 Thank you for the kind invitation. Let me share my screen and it's a pleasure to be here with you. I feel like I'm with friends and family and many of THI achievements and outstanding work is familiar with me. I'm very familiar with. So a lot of what I'm going to be discussing some of that she may be bread and butter for many of your outstanding interventional cardiologist. But this topic or this lecture I'm going to gear it towards the clinical cardiologist, as well as the interventional cardiologist. I have no relations with industry or conflict of interest related to this topic. I was a member of the writing group of the guidelines a CCH a viral heart disease guideline. And this topic will cover the issues related to aortic stenosis as well as TAV versus server. So that's my focus for the current grand rounds. I also was a member of the 2017 focused update on the viral heart disease guideline. And I was a member of the team that performed the initial TAV in the whole VA healthcare in 2011, a few weeks after the FDA approval. And just I was a member of the team that we just started at Harris Health at Bantob also the first TAV program this year. So TAV and I think valve is on the core of my interest and I would love to share with you some intricacies related to our viral heart disease guideline, as well as contrast some of our guideline recommendations with the recommendations from our European colleagues. So you're all familiar with the guideline recommendations by ECC and HA class one recommendation and these classes of recommendations are based predominantly on the ratio of benefit to risk. This is obviously separate from the level of evidence. So class one recommendation is a strong condition to do or implement a strategy because the benefit to way outweigh the risk. Obviously, as you may know, there's either no benefit or even there's harm. That's why it should not be done as class three recommendation either for no benefit, or because there's actual harm class to a and to be recommendations are really a borderline So there may be there is benefits that outweigh the risk but the magnitude of benefits is not the same as any class one with a class to be there may be benefits so it's maybe reasonable to implement the strategy. So let me start with a clinical case of a 66 year old man. He's been having progressive this one exertion for the BNP 310 known to have fully controlled hypertension to prior surgeries one cabbage and one other prior medecine surgery. STS prom score isn't the intermediate range 6.5% and echo cardogram showed a normal LV function mild LVH and all three measures indicative of severe aortic stenosis. So the intensity across the valve, more than 4.1 meter per second mean gradients, more than 42 millimeter, and I wrote it well, area of 0.9 millimeters square. This is a still images of the cats kind of this patient to the left panel, you see this calcific tricuspid iodic valve. And to the right, you see a cross section across the left ventricle. It's not an image but a hint of my or not going to go hypertrophy and I want you to focus on the apex and think what's happening at the apex of the left ventricle of this patients, and I'm going to go back to this patient at the end of my talk. So let us start with a simple. That's a really more detail of the cardiology fellows and the clinical cardiologist, according to the vital heart disease guideline. We publish in late 2020 December 2020 by a CCH what should this patient have. Should he undergo an exercise stress test. Should he have optimized blood pressure before treating his AS. Should he have aortic valve calcium score measured receive a follow up echo in six months or undergo aortic valve intervention. In stages of our heart disease at risk valve disease would be a patient like having my cuspid I think valve, who's at risk of progressing to do more significant out above stenosis and disease, progressive I think valve disease would be somebody with mild or mild aortic stenosis. Then you have a stage C which is asymptomatic severe aortic stenosis, and we divide those patients into asymptomatic with no LV or RV decompensation. So the normal structure of the function and RV function. So you have usually more than 50% C2 is asymptomatic severe aortic stenosis. But with decompensated LV or RV, usually with EF less than 50%. And we have obviously the stages D, which are the severe symptomatic. And in the case of aortic stenosis, we classify them into D1, D2 and D3. So D1 is symptomatic severe high gradient aortic stenosis, these patients are able to mount a velocity more than four meter per second and the many gradients above 40 millimeter. So we have an aortic valve area typically less than one centimeter square or index aortic valve area, less than 0.6 centimeter square per meter square. There are symptoms are anywhere between heart failure exertional angina or exertional syncope or presyncope, but really the most common symptoms in these patients are exertional this is not exertion and exertional fatigue and progressive decline in their functional activity. So D1 severe symptomatic aortic stenosis very easy to diagnose that challenge is with stages D2 and D3. So D2 is also severe aortic stenosis but these patients have compromised RV ejection fraction doesn't 50% that unable to mount a gradient or velocity more than 40 millimeter or four meter per second. And you would want to perform the middle mean stress echo