 Good morning. I am going to be talking today about how to use a strain imaging to guide clinical decisions. I don't have any disclosures to make for the content that I'm going to discuss with you today. But I want to start with a poem from one of my colleagues, Ritu Tanman, from the American Society of Echo. A strain is not a pain. There is much to gain. It's not arcane. Don't rock your brain. Know enough to come out of the rain. So this is what I want to cover with you today. I'm going to start with some fundamentals. Then I'm going to discuss with you the normal values, and I'm going to be talking about two areas where I think a strain is ready for clinical applications. Heart failure and bowel or heart disease, and then I'm going to end up with some conclusions. So in terms of the fundamentals, the whole reason why we need a new modality of imaging is because some of the imaging that we do is affected by tethering. If you allow me to use the image that you have in the screen as an example, you are able to rapidly recognize that there is an infarct in the mid-LED territory. The area proximal to the area of infarct is contracting very well. But if I ask you if the mid-segment of the anterior septum is moving, you will tell me that it's moving, but that segment is not having meaningful deformation. It's moving because it's being pulled, it's being tethered by the adjacent segment that has not been affected by the myocardial infarction. So then what are the alternatives? The alternative is I could use M-mode for each of the segments of the heart. The problem is that it will be very tedious, very time-consuming, and I will never get to go home the days that I am reading in the echo lab. But really what I need is I need a modality that will be independent from tethering from the adjacent myocardium, one that will allow me to do characterization of myocardial mechanics for each of the segments, and that is a strain. So now let's take a look over here in the image that you have in the screen, the difference between movement, which is not what I am interested on, and the formation, which is what I am interested on. So a strain is the formation. A strain is defined as the formation of an object normalized to its original shape. So in a one-dimensional object, the possible deformation is either lengthening or shortening. So let me illustrate to you with this cartoon how simple the concept is. So if you start with the blue part that has a dimension of 7, and if I go to 9 cm, then the deformation would be 2 cm, and I told you that you need to normalize it to the original dimension. So in this case it would be 2 divided by 7, and the strain would be 28%. I don't know if the way that the heart was presented to you during your training was different, but the heart was introduced to me as some three donuts, representing the base, the meat, and the apical segments that will contract towards the center of the donut. But really if we take a look at our current understanding, the motion of the heart reminds you more of the ringing of a wet towel where you have your right hand going in a clockwise direction and you have your left hand going in a counterclockwise direction. If you have done this, you recognize that from the mechanical standpoint it's actually fairly effective. It gets the water pretty dry, and you are able to appreciate in the towel that fibers will go in different directions. The same thing happens in the heart. You will have two perfectly connected helixes. We call it the right hand helix and the left hand helix, and they go in opposite directions from the subendocardium to the subepicardium and subepicardium to subendocardium respectively, and they allow for perfect connection between the mechanical and the electrical point of views. So then if we analyze the direction of the fibers, you are going to have longitudinal fibers located mostly in the subendocardium, and this is going to be very important when we talk about clinical applications, and you are going to have circumferential fibers located in the mid-aspect of the thickness of the myocardium. In terms of the technique that we use, the one that I am going to be presenting to you is called speckle tracking, and it's called speckle tracking because that's exactly what it does. It tracks the speckles during the cardiac cycle. So if you allow me to use the example in the right upper panel, you are able to appreciate two speckles. So if you follow these two speckles throughout the cardiac cycle, if the two speckles are coming one next to the other, it means that that segment is actually having meaningful deformation and not just movement. In terms of the display of the strain, it's color-coded. You will see red if the strain is appropriate and you are going to have blue if instead of having shortening, you are having elongation. You are able to appreciate in the left lower panel individual strain scores for each of the segments of the heart and on the right side you have the curves of the formation and you also have the color emote, letting you know that all of the segments are achieving maximum deformation at the same time. So let's move to discuss the normal values and this is important. So what is considered normal in most of the labs in the United States right now and all over the world is more negative than minus 18 is normal, between minus 16 to minus 18 is considered borderline and worse, i.e. less negative than minus 16, will be considered abnormal. So let's move to discuss the clinical applications