 Hello. My name is Farooz Mahmood. I'm from Boston. I'm the director of Cardiac Anesthesia at the Beth Israel Deaconess Medical Center. First of all, I want to thank the organizers of this conference, particularly Dr. Azad Mushry, for inviting me to this prestigious conference for speaking on a rather difficult topic. And that is the best papers I've read the last year. He's implying that I read a lot of papers. Having said that, I was in a little bit of a conundrum of which papers specifically to select, but I chose one which is rather a technology-oriented paper and addresses a concept that is very near and dear to me. And I believe it will be very important in the future. So let's get started with the best paper I have read in the last year. Enjoy. So let's get started with the presentation of the best paper that I've read in the last one year. I will start with my dislosures first. I'm an educator and trainer for Abbott Structural Heart and at the same time a consultant for technology development for General Electric. And none of them have anything to do with the presentation that I'm presenting right now and the slides are completely free of any commercial products. So in real time, a clinical challenge during mitral valve surgery is the resolution of the mitral valve zone of co-aptation. Now the zone of co-aptation is referred to as the area or the region of the mitral leaflets where the leaflets oppose each other. It could also be referred to as a zone of apposition between the anterior and the posterior leaflet. While that's the starting and the endpoint of a lot of interventions, but it is something very hard to visualize in real time with echocardiography, particularly so in the operating room. Number one, because of the low line density and low resolution of the images. Number three is because sometimes the image quality is not that great to resolve and truly define the extent of apposition or the co-aptation of both anterior and posterior leaflets that are across the enteral lateral to post-traumatic commissure. So that is a very real time clinical challenge because that zone of co-aptation forms the endpoint of a lot of mitral valve repair techniques, both for degenerative as well as for functional mitral regurgitation. So the paper I chose, which is still in press and not on PubMed right now, is being published in the Journal of Thoracic and Cardiovascular Surgery that relates to the quantitative in vivo assessment of mitral valve co-aptation area after undersized ring analoplasts to repair for ischemic mitral regurgitation. That's a mouthful. But anyway, the group, both Robert and Joe Gorman and Dr. Michael Sacks are colleagues for which we have collaborated in the past in a lot of NIH-related studies for prediction of ischemic mitral regurgitation recurrence after mitral valve repair. And this is really a very credible group. It does a lot of high-end mitral valve reconstruction and deconstruction and geometric analysis. And I've worked with them in the past and the quality of the work that has been done in this paper is truly astounding and mind-boggling. And also, this is important because being collaborators for an NIH study, our data sets were the ones that were used for this analysis and assessment of mitral valve geometry in this specific study. So why I specifically chose this paper, one of the most important reasons is the novel methodology. While it may appear to be a rather unique and a cumbersome and an offline methodology, but I assure you this is the first step towards getting this done in real time and with the computational power of our echocardiography equipment getting better over time, this is more than likely to become mainstream in the short span of time. And because as within the audience, I'm sure there are people who have seen this geometric analysis that were once sort of some research analytical softwares published in biomedical journals are now being published as well as being performed in real time in the operating rooms and a lot of high-end places are using these indices for intraoperative clinical decision-making. And this is also one of the major reasons for choosing this paper was that it addresses a very difficult problem and that is the degree of apposition of the both anterior and posterior leaflets in real time. Because the degree of apposition and degree of co-optation between the two leaflets is kind of the structural mitral valve reserve, which allows the valve to get, you know, stretched, which allows the valve to get retracted, which compensates for the annular dilation because the zone of co-optation gradually, you know, gets exhausted as these remodeling changes happen. And eventually, when the co-optation zone is completely exhausted, the patient tends and ends up having mitral regurgitation. So zone of co-optation is important as the starting point of the knowledge of what the mitral valve reserve function is. And also it is used as a broad and a very qualitative marker of how good the quality of repair is because a greater degree of apposition between the leaflets implies that the mitral valve has more reserve or more structural reserve to sustain ischemia-related or volume overload-related structural remodeling and therefore remain functional and that is non-regurgiton during cysts. And therefore, this paper certainly has a lot of future implications for the way we assess