up to 20 mic per kilo and try to elicit if they have a contract I'll reserve and increase gradient and velocity across the aortic valve and discern through aortic stenosis from pseudo stenosis. Stage D3 patients is even trickier to diagnose because this patient do not have low EF. These are severe aortic stenosis with paradoxically low for low gradients, because the EF is above 50%. However, they have paradoxically low stroke volume index defined as strong volume index less than 35 CC per meter square. And that's not appropriate or adequate gradient or velocity, and it's trickier to diagnose these patients, you may need to resort to a junctive diagnostic modality, like aortic valve calcium score. You will need also to optimize their afterloads and there is just their blood pressure to increase their stroke volume to be able to better assess the severity of their aortic valve. So let's go back to this patient should we perform an exercise stress test on as patients and when. So in asymptomatic patients truly asymptomatic patients who have no decompensated as we function. So normal EF above 50% exercise testing is reasonable to assess physiologic changes with exercise and to confirm absence of symptoms. And in the guidelines we say if you have symptoms on exercise. You're asymptomatic without exercise. I mean symptoms on exercise stress test are symptoms. Even if in routine daily life activities that patients asymptomatic, once you have symptoms on stress test, then you'd consider this patient as a symptomatic patient who needs aortic valve intervention. Obviously, if the patient is severe symptomatic with stage D one with high velocity high gradients, then you should not perform an exercise stress test, because of the risk of sudden cardiac deaths and ventricular arrhythmia. So in this patient absolutely no stress test. Now what about the role of medical therapy in this patients. Now, blood pressure control in patients with the stages B and C is appropriate as long as it's done very carefully, cautiously and careful titration. To use on to represent therapy, the guidelines really do not indicate preference for one versus the other, but there are some retrospective data showing that blocking the running and you test a system system with a single ARB may impart a benefit. And in retrospective studies, there are some benefit in on all cause mortality probably because of the beneficial effects of ACE inhibitors on limiting fibrosis and led ventricular hypertrophy in these patients. And that in therapy, obviously, is shown in multiple in at least three randomized control trials that it does not impact the progression of Ayurvedic stenosis. And it does not reduce other valid related events. Now, in the clinical studies of as patients, it does reduce by around 20% or so is chemical disease events in patients with Ayurvedic stenosis. In the as patients are older, they have a high atrocious risk risk, and they need to start in anyway, but it's not recommended for the lack of benefit to give it to prevent the progression of as that signal of benefit was evident in early observational retrospective analysis but did not pan out in randomized control trials. We're measuring calcium score in this particular patient remember this particular patient was a stage D one straight diagnosis of high flow high gradient as was symptoms. So really adding Ayurvedic cancer score does not help much, because you already get your diagnosis. Now, adjunctive diagnostic modalities, such as a Ayurvedic cancer score may help in those with diagnostic dilemmas, like those with stage D two. Let's say you did a DSC on them and you're unable to elicit a contractile reserve or increase their gradients, because it's not increased their cardiac output by more than 20% or in stage D three with a low stroke volume index and you're not sure whether the symptoms are this is true severe as or not, then you could measure an Ayurvedic blood calcium score. And there's such specific agates and scores. So for women we go with a threshold of 1300 for men we go with a threshold of 2000 remember in the woman there. So they may have severe aerotics noses with less calcification, because they're more prone to fibrosis of their erotic valve, while in man, there's more predominant calcification as contributing to the pathophysiology of their senior Now what about following this patient with echocardiogram and this patient had severe symptomatic stage D one, he needs to have aortic valve intervention, but let's say if he was asymptomatic or stage B, then the recommendations are as follows for those with mild hyaluronic steels as you would want to follow was a trans-rosic echocardiogram every three to five years, moderate, I would say was every one to two years with a true stage true severe asymptomatic with compensated alve function more than 50% I E stay C one, you want to follow every six to 12 months. Now if they have severe asymptomatic stage C two, then even if they're asymptomatic, because of the structural deterioration in their alve function, they would need to go towards I or take value intervention. So this patients should go undergo an aortic valve intervention. So that was a simple question just to start the discussion. Now, in our guidelines we publish a little bit more than a year ago now, we have five class one recommendation to treat symptomatic and asymptomatic and asymptomatic severe aortic stenosis. So for symptomatic