Just to follow up on that in your group, who's responsible for the ice the cardiologists or anesthesia involved in the ice cardiologists. So, right now, for example, our watchmen's roughly 30 to 40% are being done with ice I think across the street bring them they're doing more maybe 50 or 70% under ice. From what we hear from our colleagues. We still requested to do some tea once in a while because, again, it's hard to predict imaging challenges using ice and there are times when, for example, sizing of the device, or the appendage it's it's it's still not, you know, most of these guidelines are built upon T use for for sizing. So we're still struggling to actually you know, take T away during a watchmen procedure. So we're still doing T and then to intermittently helping them with imaging with deployment with sizing and things like that. Thank you. Otherwise there's no questions in the community. Okay. Thank you very much. Thank you. Thank you.