mitral valve geometry in the operating room. And the reason and the prospective statement of this paper is important where they say that patient outcomes of regurgiton mitral valve remain unpredictable. This is very poor. And one of the recent trials published in the New England Journal of Medicine where they found that at two years almost 50% of the patients who had repair had recurrent MR after surgery. And that is due to an incomplete understanding of repair complexities and limitations of our echocardiographic imaging. We can do a lot of good things, but high-resolution images to the point that we can actually define the degree of apposition and define the area of the overlap of these two leaflets is something that precludes us and something that we cannot do in the operating room reliably or at least not in a time-efficient manner to allow us to make a good decision. So therefore, this group applied that image-based simulation technique to quantify the co-optation zone in a repaired mitral valve and demonstrated that our common wisdom of increasing co-zone of co-optation between two leaflets is not necessarily a protector of competent repair and could essentially mean bad news also. So there are some lessons to be learned with this paper which I will go over in one second after. I want to go over the technique as well because that is an incredibly novel technique to do it. So the objective of this study was to quantify patients' specific mitral valve co-optation behavior from clinical echocardiographic images obtained pre- and post-repair to assess co-optation restoration and its relationship with long-term durability. What we did was that they had these intraoperative echocardiographic three-dimensional images that they used to assess the degree of co-optation of leaflets after mitral valve repair and then followed up these patients for at least six months post-operatively to see whether these patients had regurgitation or they had recurrent MR after ischemic mitral valve repair. So the step one what they had done initially was they took ovine models of mitral valve. They took fiduciary markers on the surface of the valve and let these valves be implanted in a pulse duplicator in a micro CT and that was about eight or 10 mitral valves which was simply, you know, an experiment was done in an initial publication which was their reference to develop a normal-looking model of the mitral valve which would mean that how would a mitral valve look in digital space. So with those fiduciary markers they were able to define the surface geometry, the zone of co-optation, the analogue behavior and displacement using ovine mitral valves in a pulse duplicator during cystly and diastasis. So that's step one and forget about it because once we get down to the later part of this paper we'll go over how this was applied to this specific study in which clinical data was used to define the geometry of the mitral valve. So shape matching of the mitral valve was done was that we used a previously extensive set of five in vitro ovine mitral valve meshes as the target, geometries of shape matching. So being complicated but here's what it is. So freshly implanted ovine mitral valves are instrumented with about 100 fiduciary markers uniformly distributed over the full mitral valve surface area and installed into a pulsatile flow loop to mimic a healthy left ventricle. These mitral valves are an image using micro CT scanner in both end diastaly and in cystly. So they found, they matched or marked the behavior of these valves, both at end cystly and diastaly that is when the valve was completely open and the valve was completely closed. Now this data was processed to reconstruct the end diastolic leaflet geometry and the end systolic leaflet geometry and was reconstructed by Ida Radley building correspondence between the fiduciary markers in two states with a hyperplastic fiber with finite element framework. So essentially they reconstructed the mitral valve based on these digital markers that was placed along the surface of the mitral valves as well as the analysts and found how they reacted and how they behaved in end cystly as well as in end diastaly. So in simplified the methodology of this study was that they had 3D data sets of intraoperative mitral valve repairs for ischemic mitral regurgitation. They had a cartesian export of both end systolic and end diastolic frames from this volumetric data set which was imported into the MATLAB and then there's further reconstruction of the mitral valve surface topography that was based on these cartesian coordinates. Then came the more complicated part where finite element modeling was performed to push the mitral valve from end systly to end diastaly to end systly by application of digital force and then led to finite element shape matching and finally the mitral valve was matched both digitally with the ovine models reconstruction that had been done initially from a baseline study. And as a result of that matching of mitral valve geometry with the ovine shapes that had been preserved as part of our reference method, the computation of the co-aptation zone was performed. So this is kind of a simplified methodology they used. They had 3D data sets, cartesian exports, went to MATLAB, then reconstructed the valve and applied finite element modeling to put pressure on the valve from end diastaly to end systly then