severe as patients. So class one recommendation with the highest level of evidence for those with the stage D one, who have symptoms of exertional dyspnea heart failure and general syncope or presyncope I or take valve intervention is indicated. So the symptoms are symptomatic or stage D two or D three. So low low low gradients with reduce EF or preserve the F, then it's recommended also to proceed with an aortic valve intervention. But here you may face some diagnostic challenges to really ascertain this is a true aortic stenosis. And also to ascertain at least in stage D three that the symptoms are related to the aerotic stenosis and not related to something else. Now for asymptomatic patients we have to class one recommendations. The first recommendation is to perform aortic valve intervention in asymptomatic stage C to patient with severe as so those with severe as even the asymptomatic but have an LV function less than 50% already had the structural heart disease or deterioration of the LV function they need to go with an intervention. Those asymptomatic with severe as who are already undergoing cardiac surgery makes sense to go with surgery concomitant server, in addition to their cabbage for example, and that's a class one recommendation based on non randomized data. So if it's an asymptomatic of intervention, it all depends on the symptoms. So, if the patients have symptoms, and they have stage D one. Then you go for aortic valve intervention with cyber or Davi. If the patient have symptoms, but they're unable to mounts a velocity more than four meter per second, and that there was an equivocal then you go to assess the LV function. If you have EF less than 50%. These could be stage D to or could be a pseudo aortic stenosis pseudo severe as it is then DSE to try to elicit an increase grain it would make sense. And if there's contractile reserve and the gradient above 40 or V max above four is elicited then you go with aortic valve intervention. Now, if the EF is a preserved, and you would calculate the stroke volume index, if it's compromised, then you want to control the blood pressure, and you look for other etiologies, these patients, often they are women, older, and have restricted cardiac filling. If you use what's causing their stroke volume index to be compromised, you would want to measure this when their blood pressure is well optimized, at least to remove the afterload mismatch from the high blood pressure. And that will give you a better indication about the severity and you need also at the junctive modalities such aortic valve calcium score DVI and other modalities. So what if the patient is asymptomatic. Then, if they have severe as, but they're asymptomatic but have compromised at the function isn't 50% that stays to, they need to go for aortic valve intervention. If they're undergoing cardiac surgery need to go for several concomitant. These are both class one. Now what if the patient is truly asymptomatic with normal at the function. And then, if they're truly asymptomatic severe see one stage, you can put them on a treadmill and see if you can elicit symptoms, or examine the hemodynamic and physiologic response. We have limited functional capacity to sex age adjust, adjusted functional capacity, or they drop their blood pressure by more than 10 to 20 millimeter. And then there's an indication for aortic valve intervention, and usually here it's server, because of the positive of evidence for TV in severe asymptomatic patients. Now, if the patients is severe truly severe asymptomatic, and have a preserved at the function, but have very severe or critical as defined as V max more than five meter per second or meter gradient, more than 60. They're asymptomatic but have evidence of subclinical heart failure as evidence by BMP more than three times normal, or they showed rapid disease progression and we find that us on the European guidelines as more than 0.3 meter per second velocity increase per year. And then progression is average is 0.3 meter per second velocity, seven to eight millimeter gradients, and 0.15 centimeters square reduction area, anything more than that, mostly more than 0.3 meter per second with indicate rapid disease progression. So if the patient is severe at the faster rate than this per year, provided these patients are low surgical risk. These patients can undergo a cyber. So critical asymptomatic as some clinical heart failure, rapid progression, it's reasonable to go for cyber, if the surgical risk is low. The patient had moderate as undergoing other cardiac surgery. It's a class to be maybe reasonable to undergo a cyber, and also it may be reasonable to undergo a cyber, if they have progressive reduction and I'll be function, despite severe asymptomatic aerotextenosis, and you need to do three serial studies to ascertain there's no error in readings, even if the reduction happens and the patient is still within a normal range of the function, but it went let's say from 65 to 55% on three serial testing, it's maybe reasonable to proceed with surgical as well replacements. So these are the recommendations for doing at the interventions. Now, what about that choice of server versus study in these patients, and let's go back to that particular patients. So the ATCHA guidelines, the best therapeutic strategy of this 66 year old man with severe symptomatic as his choice of therapeutic strategy is dictated solely by the surgical risk, as