and as I promised you, let's start with heart failure. So you have over here in the screen this very nice review by two of my former colleagues from Cleveland Clinic, Dr. Tom Marguic and Dr. Jim Thomas, talking about the application of a strain in patients with heart failure. You are able to see different applications in the area of risk assessment, diagnosis, management and follow-up. I wish I had time to discuss all of these applications with you, but I am going to center on three of them, on risk assessment, on diagnosis and on follow-up. So let's start with risk assessment. So ejection fraction in the patient with heart failure, as you can see from this slide, functions very well in terms of the ability to prognosticate mortality once the ejection fraction goes below 40%. But you are able to appreciate the lack of delivery of this modality when you are trying to prognosticate the patients that we call right now heart failure with preserved ejection fraction, which happens to be very prevalent in the United States with a prevalence north of 50% in terms of the patients with heart failure that we get to see on a daily basis. Now, I want to present to you two nice articles that illustrate the role in the patient with heart failure in terms of risk stratification. So the first one is this one from Tom Margwick, where he did a shoulder-to-shoulder comparison of ejection fraction and well motion score index against global longitudinal strain in the ability to prognosticate mortality in patients that are suspected or known to have LB impairment. So you see over here the methodology. They use for calculation of ejection fraction their recommendations from the American Society of ECHO and they calculated global longitudinal strain in the way that I taught you how a few minutes ago. You have over here the results, but probably the most important ones are contained over here in this table. But let me remind you of the methodology that they use. They did it exactly in the same way in which we do it when we see patients. They interview the patients first, they ask them for clinical variables and to no surprise, H diabetes and hypertension were prognostic of mortality. And then the question was what is the modality that has the biggest added value in terms of prognosticating? And you see over here using chi-squares that global longitudinal strain was the modality that had the biggest added value once I have collected my clinical variables. Dr. Marwick ends up concluding that global longitudinal strain is a superior predictor of outcome to either ejection fraction or one motion score index and that it may become the optimal method of assessment of global LB function. He comes few years later, not with 546 patients, but this time with 5721 patients and you're able to appreciate that over here in this slide the hazard ratios were clearly global longitudinal strain functions better than ejection fraction in terms of prognosticating mortality in this population. Now, when we separate from the initial publication that I showed you, the one from Estanton, patients that have an ejection fraction of more than 35 versus patients that have an ejection fraction of less than 35, you see that where global longitudinal strain will give you value is exactly in this population in which ejection fraction does not function well, which is the ones where the ejection fraction is north of 35%, as you can see in this slide. This article is very important because I think that one of the challenges that clinicians and administrators face right now is in the prevention of readmission of the patient that has heart failure. So in this particular case, what they did in this study is they were able to figure out different imaging modalities and their ability to prognosticate mortality or readmission. And as you can see, you start fairly low with just ejection fraction. Things get a little bit better when you add the E over E prime. It gets a little bit better when you add the global longitudinal strain, but you see the significant improvement in performance of the model when you add global circumferential strain. And the reason for that is that if you have two patients, and if patient A and patient B have the same ejection fraction, same E over E prime, same global longitudinal strain, but patient B has an abnormal circumferential strain, you know that this patient will have a higher possibility of dying or being readmitted with the syndrome of heart failure because this patient and the abnormality that the patient exhibits in the global circumferential strain tells you that there has been progression of disease and that you are no longer just having affection of the longitudinal fibers in the subendocardium, but that you are having compromise of the mid-aspect of the thickness of the myocardium with progression and extension of the disease. In terms of diagnosis, when I was at Cleveland Clinic, along with our group, we were the first one to report on the use of global longitudinal strain to make a specific diagnosis. And specifically, I'm talking about the patient that you see in the left upper panel with amyloid. The patient with cardiac amyloidosis has a very specific appearance in global longitudinal strain. It's called apical sparing or cherry on top appearance. And the explanation for this is that the last area that is affected in the patient that has cardiac amyloidosis is the apex. In the case that you see in the screen, you see the base and the mid-segments being affected with the apex being