shape matched with the mitral valve from the basis of those digital reconstruction of those ovine models that had been created as a reference model for the shape of a mitral valve. And after that had been done, the zone of co-aptation was created and the area was calculated. So in essence, first the images were segmented and processed. Subsequent meshes were used at the inputs for our finite element base closure simulation. So mitral valve was initially closed by applying physiological loading and boundary conditions but that technique results in sometimes an accurate representation of true end systolic stage of the mitral valve and as a result co-aptation was developed. Now based on the reconstruction of the co-aptation zone and the generation of both end diastolic and end systolic volumes, they created two states, that is an empty closed state and is an open state. And then the closed state, they were able to demonstrate the final shape of geometry which was based on the assimilated model of mitral valve that was developed on the basis of normal anatomy of mitral valve for ovine models. But the key part of this thing is that they were able to trace and the simulation model was able to track the co-aptation zone even beyond the point of co-aptation which you normally do not even see with echocardiography. So based on the artificial intelligence and the ability of the simulation to reconstruct based on the normal shape matching of the mitral valve, the co-aptation zone was not only created at the point of opposition but also the redundancy of the leaflets were defined that went and extended beyond the point of co-aptation also. So based on that, they defined the two anterior and posterior leaflets. They defined a plane from which the co-aptation zone started. This is the anterior leaflet co-act contact region and this is the posterior leaflet co-actation region and this is the anterior leaflet redundant region. So this is the anterior leaflet, posterior leaflet, this is the contact elements and this is the redundant element which you normally are unable to see with three-dimensional echocardiography because of poor resolution. Now this has the common wisdom is that the more co-aptation zone you have, the better the repair because that's kind of the holy grail of all mitral valve repairs is that you are able to generate a greater opposition between leaflets both anterior and posterior and which implies the valve has more and a greater structural reserve and it can sustain geometric distortions. So the representative mitral valve reconstructions demonstrated an open state, real-time three-dimensional echocardiography of the mitral valve with analysts and the free edge, closed state reconstruction and final simulated geometry was created and if you were to open the valves, the leaflet demonstrated a significant co-actation zone both between the anterior and posterior leaflet as well as a redundant leaflet both and more so the anterior leaflet which extended beyond the plane of the mitral valve. So however, now let's get to the finding, this is a very complicated setup but paradoxically what they found was that in patients that develop recurrent ischemic mitral regurgitation after six months after undersized ring aneloplasty repair, the contact area after immediately repair was actually greater than that of the patients who did not have recurrent mitral regurgitation in six months which means this is a paradoxical finding because this is what we essentially try to achieve when we are doing mitral valve repair is to create a greater opposition of leaflets so that we can have a greater zone of co-actation between them. Therefore, you have a greater mitral valve reserve and therefore you have a greater tendency, a greater likelihood to sustain structural abnormalities and sustain structural distortions without becoming overtly dysfunctional as regards to regurgitation. So moreover when they found that when normalized to total systolic leaflet area to account for general larger presurgical mitral valves in the recurrent group, the contact area increased more in the recurrent group compared to the non-recurrent group which means they initially thought maybe this is because they had a greater contact area because they were larger valves and therefore they were making it look like that a larger area was associated with more recurrence simply because of a larger valve and a larger analyst. But even when they normalized this thing to the size of the valve and the height in the sub-body surface area, they found that there was a significant correlation with greater co-actation or more redundant leaflet and greater, you know, recurrence of ischemic mitral regurgitation postoperably. Now, this is a very, very interesting finding. And at the same time, they also tried to correlate the absolute mitral valve tenting area which means the degree of tethering of the leaflets with the recurrence. As you can see in the study, the absolute mitral valve tenting area was higher, larger at baseline that is presurgical, had more tenting area than the non-recurrent mitral valves. But at the same time, this difference disappeared after, you know, post-surgical which means both of them had pretty much the same tenting as a non- or insignificant statistical significance was not very significant because it demonstrated that both had the similar mitral valve tenting