assessed by the surgeon and interventionist, but in vital capacity for palliative reasons, several mechanical procedures, Tavi or server with bioprocesses. Let's dissect those. So first, the first answers, obviously wrong. You need to invoke the multidisciplinary heart valve team when intervention is considered. So cardiac surgeons interventional cardiologist, possibly the primary care physician of the patient, noninvasive cardiologists. You need a physician if needed. And you need in a multidisciplinary heart valve team fashion to determine the risk benefit on alternatives that you think are reasonable for this patients. And then very importantly, obviously, that choice of a prosthetic valve and the choice of the therapeutic strategy should be done in a shared decision making process with the patients. So what are the values of the patient? Do they want to open heart surgery, or they would want a periquitinous procedure? Do they want a prolonged hospital stay or an average of a two to three day mean length of stay with Tavi? We also want to understand their preferences. Are they okay with getting anti-coagulation? As such, they would be okay with the mechanical processes. If it's an absolute preference not to take anti-coagulation, then your only choice is by a prosthesis. And then we need to also discuss the risk and indication for anti-coagulation therapy, as well as very important that durability of the valve. Mechanical processes can last forever technically conceptually while bioprocessors have more limited durability. And data for TAVR bioprocessors is even limited to five years of echocardiographic adjudicated data, and maybe eight plus years of clinical data, while we have way more experience showing the durability of the surgical bioprocessors exceed 15, 20 years. Of course, it goes down with younger Asian groups and we'll talk more about this. Evaluating with a hard valve team, share the same thing with a patient, and objective risk scores are all class one indications, by the way, in our guidelines. Now what about vivaloplast? Only in a critically ill patients based on expert opinion, it may be reasonable to do aortic periquitinous aortic balloon dilatation as a bridge to aortic valve intervention, definitive intervention, like SAVR or TAVI. There's not much data. Alan Kribi, I put this picture because Alan Kribi in 1986 was the first to describe balloon aortic vivaloplastia, and he came back along with Dr. Panagua, my colleague at Baylor and the VA. They both did the first retrograde and ontigrade periquitinous aortic valve implantation, but I like to be even before the 2003 did the first balloon aortic vivaloplastia. At that time, it was deemed a miraculous treatment, but we realized shortly after that there is no survival benefits. And the reason behind this, and also the symptoms improvement are only short lived. And the reason behind this can be really summarizing this meta analysis done by Dr. Kumar and Dr. Panagua and Dr. Phyretas and myself a few years back. We looked at all the literature published in balloon aortic vivaloplastia in the TAVI era, and we confirmed what has been known before, is that you improve severe AS from very severe to moderate to severe or the last severe. And the improvement in mean gradients is really marginal goes from 50 to 25, and they improve an aortic valve area goes from 0.6 to still less than one centimeter square. And the hemodynamic improvements because of the nature of the senile catastrophic stenosis, unlike mitral stenosis, rheumatic mitral stenosis, where it's commissural disease is diffused fibrosis and calcification of the aortic valve. But it's a mechanism, which splits the commissure does not act very well on aortic stenosis. That's different than congenital aortic stenosis in the young, obviously. So, these valves can restynaus, and the symptoms recur within a few weeks to up to three months. That's why I ordered by velocity is not a definitive treatment for severe catastrophic aortic stenosis. Now, whenever you consider the choice of TAVI versus cyber, you want to factor many things. One is the age slash life expectancy. So you want to balance the patient longevity against the durability of the prosthetic valve. So for example, the very young patients. There's a signal survival benefits when you use a very durable durable mechanical aortic valve with surgery, because these can actually last for a long time. And you don't need re-operation and you're not subject to the risk of structural valve deterioration the way you have with bioprostatic aortic valve. Patient risk and comorbids are very important, obviously, you would want to assess the risk score and we have objective risk scores. We use mostly SDS risk scores to assess the surgical risk. TAVI risk score we don't use as much because TAVI risks are really very low. But with SDS risk score, you differentiate into low, intermediate and high risk and even extreme risk which is inoperable patients. And in those with who are at high risk or inoperable risk, it does make sense to proceed with a less invasive approach like TAVI. You don't have to deal with any of the indices you have. You want to also assess other comorbidities that may not be incorporated into the risk score. For example, with SDS does not account for medicinal radiation. And this patient in particular had medicinal radiation in the past. And that accounted for in the SDS risk score and both of those, for