relatively spared from the disease. Hence, you know the name of apical sparing. Then you see other patterns. You see a patient with restrictive heart disease to the right. And this patient probably had a radiation induced heart disease and you can almost see where the radiation therapy hit the heart with the anterior and anterior septum being the most affected and the rest of the heart are relatively spared. And then at the bottom and on the left, you see your patient that has apical hypertrophic cardiomyopathy with a pattern that looks almost opposite to the one of apical sparing where the one area that is compromised is the apex of the heart with actually sparing of the base and the mid-segments. Just to finish up, if we talk about a follow-up, the use of global longitudinal strain has been extensively studied in the population of patients undergoing cancer therapy in the so-called new area of specialty called cardi oncology. So this is one of our papers. In this particular case, we evaluated breast cancer patients that were being treated with antracycline-based chemotherapy and also Trastuzumap. And as you can see, you are able to use global longitudinal strain as a way to prognosticate the patients that are going to have a subsequent reduction in ejection fraction. You are able to realize that some of these patients in parallel are also leaking troponins, giving you a mechanistic explanation as to why the global longitudinal strain is abnormal. And then you also see how if you combine both of these modalities, you will end up with a very nice negative predictive value of 91%. So this is an example of how to use it in cardi oncology. You start with a baseline global longitudinal strain of minus 25.5 and in somebody that is receiving a Trastuzumap-based chemotherapy, the global longitudinal strain goes to minus 19, having a percentage reduction of 25%. So this tells you that the mechanics of the heart have been affected by chemotherapy, giving you the opportunity to recognize that much very early. So let's switch gears to vabular heart disease. And I'm going to present to you three scenarios, aortic stenosis, aortic insufficiency, and mitral regurgitation. When this first work from some of my colleagues at Cleveland Clinic, they used two modalities to prognosticate the patient with aortic stenosis. One is a global longitudinal strain base and you can see how if the global longitudinal strain is abnormal it allows you to identify patients that are going to have mortality and to the right they use the ventricular arterial impedance to prognosticate these patients as well. I really like this article, this is in the setting of aortic regurgitation and in this particular case they are using global longitudinal strain to differentiate the patients that are going to remain stable versus the ones that are going to progress. So you see to the right that there is no statistically significant difference in ejection fraction in the dimensions of the ventricle. The only difference for the patients that will progress versus the ones that are going to remain stable is in the global longitudinal strain. Now the part that is interesting is that we were told when we were in training that aortic insufficiency was a forgiving bubble or heart disease lesion. That in the moment that you address it the ventricle is going to shrink, the ejection fraction is going to go up and the patient will live happily ever after. But if you take a look at a strain you end up realizing that once the strain is abnormal the strain will remain abnormal letting you know that the damage is permanent. Then you end up having data like this one again from the group at Cleveland Clinic where if you use a code of value of a strain as the one that you see it over here they use minus 19.5 you are able to actually prognosticate mortality in the patient with aortic insufficiency. So it's not just a biomarker that we are following in this case global longitudinal strain but one that has an impact in mortality. You are able to see the same trend in patients that have mitral regurgitation over here as you can see they use a slightly different code of value but I think the concept is the same and the concept is that if you are able to use this technology in patients that have mitral regurgitation you are able to end up coming up with a realization that ejection fraction is not enough. I think that we all have seen patients that have a normal ejection fraction they get operated on a timely fashion and then we follow them down the line and the ejection fraction will be mightily reduced in the 40s then you start kind of wondering what happened to these patients and the answer is that the ejection fraction was misleading you a little bit as to how adequate the performance of the ventricle was. So I hope that I have given you a little bit of a flavor as to what global longitudinal strain means. I walk you through the fundamentals of what the concept behind strain is. I was able to review with you the normal values. I review with you the applications in terms of prognosticating death in the patients known or suspected to have heart failure or LB impairment. I share with you how it can be used in the emergency room in patients that are presenting with acute heart failure to prognosticate death or readmission and then I show you the application in the area of cardi oncology and in the area of bubble of heart disease where this technology takes you beyond ejection fraction and with that, thank you so much for your attention.