area. So therefore, they concluded that absolute mitral valve tenting area, even presurgical, does not necessarily reflect a more swear presentation of mitral regurgitation. Now, these were contradictory results because we tend to believe that mitral valve tenting area is a very important prognostic indicator of what the chance of postoperative recurrence is. So this is, again, a very paradoxical finding. It doesn't seem to make sense because it is something that we are taught otherwise. We think we are taught that the mitral valve regurgitation is likely to, you know, not likely to recur the tenting area is large and this one seems to have no correlation at all, you know. So now, they gave it an explanation also. And they said that these observations can be explained by the fact that all patients received approximately the same size anoplastering. So there, of the 14 patients that had this thing done, there was not a significant difference between the sizes of the rings that were applied. As a result, larger mitral valves ended up having a lot of redundant mitral valve. So similarly, size rings result in very similar post-surgical annular orifice area, which means regardless of what the pre-surgical annulus area was, post-surgical annulus area ended up being the same. So therefore, recurrent mitral valves experience a larger percentage change in annular reduction postoperately. But don't you think that's great? But it turns out, but they believe that consequently the recurrent mitral valves are likely much more tethered after repair than their non-recurrent counterparts, which may explain the suboptimal long-term outcomes. Now, long and short of this thing is what they're trying to demonstrate is that by putting an annular plasty ring, which is the same for both a dilated or non-dilated annulus, what we have done is that we have created a more redundant leaflet, which is more susceptible to tethering and therefore, more than likely that this leaflet was tethered leading to more more regurgitation. And the conclusion they reached was that the current study applied a simulation-based technique to recover the full mitral valve geometry for clinically obtained echocardiographic images, which demonstrated that contrary to expectations, increased mitral valve co-optation after undersized ring annular plasty repair does not necessarily imply a more durable repair. What they are trying to say and what I think the major conclusion is is that the continuation of the adverse LB remodeling that continues even after an undersized ring annular plasty is not halted by an annular plasty and therefore, that adverse remodeling keeps playing its force, keeps retracting the leaflets, keeps tethering them to the point that they eventually become regurgitant and they lose the zone of co-optation. So therefore, adverse LB remodeling, aggravated leaflet tethering, and or advance leaflet plasticity may play a larger role in the MR disease process, suggesting that mitral valve focus treatments may not lead to optimal outcomes. That's what we commonly say that my undersized ring annular plasty is actually a valvular solution to what is a ventricular problem, and that seems to make sense. However, there are certain limitations of this study. There's only about 14 patients. But again, the methodology was incredible. The results are saying a very strong association and the results are very plausible. Now, we will extrapolate that to another study which one of our very, this is sort of before I go there, let's get to the bottom line of the study which is a visual abstract of the study where they say the question they wanted to answer was, does great post-surgical mitral valve leaflet co-optation area imply better durability? The answer to the question is saying, no, it does not. And the surgical implications of this study are co-optation area alone may not be a reliable target for repair durability. And in some patients, adversary modeling, aggravated leaflet tethering or advanced leaflet plasticity may play a larger role in the MR disease process. Therefore, patient-specific and LV and mitral valve integrated models are crucial for improved treatment planning. Now, I will take this a little further while this related to post-surgical or post-repair mitral valve assessment. We believe that the real implication of this study is that this is the first step to defining the zone of co-optation in real time while this is being done post-acquisition. But it's only a matter of time before this information we could do it with AI and higher computational power in the operating room in real time. So this is something that we have also worked in the past and that is of assessment of risk of mitral regurgitation and non-regurgital mitral valves in ischemic cardiomyopathy based on structural mitral valve reserve. As you can see the non-regurgitant mitral valve is a zoom normal. But take a look at these two mitral valves. So this valve is non-regurgitant as is this valve. However, this valve has a higher zone of co-optation and therefore a larger mitral valve structural reserve to sustain structural demodeling as opposed to this mitral valve which has very limited reserve and therefore despite being non-regurgitant this valve is much more likely to structurally fail and become regurgitant as opposed to this one. So therefore non-regurgitation should not be implied as a normal valve