example, are increased the risk of surgical risk and make surgery possibly prohibitive and make TAVI more attractive. You want to also account for anatomical and technical issues and procedure specific impediments. So anatomical consideration by Caspid aortic valve are less well studied in clinical trials, and they are at higher risk of complications with TAVI. They're more calcified, more eccentric, so IE, more PVL, although this has been going down with a newer generation TAVI platforms. And oftentimes they may have an aortic aneurysm, a scenic aortic aneurysm or abnormalities. So that makes TAVI more problematic and more tricky and sovereign these patients is preferable. Procedural consideration. If you've got peripheral disease, unable to perform transformable approach TAVI, then it's preferable to go with sovereign. Remember most of the endocrine clinical trials, and our guidelines are really based on data from RCT for the SEMRA TAVI. Alternate access TAVI has been shown promise and effectiveness and safety in multiple non randomized trials, but did not make it yet to the guidelines. The European guidelines have a soft indication for performing alternate access TAVI, but not the American guidelines. Another procedural consideration, for example, low coriosteia distance from the aortic analyst of let's say, six or seven millimeter may subject these patients to occlusion of the coriosteia during a TAVI when you do the implant of the valve, and as such, the valve would be preferable in these patients. You also want to account for the goals of care and the patient preferences and values, including the preferences and values for prosthesis and for onticoagulation. And finally, indications for aortic valve intervention. Remember, the randomized control trials for TAVI, and most of the evidence is derived, or based on patient with severe symptomatic aortic stenosis. And also asymptomatic aortic stenosis, there's a positive evidence supporting the use of TAVI. Now it does make sense that maybe beneficial, but we're waiting for the evidence. While we have decades of experience with a server for symptomatic and asymptomatic aortic stenosis, such as those going for cardiac surgery. So there's some data showing that it's reasonable to proceed with the server, even with severe asymptomatic, at least two surgical products showing benefit, small scale studies but showing benefit. So that's why an asymptomatic patient with severe as server may be the way to go for the time being. Obviously, this is a very dynamic field, and we are waiting for more evidence and more data. So let's go for the crux of the, of the topic, or the most important part of the grand runs. And this is good towards the clinical kind of what also the interventional kind of just so for severe as when to choose TAVI versus server, but the way you see me using interchangibly as of December 2020 our guidelines we are catching up with our European colleagues, and we're now phasing out the TAVI term and we're using TAVI. It's trans-cancer aortic valve implantation. So whenever you have an indication for aortic valve intervention, you want to invoke the patient in a shared decision making, as well as the hot valve team, you want to determine the surgical risk. And according to the surgical rules, you want to dichotomize these patients into either high or prohibitive risk defined by an STS more than 8%, frailty, and multi-organ dysfunction, or if they have procedural impediments like medicinal radiation, or portion higher. So these high or prohibitive risk are one category. And then the other category are not high or prohibitive risk, i.e. low or moderate risk. So if the patient have an indication for aortic valve replacement, and after shared decision making with the patients and deliberation by the heart valve team, if the patient is low to moderate risk, you would want to ask this important question. Is the patient is amenable for vitamin K antagonist, anti-calculation. Can he or she take Coumadin or Warfarin? If the answer is yes, then you would want to see what's the age of this patients. If the patient is below 50 years of age, several with a mechanical processes is the way to go because of the durability of the mechanical processes with several. In very comprehensive valve centers, in patient caretik, anti-calculation, you can entertain RAS procedure, although durability and the IOTIC accreditation with the new IOTIC valve, and complexity of the procedure may make it's really only limited to certain processes. It may be a reasonable approach, but mostly mechanical IOTIC valve. Some meta-analysis show that there may be survival benefits from using mechanical processes with several and younger patients. These patients can take anti-calculation with minimal risk, and this patient needs the long-term durability of a mechanical process. Above 65 years of age, bioprocese is the way to go because with bioproceses, it's likely that the patients will outlive the bioproceses so that durability is not an issue. And also at above age 65, the risk of bleeding with anti-calculation becomes more bigger and bigger and more problematic. At 65 and 50, mechanical or bioprostatic valve with several is the way to go because even bioprostatic several has more data for durability compared to a TAVI bioproceses. Now, what if the patient is not amenable to vitamin K anti-calculations, i.e., this patient will be destined for a bioprostatic IOTIC valve, or if the patient is above 65 and already destined to bioproceses, or patient is younger but really doesn't want to take a mechanical valve, so bioproceses. Once you have a bioproceses determined as a treatment strategy, the next question is, what stage of IOTIC systems does this patient have? If the patient have a stage C2, so anything outside D1, D2, D3, or C2, they would go for SAVR, so stage C1 they go for SAVR, but stage D1, D2, D3, or C2. So the majority of severe symptomatic AS were getting bioproceses could go the route of either TAVR or SAVR depending again on age. So, if they're above 80 of age, the American guidelines say transformable TAVI provided they're suitable for transformable TAVI is recommended as a Class 1 indication. Because the durability of the bioprocese with TAVI is long enough to likely outlive the age of the patients. And the risk of SAVR in this age group is much more pronounced than the risk of TF TAVI. So Class 1 recommendation for transformable TAVI, it's reasonable to do SAVR in lower risk patients, but in general above 80 of age transformable TAVI is recommended. Now below 65 year of age, SAVR is recommended with bioproceses. So between 65 and 80 years of age, this is where you need really a good discussion with the patients and understand the value and the preference of the patients, and you could go either with SAVR or TF TAVI. Now this is the American guidelines and these are quite different than the European guidelines. So our European colleagues and I will go over this in a minute, instead of going with this granularity of age cutoffs 65, 80, and 65 to 80, they went with a dichotomy of 75 above and below, in addition to risk. So we are factoring that I'll take a regulation, the surgical risk, and the age of the patient. So we believe we have a little bit more granularity in our decision making for TAVI versus SAVR. Now what about these patients in the American guidelines who have indication for erotic valve intervention, and have a surgical risk that's high or prohibited. So the question is, do they have a life expectancy? That's more than one quality of life here. And if the answer is yes, and they have suitable valve anatomy, and suitable peripheral anatomy for transphemeral approach, then they should go with TAVI. So we have limited quality of life, as in a year, quality of life expectancy, if they're not suitable for transphemeral TAVI, or have very, very specific, like aspirin, severe erotic stenosis, that make it very high risk, then maybe palliative care is the way to go. So that's the guidelines, because remember we do not have alternate access in the guideline as a therapeutic approach. Our European colleagues do say that you may consider doing alternate access in selected patients. And if you have poor life expectancy, obviously palliative care is the way to go. In the American guidelines, the choices of intervention start initially with determining and a shared decision making with the patient, whether the patient should receive mechanical versus bioprostatic erotic valve. Below 50 years of age, mechanical, erotic valve is the way to go, above 65 years of age, you can use bioprocesses better. You can reasonably use bioprocesses in preference to a mechanical valve between 50 and 65 either way, depending on the patient's anticoagulation risk and preference and values. Once you determine you, the patient's wanna, and it is eligible to get a bioprocesses, then again you go with the age couples, until a life expectancy. Between 65 years of age, or a life expectancy more than 20 years, several of the bioprocesses the way to go because of its durability. Above 80 years of age, or a life expectancy less than 10 years, then transformable type is the way to go, because of its safety, and because the patient is likely to outlive the Tavi by processes between 65 and 80 years of age, either or transformable Tavi is recommended. Now I can remember that there are procedure specific risk factors that are not factored in in the Tavi risk scores and in the STS scores, such as medicinal radiation, erotic classification, the extent of severity of COPD, RV dysfunction, hepatic dysfunction, all these are not factored in the STS scores and they need to be added on in your risk assessment. So these objective scores are not really, are not gospel, you need to add the clinical good stat to it. And also remember that most of these randomized clinical trials were really based on clinical efficacy studies based on the very well appropriately selected patients. Now patients with end-station disease with COPD with hepatic, adverse hepatic disease were excluded in these trials, but we have retrospective analysis and observation data showing that Tavi may be an acceptable alternative in these patients. This is one such analysis from administrative data that Dr. El-Badawi, one of our interventional fellows along with Dr. Cappadia, chair of the clinical clinic, did with myself and many of my colleagues at Baylor. What we showed is patients with a prior medicinal radiation, there's an increase in the use of Tavi over time, while the use of cyber plateaued, and even after multi-variable adjustment, of course these are confounded data because of the administrative data. But with the best multi-variable adjustment models, we showed that there's a signal of mortality benefits doing Tavi over cyber, although these are non-randomized studies. This is just one