because it really depends on the zone of co-optation and the degree of opposition of those both leaflets and therefore this is one of those studies which was presented in an abstract in European Association of Cardiothoracic Surgery and is currently under review for publication. This is we're using three-dimensional TE data. Structural mitral valve reserve was defined and compared between patients undergoing cabbage with no mitral regurgitation and with ischemic mitral regurgitation. We took the, you know, mitral valve was calculated that is the zone of co-optation between both the anterior and posterior leaflets. I'm not going to go into the detail of how we calculated but we calculated that in three zones. Zone one being entrolateral, zone two being the middle one and zone three being the post-remediate zone. And we found that in these patients that the non-regurgitant mitral, non-regurgitant mitral group had a larger mitral valve reserve than the IMR group in regions one and two which means both zone one and zone two, the non-regurgitant mitral valves had a larger co-optation reserve than the regurgitant mitral valves. However, the reserve was comparable at the post-remediate portion of the valve which is more than likely to fail in most patients which means at A3 and P3 regions even those patients who have non-regurgitant mitral valves and have ischemic cardiomyopathy, they are comparable pretty much as much reserve as a regurgitant mitral valve had which means this is one of the most susceptible regions of the mitral valve that is likely to fail when the valve retracts or there's further adverse LV remodeling. So we concluded that non-regurgitant mitral valves vary in the risk of developing mitral regurgitation and depletion of structural mitral reserve is a regional phenomena with post-remediate portion of the non-regurgitant mitral valves with ischemic cardiomyopathy at most risk of co-optation failure with regional remodeling. So therefore depletion of mitral valve reserve, this is the co-optation reserve which is very difficult or almost impossible to calculate intraoperatively, is demonstrated by progressive posterior displacement of the co-optation point which means the posterior leaflet gets retracted, the anterior leaflets tends to compensate for by stretching and lengthening and therefore the co-optation zone or the co-optation point of co-optation between anterior and posterior leaflet is shifted progressively posteriorly. Therefore valve structure and severity of regurgitation, the most important structural reserve is the co-optation reserve and is the most important predictor of the likelihood of regurgitation, not only in those patients who have no mitral regurgitation as well as the ones in which we achieve good co-optation but the adverse LV remodeling discontinues and therefore leading to valve failure and regurgitation. This is another paper which is soon which has been accepted in a publication where we tried to estimate that it is incredibly difficult to calculate this zone of co-optation in the operating room because it takes hours to calculate the lengths as well as the areas of the co-optation zone in three zones. We tried to see that is there any specific echocardiographic parameter that matches the depletion of the co-optation zone which means we could look at it and say alright if this echocardiographic parameter is present that implies a progressive depletion of the zone of co-optation between these leaflets. And again we found that zone 2, this is the A2 P2 region, has the most reserve in any mitral valve that presents for surgery and zone 1 and zone 3 have less reserves. However, we believe and we found that both the tending area and tending height did not correlate with the co-optation zone as was shown in this current study by the group at UPenn. And that I believe precisely is because the tending area and tending height represent the tomographic portion of the topography of the valve. They're not representing the entire surface of the leaflet. It just represents one significant portion at A2 and P2 and ignores the degree of tending or the degree of retraction of the leaflets at other regions. However, most interestingly what correlated most with the structural reserve was the tending volume which means an increase in tending volume was related with negative correlation with the structural reserve of the valve which means as the tending volume increased there was progressive depletion of the co-optation reserve. And that's possibly because that the co-optation reserve correlates more with the global topography of the valve and tending volume represents not a tomographic section but the entire topography of the valve. So therefore in conclusion what I wanted to suggest here is that I'm glad and I'm proud to see that these indices of mitral valve remodeling are now being used and now being applied for decision making in the operating room although retrospective in nature the one that we presented from the Journal of Thoracic and Cardiovascular Surgery was retrospective with a small number of patients but it does imply that these geometric parameters can be used prognostically to predict the patients who can have valve failure and recurrent regurgitation and make more plausible clinical decisions that are based on LV incorporating the left ventricle into the mitral decision making. Thank you very much.