example of these observational studies that showed the benefit of Tavi in patients, especially the patient population that were not included in the guidelines. This is an example of patients with a prior medicinal radiation, but we have data in anesthesia disease, in patients with liver dysfunction, probably not adverse liver dysfunction, and patients with even by caspered aortic valve, some retrospective and observational analysis showing the benefits and the merits of Tavi in these patients. Now, I want to remind you, I want to remind you of the current outcomes, contemporary outcomes of Tavi. So in the discussion with the patients, when you want to invoke the patients, they share the decision making, you want to tell the patients that 30-day mortality in Tavi has come along quite a bit from 5% to 6% at 30 days in the early expedients to now 2.3%. So the rate of 2% mortality, and it's even lower in the clinical trials, stroke rates coming down in hospital from 2.2% to 1.6%, and 2.8% to 2.3% at 30 days. The pacemaker rates as well coming down to nearly the single digit, now 8% to 10% in hospital versus 30 days. So, and depending obviously on the Tavi platform, but outcomes are improving over time, part of it because of technical improvements because of Tavi platform improvements, but also importantly, because now we're doing more and more low risk patients. Remember the initial approval in 2011 in November, when we started the first Tavi was for inoperable patients based on partner B, a cohort of 300 patients showing survival benefit of 20% of Tavi over medical therapy. Then we had the high risk indication a year after in 2016 when the intermediate risk indication and low risk in patients in the low 70, 72, 73, showing low risk benefits with Tavi compared to saver in 2019. And this is when the low risk FDA label came in. And based on this also we enlarge extends updated the guideline. So we're doing more and more Tavi procedures in low risk patients. And the contemporary data for IOT isolated IOT valve surgery showed a more tight rate of operative of 2.2%, but you had cabbage with the cost of 4%, you had double valve replacements when it's nearly 10%. So part of our leak after Tavi remains a limitation of Tavi but it's less so with the current generation Tavi platforms. Dr. Dhruv Mata, one of our cardiology fellows wrote this editorial and emphasize that really PVL now with the newer platforms, when it's approaching zero for moderate or severe PVL. Part of our leak limitation is being overcome with a better platforms. And also, there's always this question is, when you go for surgery can fix both valve there's a matter of disease, but if you go with Tavi, you're only limited to the robotic but you may need to go for a second approach. There's some data to show that this may be the case in a fraction of the patient but a lot of these patients, if they have concomitant severe AS and severe MR once you fix their IOT valve with a Tavi, what you do is you decrease their LV and systolic pressure and you decrease their pressure and with the help of guideline directed medical optimization therapy, you do not need a subsequent as catheter, I think, my intervention. So that's why in the guideline we shed away from stating that you should do concomitant percutaneous valve procedures to fix the Tavi, the IOT valve for the Tavi, and then you reassess and optimize and reassess the need for it's ER a later on. And there's something we outlined in a nice editorial with your own doctor plan and our brilliant fellow Dr. Jean Souffredi in this editorial. There are no randomized controlled beta there's good retrospective observational analysis showing that it's effective and safe and selected patient to do Tavi however you would want to do them really in a comprehensive valve center. And it's maybe reasonable to do them, preferably it's always preferable to proceed with SAVR as a first option, one these patients are young, they may need anyway mechanical procedures to they have high calcium score, they may be more prone small signal they may have anabolic stroke. They have eccentric aniline, they may have more peripheral leak, although admittedly this may be slightly overcome in the current era with a better Tavi platforms, but there's certainly more risk in these patients. So I think SAVR is preferable and maybe reasonable and selected centers, comprehensive centers to do a bicuspid optic valve Tavi's and Dr. Cayani, one of our faculty members wrote a very nice editorial at the clinical journal on this regard. Let's go back to the case of the patients. I just presented to you. Remember, I told you he had two surgeries. So one of the surgeries was cabbage, and you could see that he has a Rima, a particular Rima to the ADD, and this Rima is adherent to the Mediastinum and you call from this in our lateral view. So doing the open heart surgery may risk injuring this Rima. So that's one that's why surgery is prohibitive. And again, this is not accounted for in the STS core. In addition to that this gentleman had Mediastinum radiation. And I counted for risk. Despite his young age, this guy is at a very high surgical risk for redo, redo surgery. Now what I want you to pay attention to is this ring over here. Remember the apex of the left ventricle. This is a patient we performed a Tavi on in 2012, our early experience. This is a pigtail in the left ventricle. We're doing an LV gram injecting a radio aerated radio contrast material in the LV gram and you see the opacification of this conduit that's going from the left ventricle all the way to the Iota to decompress the severe AS in this patients. So this patients had earlier cabbage and Mediastinum radiation. He had a progression of his aortic stenosis. He's no longer eligible for saver. Tavi was not an option at that time. So he had one of the infrequent surgeries to decomp to relieve the aortic valve obstruction, which is a conduit evolved conduit from the left ventricle to the Iota and there was a valve here. That's a metronic valve. Now this patient few years afterwards came in with symptoms of aortic stenosis again. And the question is, what happened to this conduit, does he have obstruction or stenosis of the valve inside the conduit or there's any conduit problem. We're injecting dye to assess this conduit. We don't see any layering thrombus. This usually don't really form layering thrombus, but we don't see anything gross with this injection. After that, we went through the Iota retrogradually, and took us some time to find the osteum of the anastomosis of the Iota with the conduit. We catheterized it after we found it. We put a wire there and over the wire, we advanced our catheter. We injected dye to check for any obstruction at the level of the conduit. And also beforehand, we did a gradient between the left ventricle and the conduit distilled to the valve and there was no gradient at this level. So really, the valve inside the conduit was not the stenotic culprit. We did a pullback. And you could see that there's a hint of anastomosis problem at the most between the conduit and the Iota. So the conduit was non functional or the conduit is imparting a functional Iota stenosis, but it was at the level of the anastomosis. So here was the choice, should we balloon risky balloon, the anastomosis the static anastomosis between the Iota and the conduit. Or should we proceed with the newly available trans-fameral TAVI and that's what we did at that time in 2012, mid 2012. This is the early generation Edward Sapien TAVI platform. I forgot whether it was 26 or 20, 26 millimeter probably valve. There wasn't 29 at that time, if I recollect. And you see the integrity of this Iotic valve, there's no Iotic regurgitation or a part of our leak upon doing an ascending Iota, Iota angiogram. And this was done obviously under RBP basing with double base maker, nicely deployed Edward Sapien valve. I continue to follow this patient to now and he's doing very, very well. And then later, by the way, with the non-STMMI, and I had to interview on his vein grafts, and I was so happy that I put a short TAVI platform, the balloon expanded platform, because that allowed me easier access to his coriosteum. Actually, it was a vein graft intervention. So coriosteum access was not an issue with this patient. This is his hemodynamics before the TAVI, you see the delayed and diminished Iotic, systolic Iotic pressure, this coincide with his parvus etardus carotid pulse, large gradients, elevated LVDP as well. And then post-transfameral TAVI, you see now your appearance of the dichotic notch, and there's no diminished or delayed pulse and nearly superimposable curves with a very, very minimally gradient of two to three millimeter. Before I finish the topic, I just want to tell you that the European guidelines were published probably three months, two to three months ago. For the most part, they have similar guidelines recommendations to us, with the exception, instead of using the cutoffs of 65 and 83 groups, they use the cutoff of 75, one cutoff. So above 75 or higher risk, patient would go with transformer TAVI, according to the ESC European guidelines. Below 75 and low risk, you go for server. Now, any other patients would go to either server or TAVI. For example, patient below 75, but our moderate risk, they could go either TAVI or server. Above 75, it's strong preference class one for TAVI and high risk or above class one for TAVI. To go for server, you need below 75 years range and low risk to go automatically for server. So really, the European guidelines lower the threshold for the utilization or implementation of TAVI in AS patients. So the reason we did not do that, and we went with the more we think our approach is more granular, because it's, it's basically more granular it allows more choices for the practicing physicians. That's one and remember these are only guiding documents. And with the low risk patients, we really have one to two year data fall out now actually we have more data accumulating intermediate term data but still we're lacking the long term data for the durability of the TAVI by procedure, especially in younger patients, and the partner three trials are really mandated to continue for to report their 10 year outcomes. So we will know in many years from now, what's the long term outcomes of TAVI in low risk patients. So I want to end by reminding you that our team approach objective risk assessment of server risk and TAVI risk, as well as shared decision making with the patient are key. So the guideline, and you want to factor everything in your assessment of the patient treatments and the choice of treatment, including age, comorbidities, freight lead life expectancy, as well as anatomical and procedural considerations. With this I want to end and thank you all for your attention, and I'm happy to take any questions you have.